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51. Personnalisation de la dose et du fractionnement de la radiothérapie des cancers de la tête et du cou

Author: F. Nguyen, Joël Castelli, Julian Biau, Pierre Graff, Yungan Tao, Pierre Blanchard, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Méthodologie et épidémiologie clinique en oncologie moléculaire (U1018 (Équipe 2)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Planning target volume, Meta analyse, 03 medical and health sciences, 0302 clinical medicine, chimiothérapie, medicine, Radiology, Nuclear Medicine and imaging, Fractionation, Human papillomavirus, Head and neck, Radiothérapie, Nasopharyngeal cancer, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Gynecology, Virus d’Epstein-Barr, Cancer des voies aérodigestives supérieures, business.industry, Head and neck cancer, Cancer du nasopharynx, medicine.disease, Altered fractionation, 3. Good health, Radiation therapy, Fractionnement, Oncology, Méta-analyse, 030220 oncology & carcinogenesis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: National audience; Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.
Published: 2019

52. Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study

Author: Julien Taieb, Edouard Auclin, Yosra Zaimi, Maximilien Barret, Claire Gallois, Simon Pernot, Roger Faroux, Christophe Locher, Pascal Artru, Astrid Lièvre, Thierry Lecomte, Lysiane Marthey, Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Eugène Marquis (CRLCC), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital privé Jean Mermoz [Lyon], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], Centre Hospitalier de Meaux, AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Multivariate analysis, Drug-Related Side Effects and Adverse Reactions, Colorectal cancer, [SDV]Life Sciences [q-bio], Nutritional Status, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, Adverse effect, Chemotherapy toxicity, Aged, 2. Zero hunger, Metastatic colorectal cancer, business.industry, Malnutrition, Hazard ratio, Cancer, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Nutrition Assessment, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Multivariate Analysis, NRI, PG-SGA, Female, Colorectal Neoplasms, business
Abstract: Introduction The Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). Objective The objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. Methods This prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. Results A total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. Conclusion Although more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.
Published: 2019

53. Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study

Author: Marine Gross-Goupil, Sylvie Chabaud, Mathieu Laramas, Gwenaelle Gravis, Frank Priou, Lionnel Geoffrois, Stéphane Culine, C. Dalban, Philippe Barthélémy, Marina Chenot, Stéphane Oudard, Frederic Rolland, Hakim Mahammedi, Florence Tantot, Delphine Borchiellini, Bernard Escudier, Nadine Houede, Sylvie Negrier, Sylvain Ladoire, Laurence Albiges, Bérengère Narciso, Florence Joly, Ronan Flippot, Christine Chevreau, Brigitte Laguerre, Elise Deluche, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Département d'oncologie médicale [Centre Georges-François Leclerc], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Grenoble, Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
Subjects: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Standard of care, [SDV]Life Sciences [q-bio], Phases of clinical research, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Text mining, Renal cell carcinoma, Internal medicine, medicine, Humans, Carcinoma, Renal Cell, Aged, Brain Neoplasms, business.industry, Middle Aged, medicine.disease, 3. Good health, Editorial Commentary, Clear cell renal cell carcinoma, Nivolumab, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business
Abstract: PURPOSE Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population. METHODS The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor–directed therapies ( ClinicalTrials.gov identifier: NCT03013335 ). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A. RESULTS Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity. CONCLUSION Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.
Published: 2019

54. Alpelisib and fulvestrant efficacy in HR-positive HER2-negative PIK3CA -mutant advanced breast cancer: Data from the French early access program

Author: Bertucci, F., Bello, Diana, Bertucci, Alexandre, de La Motte Rouge, Thibault, Blonz, Cyriac, Akla, Sarra, Grenier, Julien, Bailleux, Caroline, Benderra, Marc Antoine, Simon, Helene, Desmoulins, Isabelle, Tharin, Zoé, Renaud, Emmanuelle, Delaloge, Suzette, Bertho, Marion, Cottu, Paul, Goncalves, Anthony, Bidard, François-Clément, Lerebours, Florence, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Eugène Marquis (CRLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université Paris Cité (UPCité), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Département d'oncologie médicale [Centre Georges-François Leclerc], UNICANCER-UNICANCER, Institut Gustave Roussy (IGR), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and Institut Curie [Paris]
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Fulvestrant, business.industry, Advanced breast, Mutant, HER2 negative, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer data, Internal medicine, medicine, business, medicine.drug
Abstract: 1064 Background: In 11.2018, the PIK3CA-inhibitor alpelisib was made available in France through an early access program (EAP), in combination with fulvestrant in pre-treated PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer (ABC) patients. Patients had to received two or more prior systemic treatments for ABC, including an aromatase inhibitor and a CDK4/6 inhibitor in the absence of contraindications. This retrospective real-life, EAP-based study aimed to assess the efficacy and safety of alpelisib/fulvestrant combination in the post CDK4/6 inhibitor setting. Methods: The IRB-approved protocol and call for data were sent on 10.2020 to the cancer centers which participated the most in the EAP prospective registry. Eligible patients were women who started alpelisib/fulvestrant between 11. 2018 and 10.2020 as part of the EAP (which excluded patients with visceral crisis or inflammatory BC). Alpelisib and fulvestrant were used at standard doses. Primary endpoint was PFS by local investigators using RECIST1.1. Secondary endpoints included objective response rate and safety (NCI CTCAE v5.0). Results: 10 centers provided individual data regarding 209 consecutive patients. Patients had received a median number of 4 (1-14) previous systemic treatments for ABC, including CDK4/6 inhibitors, chemotherapy, fulvestrant (alone or in combination) and everolimus for 206 (98.8%), 159 (76.1%), 163 (78%) and 123 (58.8%) patients, respectively. With a median FU of 7.0 months, median PFS was 4.0 months (95%CI [3.5;5.0]) and 35.4% of 164 evaluable patients had an objective response. After stratification on the number of prior lines of treatment, prior exposure to everolimus had no impact on PFS (mPFS in the 123 patients pretreated with everolimus: 4.0m, 95%CI [3.5-5.5]). Of note, this population was enriched in patients who had a long disease control by everolimus (median time spent on everolimus: 7.0m, range (6.5-9.0)). In multivariable analysis, characteristics significantly associated with longer PFS were PS < 3 (HR = 0.03, 95%CI [0.02-0.29]) and prior treatment with fulvestrant (HR = 0.53, 95%CI [0.32-0.89]). N = 81(38.8%) patients discontinued alpelisib due to adverse events (AEs). Most frequent grade 3/4 AEs were hyperglycemia, skin rash, diarrhea and fatigue occurring in 13.4, 8.1, 4.8 and 1.9 % of patients, respectively. Conclusions: Despite heavy pre-treatments, alpelisib +fulvestrant had a clinically relevant efficacy in the French EAP population. Interestingly, prior treatment with either everolimus or fulvestrant did not overtly impair alpelisib-fulvestrant efficacy. The best treatment sequence for PI3KCA/mTOR inhibitors could be examined in future trials in PIK3CA-mutant ER+/HER2- ABC patients.
Published: 2021

55. Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary

Author: Jessica Miroir, Yungan Tao, M. Doré, Shakeel Sumodhee, Nicolas Blanchard, A. Beddok, Alexandre Coutte, Matthieu Caubet, C. Pflumio, Julia Salleron, Jean-Christophe Faivre, Juliette Thariat, S. Servagi-Vernat, Valentin Calugaru, Joël Castelli, X. Sun, I. Troussier, Paul Giraud, Vincent Roth, Bruno Toussaint, Marco Krengli, J. Khalifa, Duc Trung Nguyen, Claire Petit, Florent Carsuzaa, Yazan Abu-Shama, Lionel Geoffrois, Edouard Romano, Charles Dupin, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Institut Curie [Paris], Institut Jean Godinot [Reims], Centre Eugène Marquis (CRLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Service d'oncologie-radiothérapie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Clinique des Dentellières [Valenciennes, France], CHU Amiens-Picardie, CHU Bordeaux [Bordeaux], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Easy Global Market [Sophia-Antipolis], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Chemoradiotherapy, Head and neck, Neck dissection, Neoplasms/cancers/carcinomas, Prognosis, Unknown primary, chemoradiotherapy, head and neck, 03 medical and health sciences, 0302 clinical medicine, neoplasms/cancers/carcinomas, medicine, Stage (cooking), 030223 otorhinolaryngology, neck dissection, RC254-282, Chemotherapy, business.industry, Incidence (epidemiology), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, unknown primary, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Lymphadenectomy, prognosis, business, Adenectomy
Abstract: International audience; Simple Summary: A retrospective multicentric study of 322 patients with head and neck cancers of unknown primary (HNCUP) was performed testing the impact of neck dissection (ND) extent on nodal relapse, progression-free survival and survival. After 5 years, the incidence of nodal relapse was 13.4%, and progression-free survival (PFS) was 59.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective ND or radical/modified ND but survival rates were similar. Patients undergoing lymphadenectomy or ND had significantly better PFS and a lower nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. In HNCUP, ND improves PFS regardless of nodal stage but fails to improve survival. The magnitude of the benefit of ND did not appear to depend on ND extent and decreased with a more advanced nodal stage.Abstract: Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP.Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage
Published: 2021
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56. Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study

Author: Ronan Fougeray, Mark P Saunders, Catherine Leger, Antoine Hollebecque, Laetitia Dahan, Gerald W. Prager, Julien Edeline, Alexander Stein, Gábor Rubovszky, Alessandra Auriemma, Zsuzsanna Papai, Roberto Bordonaro, Aitana Calvo, Antonio Cubillo, Guillem Argiles, V. Cattan, Thierry André, Nadia Amellal, Josep Tabernero, ARNAS 'Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli', Hospital General Universitario 'Gregorio Marañón' [Madrid], University of Verona (UNIVR), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), National Institute of Oncology [Budapest, Hungary], The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Medizinische Universität Wien = Medical University of Vienna, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Hospital Universitario HM Sanchinarro [Madrid, Spain], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre Eugène Marquis (CRLCC), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Università degli studi di Verona = University of Verona (UNIVR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, HAL Sorbonne Université 5, Service d'Oncologie Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Català de la Salut, [Bordonaro R] Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy. [Calvo A] Gregorio Marañon University General Hospital, Madrid, Spain. [Auriemma A] Azienda Ospedaliera Universitaria Integrat, University of Verona, Verona, Italy. [Hollebecque A] Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France. [Rubovszky G] Department of Medical Oncology and Clinical Pharmacology, National Institute of Oncology Hungary, Budapest, Hungary. [Saunders MP] Christie NHS Foundation Trust, Manchester, UK. [Argilés G] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, IOB-Quiron, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Pyrrolidines, Colorectal cancer, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Gastroenterology, Trifluridine, trifluridine/tipiracil, Còlon - Càncer - Tractament, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Original Research, metastatic colorectal cancer, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Bevacizumab, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Cohort, medicine.symptom, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Nausea, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, fluoropyrimidines, Quimioteràpia combinada, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], [SDV.CAN] Life Sciences [q-bio]/Cancer, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Internal medicine, Recte - Càncer - Tractament, Other subheadings::Other subheadings::/adverse effects [Other subheadings], medicine, Humans, Tipiracil, business.industry, oxaliplatin, medicine.disease, Oxaliplatin, chemistry, business, Thymine, 030215 immunology
Abstract: Background In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. Patients and methods In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. Results In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. Conclusion FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC., Highlights • This study evaluated the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab in mCRC patients. • FTD/TPI plus oxaliplatin in combination with bevacizumab or nivolumab had an acceptable and manageable safety profile. • Antitumour activity was observed following treatment with FTD/TPI plus oxaliplatin and bevacizumab. • Despite a modest RR with the addition of nivolumab, survival data were promising in these poor-prognosis patients.
Published: 2021

57. Predictive Factors of Chemotherapy Initiation after Biliary Drainage for Advanced Biliary Tract Cancer: A Retrospective Multicenter Study

Author: Brigitte Dessomme, Julien Edeline, Jaafar Bennouna, Astrid Lièvre, Maëva Salimon, Thimothee Wallenhorst, Pauline Guillouche, Yann Touchefeu, Annie Lim, Jérôme Gournay, Miloud Azarfane, Jeremy Meyer, Tamara Matysiak-Budnik, Hélène Senellart, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre René Gauducheau, CRLCC René Gauducheau, Clinique Jules Verne, Centre Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, predictive factors, Multivariate analysis, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, jaundice, biliary tract cancer, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Univariate analysis, Chemotherapy, Biliary drainage, Cholestasis, Biliary tract cancer, business.industry, prognostic factors, Bilirubin, Jaundice, 3. Good health, Biliary Tract Neoplasms, Bile Duct Neoplasms, Multicenter study, Biliary tract, Drainage, medicine.symptom, business
Abstract: International audience; Background and Aims: In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice. Methods: Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected. Results: Among 82 patients included in this study (median age 68 years, men 61%), 48 (59%) received chemotherapy. Median overall survival was 4.9 months (0.2-38.7) in the group of patients who did not receive chemotherapy and 12.2 months (1.9-61.0) in chemotherapy group (HR=2.93; 95%CI: 1.6-5.3; p
Published: 2021

58. Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database

Author: Lionel Uwer, Paule Augereau, Thierry Petit, Matthieu Carton, C. Levy, L. Larrouquere, Luc Cabel, M.-A. Mouret-Reynier, Florence Dalenc, M. Carausu, C. Lefeuvre-Plesse, Michaël Chevrot, Amélie Darlix, M. Campone, Benjamin Verret, A. Gonçalves, Jean-David Fumet, M. Leheurteur, Marc Debled, C. Courtinard, J-M Ferrero, Christelle Jouannaud, David Pasquier, Institut Curie [Paris], Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Bergonié [Bordeaux], UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre René Gauducheau [Saint-Herblain] (CRLCC Nantes-Atlantique), Centre Régional de Lutte Contre le Cancer Nantes-Atlantique, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Jean Godinot [Reims], Centre Léon Bérard [Lyon], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Université Côte d'Azur (UCA), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Admin, Oskar
Subjects: Cancer Research, Population, Breast Neoplasms, computer.software_genre, 03 medical and health sciences, intrathecal therapy, 0302 clinical medicine, Breast cancer, breast cancer, leptomeningeal metastasis, cohort study, Medicine, Humans, Breast, education, Survival rate, Original Research, education.field_of_study, Database, business.industry, Proportional hazards model, Mortality rate, Hazard ratio, Middle Aged, medicine.disease, Prognosis, Metastatic breast cancer, 3. Good health, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Concomitant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neoplasm Recurrence, Local, business, computer, Meningeal Carcinomatosis, 030217 neurology & neurosurgery
Abstract: Background Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. Methods The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Results Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. Conclusions MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used., Highlights • The outcome of BC patients with IT-treated LM is poor, with a median OS of 4.5 months. • Concomitant systemic therapy may improve the outcome in IT-treated patients. • Patients treated with IT methotrexate had better outcome than those treated with IT cytarabine/thiotepa. • The Curie and Breast-graded prognostic assessment scores were prognostic for IT-treated patients.
Published: 2021

59. Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

Author: Geneviève Perrocheau, Carine Laurent, Matthieu Carton, Audrey Hennequin, Lilian Laborde, Thierry Petit, Agnes Loeb, Laurence Vanlemnens, Damien Parent, Claire Labreveux, Thomas Bachelot, Michel Debled, Marie-Ange Mouret-Reynier, E. Chamorey, Florence Lerebours, Barbara Pistilli, Christelle Levy, Thibault De La Motte Rouge, Luc Cabel, Florence Dalenc, Mathieu Robain, Mario Campone, William Jacot, Institut Curie [Saint-Cloud], Institut Gustave Roussy (IGR), Institut Claudius Regaud, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER [Paris], Centre Léon Bérard [Lyon], COLO, Mouniati, Institut Curie - Saint Cloud (ICSC), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lille-UNICANCER, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Adult, Oncology, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Breast Neoplasms, Triple Negative Breast Neoplasms, Prognostic factors, lcsh:RC254-282, Disease-Free Survival, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Real-life, Cancer, General Medicine, Middle Aged, Nomogram, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, Prognosis, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Original Article, Female, Surgery, France, business, Heavily pretreated
Abstract: Purpose Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy. Methods The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified. Results Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively. Conclusion The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated., Highlights • After 3rd- or 4th-line therapy, PFS remained linear in the majority of women with metastatic triple-negative breast cancer. • The duration of each previous PFS had an impact on the OS associated with subsequent lines. • PFS2 was more strongly predictive of outcome than PFS1 for third-line therapy. • PFS2 and PFS3 had an impact on outcome irrespective of PFS1 for fourth-line therapy. • The clinical utility of nomograms including duration of each previous PFS to predict OS was not sufficient.
Published: 2021

60. When helping the minority of patients may hurt the majority: The case for DPD phenotyping and 5-fluorouracil therapeutic drug monitoring

Author: F Lemaitre, Emeric Boisteau, S Le Sourd, C Tron, Astrid Lièvre, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Dihydropyrimidine Dehydrogenase Deficiency, [SDV]Life Sciences [q-bio], MEDLINE, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Intensive care medicine, Dihydrouracil Dehydrogenase (NADP), ComputingMilieux_MISCELLANEOUS, Aged, Gastrointestinal Neoplasms, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], Phenotype, Head and Neck Neoplasms, Fluorouracil, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Female, Drug Monitoring, business, medicine.drug
Abstract: International audience
Published: 2021

61. Impact of body mass index on overall survival in patients with metastatic breast cancer

Author: Audrey Mailliez, Khalil Saleh, Thierry Petit, Christelle Jouannaud, Etienne Brain, Matthieu Carton, Jean Marc Ferrero, Pierre-Etienne Heudel, Elise Deluche, Marc Debled, Anne Patsouris, Anthony Gonçalves, Lionel Uwer, George Emile, Alexia Savignoni, Florence Dalenc, Marianne Leheurteur, C. Courtinard, Lucie Veron, Marie-Ange Mouret-Reynier, Paul Cottu, Véronique Diéras, Véronique D'Hondt, Suzette Delaloge, Sylvain Ladoire, Mathieu Robain, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Bergonié [Bordeaux], Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), UNICANCER [Paris], CHU Limoges, Université de Lille-UNICANCER, UNICANCER-Université Côte d'Azur (UCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLO, Mouniati, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: MBC, metastatic breast cancer, BMI, body mass index, [SDV]Life Sciences [q-bio], ESME, Epidemio-Strategy-Medical-Economical, Overweight, Body Mass Index, 0302 clinical medicine, Risk Factors, Medicine, Overall survival, 030212 general & internal medicine, Underweight, TNBC, triple negative breast cancer, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, General Medicine, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Original Article, Female, medicine.symptom, medicine.medical_specialty, BC, breast cancer, Breast Neoplasms, lcsh:RC254-282, OS, overall survival, 03 medical and health sciences, BMI, Breast cancer, Internal medicine, Humans, Obesity, Risk factor, Retrospective Studies, business.industry, HR, hormone receptor, Cancer, nutritional and metabolic diseases, medicine.disease, Surgery, business, Body mass index, PFS, progression free-survival
Abstract: Background High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). Methods The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Results Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Conclusion Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Highlights • This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.
Published: 2021

62. Peptidomimetic-based identification of FDA approved compounds inhibiting IRE1 activity

Author: Chetan Chintha, Dimitrios Doultsinos, Adrienne W. Paton, Antonio Carlesso, Leif A. Eriksson, James C. Paton, Afshin Samali, Eric Chevet, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), University of Gothenburg (GU), National University of Ireland [Galway] (NUI Galway), University of Adelaide, Fondation pour la Recherche Médicale, 2014‐3914, Agence Nationale de la Recherche, Institut National Du Cancer, 2014‐3914, Vetenskapsrådet, ANR-17-RAR3-0003,ERAAT,Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency(2017), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, and Enhancing Endoplasmic Reticulum Proteostasis to Rescue Alpha1 Antitrypsin Deficiency - - ERAAT2017 - ANR-17-RAR3-0003 - E-RARE - VALID
Subjects: 0301 basic medicine, Peptidomimetic, Leucovorin, Cefoperazone, [SDV.CAN]Life Sciences [q-bio]/Cancer, IRE1, Protein Serine-Threonine Kinases, Endoplasmic Reticulum, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Endoribonucleases, medicine, Humans, Enzyme Inhibitors, Drug Approval, Molecular Biology, Fludarabine Phosphate, Temozolomide, Molecular Structure, United States Food and Drug Administration, Chemistry, Kinase, Inhibitors, Endoplasmic reticulum, glioblastoma, Cell Biology, Endoplasmic Reticulum Stress, United States, 3. Good health, Methotrexate, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Unfolded protein response, Unfolded Protein Response, Peptidomimetics, Pharmacophore, Vidarabine Phosphate, Protein Binding, Signal Transduction, medicine.drug
Abstract: International audience; Inositol Requiring Enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the Unfolded Protein Response (UPR) during endoplasmic reticulum (ER) stress. Tumour cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein folding demand. To cope with those stresses, cancer cells utilise IRE1 signalling as an adaptive mechanism. Here we report the discovery of the FDA approved compounds methotrexate, cefoperazone, folinic acid and fludarabine phosphate as IRE1 inhibitors. These were identified through a structural exploration of the IRE1 kinase domain using IRE1 peptide fragment docking and further optimization and pharmacophore development. The inhibitors were verified to have an impact on IRE1 activity in vitro and were tested for their ability to sensitise human cell models of glioblastoma multiforme (GBM) to chemotherapy. We show that all molecules identified sensitise glioblastoma cells to the standard of care chemotherapy temozolomide (TMZ).
Published: 2021

63. Towards a Reduced In Silico Model Predicting Biochemical Recurrence After Radiotherapy in Prostate Cancer

Author: Romain Mathieu, Nathalie Rioux-Leclercq, Alain Fautrel, Pierre Fontaine, François Paris, Carlos Sosa-Marrero, Renaud de Crevoisier, Oscar Acosta, Alfredo Hernandez, Bernardo, Elizabeth, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Brittany Region, and FHU TECH-SAN, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Oncology, Biochemical recurrence, Male, medicine.medical_specialty, Angiogenesis, medicine.medical_treatment, In silico, 0206 medical engineering, Biomedical Engineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, Logistic regression, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Prostate cancer, sensitivity analysis, [SDV.CAN] Life Sciences [q-bio]/Cancer, Prostate, Internal medicine, medicine, Humans, Computer Simulation, Mitotic catastrophe, radiotherapy, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Prostatic Neoplasms, prostate cancer, medicine.disease, multiscale modeling, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 020601 biomedical engineering, tumor control probability, Radiation therapy, medicine.anatomical_structure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: Objective: Purposes of this work were i) to develop an in silico model of tumor response to radiotherapy, ii) to perform an exhaustive sensitivity analysis in order to iii) propose a simplified version and iv) to predict biochemical recurrence with both the comprehensive and the reduced model. Methods: A multiscale computational model of tumor response to radiotherapy was developed. It integrated the following radiobiological mechanisms: oxygenation, including hypoxic death; division of tumor cells; VEGF diffusion driving angiogenesis; division of healthy cells and oxygen-dependent response to irradiation, considering, cycle arrest and mitotic catastrophe. A thorough sensitivity analysis using the Morris screening method was performed on 21 prostate computational tissues. Tumor control probability (TCP) curves of the comprehensive model and 15 reduced versions were compared. Logistic regression was performed to predict biochemical recurrence after radiotherapy on 76 localized prostate cancer patients using an output of the comprehensive and the reduced models. Results: No significant difference was found between the TCP curves of the comprehensive and a simplified version which only considered oxygenation, division of tumor cells and their response to irradiation. Biochemical recurrence predictions using the comprehensive and the reduced models improved those made from pre-treatment imaging parameters (AUC = 0.81 $\pm$ 0.02 and 0.82 $\pm$ 0.02 vs. 0.75 $\pm$ 0.03, respectively). Conclusion: A reduced model of tumor response to radiotherapy able to predict biochemical recurrence in prostate cancer was obtained. Significance: This reduced model may be used in the future to optimize personalized fractionation schedules.
Published: 2021

64. A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

Author: Philippe Debourdeau, Hugues Bourgeois, D. Mayeur, Florian Scotté, C. Lefeuvre-Plesse, Jean-Baptiste Bachet, Laurent Zelek, Bruno Chauffert, Fabien Brocard, Hélène Simon, Jean Philippe Wagner, Marianne Leheurteur, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Clinique Victor Hugo [Le Mans], Centre Eugène Marquis (CRLCC), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut mediterranéen des sciences de l'information et de la communication (IMSIC), Aix Marseille Université (AMU)-Université de Toulon (UTLN), Département interdisciplinaire d’organisation des parcours patients (DIOPP), and Institut Gustave Roussy (IGR)
Subjects: Oncology, Quinuclidines, Cancer Research, medicine.medical_specialty, Vomiting, Nausea, medicine.drug_class, [SDV]Life Sciences [q-bio], Antineoplastic Agents, chemistry.chemical_compound, Double-Blind Method, Internal medicine, medicine, Humans, Netupitant, Antiemetic, Prospective Studies, Aprepitant, Antibiotics, Antineoplastic, business.industry, Palonosetron, Isoquinolines, Regimen, chemistry, Symptom Management and Supportive Care, Chemotherapy‐induced nausea and vomiting • Netupitant • Palonosetron • Aprepitant • NEPA, Antiemetics, medicine.symptom, business, Chemotherapy-induced nausea and vomiting, medicine.drug
Abstract: Background Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5‐hydroxytryptamine‐3 (5‐HT3) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy‐induced nausea and vomiting (CINV) prevention over a 5‐HT3RA plus DEX. However, studies comparing the NK1RAs in the class are lacking. A fixed combination of a highly selective NK1RA, netupitant, and the 5‐HT3RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long‐lasting protection from CINV. This study is the first head‐to‐head NK1RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy (MEC). Materials and Methods This was a pragmatic, multicenter, randomized, single‐cycle, open‐label, prospective study designed to demonstrate noninferiority of single‐dose NEPA to a 3‐day aprepitant regimen in preventing CINV in chemotherapy‐naive patients receiving AC/non‐AC MEC in a real‐life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0–120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at −10%. Results Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, −2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant. Conclusion This pragmatic study in patients with cancer receiving AC and non‐AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3‐day aprepitant regimen, with indication of a potential efficacy benefit for NEPA. Implications for Practice In the absence of comparative neurokinin 1 (NK1) receptor antagonist (RA) studies, guideline committees and clinicians consider NK1RA agents to be interchangeable and equivalent. This is the first head‐to‐head study comparing one NK1RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non‐AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single‐dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard‐of‐care., Guidelines suggest that NK1RA agents are interchangeable. This article reports the first study comparing one NK1RA (oral NEPA [netupitant/palonosetron]) with another (aprepitant) in patients receiving chemotherapy.
Published: 2021

65. Efficacy, safety and factors associated with disease progression in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: An open label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib

Author: Sandrine Mansard, Philippe Saiag, Hervé Maillard, Amine Denden, Caroline Robert, Laurent Mortier, S. Dalac-Rat, Charlée Nardin, Olivier Dereure, Thierry Lesimple, Laurent Machet, Eve-Marie Neidhardt, Florent Grange, Alexandra Szenik, Caroline Dutriaux, Christophe Bedane, Céleste Lebbé, Jean-Jacques Grob, HAL UVSQ, Équipe, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Université de Lille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], Service de Dermatologie [CHU Limoges], CHU Limoges, Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Novartis Pharma S.A.S., CHU Bordeaux [Bordeaux], Amgen, Bristol-Myers Squibb, BMS, Pfizer, Merck, Novartis, Roche, Sanofi, Meso Scale Diagnostics, MSD, Novartis Pharma, Les Laboratories Pierre Fabre, This work was supported by Novartis Pharma S.A.S. , France., Philippe Saiag has received personal fees from Amgen, Bristol-Myers Squibb, MSD, Merck-Serono, Pfizer, Roche-Genentech, Pierre Fabre, Sanofi and Novartis, he has received non-financial support from Bristol-Myers Squibb, MSD, Roche-Genentech and Novartis, and has received a funding grant from Roche-Genentech., Céléste Lebbe has received honoraria from BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer and Incyte, has acted as a consultant or has served as a member of an advisory board for BMS, and has received travel grant support from BMS and MSD., Jean-Jacques Grob has received honoraria from BMS, MSD, Merck, Pfizer, Incyte, Novartis, Roche, Amgen and Pierre Fabre, has received travel grant support from BMS, MSD and Roche, and has acted as a consultant and advisor for BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer and Incyte., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Oncology, Cancer Research, medicine.medical_specialty, Pyridones, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pyrimidinones, 030204 cardiovascular system & hematology, Regression tree, 03 medical and health sciences, BRAF V600-mutation, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Trametinib, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Oximes, medicine, Humans, Prospective Studies, Stage (cooking), Prospective cohort study, education, neoplasms, Melanoma, Aged, Neoplasm Staging, education.field_of_study, Proportional hazards model, business.industry, Dabrafenib, Imidazoles, Middle Aged, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Mutation, Disease Progression, Female, business, Brain metastasis, medicine.drug
Abstract: International audience; Background: BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600-mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups. Methods: Patients with unresectable, advanced, BRAF V600-mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan–Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis. Results: Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33–8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with
Published: 2021

66. Maintenance of Endoplasmic Reticulum Protein Homeostasis in Cancer: Friend or Foe

Author: Eric Chevet, Mari McMahon, Afshin Samali, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National University of Ireland [Galway] (NUI Galway), Centre Eugène Marquis (CRLCC), This work was funded by grants from the French National Cancer Institute (INCa, PLBIO), the Fondation pour la recherche Médicale (FRM, équipe labellisée 2018) to EC and EU H2020 MSCA ITN-675448 (TRAINERS) and MSCA RISE-734749 (INSPIRED) grants to AS and EC. MMM was funded by scholarships from the Irish Research Council and the 'Région Bretagne' (ARED international PhD) and by a travel grant from the French embassy in Dublin, Ireland., European Project: 675448,H2020,H2020-MSCA-ITN-2015,TRAIN-ERS(2015), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, proteostasis, Endoplasmic reticulum, Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease, 3. Good health, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Proteostasis, 030220 oncology & carcinogenesis, Protein biosynthesis, medicine, cancer, Protein folding, quality control, Protein quality, Homeostasis, Secretory pathway
Abstract: International audience; The endoplasmic reticulum, as the site of synthesis for proteins in the secretory pathway has evolved select machineries to ensure the correct folding and modification of proteins. However, sometimes these quality control mechanisms fail and proteins are misfolded. Other factors, such as nutrient deprivation, hypoxia or an increased demand on protein synthesis can also cause the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. There are mechanisms that recognise and deal with this accumulation of protein through degradation and/or export. Many diseases are associated with aberrant quality control mechanisms, and among these, cancer has emerged as a group of diseases that rely on endoplasmic reticulum homeostasis to sustain development and growth. The knowledge of how protein quality control operates in cancer has identified opportunities for these pathways to be pharmacologically targeted, which could lead to newer or more effective treatments in the future.
Published: 2021

67. Combining F-18-DOPA PET and MRI with perfusion-weighted imaging improves delineation of high-grade subregions in enhancing and non-enhancing gliomas prior treatment: a biopsy-controlled study

Author: Anne Devillers, Dan Cristian Chiforeanu, Antoine Girard, Xavier Palard-Novello, Elise Bannier, Beatrice Carsin Nicol, Alice Metais, Florence Le Jeune, Pierre-Jean Le Reste, Boris Campillo-Gimenez, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), This study was fully self-funded by the Eugène Marquis Center, Rennes, France. A donation of 20.000€ from the Association for the Development of Hygiene and Epidemiology in Brittany (Association pour le Developpement de l’Hygiene et de l’Epidemiologie en Bretagne: A.D.H.E.B) to the Eugène Marquis Center was dedicated to this study., Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Empenn, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Perfusion weighted imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Interquartile range, Glioma, Biopsy, medicine, Radiation treatment planning, [SDV.IB] Life Sciences [q-bio]/Bioengineering, medicine.diagnostic_test, business.industry, Astrocytoma, medicine.disease, Neurology, Oncology, Perfusion weighted, Positron emission tomography, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), Positron-emission tomography, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract: International audience; Purpose We aimed to compare spatial extent of high-grade subregions detected with combined [F-18]-dihydroxyphenylalanine (F-18-DOPA) PET and MRI to the one provided by advanced multimodal MRI alone including Contrast-enhanced (CE) and Perfusion weighted imaging (PWI). Then, we compared the accuracy between imaging modalities, in a per biopsy analysis. Methods Participants with suspected diffuse glioma were prospectively included between June 2018 and September 2019. Volumes of high-grade subregions were delineated respectively on F-18-DOPA PET and MRI (CE and PWI). Up to three per-surgical neuronavigation-guided biopsies were performed per patient. Results Thirty-eight biopsy samples from sixteen participants were analyzed. Six participants (38%) had grade IV IDH wild-type glioblastoma, six (38%) had grade III IDH-mutated astrocytoma and four (24%) had grade II IDH-mutated gliomas. Three patients had intratumoral heterogeneity with coexisting high- and low-grade tumor subregions. High-grade volumes determined with combined F-18-DOPA PET/MRI (median of 1.7 [interquartile range (IQR) 0.0, 19.1] mL) were larger than with multimodal MRI alone (median 1.3 [IQR 0.0, 12.8] mL) with low overlap (median Dice's coefficient 0.24 [IQR 0.08, 0.59]). Delineation volumes were substantially increased in five (31%) patients. In a per biopsy analysis, combined F-18-DOPA PET/MRI detected high-grade subregions with an accuracy of 58% compared to 42% (p = 0.03) with CE MRI alone and 50% (p = 0.25) using multimodal MRI (CE + PWI). Conclusions The addition of F-18-DOPA PET to multimodal MRI (CE and PWI) enlarged the delineation volumes and enhanced overall accuracy for detection of high-grade subregions. Thus, combining F-18-DOPA with advanced MRI may improve treatment planning in newly diagnosed gliomas.
Published: 2021

68. Cardio-respiratory ITV for cardiac radioablation in case of ventricular tachycardia

Author: Bellec, J., Rigal, L., Jaksic, N., Caille, P., Lederlin, Mathieu, Lafond, C., Martins, R., De Crevoisier, R., Simon, A., Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Jonchère, Laurent
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; Meeting AbstractPD-0891
Published: 2021

69. The Added Value of Bloodpool SPECT/CT in Painful Non-Operated Foot and Ankle Undiagnosed With Standard Three-Phase Bone Scintigraphy

Author: Cécile Cuvilliers, Xavier Palard-Novello, Clémence Pontoizeau, Pierre Meneret, Anne Devillers, Florence Le Jeune, Antoine Girard, Centre Eugène Marquis (CRLCC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), and Université de Rennes (UR)
Subjects: [SDV]Life Sciences [q-bio], bloodpool SPECT, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Late phase, ankle, medicine, bone scintigraphy, Original Research, lcsh:R5-920, medicine.diagnostic_test, business.industry, General Medicine, early SPECT/CT, medicine.anatomical_structure, Bone scintigraphy, 030220 oncology & carcinogenesis, foot, Etiology, Standard protocol, Medicine, Ankle, business, Nuclear medicine, lcsh:Medicine (General), Foot (unit)
Abstract: Purpose: To evaluate the interest of adding a bloodpool SPECT/CT to standard three-phase bone scintigraphy (BS) for etiological diagnosis of subacute and chronic lower extremity pains.Methods: We prospectively included patients addressed for pain of lower extremities lasting for at least 6 weeks, without previous surgery. They underwent a standard three-phase BS including late phase SPECT/CT, modified with an additional bloodpool SPECT/CT acquisition. Two independent physicians interpreted the images provided by both protocols. Diagnostic conclusion, diagnostic confidence, and interrater agreements were compared.Results: One hundred and eighteen lower extremities from 113 patients were analyzed (71 men, median age of 53 years). Adding bloodpool SPECT/CT to standard three-phase BS changed diagnostic conclusions in 24.6% (29/118) of lower extremities. The modified protocol revealed at least one diagnostic conclusion explaining the pain in 89% of extremities, rather than 83.1% with the standard protocol (p = 0.02). Tendinopathies were diagnosed in 12.7% of lower extremities, rather than 4.2% with standard BS (p = 0.002). Adding bloodpool SPECT/CT substantially increased overall confidence of each reader (p < 0.001). Inter-reader agreement was not significantly impacted.Conclusion: Adding bloodpool SPECT/CT to standard three-phase BS impacted diagnostic conclusion in a quarter of the patients with painful lower extremities, notably by revealing significantly more tendonitis.
Published: 2021

70. Impact of Point-Spread Function Reconstruction on Dynamic and Static FDOPA PET/CT Quantitative Parameters in Glioma

Author: Girard, A., Madani, F., Chaboub, N., Le Reste, P.-J., Devillers, A., Saint-Jalmes, H., Le Jeune, Florence, Palard-Novello, X., Centre Eugène Marquis (CRLCC), Université de Rennes (UR), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; Meeting AbstractOP-0665
Published: 2021

71. A simple score (Biovid-19) based on biological parameters predicts transfer to intensive care units and death in COVID-19 patients

Author: Guillaume Couillez, Julien Maizel, Thomas Boyer, Jean-Luc Schmit, Ophélie Evrard, Etienne Brochot, Alexis Caulier, Catherine François, Rémy Nyga, Chloé Sauzay, Claire Andrejak, Sandrine Castelain, Loïc Garçon, Maïlys Le Guyader, DESSAIVRE, Louise, WEB Architecture x Semantic WEB x WEB of Data (WEB3), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Virologie [CHU Amiens], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), and Laboratoire d'Hématologie [CHU Amiens]
Subjects: Adult, Male, Patient Transfer, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Risk Assessment, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Young Adult, Intensive care, Transfer (computing), Severity of illness, medicine, Humans, Hospital Mortality, Patient transfer, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, business.industry, SARS-CoV-2, Sodium, COVID-19, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, Triage, Death, [SDV] Life Sciences [q-bio], Intensive Care Units, Research Design, Emergency medicine, Potassium, Female, France, business, Biomarkers, Blood Chemical Analysis, Cohort study
Abstract: International audience; No abstract available
Published: 2021

72. Efficacy of Circulating Tumor Cell Count–Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer

Author: Bidard, François-Clément, Jacot, William, Kiavue, Nicolas, Dureau, Sylvain, Kadi, Amir, Brain, Etienne, Bachelot, Thomas, Bourgeois, Hugues, Gonçalves, Anthony, Ladoire, Sylvain, Naman, Hervé, Dalenc, Florence, Gligorov, Joseph, Espié, Marc, Emile, George, Ferrero, Jean-Marc, Loirat, Delphine, Frank, Sophie, Cabel, Luc, Diéras, Véronique, Cayrefourcq, Laure, Simondi, Cécile, Berger, Frédérique, Alix-Panabières, Catherine, Pierga, Jean-Yves, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Curie - Saint Cloud (ICSC), CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Centre Léon Bérard [Lyon], Clinique Victor Hugo [Le Mans], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Azuréen de Cancérologie [Mougins, France], Institut Claudius Regaud, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Eugène Marquis (CRLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), and Daulat, Avais
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Importance: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).Objective: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.Interventions: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if
Published: 2021

73. Evaluation of the Octavius 1600 SRS detector array for CyberKnife treatment plan verification

Author: Blin, A., Legavre, J., Trifard, E., Lefeuvre, R., Lafond, C., Bellec, J., Jonchère, Laurent, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; Meeting AbstractPO-1607
Published: 2021

74. Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort

Author: Thomas Grinda, Marc Debled, Thomas Bachelot, Magali Lacroix-Triki, Paul-Henri Cottu, Audrey Mailliez, Anne Patsouris, Lionel Uwer, Thierry Petit, Isabelle Desmoulins, M. Robain, A. Gonçalves, Etienne Brain, Florence Dalenc, D. Perol, C. Courtinard, Suzette Delaloge, Véronique Diéras, C. Levy, Elise Deluche, C. Blaye, M.-A. Mouret-Reynier, Christelle Jouannaud, William Jacot, Alison Antoine, J-M Ferrero, Florian Clatot, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Jean Godinot [Reims], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and UNICANCER-Université Côte d'Azur (UCA)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, overall survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, Triple Negative Breast Neoplasms, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Internal medicine, HER2, Medicine, Humans, 030212 general & internal medicine, real-life, skin and connective tissue diseases, Retrospective Studies, Original Research, Everolimus, Epidermal Growth Factor, new drugs, business.industry, Cancer, medicine.disease, Metastatic breast cancer, Penetrance, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pertuzumab, metastatic breast cancer, business, medicine.drug, Eribulin
Abstract: Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.
Published: 2020

75. Review of clinical applications of radiation-enhancing nanoparticles

Author: E. Chajon, Valentin Calugaru, N. Scher, C. Le Tourneau, Sylvie Bonvalot, Juliette Thariat, C. Verry, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Centre Eugène Marquis (CRLCC), CHU Grenoble, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CCSD, Accord Elsevier, and MINES ParisTech - École nationale supérieure des mines de Paris
Subjects: 0106 biological sciences, Oncology, medicine.medical_specialty, Gadolinium, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Biotechnology, chemistry.chemical_element, Review Article, 01 natural sciences, Applied Microbiology and Biotechnology, 03 medical and health sciences, 010608 biotechnology, Internal medicine, lcsh:TP248.13-248.65, medicine, 030304 developmental biology, Radiothérapie, Cancer, Cervical cancer, 0303 health sciences, Radiotherapy, business.industry, Nanoparticules, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Clinical trial, Radiation therapy, [SDV] Life Sciences [q-bio], chemistry, Nanoparticles, Sarcoma, Liver cancer, business, Biotechnology
Abstract: Highlights • Inorganic nanoparticles activated by radiotherapy (RT) increase dose deposition within cancer cells compared to RT alone. • Recently, clinical evidence of the radiation-enhancing effects of NP has emerged. • Two radio-enhancement NP are currently under investigation in clinical trials: hafnium oxide NP and gadolinium-based NP. • So far, 229 patients have been treated with NP and RT for soft tissue sarcoma, head and neck cancers or liver cancer. • Intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma., Purpose Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. Materials and methods We searched the literature in English and French on PubMed up to October 2019. The search term was “nanoparticle” AND “radiotherapy”, yielding 1270 results. Results The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. Conclusion So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.
Published: 2020

76. Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study

Author: Jean-Yves Pierga, Alina Berriolo-Riedinger, Thierry Petit, Laurent Arnould, David Coeffic, Abdennour Ferhat, Gilles Paintaud, Jean-Briac Prevost, Pierre-Francois Dupre, Fanny Le Du, Thomas Bachelot, Marie-Pierre Chauvet, Jean-Marc Ferrero, Gilles Thibault, Kaldoun Kerrou, Philippe Gabelle, Catherine Barbe, Julien Dupin, Bruno Coudert, Marie-Ange Mouret-Reynier, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Paul Strauss, CRLCC Paul Strauss, Centre Eugène Marquis (CRLCC), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Roche France, Département d'information médicale [Centre Georges-François Leclerc] (DIM), UNICANCER-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_specialty, Positron emission tomography, Early pet assessment, Bevacizumab, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 01 natural sciences, Group B, 03 medical and health sciences, Her-2 positive breast cancer, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, medicine, Adjuvant therapy, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Long-term follow-up, Neoadjuvant therapy, lcsh:R5-920, business.industry, 010102 general mathematics, General Medicine, medicine.disease, 3. Good health, Docetaxel, pathological complete response, Δsuvmax, Neoadjuvant, lcsh:Medicine (General), business, Research Paper, medicine.drug
Abstract: Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax
Published: 2020

77. Feasibility and efficacy of a supervised home-based physical exercise program for metastatic cancer patients receiving oral targeted therapy: study protocol for the phase II/III - UNICANCER SdS 01 QUALIOR trial

Author: Sophie Abadie-Lacourtoisie, Isabelle Durand-Zaleski, Jean-Marc Descotes, C. Lefeuvre-Plesse, Nadine Houede, Nathalie Menneveau, Amélie Anota, Claire Garnier-Tixidre, Carole Helissey, Laetitia Stefani, Soazig Nenan, Florence Joly, Isabelle Rieger, Alain Zannetti, Sébastien Salas, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Eugène Marquis (CRLCC), Institut Daniel Hollard [Grenoble], HIA Bégin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de Cholet (CHC), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, CH Annecy Genevois, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and CAMI Sport et Cancer
Subjects: Quality of life, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, Medico-economy, medicine.medical_treatment, Pain, Administration, Oral, Physical exercise, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Targeted therapy, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Breast cancer, Internal medicine, Genetics, medicine, Humans, 030212 general & internal medicine, Oral targeted therapy, Neoplasm Metastasis, Lung cancer, Fatigue, business.industry, Cancer, Adherence to treatment, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Supervised physical exercise programs, 3. Good health, Exercise Therapy, Oncology, 030220 oncology & carcinogenesis, Feasibility Studies, Psychological and cognitive functions, Female, business, Kidney cancer, Metastatic cancer, Supportive care
Abstract: Background Currently, oral targeted therapies are known to be effective and are frequently used to treat metastatic cancer patients, but fatigue is a frequently reported early side effect of these treatments. This fatigue may impact the patient’s treatment adherence and result in a negative impact on quality of life. Physical exercise significantly improved the general well-being and quality of life of advanced cancer patients. However, there is no specific physical activity program adapted for patients with advanced disease. Methods QUALIOR is a two-part, randomized, open-label, and multicenter with two arms phase II/III trial. Patients (phase II: n = 120; phase III: n = 312) with metastatic cancer (breast cancer, kidney cancer, lung cancer, and other cancers [including but not limited to colon cancer, melanoma, sarcoma, or hepatocarcinoma]) treated with a first- or second-line oral targeted therapy without chemotherapy will be included. Patients will be randomized (2:1) to a 3-month supervised home-based standardized physical activity program or to a recommended adapted physical activity (via a booklet). The primary objective of the phase II is to evaluate the feasibility of the supervised program. The primary objective of the phase III is the evaluation of the benefit of the supervised home-based program compare to the recommended program in terms of fatigue and quality of life at 3 months. The secondary objectives aim to evaluate the impact of the supervised program on fatigue over time, pain, physical capacities, psychosocial and cognitive functions, general quality of life, frequency of dose reduction and patients’ adherence to the targeted therapy, overall survival, and progression-free survival. This study will also evaluate the medico-economic impact of supervised program compared to the recommended adapted physical activity program. Discussion The aim of this study is to evaluate home-based physical exercise program for metastatic cancer patients treated with oral targeted therapies to help patients to cope with fatigue and improve quality of life. Trial registration This trial was registered in ClinicalTrials.gov since May 2017 (NCT03169075).
Published: 2020

78. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Hyo Sook Han, Jean Pierre Ayoub, Shannon Puhalla, Erik Jakobsen, Yaroslav Shparyk, David Maag, Igor Bondarenko, Marketa Palacova, Christine K. Ratajczak, Hans Wildiers, Michael Friedlander, Nikhil Khandelwal, Cristina Oprean, Madan G. Kundu, Yeon Hee Park, Mario Campone, Banu Arun, Mathilde Jalving, Eduardo Yanez, Bella Kaufman, Matthew W. Dudley, Véronique Diéras, Targeted Gynaecologic Oncology (TARGON), Centre Eugène Marquis (CRLCC), Tel Aviv University [Tel Aviv], University Medical Center Groningen [Groningen] (UMCG), Victor Babeş University of Medicine and Pharmacy (UMFT), Masaryk Memorial Cancer Institute (RECAMO), Universidad de la frontera [Chile], and The University of Texas M.D. Anderson Cancer Center [Houston]
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Veliparib, Drug-Related Side Effects and Adverse Reactions, Organoplatinum Compounds, Paclitaxel, [SDV]Life Sciences [q-bio], Population, Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Placebo, Drug Administration Schedule, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Double-Blind Method, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, education, Germ-Line Mutation, education.field_of_study, business.industry, BRCA mutation, Middle Aged, medicine.disease, Progression-Free Survival, 3. Good health, 030104 developmental biology, Treatment Outcome, chemistry, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Benzimidazoles, Female, business
Abstract: BACKGROUND: BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation.METHODS: BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days -2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694.FINDINGS: Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5-17·7) in the veliparib group versus 12·6 months (10·6-14·4) in the control group (hazard ratio 0·71 [95% CI 0·57-0·88], p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 [81%] of 336 patients in the veliparib group vs 143 [84%] of 171 patients in the control group), anaemia (142 [42%] vs 68 [40%]), and thrombocytopenia (134 [40%] vs 48 [28%]). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths.INTERPRETATION: The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population.FUNDING: AbbVie.
Published: 2020

79. Factors associated with compliance to cervical cancer screening in France: The EDIFICE 6 survey

Author: Thibault De La Motte Rouge, Chantal Touboul, Christine Lhomel, Morgan Rouprêt, Jean-François Morère, Centre Eugène Marquis (CRLCC), Roche France, Groupe de Recherche Clinique Onco-Urologie Prédictive [CHU Tenon] (GRC 5), CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, [SDV]Life Sciences [q-bio], Uterine Cervical Neoplasms, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Cancer screening, medicine, Humans, 030212 general & internal medicine, Social Factors, Mass screening, Early Detection of Cancer, Aged, Cervical cancer, business.industry, Age Factors, Obstetrics and Gynecology, Cancer, Stepwise regression, Middle Aged, Patient Acceptance of Health Care, medicine.disease, 3. Good health, Test (assessment), Treatment Adherence and Compliance, Oncology, 030220 oncology & carcinogenesis, Female, France, medicine.symptom, business, Social vulnerability, Demography, Papanicolaou Test
Abstract: A nationwide cervical cancer (CC) screening program was implemented in France in 2018. Asymptomatic women are invited for a cytological test once every 3 years (age, 25-29 years), and an HPV test every 5 years (age, 30-65 years). We investigated the characteristics of women who are resistant to CC screening.Since 2005, the EDIFICE survey program has assessed attitudes toward cancer screening in France. The 6th edition (2017) included 12,046 representative women (age, 18-69 years). Social vulnerability was assessed using the EPICES score. Multivariate stepwise logistic regression analysis identified factors correlated with nonuptake of CC screening.Questionnaires from 4499 women (age, 25-65 years) with no history of cancer were analyzed; 88% (N = 3960) reported at least one test in their lifetime, and 73% (N = 3262) did the test in the previous 3 years. Compared to ever-screened women, never-screened women were younger (38 ± 11 yrs. vs 44 ± 12 yrs., P 0.05), and more likely to be single (48% vs 20%, P 0.05) and/or socially vulnerable (59% vs 38%, P 0.05). In multivariate analysis, items significantly (P 0.05) associated with never screening included living alone (OR = 2.26, 95% CI [1.85-2.75]) and social vulnerability (OR = 1.95 [1.59-2.40]). Women who were not compliant with recommendations were more likely to be older (mean age, 49.2 yrs. vs. 43.2 yrs), living alone (single, widowed or divorced, 40% vs. 30%, P 0.05), and/or socially vulnerable (55% vs. 35%, P 0.05; OR = 1.78, 95% CI [1.49-2.12]).This analysis identified several factors associated with never screening and under-screening. Effective prevention messages should specifically target these populations.
Published: 2020

80. Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network

Author: Derquin, F., Floquet, A., Hardy-Bessard, A.C., Edeline, J., Lotz, J.P., Alexandre, J., Pautier, P., Angeles, M.A., Delanoy, N., Lefeuvre-Plesse, C., Cancel, M., Treilleux, I., Augereau, P., Lavoue, V., Kalbacher, E., Berton Rigaud, D., Selle, F., Nadeau, C., Gantzer, J., Joly, F., Guillemet, C., Pomel, C., Favier, L., Abdeddaim, C., Venat-Bouvet, L., Provansal, M., Fabbro, M., Kaminsky, M.C., Lortholary, A., Lécuru, F., Coquard, I Ray, de La Motte Rouge, T., Coquard, I. Ray, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Medical Oncology, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Limoges, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Radio-Oncologie [Nantes] (Centre Catherine de Sienne), Centre Catherine-de-Sienne [Nantes] (CCS), Department of Gynecologic and Oncologic Surgery Hopital Européen Georges Pompidou, CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut des Sciences Chimiques de Rennes (ISCR), Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Yves LE FOLL [Saint-Brieuc], Institut Bergonié [Bordeaux], Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Centre Eugène Marquis (CRLCC), Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Claudius Regaud, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Diaconesses Croix Saint-Simon, Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Dupuytren [CHU Limoges], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Hôpital privé du Confluent [Nantes], and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Oncology, Adult, medicine.medical_specialty, Adolescent, Adjuvant chemotherapy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Dysgerminoma, Favorable prognosis, Prognostic factors, TMRG, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Overall survival, Humans, Choriocarcinoma, Watchful Waiting, Aged, Neoplasm Staging, Retrospective Studies, Ovarian Neoplasms, Rare malignant ovarian tumors, Chemotherapy, business.industry, Endodermal Sinus Tumor, Teratoma, Obstetrics and Gynecology, Histology, Middle Aged, Neoplasms, Germ Cell and Embryonal, medicine.disease, Prognosis, Stage I, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Germ cell tumors, First line chemotherapy, business, Adjuvant
Abstract: International audience; Background - Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. Patients and methods - Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. Results - We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P
Published: 2020

81. The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

Author: Laurent Dercle, Mathieu Rouanne, Pierre-Yves Salaun, Helena Vila Reyes, Hiram Shaish, Antoine Girard, Olivier Delcroix, Jean-François Grellier, Centre Eugène Marquis (CRLCC), Columbia University Irving Medical Center (CUIMC), Centre cardiologique du Nord (CCN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: 0301 basic medicine, PET – Positron Emission Tomography, Cancer Research, medicine.medical_specialty, Mini Review, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, lcsh:RC254-282, muscle invasive bladder cancer, 03 medical and health sciences, 0302 clinical medicine, medicine, Carcinoma, Adverse effect, Bladder cancer, medicine.diagnostic_test, business.industry, Cancer, staging, Precision medicine, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, bladder cancer, Personalized medicine, Radiology, immunotherapy, business
Abstract: International audience; Bladder cancer (BC) is the 10th most common cancer worldwide. Approximately one quarter of patients with BC have muscle-invasive disease (MIBC). Muscle-invasive disease carries a poor prognosis and choosing the optimal treatment option is critical to improve patients’ outcomes. Ongoing research supports the role of 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18F-FDG PET) in guiding patient-specific management decisions throughout the course of MIBC. As an imaging modality, 18F-FDG PET is acquired simultaneously with either computed tomography (CT) or MRI to offer a hybrid approach combining anatomical and metabolic information that complement each other. At initial staging, 18F-FDG PET/CT enhances the detection of extravesical disease, particularly in patients classified as oligometastatic by conventional imaging. 18F-FDG PET/CT has value in monitoring response to neoadjuvant and systemic chemotherapy, as well as in localizing relapse after treatment. In the new era of immunotherapy, 18F-FDG PET/CT may also be useful to monitor treatment efficacy as well as to detect immune-related adverse events. With the advent of artificial intelligence techniques such as radiomics and deep learning, these hybrid medical images can be mined for quantitative data, providing incremental value over current standard-of-care clinical and biological data. This approach has the potential to produce a major paradigm shift toward data-driven precision medicine with the ultimate goal of personalized medicine. In this review, we highlight current literature reporting the role of 18F-FDG PET in supporting personalized management decisions for patients with MIBC. Specific topics reviewed include the incremental value of 18F-FDG PET in prognostication, pre-operative planning, response assessment, prediction of recurrence, and diagnosing drug toxicity.
Published: 2020

82. COVID-19 and people followed for breast cancer: French guidelines for clinical practice of Nice-St Paul de Vence, in collaboration with the Collège Nationale des Gynécologues et Obstétriciens Français (CNGOF), the Société d’Imagerie de la Femme (SIFEM), the Société Française de Chirurgie Oncologique (SFCO), the Société Française de Sénologie et Pathologie Mammaire (SFSPM) and the French Breast Cancer Intergroup-UNICANCER (UCBG)

Author: Gligorov, Joseph, Bachelot, Thomas, Pierga, Jean-Yves, Antoine, Eric-Charles, Balleyguier, Corinne, Barranger, Émmanuel, Belkacemi, Yazid, Bonnefoi, Hervé, Bidard, François-Clément, Ceugnart, Luc, Classe, Jean-Marc, Cottu, Paul, Coutant, Charles, Cutuli, Bruno, Dalenc, Florence, Darai, Émile, Dieras, Veronique, Dohollou, Nadine, Giacchetti, Sylvie, Gonçalves, Anthony, Hardy-Bessard, Anne-Claire, Houvenaeghel, Gilles, Jacquin, Jean-Philippe, Jacot, William, Levy, Christelle, Mathelin, Carole, Nisand, Israël, Petit, Thierry, Poncelet, Edouard, Rivera, Sofia, Rouzier, Roman, Salmon, Remy, Scotté, Florian, Spano, Jean-Philippe, Uzan, Catherine, Zelek, Laurent, Spielmann, Marc, Penault-Llorca, Frédérique, Namer, Moïse, Delaloge, Suzette, Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Institut Curie [Paris], Institut Gustave Roussy (IGR), Département d'imagerie médicale [Gustave Roussy], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Henri Mondor [Créteil], Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Claudius Regaud, Centre Eugène Marquis (CRLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Strasbourg, Centre Paul Strauss, CRLCC Paul Strauss, Centre hospitalier [Valenciennes, Nord], Clinique Saint Jean de Dieu, Département interdisciplinaire d’organisation des parcours patients (DIOPP), Hôpital Avicenne [AP-HP], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Henri Mondor, Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Breast cancer, Recommandation, SARS-CoV-2, [SDV]Life Sciences [q-bio], Guidelines, Covid-19, Cancer du sein, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Nous sommes confrontés à la pandémie COVID-19 qui est certes sans conséquences graves chez près de 85 % de la population générale mais qui peut engager le pronostic vital, plus particulièrement dans une population fragile. Le taux de mortalité estimé du COVID-19 est de 1 à 3 % soit entre 10 et 30 fois plus que le virus saisonnier de la grippe, et ceci sous réserve de données épidémiologiques imparfaites liées au fait que la recherche de SARS-CoV-2 n’est pas systématique dans une population asymptomatique, voire même symptomatique sans critères de gravité.
Published: 2020

83. Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions

Author: Magali Lacroix Triki, Monique Cohen, Corinne Balleyguier, Stefan Michiels, Catherine Uzan, Joelle Mollard, M. Espie, Suzette Delaloge, Anne Vincent Salomon, Pierre de Saint Hilaire, Natacha Joyon, L. Boulanger, Veronique Boussion, Flore Salviat, Christine Tunon de Lara, Brigitte De Korvin, Isabelle Doutriaux-Dumoulin, Charles Coutant, Caroline Rossoni, Nathalie Chabbert, Frédéric Marchal, Carole Mathelin, Chafika Mazouni, Sonia Zilberman, Eva Jouve, Service de Chirurgie et Cancérologie Gynécologique et Mammaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Centre Eugène Marquis (CRLCC), Institut Bergonié [Bordeaux], UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de chirurgie gynécologique et mammaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Lille-UNICANCER, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biopsy, Unnecessary Surgery, Population, Breast Neoplasms, Atypical ductal hyperplasia, Unnecessary Procedures, 03 medical and health sciences, Atypical breast lesion, 0302 clinical medicine, Breast cancer, Surgical oncology, medicine, Humans, Breast, Prospective Studies, education, B3 lesion, education.field_of_study, Hyperplasia, medicine.diagnostic_test, business.industry, Lumpectomy, Carcinoma, Ductal, Breast, Ductal carcinoma in situ, Cancer, medicine.disease, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Carcinoma, Intraductal, Noninfiltrating, Oncology, Multicenter study, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, business, Carcinoma in Situ, Model
Abstract: International audience; Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.- methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.
Published: 2020

84. Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis

Author: Thierry Petit, Brigitte De La Lande, Jean-Marc Ferrero, Audrey Mailliez, Amélie Lusque, Clémentine Jankowski, Nelly Firmin, Florence Dalenc, Elvire Pons-Tostivint, Lionel Uwer, David Pasquier, Marie-Ange Mouret-Reynier, Delphine Mouttet-Boizat, Thomas Filleron, N. Madranges, Anthony Gonçalves, Julien Geffrelot, Youlia M. Kirova, Mario Campone, Agathe Crouzet, Mathieu Robain, Sofia Rivera, Jean-Christophe Eymard, Thibault De La Motte Rouge, C. Courtinard, Nicolas Pouget, Département de radiothérapie oncologique [Paris], Institut Curie [Paris], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre Eugène Marquis (CRLCC), Department of Surgery [Saint-Cloud], Institut Curie [Saint-Cloud], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut Jean Godinot [Reims], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Paul Strauss, CRLCC Paul Strauss, Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_specialty, Propensity score, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, de novo metastatic breast cancer, Retrospective Studies, Models, Statistical, business.industry, Hazard ratio, Locoregional treatment, Hematology, medicine.disease, Exclusive radiotherapy, Metastatic breast cancer, Primary tumor, 3. Good health, Survival Rate, Radiation therapy, 030220 oncology & carcinogenesis, Cohort, Propensity score matching, business, Cohort study
Abstract: The impact of locoregional treatment (LRT) on overall survival (OS) in de novo metastatic breast cancer (dnMBC) is still under debate, with very few data available regarding exclusive radiotherapy (ERT) as a therapeutic modality.We evaluated the impact of ERT, exclusive surgery, or a combination of surgery plus radiotherapy (bimodality therapy, BMT) on survival outcomes in a national real-life dnMBC cohort. The primary and secondary end points were OS and progression free survival (PFS) according to LRT (ERT, exclusive surgery, BMT) and no LRT. Sensitivity analyses were performed using propensity score matched analyses.From 2008 to 2014, 4507 dnMBC patients were identified. Only patients alive and free from progression under systemic therapy at least 1 year after diagnosis were included (n = 1965). Forty-five percent of patients (891/1965) underwent LRT: 41.1% (n = 366) ERT, 13.7% (n = 122) exclusive surgery, and 45.2% (n = 403) BMT. OS adjusted for major prognostic factors was significantly longer in the ERT and BMT group compared with no-LRT group, but not exclusive surgery (hazard ratio (HR) = 0.63, 95% confidence interval (CI) [0.49, 0.80], p 0.001, HR = 0.61, 95%CI [0.47, 0.78], p 0.001 and HR = 0.87, 95%CI [0.61, 1.26], p = 0.466 respectively). Results were similar after matching on a propensity score. ERT, surgery and BMT were all associated with a significantly better PFS in multivariable analysis.ERT was significantly associated with better OS in dnMBC, in the same magnitude as BMT, compared with no-LRT. However, even with statistical models adjusted for known prognostic factors and propensity score analysis, selection biases cannot be eliminated from observational studies.
Published: 2020

85. Immunotherapy in Renal Cell Carcinoma: The Future Is Now

Author: Laurence Crouzet, Antoine Deleuze, Frédéric Dugay, Judikaël Saout, Marc-Antoine Belaud-Rotureau, Brigitte Laguerre, Benoit Peyronnet, Karim Bensalah, Solène-Florence Kammerer-Jacquet, Gregory Verhoest, N. Rioux-Leclercq, Romain Mathieu, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Service de Pathologie [Rennes] = Pathology [Rennes], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: Oncology, medicine.medical_treatment, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], Review, lcsh:Chemistry, immune checkpoint inhibitors, 0302 clinical medicine, Renal cell carcinoma, PD-1, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, Clinical Trials as Topic, biology, Treatment options, General Medicine, Kidney Neoplasms, 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], emerging drugs, 030220 oncology & carcinogenesis, Urologic cancer, Immunotherapy, PD-L1, medicine.medical_specialty, Poor prognosis, renal cell carcinoma, Catalysis, Unmet needs, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, ongoing trials, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, Carcinoma, Renal Cell, 030304 developmental biology, business.industry, Organic Chemistry, biomarkers, medicine.disease, lcsh:Biology (General), lcsh:QD1-999, biology.protein, business
Abstract: International audience; Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.
Published: 2020

86. Implementation of an optimization method for parotid gland sparing during inverse planning for head and neck cancer radiotherapy

Author: A. Barateau, O. Henry, Shannon K. Martin, Enrique Chajon, Joël Castelli, N. Perichon, N. Delaby, Cynthia LaFond, R. de Crevoisier, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Organs at Risk, Prédiction de la dose, medicine.medical_treatment, VMAT, Standard deviation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Parotid Gland, Radiology, Nuclear Medicine and imaging, Specific model, Radiation treatment planning, Planification dosimétrique, Prediction dose, business.industry, Radiotherapy Planning, Computer-Assisted, Head and neck cancer, Quality control, Radiotherapy Dosage, medicine.disease, 3. Good health, Parotid gland, Radiation therapy, medicine.anatomical_structure, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Organ at risk, Carcinoma, Squamous Cell, Dose reduction, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiotherapy, Intensity-Modulated, Nuclear medicine, business, Contrôle qualité, Treatment planning
Abstract: International audience; Purpose - To guide parotid gland (PG) sparing at the dose planning step, a specific model based on overlap between PTV and organ at risk (Moore et al.) was developed and evaluated for VMAT in head-and-neck (H&N) cancer radiotherapy. Materials and methods - One hundred and sixty patients treated for locally advanced H&N cancer were included. A model optimization was first performed (20 patients) before a model evaluation (110 patients). Thirty cases were planned with and without the model to quantify the PG dose sparing. The inter-operator variability was evaluated on one case, planned by 12 operators with and without the model. The endpoints were PG mean dose (D), PTV homogeneity and number of monitor units (MU). Results - The PG D predicted by the model was reached in 89% of cases. Using the model significantly reduced the PG D: -6.1±4.3Gy. Plans with the model showed lower PTV dose homogeneity and more MUs (+10.5% on average). For the inter-operator variability, PG dose volume histograms without the optimized model were significantly different compared to those with the model; the D standard deviation for the ipsilateral PG decreased from 2.2Gy to 1.2Gy. For the contralateral PG, this value decreased from 2.9Gy to 0.8Gy. Conclusion - During the H&N inverse planning, the optimized model guides to the lowest PG achievable mean dose, allowing a significant PG mean dose reduction of -6.1Gy. Integrating this method at the treatment-planning step significantly reduced the inter-patient and inter-operator variabilities.
Published: 2020

87. CinéBreast-factors influencing the time to first metastatic recurrence in breast cancer: Analysis of real-life data from the French ESME MBC database

Author: Lionel Uwer, A. Gonçalves, A. Hennequin, C. Le Tourneau, Paul Gougis, Thomas Bachelot, C. Levy, Grégory Simon, William Jacot, Matthieu Carton, Corinne Tchokothe, M.-A. Mouret-Reynier, M. Saghatchian, Thierry Petit, Marc Debled, Christian Cailliot, M. Leheurteur, Audrey Mailliez, Christophe Perrin, M. Campone, Florence Dalenc, J.-C. Eymard, E. Chamorey, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie - Saint Cloud (ICSC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Jean Godinot, Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), R&D Unicancer [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CCSD, Accord Elsevier, Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut Curie [Saint-Cloud], MINES ParisTech - École nationale supérieure des mines de Paris, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hydrosystèmes et Bioprocédés (UR HBAN), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Biostatistics Unit, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Biologie et écologie tropicale et méditerranéenne [2007-2010] (BETM), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Time Factors, Databases, Factual, [SDV]Life Sciences [q-bio], Estrogen receptor, Triple Negative Breast Neoplasms, Real-life data, computer.software_genre, Metastasis, 0302 clinical medicine, Breast cancer, Risk Factors, Epidemiology, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, 80 and over, Database, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Original Article, Female, Metastatic recurrence, France, Adult, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Median follow-up, Biomarkers, Tumor, medicine, Humans, Aged, Retrospective Studies, Growth rate, business.industry, Cancer, medicine.disease, Survival Analysis, Surgery, Neoplasm Recurrence, Local, business, computer, Follow-Up Studies
Abstract: Purpose The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR. Methods The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated. Results Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p, Highlights • ESME is a large-scale real-life database of 16 702 metastatic breast cancer patients. • A short time to first metastatic recurrence is associated with poor overall survival. • Triple-negative tumours were more likely to recur early than HR+ and HER2+ tumours.
Published: 2020

88. Traitement adjuvant des voies biliaires : qui et comment ?

Author: Julien Edeline and Centre Eugène Marquis (CRLCC)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Gastroenterology, law.invention, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Clinical endpoint, medicine, Radiology, Nuclear Medicine and imaging, Gallbladder cancer, Intention-to-treat analysis, business.industry, Cancer, Hematology, General Medicine, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Biliary tract, 030220 oncology & carcinogenesis, business, Adjuvant, medicine.drug
Abstract: The adjuvant treatment of biliary tract cancers has long been poorly defined. In recent years, randomized trial data have been used to define treatment references. The French Prodige 12 and Japanese BCAT trials have not demonstrated any benefit of adjuvant chemotherapy. The English BILCAP trial tested adjuvant capecitabine for six months at the usual dose in a randomized, controlled-only trial involving nearly 450 patients. Although the results in intention to treat were borderline significant on the primary endpoint, overall survival (P=0.097), sensitivity analyzes adjusted for prognostic factors and relapse-free survival analyses are clearly positive. The absolute benefit of +5%/+10% overall survival, combined with low and known toxicity profile, leads to recommending treatment for any cancer of the resected bile ducts (with the exception of gallbladder cancer pT1N0).
Published: 2020

89. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy – a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol

Author: Veronica Pezzella, Maximiliano Gelli, Julien Taieb, Christophe Laurent, Veronique Guerin-Meyer, Diane Goéré, Mathilde Wagner, Valérie Boige, Eric Dupont Bierre, Aline Maillard, Ayhan Ulusakarya, Samuel Le Sourd, Denis Smisth, Alice Boilève, Thierry de Baere, Clarisse Dromain, Franck Audemar, Gestionnaire, Hal Sorbonne Université, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), Le CHCB, Centre Hospitalier de la Côte Basque, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Sorbonne Paris Cité (USPC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), This study is financially supported by a governmental grant from the National Institute of Cancer (INCa)., This study is sponsored by UNICANCER and supported by PRODIGE group which regroup FFCD (Féderation Francophone de Cancérologie Digestive), GERCOR (Groupe Coopérateur Multidisciplinaire en Oncologie) and UNICANCER gastrointestinal group. The manuscript was peer reviewed by the funding body and the sponsor (UNICANCER)., Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Cancer Research, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, Salvage therapy, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Gastroenterology, Targeted therapy, Study Protocol, Liver metastases, 03 medical and health sciences, Hepatic Artery, 0302 clinical medicine, Hepatic arterial infusion, Clinical Protocols, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Genetics, Humans, Infusions, Intra-Arterial, Medicine, Liver resection, business.industry, Liver Neoplasms, Induction chemotherapy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Induction Chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Colorectal cancer, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Oxaliplatin, Oncology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, FOLFIRI, Female, 030211 gastroenterology & hepatology, Randomized trial, Colorectal Neoplasms, business, medicine.drug
Abstract: Background Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10–15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low ( Objectives and endpoints of the phase II study Our main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0). Methods This study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients. Trial registration ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.
Published: 2020

90. Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials

Author: B Sigal, Christel Breton-Callu, Emmanuelle Fourme, Laurence Venat-Bouvet, Jérôme Lemonnier, N Quenel-Tueux, Thibault De La Motte Rouge, Jean-Yves Pierga, Marie-Ange Mouret-Reynier, Simone Mathoulin-Pélissier, Thomas Bachelot, Florence Lerebours, Hervé Bonnefoi, Véronique Becette, Gaëtan MacGrogan, Sofia Rivera, Marina Pulido, Christine Tunon de Lara, Marc Debled, Florence Dalenc, Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Veille Sanitaire, Institut national de veille sanitaire, Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Validation et identification de nouvelles cibles en oncologie (VINCO), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service de Chirurgie, Institut Curie [Paris], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Plateforme de génétique moléculaire des cancers d'Aquitaine, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER [Paris], and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Time Factors, Multivariate analysis, [SDV]Life Sciences [q-bio], education, Phases of clinical research, Anastrozole, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Internal medicine, medicine, Humans, Endocrine system, 030212 general & internal medicine, Pathological, Aged, Univariate analysis, Fulvestrant, business.industry, EPICENE, Prognosis, medicine.disease, Survival Analysis, Neoadjuvant Therapy, 3. Good health, Risk factors, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: Background Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). Methods This is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies. Results In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9–88) and 92.7% (95% CI: 88.2–95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3–4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1–2 vs pT3–4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39–7.98)). Conclusions Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.
Published: 2020

91. Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial

Author: Boris Guiu, Eveline Boucher, Samuel Le Sourd, Olivier Farge, David Tougeron, Astrid Lièvre, Karim Boudjema, Yann Touchefeu, Isabelle Baumgaertner, Ahmet Ayav, Etienne Garin, Luc Beuzit, Marc Pracht, Julien Edeline, Yan Rolland, Boris Campillo-Gimenez, Jonchère, Laurent, Centre Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Anatomie Pathologique [CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was partially funded by BTG Corporation and the Ligue Contre le Cancer., Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil]
Subjects: Male, Cancer Research, medicine.medical_specialty, Phases of clinical research, Gastroenterology, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Progression-free survival, Prospective cohort study, Aged, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Combination chemotherapy, Middle Aged, Chemotherapy regimen, Gemcitabine, 3. Good health, Bile Ducts, Intrahepatic, Treatment Outcome, Bile Duct Neoplasms, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Concomitant, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: International audience; Importance - Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have a poor prognosis. Selective internal radiotherapy (SIRT) is a promising treatment option for hepatic tumors, but no prospective studies of combination SIRT with chemotherapy have been published to our knowledge. Objective - To determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC. Design, setting, and participants - This phase 2 clinical trial, the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) trial, included patients with unresectable ICC who have never received chemotherapy or intra-arterial therapy and were treated at 7 centers which had experience with SIRT between November 12, 2013, and June 21, 2016. Statistical analysis was performed from March 31, 2017, to June 17, 2019. Interventions - Concomitant first-line chemotherapy with cisplatin, 25 mg/m2, and gemcitabine, 1000 mg/m2 (gemcitabine reduced to 300 mg/m2 for the cycles just before and after SIRT), on days 1 and 8 of a 21-day cycle for 8 cycles. Selective internal radiotherapy was administered during cycle 1 (1 hemiliver disease) or cycles 1 and 3 (disease involving both hemilivers) using glass Y90 microspheres. Main outcomes and measures - Response rate at 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary end points were toxic effects, progression-free survival, overall survival, disease control rate, and response rate according to Choi criteria. Results - Of 41 patients included in the study, 26 (63%) were male, with a mean (SD) age of 64.0 (10.7) years. Response rate according to RECIST was 39% (90% CI, 26%-53%) at 3 months according to local review and was confirmed at 41% as best response by central review; disease control rate was 98%. According to Choi criteria, the response rate was 93%. After a median follow-up of 36 months (95% CI, 26-52 months), median progression-free survival was 14 months (95% CI, 8-17 months), with progression-free survival rates of 55% at 12 months and 30% at 24 months. Median overall survival was 22 months (95% CI, 14-52 months), with overall survival rates of 75% at 12 months and 45% at 24 months. Of 41 patients, 29 (71%) had grades 3 to 4 toxic effects; 9 patients (22%) could be downstaged to surgical intervention, with 8 (20%) achieving R0 (microscopic-free margins) surgical resection. After a median of 46 months (95% CI, 31 months to not reached) after surgery, median relapse-free survival was not reached among patients who underwent resection. Conclusions and relevance - Combination chemotherapy and SIRT had antitumor activity as first-line treatment of unresectable ICC, and a significant proportion of patients were downstaged to surgical intervention. A phase 3 trial is ongoing.
Published: 2020

92. Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas

Author: Coralie Bloch-Queyrat, Florent Grange, Lydia Deschamps, Sandrine Mansard, Nicole Basset-Seguin, Annick Tibi, Vincent Levy, Sarah Guégan, D. Legoupil, Jean-Philippe Arnault, Henri Montaudié, Marouane Boubaya, Olivier Dereure, Yannick Le Corre, A. Stefan, François Aubin, Céline Alloux, Jean-Jacques Grob, Peter Petrow, Soufian Cherbal, Groupe de cancérologie cutanée, Philippe Saiag, Nicolas Meyer, Isabelle Lopez, Marie Beylot-Barry, Eve Maubec, Marie-Thérèse Leccia, Brigitte Dréno, Ouidad Zehou, Laurent Machet, Julie De Quatrebarbes, Sophie Dalac, Monica Dinulescu, E. Wierzbicka-Hainaut, Isabelle Scheer-Senyarich, Herrada, Anthony, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Polyclinique Saint Côme, Institut Curie [Paris], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Grenoble, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Hôpital Cochin [AP-HP], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, Time Factors, MESH: Immune Checkpoint Inhibitors, Cell, Phases of clinical research, Pembrolizumab, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Progression-Free Survival, MESH: B7-H1 Antigen, Medicine, Immune Checkpoint Inhibitors, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Carcinoma, Squamous Cell, Middle Aged, Progression-Free Survival, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Monoclonal, Carcinoma, Squamous Cell, Disease Progression, Female, MESH: Disease Progression, France, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Pharmacotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Humans, Progression-free survival, Aged, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH: Time Factors, MESH: Quality of Life, MESH: Adult, medicine.disease, MESH: Antineoplastic Agents, Immunological, MESH: Male, Clinical trial, MESH: France, 030104 developmental biology, MESH: Antibodies, Monoclonal, Humanized, Quality of Life, business, MESH: Female
Abstract: PURPOSE To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS Patients, predominantly men, with their CSSCs’ immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort’s objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy–General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1– patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS Median age of all patients was 79 years. The primary cohort’s ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1– patients (17%; P = .02). Responders’ W15 total FACT-G score had improved ( P = .025) compared with nonresponders. CONCLUSION First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.
Published: 2020

93. Adverse events of targeted therapies reported by patients with cancer treated in primary care

Author: Boris Campillo-Gimenez, Marie-Eve Rouge-Bugat, Elodie Ventroux, Samuel Roger, Anthony Chapron, Julien Edeline, Jonchère, Laurent, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and CHU Toulouse [Toulouse]
Subjects: medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Primary care, Adverse effect, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Surveys and Questionnaires, Medicine, Humans, cancer survivors, 030212 general & internal medicine, Molecular Targeted Therapy, Prospective Studies, Intensive care medicine, Qualitative Research, Aged, [SDV.IB] Life Sciences [q-bio]/Bioengineering, lcsh:R5-920, Primary Health Care, business.industry, 030503 health policy & services, questionnaire, Cancer, Middle Aged, medicine.disease, targeted therapies, 3. Good health, Cancer treatment, ambulatory monitoring, Quality of Life, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, France, 0305 other medical science, Family Practice, business, lcsh:Medicine (General), Research Article
Abstract: International audience; Background Targeted Therapies (TT) are among the therapeutic innovations for cancer treatment in outpatient settings. TT-related Adverse Events (AEs) are a source of loss of opportunity for patients if their management is inappropriate. Objectives The objective of this study was to describe the AE frequency and severity as reported by patients with cancer who received TT in ambulatory settings. A second objective was to describe the role of the general practitioner (GP) in the management of AEs. Methods All patients who started TT at a French Regional Cancer Centre in 2017-2018 were eligible for this 12-month prospective study. A self-administered questionnaire was distributed at inclusion and returned after three months. In the questionnaire, patients listed all AEs that occurred during this period and rated their severity. Occurrence and severity were compared with the rating by a specialised nurse. Patients also indicated the health professional they contacted first for the reported AE. Results Among the 247 eligible patients, 15 were excluded and 144 responded to the questionnaire. Fourteen different TTs have been prescribed. Asthenia (92.4%) and anorexia (64.6%) were the most frequent AE. Patients' AE severity rating was more severe than the nurse's rating for all drugs (p < 0.001). Patients first contacted their GP for 15.6% of AEs, whereas 20.7% of AEs were not reported to any health professional. Conclusion Patients experienced an average of 4 AEs. AE severity rating was significantly different between patients and nurses. Patients do not always communicate AEs to health care professionals.
Published: 2020

94. Optimization of time frame binning for FDOPA uptake quantification in glioma

Author: Girard, Antoine, Saint-Jalmes, Hervé, Chaboub, Nibras, Le Reste, Pierre-Jean, Metais, Alice, Devillers, Anne, Le Jeune, Florence, Palard-Novello, Xavier, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Jonchère, Laurent, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Male, Statistical methods, Physiology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biopsy, Pharmacokinetic Analysis, Pathology and Laboratory Medicine, Compartment Models, Diagnostic Radiology, Drug Metabolism, Medicine and Health Sciences, Neurological Tumors, Tomography, Blood Volume, Brain Neoplasms, Radiology and Imaging, Statistics, Brain, Glioma, Middle Aged, Body Fluids, Monte Carlo method, Physical sciences, Blood, Oncology, Neurology, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, Research Article, Adult, Imaging Techniques, Phenylalanine, Science, Neuroimaging, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Research and Analysis Methods, Young Adult, Signs and Symptoms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Humans, Pharmacokinetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Pharmacology, Cancers and Neoplasms, Biology and Life Sciences, Biological Transport, Kinetics, Pharmacologic Analysis, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Positron-Emission Tomography, Lesions, Mathematical and statistical techniques, Radiopharmaceuticals, Positron Emission Tomography, Mathematics, Neuroscience
Abstract: Introduction3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA) uptake quantification in glioma assessment can be distorted using a non-optimal time frame binning of time-activity curves (TAC). Under-sampling or over-sampling dynamic PET images induces significant variations on kinetic parameters quantification. We aimed to optimize temporal time frame binning for dynamic FDOPA PET imaging.MethodsFourteen patients with 33 tumoral TAC with biopsy-proven gliomas were analysed. The mean SUVmax tumor-to-brain ratio (TBRmax) were compared at 20 min and 35 min post-injection (p.i). Five different time frame samplings within 20 min were compared: 11x10sec-6x15sec-5x20sec-3x300sec; 8x15sec- 2x30sec- 2x60sec- 3x300sec; 6x20sec- 8x60sec- 2x300sec; 10x30sec- 3x300sec and 4x45sec- 3x90sec- 5x150sec. The reversible single-tissue compartment model with blood volume parameter (VB) was selected using the Akaike information criterion. K1 values extracted from 1024 noisy simulated TAC using Monte Carlo method from the 5 different time samplings were compared to a target K1 value as the objective, which is the average of the K1 values extracted from the 33 lesions using an imaging-derived input function for each patient.ResultsThe mean TBRmax was significantly higher at 20 min p.i. than at 35 min p.i (respectively 1.4 +/- 0.8 and 1.2 +/- 0.6; p ConclusionsThis optimal sampling schedule design (8x15sec- 2x30sec- 2x60sec- 3x300sec) could be used to minimize bias in quantification of FDOPA uptake in glioma using kinetic analysis.
Published: 2020

95. Kidney ccRCC immune classification (KIC) enhances the predictive value of T effector (Teff) and angiogenesis (Angio) signatures in response to nivolumab (N)

Author: Meylan, M., Beuselinck, B, Dalban, C., Vano, Y., Leclercq, N. Rioux, Sautès-Fridman, C., Roussel, E., Verbiest, A, Chaput, N., Terry, S., Chevreau, C., Gross-Goupil, M., Flechon, A, Laguerre, B., Chabaud, S., Tantot, F., Lambrechts, D., Escudier, B., Fridman, W.-H., Albiges, L., Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), University Hospitals Leuven [Leuven], Centre Léon Bérard [Lyon], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Institut Claudius Regaud, CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), UNICANCER, Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Institut National du CancerInstitut National du Cancer (INCA) France, Bristol-Myers SquibbBristol-Myers Squibb, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

96. Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Author: Céleste Lebbé, Armin Schueler, Richard Isaacs, Giorgio Massimini, Willem Kruit, Brigitte Dreno, Virginia Ferraresi, Caroline Robert, Luc Thomas, Enrique Espinosa, Carmen Loquai, Paul Vasey, Joseph Kerger, Bernard Guillot, Jean-Jacques Grob, Robert M. Conry, Caroline Dutriaux, Claus Garbe, Filippo de Braud, Thierry Lesimple, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de dermatologie Hôpital Saint-André Bordeaux, CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), IRCCS Istituto Nazionale dei Tumori [Milano], Università degli Studi di Milano [Milano] (UNIMI), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), University Medical Center [Mainz], IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University of Alabama at Birmingham [ Birmingham] (UAB), Palmerston North Hospital [Palmerston North], Hospital Universitario La Paz, Merck [Darmstadt], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Medical Oncology, Herrada, Anthony, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Milano = University of Milan (UNIMI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Cancer Research, Gastroenterology, pimasertib, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, 030212 general & internal medicine, Malignant melanoma, Hazard ratio, Progression-free survival, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Dacarbazine, Oncology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, medicine.symptom, Pimasertib, medicine.drug, Quality of life, medicine.medical_specialty, Nausea, malignant melanoma, dacarbazine, [SDV.CAN]Life Sciences [q-bio]/Cancer, N-(2 3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide, Neutropenia, N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide, lcsh:RC254-282, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Adverse effect, business.industry, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, adverse events, Cancérologie, quality of life, Adverse events, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, progression-free survival, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg, oral twice-daily) or DTIC (1000 mg/m2, intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS), secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively, hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42&ndash, 0.83, p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00&ndash, 4.98, p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively, HR 0.89, 95% CI 0.61&ndash, 1.30), 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade &ge, 3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068
Published: 2020

97. Assessment of Glioma Aggressiveness Using Dynamic FDOPA PET/CT

Author: Girard, A., Le Reste, P, Metais, A., Chaboub, N., Devillers, A., Saint-Jalmes, Hervé, Le Jeune, Florence, Palard-Novello, X., Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

98. ITV versus mid-ventilation for treatment planning in lung SBRT: a comparison of target coverage and PTV adequacy by using in-treatment 4D cone beam CT

Author: Joël Castelli, Caroline Lafond, Enrique Chajon, J. Bellec, F. Arab-Ceschia, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: lcsh:Medical physics. Medical radiology. Nuclear medicine, Lung Neoplasms, medicine.medical_treatment, lcsh:R895-920, ITV, Planning target volume, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Radiosurgery, lcsh:RC254-282, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030218 nuclear medicine & medical imaging, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Stereotactic body radiation therapy (SBRT), 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Radiology, Nuclear Medicine and imaging, Four-Dimensional Computed Tomography, Planning strategy, Radiation treatment planning, Image guidance, Cone beam ct, Lung, business.industry, Radiotherapy Planning, Computer-Assisted, Research, Mid-ventilation, Cone-Beam Computed Tomography, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, Geometric uncertainties, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Breathing, Respiratory motions, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Radiotherapy, Intensity-Modulated, Lung cancer, Nuclear medicine, business, Stereotactic body radiotherapy, 4D-CBCT
Abstract: Background The internal target volume (ITV) approach and the mid-ventilation (MidV) concept are the two main respiratory motion-management strategies under free breathing. The purpose of this work was to compare the actual in-treatment target coverage during volumetric modulated arctherapy (VMAT) delivered through both ITV-based and MidV-based planning target volume (PTV) and to provide knowledge in choosing the optimal PTV for stereotactic body radiotherapy (SBRT) for lung lesions. Methods and materials Thirty-two lung cancer patients treated by a VMAT technique were included in the study. For each fraction, the mean time-weighted position of the target was localized by using a 4-dimensional cone-beam CT (4D-CBCT)-based image guidance procedure. The respiratory-correlated location of the gross tumor volume (GTV) during treatment delivery was determined for each fraction by using in-treatment 4D-CBCT images acquired concurrently with VMAT delivery (4D-CBCTin-treat). The GTV was delineated from each of the ten respiratory phase-sorted 4D-CBCTin-treat datasets for each fraction. We defined target coverage as the average percentage of the GTV included within the PTV during the patient’s breathing cycle averaged over the treatment course. Target coverage and PTVs were reported for a MidV-based PTV (PTVMidV) using dose-probabilistic margins and three ITV-based PTVs using isotropic margins of 5 mm (PTVITV + 5mm), 4 mm (PTVITV + 4mm) and 3 mm (PTVITV + 3mm). The in-treatment baseline displacements and target motion amplitudes were reported to evaluate the impact of both parameters on target coverage. Results Overall, 100 4D-CBCTin-treat images were analyzed. The mean target coverage was 98.6, 99.6, 98.9 and 97.2% for PTVMidV, PTVITV + 5mm, PTVITV + 4mm and PTVITV + 3mm, respectively. All the PTV margins led to a target coverage per treatment higher than 95% in at least 90% of the evaluated cases. Compared to PTVITV + 5mm, PTVMidV, PTVITV + 4mm and PTVITV + 3mm had mean PTV reductions of 16, 19 and 33%, respectively. Conclusion When implementing VMAT with 4D-CBCT-based image guidance, an ITV-based approach with a tighter margin than the commonly used 5 mm margin remains an alternative to the MidV-based approach for reducing healthy tissue exposure in lung SBRT. Compared to PTVMidV, PTVITV + 3mm significantly reduced the PTV while still maintaining an adequate in-treatment target coverage.
Published: 2020

99. Lymphocytes and Neutrophil-to-Lymphocyte Ratio Variations After Selective Internal Radiation Treatment for HCC: A Retrospective Cohort Study

Author: Etienne Garin, Florian Estrade, Céline Lescure, Léa Muzellec, Yan Rolland, Thomas Uguen, Marc Pracht, Julien Edeline, Maud Pedrono, Xavier Palard, Samuel Le Sourd, Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Jonchère, Laurent, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Yttrium-90, Neutrophils, Lymphocyte, Brachytherapy, Gastroenterology, 030218 nuclear medicine & medical imaging, Cohort Studies, 0302 clinical medicine, Medicine, Lymphocytes, Aged, 80 and over, Selective internal radiation therapy, Liver Neoplasms, Liter, Middle Aged, Prognosis, Anti-PD-1, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Hepatocellular carcinoma, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Immune checkpoint inhibitors, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Lymphopenia, Humans, Radiology, Nuclear Medicine and imaging, Lymphocyte Count, Neutrophil to lymphocyte ratio, Radioembolization, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, Proportional hazards model, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver malignancies, business
Abstract: International audience; Purpose Selective internal radiation therapy (SIRT) has been proposed for combination with immunotherapy to treat hepatocellular carcinoma (HCC). However, the toxicity of radiation toward lymphocytes is understudied after SIRT. The aim of this study was to describe variations of lymphocytes following SIRT and their potential prognostic impact.Materials and Methods This is a retrospective cohort study of 164 patients treated with SIRT for HCC. Lymphocyte count and neutrophil-to-lymphocyte (NLR) ratio were evaluated at baseline and at 3 months. Primary endpoint was overall survival (OS).Results Median baseline lymphocyte count was 1.32 Giga/Liter (G/L) (standard deviation (SD) 0.64) at baseline versus 0.68 G/L (SD 0.41) at 3 months. The mean decrease of lymphocyte count was - 44% (standard deviation 0.24). At 3 months, only 21% of patients had normal (1 G/L or more) lymphocyte count, and 23% had lymphocyte count < 0.5 G/L. NLR at 3 months was significantly and independently associated with OS in multivariate Cox model. Median OS was 9.9 months (95% confidence interval (CI) 6.2-13.5) for patients with NLR at 3 months higher than 7.2 compared to 19.9 months in patients with an NLR lower that the 7.2 threshold (95% CI 16.3-23.3) (p = 0.003).Conclusions The decrease in lymphocytes was frequent and deep after SIRT for HCC. NLR increase at 3 months was associated with poor survival.
Published: 2020

100. Downstaging with Radioembolization or Chemotherapy for Initially Unresectable Intrahepatic Cholangiocarcinoma

Author: Héloïse Bourien, Laurent Sulpice, Lucas Verdure, Damien Bergeat, Julien Edeline, Astrid Lièvre, Diane Riby, Karim Boudjema, Etienne Garin, Alessandro Mazzotta, Yan Rolland, Centre Eugène Marquis (CRLCC), and CHU Pontchaillou [Rennes]
Subjects: medicine.medical_specialty, medicine.medical_treatment, Brachytherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Medicine, Humans, Embolization, Intrahepatic Cholangiocarcinoma, Neoadjuvant therapy, Retrospective Studies, business.industry, Hazard ratio, Selective internal radiation therapy, Retrospective cohort study, Embolization, Therapeutic, 3. Good health, Surgery, Bile Ducts, Intrahepatic, Treatment Outcome, Oncology, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract: International audience; Objective The aim of this retrospective study was to compare the outcomes of patients resected for intrahepatic cholangiocarcinoma (ICC) with upfront surgery or after downstaging treatment. Methods All consecutive patients with ICC between January 1997 and November 2017 were included in a single-center database and retrospectively reviewed. Patients were divided into two groups: upfront resection or resection after downstaging using either chemotherapy alone or selective internal radiation therapy (SIRT) combined with chemotherapy. Survival rates of patients who underwent upfront surgery for ICC were compared with those of patients who underwent surgery after downstaging therapy. Results A total of 169 patients resected for ICC were included: 137 underwent upfront surgery and 32 received downstaging treatment because their tumor was initially unresectable (13 received chemotherapy, 19 received SIRT). Median OS was not different between the two groups: 32.3 months [95% confidence interval (CI) 23.9-40.7] with primary surgery versus 45.9 months (95% CI 32.3-59.4) with downstaging treatment (p = 0.54, log-rank test). In a multivariable Cox regression model, downstaging treatment was not associated with a better or worse prognosis; however, delivery of SIRT as a downstaging treatment was associated with a significant benefit in multivariable analysis (hazard ratio 0.34, 95% CI 0.14-0.84; p = 0.019). Conclusions Overall survival of patients resected after downstaging treatment was not different compared with the OS of patients resected upfront. Patients should therefore again be discussed with the surgeon following medical treatment. SIRT may be an efficient neoadjuvant therapy in patients with resectable ICC, in order to improve surgical results.
Published: 2020

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