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10 results on '"Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD)"'

1. Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial

Author

Aparicio, T., Bouché, O., Etienne, P. L., Barbier, E., Mineur, L., Desgrippes, R., Guerin-Meyer, V., Hocine, F., Martin, J., Le Brun-Ly, V., Cretin, J., Desramé, J., Rinaldi, Y., Cany, L., Falandry, C., Lefevre, L. B., Marous, M., Terrebonne, E., Mosser, L., Turpin, J., Turpin, A., Bauguion, L., Reichling, C., Eynde, M., Carola, E., Hiret, S., UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'oncologie médicale, UCL - (SLuc) Service d'hépato-gastro-entérologie, CarMeN, laboratoire, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Privé des Côtes d'Armor (HPCA), Lipides - Nutrition - Cancer (U866) (LNC), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fédération Francophone de Cancérologie Digestive (FFCD), Institut Sainte Catherine [Avignon], CH de Saint-Malo [Broussais], Service d'Oncologie Médicale [Angers], Centre Paul Papin, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Simone Veil de Beauvais [Beauvais], Clinique François Chénieux, Hôpital Dupuytren [CHU Limoges], Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Hôpital privé Jean Mermoz [Lyon], Hôpital Européen [Fondation Ambroise Paré - Marseille], Clinique Francheville [Périgueux], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, CHU de la Martinique [Fort de France], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Clinique Sainte Isabelle [Abbeville, France], Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CH Colmar, Cliniques Universitaires Saint-Luc [Bruxelles], Groupe Hospitalier Public du Sud de l'Oise [Creil] (GHPSO), CRLCC René Gauducheau, and Département d'oncologie médicale [Saint Herblain]

Subjects
Geriatric evaluation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Hepatology, Older, Gastroenterology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Adjuvant chemotherapy, Colon cancer
Abstract

International audience; BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.

Published
2022
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2. Cabozantinib-nivolumab sequence in metastatic renal cell carcinoma: The CABIR study

Author

Yann‐Alexandre Vano, Letuan Phan, Gwenaelle Gravis, Iphigénie Korakis, Friederike Schlürmann, Denis Maillet, Mostefa Bennamoun, Nadine Houede, Delphine Topart, Delphine Borchiellini, Philippe Barthelemy, Raffaele Ratta, Thomas Ryckewaert, Ali Hasbini, Sophie Hans, Sheik Emambux, Sandra Cournier, Elena Braychenko, Réza‐Thierry Elaidi, Stéphane Oudard, 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Département de Radio-Oncologie [Brest] (Clinique Pasteur), Clinique Pasteur [Brest], Département de radiologie, Institut Gustave Roussy (IGR), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), 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), Service d'Oncologie Médicale [Montsouris], Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), 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), Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpital Foch [Suresnes], 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), and PSEN Pharm

Subjects
Cancer Research, Pyridines, [SDV]Life Sciences [q-bio], Tyrosine kinase inhibitor, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Anilides, Humans, MESH: Protein Kinase Inhibitors, Anilides, Carcinoma, Renal Cell, Protein Kinase Inhibitors, Retrospective Studies, MESH: Humans, MESH: Pyridines, Cabozantinib, MESH: Retrospective Studies, MESH: Carcinoma, Renal Cell, Kidney Neoplasms, Renal cell carcinoma, Nivolumab, Oncology, Matching-adjusted study, MESH: Antineoplastic Agents, MESH: Nivolumab, Immunotherapy, MESH: Kidney Neoplasms
Abstract

International audience; Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR-TKI. In this multicenter retrospective study, we collected data from mRCC pts receiving CN or NC, after frontline VEGFR-TKI. A propensity score (PrS) was calculated to manage bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. The primary endpoint was progression-free survival (PFS) from the start of second line to progression in third line (PFS2-3 ). Key secondary endpoints included overall survival from second line (OS2 ). Out of 139 included mRCC patients, 38 (27%) and 101 (73%) received CN and NC, respectively. Overlap in PrS allowed 1:1 matching for each CN pts, with characteristics well balanced. For both PFS2-3 and OS2 , NC sequence was superior to CN (PFS2-3 : HR = 0.58 [0.34-0.98], P = .043; OS2 : 0.66 [0.42-1.05], P = .080). Superior PFS2-3 was in patients treated between 6 and 18 months with prior VEGFR-TKI (P = .019) and was driven by a higher PFSL3 with cabozantinib when given after nivolumab (P

Published
2022
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3. A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy

Author

Elodie Chartron, Nelly Firmin, Célia Touraine, Angélique Chapelle, Eric Legouffe, Lobna Rifai, Stéphane Pouderoux, Lise Roca, Véronique D’Hondt, William Jacot, Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, Institut du Cancer de Montpellier (ICM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ONCOGARD - NIMES, Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), 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), and UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM)

Subjects
Adult, Nutrition and Dietetics, Nutrition. Foods and food supply, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Middle Aged, Vitamin D Deficiency, Article, adjuvant chemotherapy, Treatment Outcome, breast cancer, Chemotherapy, Adjuvant, Dietary Supplements, Humans, TX341-641, Female, Vitamin D, vitamin D insufficiency, Biomarkers, Food Science, hypercalciuria, Aged
Abstract

International audience; Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0–62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.

Published
2021
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4. PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1

Author

Hanane Agherbi, Fanny Leenhardt, Litaty Mbatchi, Aurélie Garcin, Philippe Pourquier, Alexandre Evrard, Candice Marchive, Alice Matheux, Matthieu Gassiot, Nadine Houede, Abdelhay Boulahtouf, Gaëlle Fromont, Patrick Balaguer, Eve Combes, Céline Gongora, Eric Fabbrizio, 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), Gongora, Céline, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut du Cancer de Montpellier (ICM), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD)

Subjects
0301 basic medicine, Cancer Research, Afatinib, PXR, [SDV]Life Sciences [q-bio], afatinib, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, digestive system, Article, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Prostate, medicine, kinase inhibitors, RC254-282, Pregnane X receptor, Chemistry, Kinase, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, biomarkers, Dabrafenib, medicine.disease, prostate cancer, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, digestive system diseases, 3. Good health, Dasatinib, 030104 developmental biology, medicine.anatomical_structure, Oncology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer research, SLC16A1, Erlotinib, Biomakers, medicine.drug
Abstract

Simple Summary Many kinase inhibitors have been tested as potential alternatives for the treatment of castration-resistant prostate cancers. However, none of these clinical trials led to drug approval despite interesting responses. Our study reveals that genes involved in drug metabolism and their master regulator PXR (Pregnane X Receptor) could be responsible, at least in part, for these disappointing results as they can modulate tumor cell response to specific kinase inhibitors. We found that stable expression of PXR sensitized prostate cancer cells to erlotinib, dabrafenib, and afatinib, while it rendered cells resistant to dasatinib and had no effect for other inhibitors tested. We also report for the first time that sensitization to afatinib is due to an alteration in drug transport that involves the SLC16A1 monocarboxylate transporter. Together, our results further indicate that PXR might be considered as a biomarker of response to kinase inhibitors in castration-resistant prostate cancers. Abstract Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level. Here, we studied the role of PXR (Pregnane X Receptor), a master regulator of metabolism, in the resistance to KIs in a prostate cancer setting. We confirmed that PXR is expressed in prostate tumors and is more frequently detected in advanced forms of the disease. We showed that stable expression of PXR in 22Rv1 prostate cancer cells conferred a resistance to dasatinib and a higher sensitivity to erlotinib, dabrafenib, and afatinib. Higher sensitivity to afatinib was due to a ~ 2-fold increase in its intracellular accumulation and involved the SLC16A1 transporter as its pharmacological inhibition by BAY-8002 suppressed sensitization of 22Rv1 cells to afatinib and was accompanied with reduced intracellular concentration of the drug. We found that PXR could bind to the SLC16A1 promoter and induced its transcription in the presence of PXR agonists. Together, our results suggest that PXR could be a biomarker of response to kinase inhibitors in castration-resistant prostate cancers.

Published
2021
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5. Clinical and biological characteristics of leukemia cutis in chronic lymphocytic leukemia: A study of the French innovative leukemia organization (FILO)

Author

Anne Lavaud, Audrey Bidet, Damien Roos-Weil, Benjamin Carpentier, Stéphane Leprêtre, Antoine Martin, Lauren Veronese, Alain Delmer, Loic Ysebaert, Bénédicte Hivert, Julien Broséus, Anne Corby, Eric Van Den Neste, Stéphanie Poulain, Agathe Waultier Rascalou, Kamel Laribi, Damien Luque Paz, Romain Guieze, Lise Willems, Jérôme Paillassa, Fatiha Merabet, Jean-Philippe Vial, Fanny Baran-Marszak, Pierre Feugier, Albane Ledoux-Pilon, Anne Quinquenel, Michaël Munger, Florence Cymbalista, Virginie Eclache, Eve Maubec, Chloé Friedrich, Marie-Sarah Dilhuydy, Lysiane Molina, Grégory Lazarian, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Hôpital de l'Enfant-Jésus [CHU Québec] (HEJ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), CRHU Nancy, Unité clinique de pathologie neuromusculaire [CHU Pitié-Salpêtrière], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Le Mans (CH Le Mans), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Hôpital Cochin [AP-HP], 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier de la Rochelle (CH la Rochelle), Centre de Biologie Pathologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), FAYE, Fatimata, Signalisation, Microenvironnement et Hémopathies Lymphoïdes B (SIMHEL), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, Adult, Male, medicine.medical_specialty, Skin Neoplasms, Chronic lymphocytic leukemia, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Skin, Aged, 80 and over, B-Lymphocytes, business.industry, Leukemia cutis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Leukemia, Treatment Outcome, Mutation, Female, France, medicine.symptom, business
Abstract

TO THE EDITOR : Patients with chronic lymphocytic leukemia (CLL) exhibit a variety of skin lesions including mostly non-specific cutaneous manifestations (such as cutaneous infections or exaggerated reactions to insect bite) and secondary cutaneous malignancies, as patients are at high risk of developing basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Specific cutaneous infiltration by neoplastic B lymphocytes with clinically identifiable skin lesions, also called leukemia cutis (LC), is more uncommon and has seldom been reported in chronic lymphocytic leukemia. [...]

Published
2021
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6. 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
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7. Traitement des oligometastases et oligoprogression

Author

I. Latorzeff, O. Riou, M.-P. Farcy-Jacquet, C. Lemanski, P. Boisselier, D. Azria, C. Llacer, Céline Bourgier, Pascal Fenoglietto, M. Charissoux, CCSD, Accord Elsevier, 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 du Cancer de Montpellier (ICM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD)

Subjects
Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Oligométastases, 3. Good health, Stereotactic radiotherapy, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Radiothérapie stéréotaxique, medicine, Radiology, Nuclear Medicine and imaging, business, Oligometastases
Abstract

Resume Nous proposons dans cette revue de rapporter l’impact de la radiotherapie stereotaxique chez les patients ayant un cancer oligometastatique ou en oligoprogression en termes de survie sans progression metastatique et globale, et d’identifier quelle est la place de cette modalite de radiotherapie au sein du parcours–patient.

Published
2019
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8. OC-0284: First results of the French cohort ANABASE : treatment and outcome in non-metastatic anal cancer

Author

C. Lemanski, David Tougeron, A. de la Rochefordière, M. Saliou, Véronique Vendrely, Eric Francois, Côme Lepage, O. Bouche, J. Cretin, N. Bonichon-Lamichhane, Emilie Barbier, P. Pommier, O. Diaz, Laurent Quero, P. Ronchin, N. Baba Hamed, CHU Bordeaux [Bordeaux], UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, Fédération Francophone de la Cancérologie Digestive, FFCD, Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Tivoli Ducos [Bordeaux], Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d’hépato-gastro-entérologie et assistance nutritive [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Daniel Hollard [Grenoble], Centre Léon Bérard [Lyon], Centre Azureen de cancérologie, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), université de Bourgogne, LNC, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Centre Antoine Lacassagne de Nice, Groupe hospitalier Paris Saint-Joseph - Hôpital, Clinique Tivoli-Ducos, Institut Curie, Institut de Cancérologie du GARD (Instit Cancéro - GARD), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Oncology, medicine.medical_specialty, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, Hematology, 021001 nanoscience & nanotechnology, medicine.disease, Outcome (game theory), 3. Good health, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Internal medicine, Cohort, 0202 electrical engineering, electronic engineering, information engineering, medicine, Non metastatic, Anal cancer, 020201 artificial intelligence & image processing, Radiology, Nuclear Medicine and imaging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0210 nano-technology, business
Abstract

IF 4.942 (2017); International audience

Published
2018

9. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations

Author

Serge Carillo, Aurélie Chauveau, Stéphane Giraudier, Jean-Jacques Kiladjian, Emmanuelle Verger, Valérie Ugo, Mohammed A. Yassin, Bruno Cassinat, Christine Chomienne, Marie-Hélène Schlageter, Jean-Christophe Ianotto, Eric Legouffe, Nader Al-Dewik, Christine Dosquet, Unite de Biologie Cellulaire (Biol Cell - ST LOUIS - PARIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité de Formation de Recherche de Médecine (UFRM - BREST), Université de Brest (UBO), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Hematology and Bone Marrow Transplant (DHBMT - DOHA - QATAR), National Center for Cancer Care and Research (NCCCR - DOHA - QATAR), Qatar Medical Genetic Center (QMGC - DOHA - QATAR), Hamad medical corporation, Département de Cytologie Clinique (Dep Cyto Clin - NIMES), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), ONCOGARD - NIMES, Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Université d'Angers - Faculté de médecine (UA UFR Médecine), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), Centre Hospitalier Universitaire d'Angers (CHU Angers), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigations Cliniques, 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), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Oncology, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Gene mutation, medicine.disease_cause, Biochemistry, Somatic evolution in cancer, Polyethylene Glycols, 0302 clinical medicine, Hydroxyurea, interferon-a therapy, 0303 health sciences, Mutation, essential thrombocythemia, biology, Remission Induction, Hematology, Middle Aged, Isocitrate Dehydrogenase, Recombinant Proteins, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Female, Thrombocythemia, Essential, CALR mutations, Adult, medicine.medical_specialty, Adolescent, Immunology, Alpha interferon, IDH2, Dioxygenases, Clonal Evolution, Young Adult, 03 medical and health sciences, Proto-Oncogene Proteins, Internal medicine, medicine, Humans, Allele, Alleles, 030304 developmental biology, Aspirin, Essential thrombocythemia, Interferon-alpha, Off-Label Use, Cell Biology, Genes, p53, medicine.disease, Clone Cells, Repressor Proteins, biology.protein, Calreticulin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

International audience; Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy.

Published
2015
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10. Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by 18 F-Misonidazole PET/CT in Patients with Non–Small Cell Lung Carcinoma (RTEP5 Study)

Author

Romain Modzelewski, Mathieu Salaün, Fabrice Denis, Naji Salem, Pierre Bohn, Jean-Pierre Muratet, Pierre Olivier, Sophie Guillemard, Nicolas Aide, Enrique Chajon, Laurent Vervueren, Pierre Vera, Alina Berriolo Riedinger, Claire Houzard, Marie Lacombe, Françoise Mornex, Etienne Martin, Maximilien Vermandel, Nathalie Charrier, P.O. Kotzki, Frédéric Courbon, Anne Devillers, Véronique Beckendorf, S. Danhier, Carole Massabeau, Marc-André Mahé, Eric Dansin, P. Boisselier, Philippe Chaumet-Riffaud, Philippe Fernandez, Sébastien Thureau, Amaury Paumier, Marie-Pierre Farcy Jacquet, Hélène Kolesnikov-Gauthier, Amandine Pallardy, Sébastien Hapdey, Bernard Dubray, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-CRLCC Henri Becquerel, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service de Biophysique et de Médecine Nucléaire, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Therapies Interventionnelles Assistees Par l'Image et la Simulation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, CRLCC René Gauducheau, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, 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), Service de médecine nucléaire [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Lab-STICC_UBO_CACS_MOCS, Université de Brest (UBO)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Centre Alexis Vautrin (CAV), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CRLCC Eugène Marquis (CRLCC), Département de médecine nucléaire [Rennes], Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire [CHU Caen], 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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre Jean Bernard (ILC Le Mans), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), 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 Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), UNICANCER-Université Lille Nord de France (COMUE), 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), Centre de Recherches en Cancérologie de Toulouse (CRCT), Centre National de la Recherche Scientifique (CNRS)-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), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CRLCC Paul Papin, Centre des Sciences de la Terre, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Département de radiothérapie et de physique médicale, CRLCC Henri Becquerel, Département de Radiothérapie, Centre René Gauducheau-Institut de Cancérologie de l'Ouest (ICO)-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiation oncologie, CGFL, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Department of Radiation Oncology, Centre Hospitalier Universitaire Lyon Sud, Pierre Benite, France

Subjects
Misonidazole, positron emission tomography, medicine.medical_treatment, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Carcinoma, medicine, Radiology, Nuclear Medicine and imaging, fluoro-deoxy-D-glucose, Lung cancer, Survival rate, Radiation oncologist, Pneumonitis, f-misonidasole, business.industry, hypoxia, medicine.disease, 3. Good health, radiotherapy dose, Radiation therapy, lung cancer, chemistry, 030220 oncology & carcinogenesis, business, Nuclear medicine
Abstract

International audience; See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant (18)F-misonidazole ((18)F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The (18)F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In (18)F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were (18)F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the (18)F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the (18)F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the (18)F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. (18)F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.

Published
2017
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