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1. Management and outcomes of brain metastases from pancreatic adenocarcinoma: a pooled analysis and literature review

Author: Etienne Gouton, Marine Gilabert, Simon Launay, Elika Loir, Marguerite Tyran, Philippe Rochigneux, Olivier Turrini, Jonathan Garnier, Emmanuel Mitry, and Brice Chanez
Subjects: pancreatic cancer, brain metastases, brain surgery, machine learning, data mining, big data, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: BackgroundBrain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes.AimWe aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature.MethodsWe conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1). Simultaneously, we reviewed and pooled the case reports and case series of patients with PDAC and BM in the literature (cohort 2). The clinical characteristics of patients in each cohort were described and survival analyses were performed using the Kaplan-Meier method.ResultsIn cohort 1, 19 patients (0.3%) with PDAC and BM were identified with a median age of 69 years (range: 39-81). Most patients had metastatic disease (74%), including 21% with BM, at diagnosis. Lung metastases were present in 58% of patients. 68% of patients had neurological symptoms and 68% were treated by focal treatment (surgery: 21%, radiotherapy: 42%, Gamma Knife radiosurgery: 5%). In cohort 2, among the 61 PDAC patients with BM described in the literature, 59% had metastatic disease, including 13% with BM at diagnosis. Lung metastases were present in 36% of patient and BM treatments included: surgery (36%), radiotherapy (36%), radiosurgery (3%), or no local treatment (25%). After the pancreatic cancer diagnosis, the median time to develop BM was 7.8 months (range: 0.0-73.9) in cohort 1 and 17.0 months (range: 0.0-64.0) in cohort 2. Median overall survival (OS) in patients of cohort 1 and cohort 2 was 2.9 months (95% CI [1.7,4.0]) and 12.5 months (95% CI [7.5,17.5]), respectively.ConclusionBM are very uncommon in PDAC and seem to occur more often in younger patients with lung metastases and more indolent disease. BM are associated with poor prognosis and neurosurgery offers the best outcomes and should be considered when feasible.
Published: 2024
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2. OncoSNIPE® Study Protocol, a study of molecular profiles associated with development of resistance in solid cancer patients

Author: Sébastien Vachenc, Jessica Gobbo, Sarah El Moujarrebe, Isabelle Desmoulins, Marine Gilabert, Michelle Beau-Faller, Emmanuel Mitry, Nicolas Girard, Aurélie Bertaut, Nelson Dusetti, Juan L. Iovanna, Rahima Yousfi, Fabien Pierrat, Roman Bruno, Adèle Cueff, Romain Boidot, and Philippe Genne
Subjects: Early/ late resistance marker, NGS, Immunological profile, Triple negative breast or Luminal Breast Cancer, Non small-cell lung cancer, Pancreatic ductal adenocarcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Nowadays, evaluation of the efficacy and the duration of treatment, in context of monitoring patients with solid tumors, is based on the RECIST methodology. With these criteria, resistance and/or insensitivity are defined as tumor non-response which does not allow a good understanding of the diversity of the underlying mechanisms. The main objective of the OncoSNIPE® collaborative clinical research program is to identify early and late markers of resistance to treatment. Methods Multicentric, interventional study with the primary objective to identify early and / or late markers of resistance to treatment, in 600 adult patients with locally advanced or metastatic triple negative or Luminal B breast cancer, non-small-cell lung cancer or pancreatic ductal adenocarcinoma. Patients targeted in this study have all rapid progression of their pathology, making it possible to obtain models for evaluating markers of early and / or late responses over the 2-year period of follow-up, and thus provide the information necessary to understand resistance mechanisms. To explore the phenomena of resistance, during therapeutic response and / or progression of the pathology, we will use a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq), clinical data, medical images and immunological profile by ELISA. Patients will have long-term follow-up with different biological samples, at baseline (blood and biopsy) and at each tumoral evaluation or tumoral progression evaluated by medical imaging. Clinical data will be collected through a dedicated Case Report Form (CRF) and enriched by semantic extraction based on the French ConSoRe (Continuum Soins Recherche) initiative, a dedicated Semantic Clinical Data Warehouse (SCDW) to cancer. The study is sponsored by Oncodesign (Dijon, France) and is currently ongoing. Discussion The great diversity of intrinsic or acquired molecular mechanisms involved in resistance to treatment constitutes a real therapeutic issue. Improving understanding of mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major challenge. The OncoSNIPE cohort will lead to a better understanding of the mechanisms of resistance and will allow to explore new mechanisms of actions and to discover new therapeutic targets or strategies making it possible to circumvent the escape in different types of cancer. Trial registration Clinicaltrial.gov. Registered 16 September 2020, https://clinicaltrials.gov/ct2/show/NCT04548960?term=oncosnipe&draw=2&rank=1 and ANSM ID RCB 2017-A02018-45.
Published: 2022
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3. Impact of fiducial markers placement on the delineation of target volumes in radiation therapy for oesophageal cancer: FIDUCOR study

Author: Philippe Rochigneux, Marguerite Tyran, Aurélie Autret, Leonor Lopez Almeida, Jérôme Guiramand, Marjorie Ferre, Brice Chanez, Emmanuel Mitry, Jean Philippe Ratone, Marc Giovannini, Agnès Tallet, Laurence Moureau-Zabotto, and Fabrice Caillol
Subjects: oesophageal cancer, radiation therapy (radiotherapy), fiducial markers (FMs), target volumes, endoscopic ultrasound, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: PurposeThis prospective monocentric phase II study (FIDUCOR-study, NCT02526134) aimed to assess the impact of fiducial markers (FMs) implantation on conformal chemo-radiation therapy (CRT) planning in oesophageal carcinoma (EC) patients.Methods/materialsFifteen EC patients were enrolled in the study. Each patient underwent two simulation CT-scans before (CT1) and after (CT2) FMs implantation, in the same position. FMs (3 mm length gold markers, preloaded in a 22G needle) were implanted after sedation, under endoscopic ultrasound (EUS) and X-Ray guidance, and were placed at the tumor’s extremities, and in the visible lymph nodes. Target delineation and treatment plan were both performed first on CT1 with the assistance of diagnosis CT, gastroscopy and EUS details, and second on CT2 using FMs and CT-data. The value of FMs implantation was assessed by the difference of growth-tumor-volume (GTV) and clinical-target-volume (CTV) between CT1-based and CT2-based delineation. A significant difference was defined as a ≥5 mm-difference on axial(x) or coronal(y) slices, a ≥10mm-difference on sagittal slices, or a ≥20%-difference in GTV. The impact on dose distribution in organs at risk (OAR) (lung, heart, liver) was also studied.ResultsBetween 09/2014 and 12/2015, 15 patients could achieve fiducial procedures, without any complication. One FM migration occurred. We observed a significant modification of the GTV-dimension in 100% of the cases (15/15, 95%CI: [78.2;100.0]), mainly due to a difference in sagittal dimension with a mean variation of 11.2 mm and a difference> 10 mm for 8/15 patients (53.3%). One patient had a significant isocenter displacement as high as 20 mm. The oesophagus tumor was not seen on the CT-scan in one patient due to its small size. One patient had a distant lymph node metastasis not visible on CT-scan. We observed no significant impact on OAR distribution.ConclusionIn our study, FMs-implantation under EUS had a positive impact on accurate volume definition in EC-patients (modification of GTV in 15/15 patients). Close cooperation between gastroenterologist and radiation oncologist has the potential to improve local treatment of oesophageal carcinoma.
Published: 2022
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4. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Author: Robert J. Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Tadeusz Robak, Philipp D. le Coutre, Bjørn T. Gjertsen, Xavier Troussard, Gail J. Roboz, Lionel Karlin, Douglas E. Gladstone, Nataliya Kuptsova-Clarkson, Shiyao Liu, Priti Patel, Federico Rotolo, Emmanuel Mitry, Ira Pastan, Francis Giles, and the Study 1053 investigators
Subjects: Hairy cell leukemia (HCL), B cell malignancy, Relapsed/refractory, CD22, Immunotoxin, Moxetumomab pasudotox, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711
Published: 2021
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5. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

Author: Wulfran Cacheux, Petros Tsantoulis, Adrien Briaux, Sophie Vacher, Pascale Mariani, Marion Richard‐Molard, Bruno Buecher, Sophie Richon, Emmanuelle Jeannot, Julien Lazartigues, Etienne Rouleau, Odette Mariani, Elsy El Alam, Jérôme Cros, Sergio Roman‐Roman, Emmanuel Mitry, Elodie Girard, Virginie Dangles‐Marie, Astrid Lièvre, and Ivan Bièche
Subjects: anal squamous cell carcinoma, array comparative genomic hybridization, copy number alterations, PI3K/Akt/mTOR signaling pathway, somatic mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
Published: 2018
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6. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial

Author: Thierry, Conroy, Florence, Castan, Anthony, Lopez, Anthony, Turpin, Meher, Ben Abdelghani, Alice C, Wei, Emmanuel, Mitry, James J, Biagi, Ludovic, Evesque, Pascal, Artru, Thierry, Lecomte, Eric, Assenat, Lucile, Bauguion, Marc, Ychou, Olivier, Bouché, Laure, Monard, Aurélien, Lambert, Pascal, Hammel, and Chris, O'Callaghan
Subjects: Male, Cancer Research, Canada, Leucovorin, Irinotecan, Gemcitabine, Oxaliplatin, Pancreatic Neoplasms, Oncology, Chemotherapy, Adjuvant, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Fluorouracil, Neoplasm Recurrence, Local, Carcinoma, Pancreatic Ductal
Abstract: ImportanceEarly results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available.ObjectiveTo report 5-year outcomes and explore prognostic factors for overall survival.Design, Setting, and ParticipantsThis open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021.InterventionsA total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m2 of body surface area; irinotecan, 150-180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 2400 mg/m2, every 2 weeks) or gemcitabine (1000 mg/m2, days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks.Main Outcomes and MeasuresPrimary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined.ResultsOf the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months’ follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P P Conclusions and RelevanceThe final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma.Trial RegistrationEudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135
Published: 2023

7. The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments

Author: Leonel Varela Cagetti, Laurence Moureau-Zabotto, Christophe Zemmour, Marjorie Ferré, Marc Giovaninni, Flora Poizat, Bernard Lelong, Cecile De Chaisemartin, Emmanuel Mitry, Marguerite Tyran, Amira Zioueche-Mottet, Naji Salem, and Agnès Tallet
Subjects: Oncology, Radiology, Nuclear Medicine and imaging
Published: 2023
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8. A Transcriptomic-Based Tool to Predict Gemcitabine Sensitivity in Advanced Pancreatic Adenocarcinoma

Author: Nicolas Fraunhoffer, Brice Chanez, Carlos Teyssedou, Juan L. Iovanna, Emmanuel Mitry, Nelson J. Dusetti, Martin Bigonnet, Claire Bongrain, Emilie Lermite, Patrick Pessaux, Fabio Giannone, Marie-Pierre Chenard, Sophie Michalak, Rémy Nicolle, Marion Rubis, Flora Poizat, Marc Giovannini, Fabrice Caillol, and Philippe Rochigneux
Subjects: Hepatology, Gastroenterology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Abstract: research support, non-u.s. gov't letter 2023 Mar 2022 12 07 imported
Published: 2022

9. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer

Author: Violaine Randrian, Simon Pernot, Karine Le Malicot, Vittorio Catena, Isabelle Baumgaertner, Vania Tacher, Julien Forestier, Vincent Hautefeuille, Claire Tabouret-Viaud, Alice Gagnaire, Emmanuel Mitry, Boris Guiu, Thomas Aparicio, Denis Smith, Anthony Dhomps, Jean-Pierre Tasu, Rémy Perdrisot, Julien Edeline, Claude Capron, Catherine Cheze-Le Rest, Jean-François Emile, Pierre Laurent-Puig, Theodora Bejan-Angoulvant, Harry Sokol, Come Lepage, Julien Taieb, David Tougeron, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Bergonié [Bordeaux], UNICANCER, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Fédération Francophone de Cancérologie Digestive (FFCD), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 Amiens-Picardie, Université de Genève = University of Geneva (UNIGE), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Universitaire [Rennes], CRLCC Eugène Marquis (CRLCC), Hôpital Ambroise Paré [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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This study was supported in part by Roche and Biocompatibles UK Ltd, a wholly owned subsidiary of Boston Scientific Corporation. Fédération Francophone de Cancérologie Digestive (FFCD) is funding the bio-bank and molecular analysis.
Subjects: Hepatology, Rectal Neoplasms, Selective internal radiation therapy, Liver Neoplasms, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immune checkpoint inhibitor, Antibodies, Monoclonal, Humanized, Colorectal cancer, Bevacizumab, Liver metastases, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Humans, Sirtuins, Prospective Studies, Colorectal Neoplasms
Abstract: International audience; Abstract The cellular prion protein PrP C partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrP C and CAV1 across cancer. Using cell-based assays, we show that PrP C regulates the expression of and interacts with CAV1. PrP C additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrP C -dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrP C interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrP C -dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrP C axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.
Published: 2022
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10. Avdoralimab (anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FORCE)

Author: Julien Carvelli, Ferhat Meziani, Jean Dellamonica, Pierre-Yves Cordier, Jerome Allardet-Servent, Megan Fraisse, Lionel Velly, Saber Barbar, Samuel Lehingue, Christophe Guervilly, Maxime Desgrouas, Fabrice Camou, Christelle Piperoglou, Frederic Vely, Robert Zerbib, Emmanuel Mitry, Joyson Karakunnel, Joanna Fares, Luciana Batista, Federico Rotolo, Julien Viotti, Agnès Boyer-Chammard, Sabrina Carpentier, Olivier Demaria, Karine Lacombe, Erwan Le Dault, Nassima Chouaki-Benmansour, michel Carles, Nicolas Schleinitz, Eric Vivier, and The Force Study Group
Published: 2022
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11. Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Author: Yanis Dahel, Brice Chanez, Christophe Zemmour, Gilles Piana, Emmanuel Mitry, and Marc Giovannini
Subjects: Hepatology, Gastroenterology, Radiology, Nuclear Medicine and imaging
Published: 2023
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12. A randomized, non-comparative, phase II study of maintenance OSE2101 vaccine alone or in combination with nivolumab (nivo) or FOLFIRI after induction with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): First interim results of the TEDOPAM GERCOR D17-01 PRODIGE 63 STUDY

Author: Marc Hilmi, Emmanuel Mitry, Anthony Turpin, Olivier Bouché, Jean-Philippe Metges, François Ghiringhelli, Isabelle Trouilloud, Gaël Roth, Isabelle Baumgaertner, Christophe Borg, Hanifa Ammarguellat, Marielle Guillet, Yves Rinaldi, Thierry Lecomte, Christophe Louvet, Aurélien Lambert, Vincent Hautefeuille, Marie-Line Garcia-Larnicol, Julie Henriques, and Cindy Neuzillet
Subjects: Cancer Research, Oncology
Abstract: 4148 Background: OSE2101 is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts. This study aimed to assess the efficacy and safety of OSE2101 ± anti-PD1 nivo as maintenance therapy in Pts with aPDAC after FOLFIRINOX induction chemotherapy. Methods: TEDOPaM-PRODIGE 63 was initially a 3-arm, open-label, randomized, non-comparative phase II study. Pts with aPDAC, HLA-A2 positive (blood) and no progression after 8 cycles of (modified) FOLFIRINOX were randomized 1:1:1 to receive FOLFIRI (standard Arm A), OSE2101 (subcutaneous injection on D1 Q3W x 6 doses then Q8W until M12 then Q12W up to M24, experimental Arm B) or OSE2101 + nivo (360 mg IV on D1 Q3W x 6 then 480 mg Q4W up to M24, experimental Arm C). FOLFIRI was reintroduced at disease progression in Arms B and C. Primary endpoint was overall survival (OS) rate at 12 months (M12) (Fleming two-stage design, H0: 25%; H1: 50%, one-sided alpha: 2.5%, power: 90%). 156 Pts were planned. Results: Following the occurrence of 2 tumor flares in Arm C, an Independent Data Monitoring Committee (IDMC) recommended to continue FOLFIRI as backbone in experimental Arm B and stop Arm C. Interim analysis results refer to 29 randomized Pts: 9/10/10 in Arm A/B/C, respectively. Median age was 63 years, 52% were men, 55% had ECOG PS 0, and 83% were metastatic. Best response to induction FOLFIRINOX was partial response in 48% and stable disease in 52%. With a median follow-up of 23 months, M12-OS rate was 44%, 40%, and 30% in Arm A, B and C. Other efficacy results are summarized in Table below. No OSE2101-related toxicity of grade ≥ 3 (G≥3) were observed in Arm B; 1 G3 cytokine-release syndrome (OSE2101-related) and 2 tumor flares (nivo-related) leading to death were observed in Arm C. Conclusions: Maintenance OSE2101 monotherapy showed a favorable safety profile and encouraging time to strategy failure warranting further evaluation. OSE2101 + nivo was associated with poorer outcomes leading to close Arm C. Following IDMC recommendation, the study is ongoing with the new design (maintenance FOLFIRI vs. FOLFIRI + OSE2101). Clinical trial information: NCT03806309. [Table: see text]
Published: 2022
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13. Sequential treatment with gemcitabine/nab-paclitaxel (GA) and FOLFIRINOX (FFX) followed by stereotactic MRI-guided adaptive radiation therapy (SMART) in patients with locally advanced pancreatic cancer (LAPC): GABRINOX-ART phase 2, multicenter trial

Author: Fabienne Portales, Marc Ychou, Emmanuelle Samalin, Eric Assenat, Stephane Obled, Marguerite Tyran, Emmanuel Mitry, Magali Rouffiac, François Ghiringhelli, Jean-Baptiste Bachet, Jean-Marc Simon, Mark De Ridder, Catherine Fiess, Aurore Moussion, Stephanie Delaine, Florin Grigorescu, Sophie Gourgou, and Olivier Riou
Subjects: Cancer Research, Oncology
Abstract: TPS4191 Background: LAPC represents a major challenge with no standardized chemotherapy (CT) and radiotherapy (RT) treatment. Phase 2 studies (LAPACT/NEOLAP) indicated efficacy of FFX and GA, although addition of conventionally fractionated RT remains controversial. Phase 3 LAP07 trial obtained a reduction of progression free survival (PFS), albeit with no overall survival (OS) advantage. Since in metastatic pancreatic cancer we recently attained with GA/FFX sequential combination (GABRINOX) high objective response rate and promising OS with acceptable toxicity and no limiting neurotoxicity, we proposed in LAPC to complement GABRINOX with SMART, recently recognized beneficial in pancreatic tumors by a retrospective multicenter study (OS at 2 years) and our prospective registry study (dosimetric benefit of adaptation). In a first step (SEQ1), we will evaluate GABRINOX efficacy and select patients without progression for a second step (SEQ2), to evaluate feasibility and tolerance in patients without disease progression after SEQ1. Secondarily we will evaluate CT tolerance (SEQ1), acute toxicities and dosimetric results (SEQ2) and for both SEQ1+2, late toxicities, response to treatment, PFS, OS and quality of life (QoL). Methods: Naive patients with confirmed non-metastatic unresectable adenocarcinoma by centralized reading (WHO 0/1) and adequate organ function will receive in SEQ1 two cycles of GABRINOX, GA (1000 mg/m2, 125 mg/m2) on days 1, 8, and 15 followed by FFX on day 29 and 43. After 3-4 weeks, patients without progression or unacceptable toxicity will benefit from SMART (5 fractions of 10 Gy/day over 5 consecutive days). Specific dummy-run, contouring quality assurance and dosimetric plans will precede post-treatment monitoring every 6 weeks for 6 months for non-progressive patients and then every 2 months until progression: radiological assessment, biological markers (circulating tumor DNA) and QoL evaluation. Co-primary endpoints include success of SEQ1 (non-progression at 4 months, RECIST v1.1) and that of SEQ2 as absence of acute digestive non-toxicity rate > grade 3 (NCI-CTCAE v5.0) within 90 days. Based on Fleming design with maximal inefficacy (p0) of 70% and 90% (α = 2.5% and β = 5%) we need 98 and 70 patients (SEQ1 and SEQ2), and total of 103 cases considering those entering in SEQ 2 (70%) and non-evaluable patients. Success rate, toxicities (by treatment sequences) and safety (System Organ Class) by patient and cycle will be considered while dosimetry will be correlated with gastro-intestinal toxicities. Median follow-up, OS and PFS will be expressed as medians and rates with 95% CI while QoL will be explored by QLQ-C30 and QLQ-PAN26 analyses using the time to definitive deterioration. From 2021, we included 5 patients (NCT04570943). Clinical trial information: NCT04570943.
Published: 2022
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14. Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

Author: Marine Gilabert, Brice Chanez, Philippe Rochigneux, Emmanuel Mitry, Bernadette De Rauglaudre, Christian Chabannon, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Institut Curie [Paris], and ROCHIGNEUX, Philippe
Subjects: 0301 basic medicine, Cancer Research, Adoptive cell transfer, CAR-T cells, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cell, engineered TCR, Review, lcsh:RC254-282, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, adoptive cell transfer, business.industry, T-cell receptor, Immunotherapy, hepatocellular carcinoma, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Chimeric antigen receptor, digestive system diseases, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer research, immunotherapy, business
Abstract: Simple Summary The mortality of hepatocellular carcinoma (HCC) is quickly increasing worldwide. Immunotherapy enables the immune defense of the organism to target liver cancer cells. Recent technologies enable engineering of immune cells, and notably T lymphocytes, to make them more efficient against the tumor. These technics (called TCR engineered T cells and CAR-T cells) are promising and are actually tested in clinical trials. This review explains the concept of TCR modified and CAR-T cells in liver cancer (targets and mechanisms of action) and reports the results from recent clinical trials. Abstract The mortality of hepatocellular carcinoma (HCC) is quickly increasing worldwide. In unresectable HCC, the cornerstone of systemic treatments is switching from tyrosine kinase inhibitors to immune checkpoints inhibitors (ICI). Next to ICI, adoptive cell transfer represents another promising field of immunotherapy. Targeting tumor associated antigens such as alpha-fetoprotein (AFP), glypican-3 (GPC3), or New York esophageal squamous cell carcinoma-1 (NY-ESO-1), T cell receptor (TCR) engineered T cells and chimeric antigen receptors (CAR) engineered T cells are emerging as potentially effective therapies, with objective responses reported in early phase trials. In this review, we address the biological rationale of TCR/CAR engineered T cells in advanced HCC, their mechanisms of action, and results from recent clinical trials.
Published: 2021
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15. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences

Author: Sergio Roman-Roman, Pascale Mariani, Ivan Bièche, Elodie Girard, Astrid Lièvre, Marion Richard-Molard, Elsy El Alam, Jérôme Cros, Sophie Vacher, Wulfran Cacheux, Adrien Briaux, Sophie Richon, Julien Lazartigues, Petros Tsantoulis, Emmanuel Mitry, Etienne Rouleau, Bruno Buecher, Odette Mariani, Emmanuelle Jeannot, and Virginie Dangles-Marie
Subjects: 0301 basic medicine, Cancer Research, Somatic cell, Biology, 03 medical and health sciences, 0302 clinical medicine, Cyclin D1, anal squamous cell carcinoma, medicine, Anal cancer, Radiology, Nuclear Medicine and imaging, Protein kinase B, Gene, PI3K/AKT/mTOR pathway, RC254-282, Original Research, Cancer Biology, copy number alterations, Anal Squamous Cell Carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, array comparative genomic hybridization, Cancer research, somatic mutations, PI3K/Akt/mTOR signaling pathway, Comparative genomic hybridization
Abstract: Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
Published: 2018

16. LBA57 Unicancer PRODIGE 24/CCTG PA6 trial: Updated results of a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX (mFFX) versus gemcitabine (gem) in patients (pts) with resected pancreatic ductal adenocarcinomas (PDAC)

Author: A. Lambert, E. Francois, Anthony Turpin, L. Monard, Marc Ychou, James Joseph Biagi, Thierry Lecomte, A. Lopez, Roger Faroux, Alice C. Wei, J-B. Bachet, Florence Castan, C. Belletier, Patrick Rat, O. Bouche, Pascal Hammel, Eric Assenat, T. Conroy, Pascal Artru, and Emmanuel Mitry
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Hematology, Gemcitabine, Internal medicine, Medicine, In patient, Pancreatic carcinoma, business, Adjuvant, medicine.drug
Published: 2021
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17. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer

Author: Rafael Rosell, Alice T. Shaw, Ali Zeaiter, Shirish M. Gadgeel, Emmanuel Mitry, Bogdana Balas, Jin S. Ahn, Maurice Perol, Johannes Noe, Sai-Hong Ignatius Ou, Peter N. Morcos, D. Ross Camidge, Solange Peters, Tony Mok, Dong Wan Kim, Rafal Dziadziuszko, Sophie Golding, ALEX Trial Investigators, Nordman, I., Pittman, K., Dear, R., Lwin, Z., Briggs, P., Pavlakis, N., Ceric, T., Mehic, B., Stanetic, M., Franke, F.A., Castro, G., Santo Borges, G., Pereira, J., Brust, L., Santos, L., Cruz, M., Ribeiro, R., De Azevedo, S., Neron, Y.V., Sangha, R., Cohen, V., Burkes, R., Abdelsalam, M., Yadav, S., Cheema, P., Yanez, E., Aren, O., Zhou, C., Zhang, L., Liu, X., Corrales Rodriguez, L., Meldgaard, P., Soerensen, J.B., McCulloch, T., Rodriguez, N., Gaafar, R., Abdel Azeem, H., Coudert, B., Moro-Sibilot, D., Lena, H., Bennouna, J., Cortot, A., Veillon, R., Cadranel, J., Barlesi, F., Reck, M., Mezger, J., von Pawel, J., Fischer, J.R., Dickgreber, N.K., Zarogoulidis, K., Syrigos, K., Georgoulias, V., Agelaki, S., Castro-Salguero, H., Ho, J., Chan, S.H., Cheng, C.K., Ng, A., Stemmer, S., Wollner, M., Gottfried, M., Dudnik, J., Cyjon, A., Heching, N., Novello, S., Tiseo, M., Platania, M., Misino, A., Gridelli, C., Ciardiello, F., Favaretto, A., De Marinis, F., Longo, F., Bordonaro, R., Dazzi, C., Chiari, R., Mercuri, E., Macedo, E., Rodriguez Cid, J.R., McKeage, M., Vera, L., Morón Escobar, H.D., Rodriguez, M., Mas, L., Ramlau, R., Kowalski, D., Szczesna, A., Kazarnowicz, A., Milanowski, J., Luboch-Kowal, J., Oliveira, J., Barata, F., Almodovar, T., Lee, J.S., Cho, B.C., Kim, S.W., Han, J.Y., Karaseva, N., Stroyakovskii, D., Kuzmin, A., Smolin, A., Laktionov, K., Ragulin, Y., Filippov, A., Levchenko, E., Jovanovic, D., Perin, B., Andric, Z., Soo, R., Tan, E.H., De Castro Carpeno, J., Provencio Pulla, M., Garrido Lopez, P., Felip Font, E., Morano Bueno, T., Sanchez, A., Isla Casado, D., Ponce Aix, S., Reguart Aransay, N., Viteri Ramirez, S., Rodriguez Abreu, D., Sanchez Torres, J.M., Massuti Sureda, B., Ramos Vazquez, M., Tabernero, J.M., Curioni, A., Rothschild, S., Scherz, A., Chiu, C.H., Su, W.C., Yang, CHJ, Chang, G.C., Hsia, T.C., Yang, C.T., Tharavichitkul, E., Pongthai, P., Arpornwirat, W., Geater, S., Srimuninnimit, V., Sriuranpong, V., Demirkazik, A., Goker, E., Harputluoglu, H., Cicin, I., Kose, F., Erman, M., Bondarenko, I., Vinnyk, Y., Shparyk, Y., Golovko, Y., Lal, R., Forster, M., Califano, R., Skailes, G., Thompson, J., Mekhail, T., Polikoff, J., Spigel, D., Waqar, S., Hermann, R., Deo, E., Simon, G., Rybkin, I., Kaywin, P.R., Uyeki, J., Gubens, M., Limaye, S., Gerber, D.E., Leal, T., Spira, A.I., Bazhenova, L., Cetnar, J., Socinski, M., Jahanzeb, M., Kabbinavar, F., Lawler, W.E., Hancock, M.R., Raez, L.E., DiCarlo, B.A., Lowe, T.E., Fidler, M., Ross, H., Davidson, S.J., Sanchez, J.D., Hamm, J., Kerr, S., Belman, N., Baker, S., Naraev, B., Jung, G., Edelman, M., Feldman, L., Belani, C., and Pakkala, S.
Subjects: Adult, Male, 0301 basic medicine, Oncology, Alectinib, medicine.medical_specialty, Pathology, Lung Neoplasms, Brigatinib, Pyridines, medicine.drug_class, Carbazoles, Antineoplastic Agents, Kaplan-Meier Estimate, Aged, 80 and over, Animals, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Carbazoles/adverse effects, Carbazoles/therapeutic use, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/mortality, Central Nervous System Neoplasms/drug therapy, Central Nervous System Neoplasms/secondary, Disease-Free Survival, Female, Follow-Up Studies, Humans, Intention to Treat Analysis, Lung Neoplasms/drug therapy, Lung Neoplasms/mortality, Middle Aged, Piperidines/adverse effects, Piperidines/therapeutic use, Protein Kinase Inhibitors/adverse effects, Protein Kinase Inhibitors/therapeutic use, Pyrazoles/adverse effects, Pyrazoles/therapeutic use, Pyridines/adverse effects, Pyridines/therapeutic use, Receptor Protein-Tyrosine Kinases/analysis, Receptor Protein-Tyrosine Kinases/antagonists & inhibitors, Young Adult, Central Nervous System Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Piperidines, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, Internal medicine, medicine, Anaplastic lymphoma kinase, Lung cancer, Protein Kinase Inhibitors, Crizotinib, Ceritinib, business.industry, Receptor Protein-Tyrosine Kinases, General Medicine, medicine.disease, Lorlatinib, ALK inhibitor, 030104 developmental biology, 030220 oncology & carcinogenesis, Pyrazoles, business, medicine.drug
Abstract: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P
Published: 2017
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18. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer

Author: Walter Bordogna, Sanjay Popat, Bogdana Balas, Emmanuel Mitry, Luigi De Petris, Fabrice Barlesi, Alice T. Shaw, Ramaswamy Govindan, James Chih-Hsin Yang, Dong Wan Kim, Shirish M. Gadgeel, Barbara Muller, Anne-Marie C. Dingemans, Peter N. Morcos, Jin Seok Ahn, Eric Dansin, Lucio Crinò, Sai-Hong Ignatius Ou, Hervé Lena, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Assistance Publique - Hôpitaux de Marseille (APHM), 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), Department of Microbiology, Chang Won National University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Département de Cancérologie Générale [Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut Curie [Paris], Savoirs dans l'espace anglophone : représentations, culture, histoire (SEARCH), Université de Strasbourg (UNISTRA), Roche, 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), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE), and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER
Subjects: 0301 basic medicine, Alectinib, Oncology, Male, Cancer Research, Lung Neoplasms, ALK+, [SDV]Life Sciences [q-bio], Peripheral edema, NSCLC, 0302 clinical medicine, alk, Piperidines, Carcinoma, Non-Small-Cell Lung, Anaplastic Lymphoma Kinase, education.field_of_study, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, medicine.symptom, medicine.drug, Pulmonary and Respiratory Medicine, safety, medicine.medical_specialty, Nausea, overall survival, Population, Carbazoles, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Pooled analysis, 03 medical and health sciences, Internal medicine, medicine, Humans, Lung cancer, education, Adverse effect, Protein Kinase Inhibitors, Aged, crizotinib, Crizotinib, business.industry, medicine.disease, Confidence interval, 030104 developmental biology, business, Follow-Up Studies
Abstract: International audience; Objectives - A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods - The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan-Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer-Crowley method. Safety was assessed through adverse event (AE) reporting. Results - Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3-39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion - Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.
Published: 2020
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19. Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer

Author: Evgeny Levchenko, Eveline Nüesch, Ting Liu, Nick Pavlakis, Solange Peters, Bogdana Balas, Silvia Novello, Marco Platania, Teresa Moran, Emmanuel Mitry, Julio Oliveira, Maurice Pérol, Rita Chiari, Krzysztof Konopa, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Petrov Research Insitut of Oncology, Fondazione Ospedale San Camillo [Venezia] (IRCCS), Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University of Turin, F. Hoffmann-La Roche [Basel], and Medical University of Gdańsk
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Alectinib, Male, Cancer Research, medicine.medical_specialty, Randomization, Lung Neoplasms, [SDV]Life Sciences [q-bio], Population, Carbazoles, Chest pain, NSCLC, 03 medical and health sciences, 0302 clinical medicine, Crizotinib, Piperidines, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Anaplastic Lymphoma Kinase, Patient Reported Outcome Measures, education, Lung cancer, ALK-positive, Patient-reported outcomes, education.field_of_study, business.industry, Hazard ratio, Middle Aged, medicine.disease, Prognosis, 3. Good health, Survival Rate, 030104 developmental biology, Oncology, Tolerability, 030220 oncology & carcinogenesis, Quality of Life, Female, medicine.symptom, business, medicine.drug
Abstract: Objectives: Alectinib demonstrated superior efficacy and a safety profile that compared favorably with crizotinib in treatment-na ve ALK + non-small-cell lung cancer (NSCLC) in the phase III ALEX study. We present patient-reported outcomes (PROs) from ALEX to assess disease burden, treatment-related symptom tolerability, and health-related quality of life (HRQoL) with alectinib versus crizotinib. Materials and Methods: Patients were randomized to receive alectinib 600 mg or crizotinib 250 mg twice daily until disease progression, death, or withdrawal. Pre-specified PRO endpoints were: mean change from baseline in symptoms, HRQoL, and functioning; and time to deterioration (TTD) in cough, dyspnea, chest pain, arm/shoulder pain, fatigue, and a composite of three symptoms (cough, dyspnea, chest pain). PRO data were collected using EORTC QLQ-C30 and LC13 questionnaires. Raw scores were standardized to a 0-100-point range, with a >= 10-point score change defined as clinically meaningful. TTD was defined as the time from randomization until confirmed clinically meaningful deterioration (i.e., a 10-point score change from baseline). Results: Baseline completion rates and characteristics were balanced in the PRO-evaluable population (alectinib n = 100, 66%; crizotinib n = 97, 64%). On average, alectinib-treated patients reported clinically meaningful improvements in lung cancer symptoms for longer than crizotinib-treated patients. Between-treatment differences in lung cancer symptoms tended to favor alectinib from 11.1 months (45 weeks) onwards, around the time of median PFS with crizotinib (11.1 months). TTD in lung cancer symptoms was similar between treatment arms, despite longer duration of symptom improvement with alectinib; composite symptom endpoint (hazard ratio 1.10 [95% confidence interval: 0.72-1.68]). Duration of clinically meaningful improvement in HRQoL was longer with alectinib versus crizotinib (Week 88 vs. Week 68, respectively). Better patient-reported tolerability was observed with alectinib versus crizotinib on common treatment-related symptoms. Conclusion: PRO data support the superior efficacy and tolerability of alectinib relative to crizotinib demonstrated in the ALEX study.
Published: 2019
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20. ENCORE: Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs. crizotinib (CZ) in untreated advanced ALK+ NSCLC

Author: F. De Marinis, Lanjun Zhang, Emmanuel Mitry, Alice T. Shaw, Parneet Cheema, Shirish M. Gadgeel, Barbara Muller, Michael Thomas, Byoung Chul Cho, Solange Peters, Camidge, Bogdana Balas, Denis Moro-Sibilot, Ali Zeaiter, D Stroyakovskii, Nick Pavlakis, and Tony Mok
Subjects: Alectinib, Oncology, medicine.medical_specialty, Crizotinib, business.industry, Internal medicine, medicine, business, medicine.drug
Published: 2019
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21. Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection

Author: Sophie Richon, Marie-Christine Falcou, Emmanuel Mitry, Xavier Sastre-Garau, Adrien Briaux, Julien Lazartigues, Wulfran Cacheux, Fereshteh Farkhondeh, Etienne Rouleau, Petros Tsantoulis, Arnaud Roth, Emmanuelle Jeannot, Virginie Dangles-Marie, Bruno Buecher, Anne de la Rochefordière, Pascale Mariani, Sergio Roman-Roman, Ivan Bièche, Marion Richard-Molard, D. Stevens, Astrid Lièvre, A. Labib, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut Curie [Paris], Département de chirurgie, Service de Génétique Oncologique, Département de Recherche Translationnelle, Centre de Recherche, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-Institut Curie [Paris], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biostatistique, Facultés des sciences pharmaceutiques et biologiques, Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pontchaillou [Rennes], CEST (Comite d'Evaluation et de Suivi des projets de recherche de Transfert) from the Institut Curie, Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-PRES Sorbonne Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-PRES Sorbonne Paris Cité, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service des Maladies de l'Appareil Digestif [CHU Rennes], INSTITUT CURIE, Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-INSTITUT CURIE, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Compartimentation et dynamique cellulaires ( CDC ), Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, Male, Cancer Research, medicine.medical_treatment, DNA Mutational Analysis, growth-factor-receptor, medicine.disease_cause, human-papillomavirus, chemoradiotherapy, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, anal squamous cell carcinoma, prognostic factor, abdominoperineal resection, Cervical cancer, Aged, 80 and over, Abdominoperineal resection, epidermoid carcinoma, therapeutic target, Middle Aged, Anus Neoplasms, 3. Good health, Epidermoid carcinoma, 030220 oncology & carcinogenesis, Female, KRAS, Adult, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, chemoradiation therapy, mutation status, survival, 03 medical and health sciences, Internal medicine, expression, medicine, Humans, HRAS, neoplasms, Molecular Diagnostics, Aged, Retrospective Studies, cervical-cancer, Salvage Therapy, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, squamous-cell carcinoma, PIK3CA, medicine.disease, Radiation therapy, 030104 developmental biology, comprehensive molecular characterization, Mutation, Neoplasm Recurrence, Local, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, Chemoradiotherapy
Abstract: International audience; Background: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. Methods: We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. Results: Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P = 0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n = 38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P = 0.048), gender (P = 0.045) and PIK3CA mutation (P = 0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P = 0.025). Conclusions: Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.
Published: 2016
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22. Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Author: Mireille Mousseau, Eric Francois, A. Fatisse, A. Bedjaoui, Abakar Mahamat, C. Lombard-Bohas, J. Ezenfis, Marc Porneuf, F. Subtil, M. Tissot, Emilie Maillard, M. Fayolle, J.F. Dor, A. Votte, P. Chiappa, P. Prost, Denis Cléau, P. Bergerault, J.C. Souquet, K. Beerblock, P. Chatrenet, J.M. Sabate, M. Carreiro, S. Beorchia, Vincent Hautefeuille, Jessika Moreau, N. Delas, C. Vilain, Christian Borel, Franck Audemar, M. Duluc, Touraj Mansourbakht, Bernard Denis, Gael Deplanque, Jean-Marc Phelip, C. Brezault, Anne Thirot-Bidault, L. Gasnault, Jean-Louis Jouve, Y. Rinaldi, B. Leduc, Y. Courouble, A. Alessio, Matthieu Schnee, P. Cassan, Antoine Adenis, Jocelyne Provencal, A. Botton, Laurent Cany, Françoise Desseigne, Marie-Christine Kaminsky, Mohamed Ramdani, B. Lafforgue, L. Rob, J.C. Barbare, S. Jacquot, A. Zaanan, J.-Y. Douillard, C. Cornila, B. Rhein, Benjamin Linot, Z. Ladhib, D. Zylberait, Cedric Lecaille, N. Hess-Laurens, H. Brixi-Benmansour, C. Rebischung, C. Giraud, L. Stefani, D. Pillon, J.P. Lafargue, J. Forestier, P. Laplaige, C. Paoletti, S. Lavau Denes, Etienne Suc, A. Patenotte, E. Echinard, François-Xavier Caroli-Bosc, D. Goldfain, V. Quentin, Hervé Perrier, J.D. Grangé, A. Marre, M. Baconnier, Bruno Coudert, Thomas Walter, R. Benoit, A. Blanchi, A.C. Dupont-Gossart, Emilie Barbier, X. Coulaud, D. Besson, Isabelle Trouilloud, D. Sevin-Robiche, M Giovannini, O. Boulat, C. Lobry, H. Castanie, Y. Molin, Thomas Aparicio, Valérie Boige, P. Lehair, J.P. Robin, J.P. Latrive, J. Goineau, Clément Belletier, G. Medinger, C. Lepere, Philippe Rougier, N. Bouaria, E. Carola, V. Derias, Bernard Paillot, Yves Becouarn, F. Kikolski, Martin Combe, Julie Vincent, C. Briac-Levaché, C. Becht, François Ghiringhelli, J. Charneau, Dany Gargot, Julien Vergniol, Denis Péré-Vergé, P. Pienkowski, Patrick Texereau, I. Baumgaertner, J.P. Ramain, Pierre-Luc Etienne, P. Claudé, Jean Francois Paitel, J.P. Plachot, M.-C. Clavero-Fabri, P. Geoffroy, A. Cadier-Lagnes, Y. Le Bricquir, S. Fratte, O. Favre, Aimery de Gramont, J. Butel, David Tougeron, B. Winkfield, E. Janssen, J. Meunier, Julien Volet, N. Gérardin, D. Soubrane, Vincent Bourgeois, Xavier Adhoute, Y.H. Lam, P.A. Haineaux, A. Rotenberg, J-B. Bachet, C. Berger, F. Almaric, J. Tuaillon, G. Gatineau-Saillant, F. Zerouala-Boussaha, E. Cuillerier, R. Lamy, D. Luet, D. Baudet-Klepping, E.A. Pariente, M. Gignoux, J. Martin, M. Blasquez, Romain Coriat, C. Bineau, J. Boutin, A. Aouakli, F. Dewaele, A.M. Queuniet, V. Sebbagh, P. Couzigou, N. Barrière, Faiza Khemissa, P. Follana, Laurence Chone, F. Petit-Laurent, N. Abdelli, Olivier Capitain, D. Bechade, Corinne Sarda, J.P. Herr, P. Pouderoux, Julien Taieb, M. Pauwels, E. Zrihen, L. Wander, Gael Goujon, G. Boilleau-Jolimoy, Anne Thirot Bidault, B. Landi, V. Jestin Le Tallec, Jaafar Bennouna, O. Berthelet, M. Glikmanas, H. Salloum, Côme Lepage, Thierry Lecomte, P. Amoyal, C. Platini, Veronique Guerin-Meyer, B. Garcia, Laetitia Dahan, Pascal Burtin, J. Villand, S. Nguyen, A. Roussel, F. Di Fiore, S. Oddou-Lagraniere, J.P. Aucouturier, Veronique Lorgis, Gerard Cavaglione, J.P. Lagasse, Dominique Auby, Pierre Michel, F. Bonnetain, Gilles Breysacher, R. Mackiewicz, Philippe Ruszniewski, T. Morin, J. Thaury, Clara Locher, J.M. Vantelon, S. Nasca, J.P. Barbieux, H. Maechel, Y. Coscas, May Mabro, S. Montembault, P. Novello, M. Charbit, J. Deguiral, A. Gagnaire, D. Festin, A. Gueye, Hélène Senellart, Achim Weber, Nadia Bouarioua, Jérôme Dauba, Michel Ducreux, Jean-Luc Raoul, G. Coulanjon, J.N. Vaillant, S. Chaussade, A. Gilbert, Anne-Laure Villing, Dominique Genet, P. Martin, M. Ben Abdelghani, M.P. Galais, A. Azzedine, A. Lemaire, C. Barberis, C. Buffet, J. Egreteau, G. Roquin, M. Mornet, Isabelle Cumin, M. Pelletier, P. Feydy, J. Lacourt, T. Chatellier, Jean-Louis Legoux, M. Benchalal, I. Graber, S. Nahon, P. Pantioni, A. Hollebecque, M. Zawadi, Pascal Hammel, M. Mignot, Roger Faroux, J. Lafon, Mohamed Gasmi, Jean-Philippe Spano, S. Pesque-Penaud, C. de la Fouchardiere, J. Cretin, Olivier Bouché, D. Smith, E. Norguet-Monnereau, G. Bordes, Sylvain Manfredi, Thévenet P, Herve Lacroix, E. Dorval Danquechin, Eric Terrebonne, Laurent Bedenne, P. Godeau, David Malka, V. Veuillez, Emmanuel Mitry, F. Riot, Sandrine Hiret, François Morvan, M.C. Gouttebel, Jean-François Seitz, Karine Bouhier-Leporrier, N. Stremsdoerfer, P. Souillac, M. Mozer, C. Couffon, F. Husseini, J.M. Cheula, J.-M. Gornet, K. Slimane Fawzi, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris-Saclay, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (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, Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Privé des Côtes d'Armor (HPCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de la Loire [Saint-Priest en Jarez], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service De Gastroenterologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Hôpital Louis Pasteur [Colmar] (CH Colmar), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Overweight, Gastroenterology, Pooled analysis, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, Individual data, medicine, Overall survival, Humans, Neoplasm Metastasis, Objective response, Aged, 2. Zero hunger, Clinical Trials as Topic, Prognostic factor, business.industry, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Normal weight, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract: IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI
Published: 2018
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23. Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography in gastrointestinal cancers

Author: Pierre Michel, Mathieu Gauthé, Marion Richard-Molard, Astrid Lièvre, Jean-Louis Alberini, Jean-Louis Jouve, Emmanuel Mitry, and Wulfran Cacheux
Subjects: medicine.medical_specialty, Colorectal cancer, Colonoscopy, Digestive System Neoplasms, Multimodal Imaging, Patient Care Planning, Fluorodeoxyglucose positron emission tomography, Fluorodeoxyglucose F18, Pancreatic cancer, Humans, Medicine, Positron Emission Tomography-Computed Tomography, Fluorine-18-fluorodeoxyglucose, Hepatology, medicine.diagnostic_test, business.industry, Oesophageal cancer, Gastroenterology, Radiotherapy treatment planning, Prognosis, medicine.disease, FDG-PET/CT, Anal canal cancer, Review article, Neuroendocrine Tumors, Positron-Emission Tomography, Practice Guidelines as Topic, Radiology, Neoplasm Recurrence, Local, Radiopharmaceuticals, Tomography, X-Ray Computed, business
Abstract: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a routine imaging modality for many malignancies and its use is currently increasing. In the present review article, we will summarize the evidence for FDG-PET/CT use in digestive cancers (excluding neuroendocrine tumours), and review the existing recommendations. While PET/CT is nowadays considered to be an important tool in the initial workup of oesophageal and anal cancers, new data are emerging regarding its use in assessing therapeutic efficacy, radiotherapy treatment planning, and detection of recurrence in case of isolated tumour marker elevation. Moreover, PET/CT may help decision making by detecting distant metastatic sites especially in potentially resectable metastatic colorectal cancer and, to a lesser extent, in localized gastric and pancreatic cancers. Finally, incidental focal colonic FDG uptakes require exploration by colonoscopy, as they are often associated with premalignant or malignant lesions.
Published: 2015
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24. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013

Author: Emmanuel Mitry, Riccardo A. Audisio, Naureen Starling, A. de Gramont, Demetris Papamichael, Bengt Glimelius, Javier Sastre, Siri Rostoft, Valery E.P.P. Lemmens, Matthew T. Seymour, Daniel G. Haller, C.-H. Köhne, Rob Glynne-Jones, Harm J. T. Rutten, Daniel J. Sargent, Matti Aapro, E. Van Cutsem, Public Health, Surgery, RS: GROW - Oncology, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
Subjects: Oncology, medicine.medical_specialty, Consensus, Internationality, Palliative care, Colorectal cancer, colorectal cancer, Disease, SIOG, SDG 3 - Good Health and Well-being, Internal medicine, Epidemiology, older, medicine, Humans, guidelines, Geriatric Assessment, Societies, Medical, Aged, Aged, 80 and over, Geriatrics, International Society of Geriatric Oncology, business.industry, General surgery, Palliative Care, Cancer, Hematology, medicine.disease, Comorbidity, Europe, Treatment Outcome, Geriatric oncology, Chemotherapy, Adjuvant, Colorectal Neoplasms, business
Abstract: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in Europe and worldwide, with the peak incidence in patients >70 years of age. However, as the treatment algorithms for the treatment of patients with CRC become ever more complex, it is clear that a significant percentage of older CRC patients (>70 years) are being less than optimally treated. This document provides a summary of an International Society of Geriatric Oncology (SIOG) task force meeting convened in Paris in 2013 to update the existing expert recommendations for the treatment of older (geriatric) CRC patients published in 2009 and includes overviews of the recent data on epidemiology, geriatric assessment as it relates to surgery and oncology, and the ability of older CRC patients to tolerate surgery, adjuvant chemotherapy, treatment of their metastatic disease including palliative chemotherapy with and without the use of the biologics, and finally the use of adjuvant and palliative radiotherapy in the treatment of older rectal cancer patients. An overview of each area was presented by one of the task force experts and comments invited from other task force members.
Published: 2015
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25. Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE)

Author: Anne Couvelard, Eric Baudin, François-Xavier Caroli-Bosc, Guillaume Roquin, Aline Ramond-Roquin, Jean-Yves Scoazec, Jean-Louis Legoux, Olivia Hentic, Vincent Rohmer, C. Lombard-Bohas, Sophie Dominguez, Guillaume Cadiot, Michel Ducreux, Patricia Niccoli, Thomas Walter, Rosine Guimbaud, Philippe Ruszniewski, Emmanuel Mitry, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Gustave Roussy (IGR), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'oncologie médicale, Institut Claudius Regaud, Biochimie Endocrinienne et Métabolique [Marseille] (U38 Inserm - CHU Timone), Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Institut Curie [Paris], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), DOCOMO Euro-Labs, DOCOMO Communications Laboratories Europe GmbH, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de pathologie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de biologie et pathologie médicales [Gustave Roussy], Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), 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)-Institut de Veille Sanitaire (INVS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de Gastroentérologie [Hôpital Beaujon], and Hôpital Beaujon [AP-HP]
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Antineoplastic Agents, Neuroendocrinology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Endocrine system, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, biology, Endocrine and Autonomic Systems, business.industry, Middle Aged, Chemotherapy regimen, 3. Good health, Well differentiated, Pancreatic Neoplasms, [STAT]Statistics [stat], Regimen, Neuroendocrine Tumors, Ki-67 Antigen, 030220 oncology & carcinogenesis, Ki-67, biology.protein, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: Background: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. Methods: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. Results: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). Conclusions: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.
Published: 2017
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26. Exome sequencing reveals aberrant signalling pathways as hallmark of treatment-naive anal squamous cell carcinoma

Author: Emmanuelle Jeannot, Astrid Lièvre, Virginie Dangles-Marie, Bruno Buecher, Julien Lazartigues, Wulfran Cacheux, Ivan Bièche, Thomas Rio-Frio, Odette Mariani, Etienne Rouleau, Fereshteh Farkhondeh, Marion Richard-Molard, Elodie Girard, Pascale Mariani, Nicolas Servant, S.R. Roman, Adrien Briaux, Emmanuel Mitry, Sophie Richon, Sophie Vacher, Jonchère, Laurent, CRLCC René Huguenin, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche de l'Institut Curie [Paris], 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), Morphogénèse et Signalisation Cellulaires, Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Département de Recherche Translationnelle, Plateforme de sequencage ICGEX, Génétique, physiopathologie et approches thérapeutiques des maladies héréditaires du système nerveux (EA 7331), Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Département de recherche translationnelle
Subjects: 0301 basic medicine, Somatic cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, whole exome sequencing, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, anal squamous cell carcinoma, medicine, Exome sequencing, PI3K/AKT/mTOR pathway, Somatic mutation, Anal Squamous Cell Carcinoma, Cancer, Copy number alteration, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, somatic mutation, copy number alteration, 030220 oncology & carcinogenesis, signalling pathway, Cancer research, Carcinogenesis, FAT1, Research Paper
Abstract: International audience; Anal squamous cell carcinomas (ASCC) are rare tumours in humans. The etiological role of HPV infection is now well established but little is known about the molecular landscape and signalling pathways involved in the pathogenesis of this cancer. Here we report the results from a whole exome sequencing of a homogeneous group of 20 treatment-naive ASCC. A total of 2422 somatic single nucleotide variations (SNV) were found, with an overall moderate rate of somatic mutations per tumour (median 105 relevant SNV per tumour) but a high mutational load in 3 tumours. The mutational signatures associated with age and APOBEC were observed in 100% and 60% of tumours respectively. The most frequently mutated genes were PIK3CA (25%) followed by FBXW7 (15%), FAT1 (15%), and TRIP12 (15%), the two last ones having never been described in ASCC. The main copy number alterations were gains of chromosome 3q (affecting PIK3CA) and losses of chromosome 11q (affecting ATM). The combined analysis of somatic mutations and copy number alterations show that recurrent alterations of the PI3K/AKT/mTOR pathway are frequent (60%) in these tumours, as well as potentially targetable alterations of other signalling pathways that have never been described in ASCC such as chromatin remodelling (45%) and ubiquitin mediated proteolysis (35%). These results highlight the possible implication of these aberrant signalling pathways in anal carcinogenesis and suggest promising new therapeutic approaches in ASCC. The high somatic mutation burden found in some tumours, suggesting an elevated neoantigen load could also predict sensitivity of ASCC to immunotherapy.
Published: 2017
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27. Erratum to: Chemoembolization of Neuroendocrine Liver Metastases Using Streptozocin and Tris-acryl Microspheres: Embozar (EMBOsphere + ZAnosaR) Study

Author: Philippe Rougier, Jean-Pierre Pelage, Audrey Fohlen, Alain Beauchet, C. Lagrange, Emmanuel Mitry, Service d'Imagerie Diagnostique et de Radiologie Thérapeutique [CHU Caen], 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), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré [AP-HP], Department of Radiology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Department of Biostatistics and Public Health, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Neuroendocrine tumors, medicine.disease, Primary tumor, 030218 nuclear medicine & medical imaging, 3. Good health, Streptozocin, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Tolerability, 030220 oncology & carcinogenesis, medicine, Lipiodol, Radiology, Nuclear Medicine and imaging, Radiology, Embolization, Cardiology and Cardiovascular Medicine, business, Carcinoid syndrome, medicine.drug
Abstract: The purpose of this prospective observational study was to evaluate the efficacy and tolerability of transarterial chemoembolization (TACE) for neuroendocrine liver metastases using a combination of streptozocin, Lipiodol, and tris-acryl microspheres. A total of 16 men and 9 women aged 59.6 ± 11.3 years, all with predominant liver disease, underwent 54 courses of TACE using an emulsion of 1.5 g of streptozocin and 10 ml of Lipiodol. Additional embolization was performed using 300–500 µm tris-acryl microspheres. Morphological response was evaluated using the RECIST criteria on multi-detector computed tomography or MRI. Clinical efficacy was evaluated particularly in patients with carcinoid syndrome. The primary tumor was located in the small bowel or pancreas in 21 (84%) patients. Eleven (44%) patients presented with a carcinoid syndrome. Nineteen (76%) patients presented with more than 10 liver nodules. One delayed case of ischemic cholecystitis was treated conservatively. After a median follow-up of 36.1 months, 1 (4%) patient had a complete response, 12 (48%) patients had a partial response, and 7 (28%) patients had a stable disease corresponding to a disease control rate of 80%. All patients with carcinoid syndrome had significant improvement. Median time to progression was 18.8 months and overall survival was 100, 100, and 92% at 1, 2, and 3 years, respectively. Seven patients presented with extrahepatic progression with abdominal lymphadenopathies or metastases to the brain, ovary, adrenal gland, or lung. Optimized TACE using a combination of streptozocin, Lipiodol, and tris-acryl microspheres is effective and well tolerated.
Published: 2017
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28. Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial) – A phase II non-randomised trial

Author: Sophie Dominguez-Tinajero, Leila Bengrine-Lefevre, Françoise Farace, Michel Ducreux, Guillaume Cadiot, Eric Baudin, Philippe Rougier, Jean-Emmanuel Kurtz, Thomas Walter, Emmanuel Mitry, Philippe Ruszniewski, and Clarisse Dromain
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Administration, Oral, Neuroendocrine tumors, Antibodies, Monoclonal, Humanized, Deoxycytidine, Disease-Free Survival, Capecitabine, chemistry.chemical_compound, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, Infusions, Intravenous, Aged, Gastrointestinal Neoplasms, Aged, 80 and over, Response rate (survey), business.industry, Middle Aged, medicine.disease, Well differentiated, Vascular endothelial growth factor, Neuroendocrine Tumors, Treatment Outcome, chemistry, Female, Fluorouracil, business, medicine.drug
Abstract: Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients.BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life.Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%).The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial.
Published: 2014
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29. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

Author: Manfred B. Lutz, Roberto Labianca, Patrick Pessaux, Bert A. Bonsing, Benoist Chibaudel, David Malka, Claudio Bassi, Sophie Gourgou-Bourgade, Geertjan van Tienhoven, Pascal Hammel, Carine Bellera, Laeticia Dahan, Jean-Luc Van Laethem, Daniela Aust, Emmanuel Chamorey, Jean Robert Delpero, Josep Tabernero, Adelaide Dousseau, Teresa Macarulla, Franck Bonnetain, Julien Taieb, Karin Haustermans, Laurence Collette, Thomas Aparicio, François Lacaine, John P. Neoptolemos, Simone Mathoulin-Pélissier, Bengt Glimelius, Thierry Conroy, Paula Ghaneh, Alain Sauvanet, Erich Gerber, Christos Dervenis, Aurélien Latouche, Murielle Mauer, Michel Ducreux, Valérie Jooste, Virginie Berger, Jocelyn Gal, Alain Hendlisz, Aimery de Gramont, Emmanuel Mitry, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), 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), UNICANCER, Leiden University Medical Center (LUMC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Université Victor Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Uppsala Universitet [Uppsala], University Hospitals Leuven [Leuven], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), G.B. Rossi Hospital, Verona University, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cooperator Multidisciplinary Oncology Group (GERCOR), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Agia Olga Hospital [Athènes] (Konstantopoulio ), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut für Radioonkologie, Royal Liverpool University Hospital, University of Liverpool-Royal Liverpool and Broadgreen University Hospital NHS Trust, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut Jules Bordet [Bruxelles], Registre Bourguignon des Cancers Digestifs, 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)-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)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Azienda Ospedaleria Ospedali Riuniti di Bergamo, 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), CaritasKlinikum Saarbrücken, Vall d'Hebron University Hospital [Barcelona], European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Curie [Paris], CRLCC René Huguenin, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service d’Hépatologie [Hôpital Beaujon], Service de gastroenterologie [CHU HEGP], 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Academisch Medisch Centrum bij, Universiteit van Amsterdam (UvA), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU Tenon [APHP], Hôpital Erasme (Bruxelles), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Carl Gustav Carus University ( DRESDEN - CGCU ), Technische Universität Dresden ( TUD ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Antoine Lacassagne, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group ( GERCOR ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut Paoli Calmettes, Agia Olga Hospital [Athènes] ( Konstantopoulio ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Beaujon, Institut Jules Bordet, 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 ) -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 ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), 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)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), European Organisation for Research and Treatment of Cancer [Bruxelles] ( EORTC ), European Cancer Organisation [Bruxelles] ( ECCO ), Institut Curie, L'Institut hospitalo-universitaire de Strasbourg ( IHU Strasbourg ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Universiteit van Amsterdam ( UvA ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Bergonié - CRLCC Bordeaux, Universiteit Leiden, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Verona = University of Verona (UNIVR), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-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)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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 CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Oncology, Cancer Research, Pathology, Delphi Technique, MESH : Randomized Controlled Trials as Topic, MESH: Delphi Technique, MESH : Consensus, law.invention, Clinical trials, 0302 clinical medicine, Pancreatic cancer, Time to event end-point, Consensus, Guidelines, Methodology, Clinical trials, Randomized controlled trial, law, 030212 general & internal medicine, Time to event end-point, Randomized Controlled Trials as Topic, Event (probability theory), MESH: Endpoint Determination, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 16. Peace & justice, 3. Good health, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, MESH : Endpoint Determination, MESH: Pancreatic Neoplasms, medicine.medical_specialty, Consensus, Endpoint Determination, Guidelines, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Pancreatic cancer, medicine, Overall survival, Humans, MESH: Consensus, Distributed File System, neoplasms, MESH: Humans, End point, business.industry, MESH : Humans, Methodology, Cancer, medicine.disease, Pancreatic Neoplasms, Clinical trial, MESH: Randomized Controlled Trials as Topic, MESH : Delphi Technique, MESH: Disease-Free Survival, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Pancreatic Neoplasms
Abstract: International audience; BACKGROUND:Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.METHODS:Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).RESULTS:For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.CONCLUSION:The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
Published: 2014
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30. Management of patients over 80 years of age treated with resection for localised colon cancer: Results from a French referral centre

Author: Astrid Lièvre, Christophe Penna, Laurent Teillet, Robert Malafosse, Stéphane Benoist, Bernard Nordlinger, Tristan Cudennec, Philippe Rougier, Frédérique Peschaud, Valérie Laurent, Jean-Nicolas Vaillant, Céline Lepère, Catherine Julié, and Emmanuel Mitry
Subjects: Male, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Humans, Medicine, Stage (cooking), Medical prescription, Referral and Consultation, Colectomy, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Chemotherapy, Hepatology, business.industry, Mortality rate, General surgery, Gastroenterology, Perioperative, medicine.disease, Combined Modality Therapy, Surgery, Survival Rate, Treatment Outcome, Colonic Neoplasms, Referral centre, Female, France, Morbidity, Metastasectomy, business, Follow-Up Studies
Abstract: Background Few data are available on management of very elderly colon cancer patients, especially concerning the parameters of therapeutic decisions and the role of geriatricians. Methods We retrospectively reviewed the charts of patients over 80 years of age who underwent surgery for a localised colon cancer in a French academic hospital. Results A total of 176 patients underwent surgery (postoperative morbidity and mortality rates: 25% and 6.7%). Adjuvant chemotherapy was discussed at a multidisciplinary team meeting for 91% of stage III patients, but only 13.5% of them were treated. Twenty-five patients relapsed: 19 were discussed at the multidisciplinary meeting and 16 were treated (5 had a metastasectomy). Despite their increase with time, geriatric assessments were infrequent, 17% (33% after 2006), and had no impact on postoperative morbi-mortality. Median overall survival and recurrence-free survival were 65.3 months and 65.1 months, respectively. Age, emergency surgery, and Charlson comorbidity index were independent prognostic factors. Conclusion Selected elderly colon cancer patients have significant access to surgery. However, postoperative morbi-mortality rates remain high and adjuvant chemotherapy rarely prescribed. Perioperative geriatric assessment, especially before surgery, should be routinely proposed to these patients to evaluate its impact on postoperative morbi-mortality and prescription of adjuvant treatment.
Published: 2014
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31. Recommandations pour la prise en charge de l’insulinome malin

Author: Guillaume Cadiot, Antoine Tabarin, Jean-Yves Scoazec, Françoise Borson-Chazot, François Pattou, Christine Do Cao, Emmanuel Mitry, Pierre Goudet, Eric Baudin, Catherine Lombard-Bohas, David Taïeb, Delphine Vezzosi, Philippe Caron, and Yves Reznick
Subjects: Gynecology, medicine.medical_specialty, business.industry, Neoplasm Invasiveness, Tumor burden, Medicine, General Medicine, business
Abstract: Resume Les insulinomes sont malins dans 4 a 14 % des cas. Leur rarete et la relative pauvrete des donnees de la litterature ont limite la publication de recommandations specifiques. Cette revue propose une mise a jour de leur prise en charge en 2014 incluant l’integration des facteurs histo-pronostiques dans leur caracterisation initiale, le traitement symptomatique des hypoglycemies, les strategies anti-tumorales et le suivi a long terme. Seront notamment detaillees les indications respectives de la chirurgie, du diazoxide, des analogues de la somatostatine, de l’everolimus, du sunitinib, des traitements du foie tumoral dont la chimio-embolisation arterielle, de la chimiotherapie et de la radiotherapie metabolique. Les mots-cles « insulinoma », « neuroendocrine pancreatic tumors », « islet cell carcinoma », « malignant insulinoma » ont ete utilises pour la recherche bibliographique sur Medline en limitant la selection des references aux articles en langue anglaise et aux cas chez l’adulte.
Published: 2014
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32. Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: results of the feasibility part of the SHIVA trial

Author: A. Gonçalves, David Gentien, J. Wong, Quentin Leroy, L. Escalup, Cecile Mauborgne, Etienne Rouleau, T. Rio Frio, Virginie Bernard, J.-P. Delord, Pierre Gestraud, E Henry, Olivier Tredan, Céline Gavoille, Gaëlle Pierron, Céline Callens, Emmanuel Mitry, Ivan Bièche, Nicolas Isambert, Mario Campone, Vincent Servois, P Huppe, Anne Vincent-Salomon, Julien Roméjon, Odette Mariani, P La Rosa, Nicolas Servant, F. Mulot, Maud Kamal, C. Le Tourneau, Cécile Reyes, and Xavier Paoletti
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, DNA Mutational Analysis, Gene Dosage, Gene dosage, Targeted therapy, law.invention, Randomized controlled trial, law, Neoplasms, Internal medicine, Biopsy, medicine, Humans, Molecular Targeted Therapy, Precision Medicine, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, personalised medicine, randomised study, sequencing, Middle Aged, Molecular Abnormality, Precision medicine, Immunohistochemistry, Surgery, Clinical trial, Clinical Study, SHIVA, Female, molecular profile, business, Algorithms, feasibility
Abstract: Background: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. Results of the feasibility study on the first 100 enrolled patients are presented. Methods: Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and included mutations and gene copy number alteration analyses using high-throughput technologies, as well as the determination of oestrogen, progesterone, and androgen receptors by immunohistochemistry (IHC). Results: Biopsy was safely performed in 95 of the first 100 included patients. Median time between the biopsy and the therapeutic decision taken during a weekly molecular biology board was 26 days. Mutations, gene copy number alterations, and IHC analyses were successful in 63 (66%), 65 (68%), and 87 (92%) patients, respectively. A druggable molecular abnormality was present in 38 patients (40%). Conclusions: The establishment of a comprehensive tumour molecular profile was safe, feasible, and compatible with clinical practice in refractory cancer patients.
Published: 2014
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33. Chemotherapy versus self-expanding metal stent as primary treatment of severe dysphagia from unresectable oesophageal or gastro-oesophageal junction cancer

Author: Bruno Landi, Philippe Rougier, Isabelle Archambeaud, Emmanuel Mitry, Yann Touchefeu, Céline Lepère, and Astrid Lièvre
Subjects: Adult, Male, medicine.medical_specialty, Esophageal Neoplasms, Organoplatinum Compounds, medicine.medical_treatment, Leucovorin, Adenocarcinoma, Severity of Illness Index, Endoscopy, Gastrointestinal, Severe dysphagia, Antineoplastic Combined Chemotherapy Protocols, Gastroscopy, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, Hepatology, business.industry, Palliative Care, Gastroenterology, Stent, Cancer, Gastro oesophageal junction, Middle Aged, medicine.disease, University hospital, Dysphagia, Surgery, Metals, Carcinoma, Squamous Cell, Esophageal Stenosis, Quality of Life, Female, Stents, Primary treatment, Esophagogastric Junction, Esophagoscopy, Fluorouracil, Cisplatin, medicine.symptom, Deglutition Disorders, business
Abstract: Objective To compare chemotherapy first (group 1) versus self-expanding metal stent first (group 2) for the management of malignant dysphagia in unresectable oesophageal or gastro-oesophageal junction cancer. Methods Patients from two university hospitals with severe malignant dysphagia (dysphagia score ≥ 2) uneligible for surgery or radiochemotherapy were evaluated retrospectively. Results Forty-two patients were included in group 1, and 29 in group 2. After 4 weeks, dysphagia scores improved by at least 1 point in 67% of patients in group 1 versus 93% in group 2 ( p = 0.01); 48% of patients in group 1 were able to eat solid food versus 68% in group 2 ( p = 0.054). In group 1, a self-expanding metal stent was secondarily placed in 18 patients (42.9%), whereas in group 2 dysphagia required a second self-expanding metal stent placement in 33.3% of patients. Conclusion Chemotherapy as the first treatment may be a valid option, avoiding self-expanding metal stent insertion in half of the patients.
Published: 2014
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34. Improvement in survival of metastatic colorectal cancer: Are the benefits of clinical trials reproduced in population-based studies?

Author: Anne Marie Bouvier, François Ghiringhelli, Jean Faivre, Valérie Jooste, Côme Lepage, Boris Guiu, Emmanuel Mitry, and Fabien Rollot
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Time Factors, Colorectal cancer, medicine.medical_treatment, Population, Antineoplastic Agents, Population based, Health Services Accessibility, Internal medicine, medicine, Humans, Molecular Targeted Therapy, Registries, Healthcare Disparities, education, Aged, Clinical Trials as Topic, Chemotherapy, education.field_of_study, Evidence-Based Medicine, Medical treatment, business.industry, Patient Selection, Palliative Care, Age Factors, Treatment options, Middle Aged, medicine.disease, Survival Analysis, Survival Rate, Clinical trial, Treatment Outcome, Female, France, Diffusion of Innovation, Colorectal Neoplasms, business, Medical therapy
Abstract: To describe trends in survival of non-resectable metastatic colorectal cancer (MCRC) over a 34-year period in a French population-based registry taking into account major advances in medical therapy.3804 patients with non-resectable metastatic colorectal cancer diagnosed between 1976 and 2009 were included. Three periods (1976-96, 1997-2004 and 2005-09) were considered.The proportion of patients receiving chemotherapy dramatically increased from 19% to 57% between the first two periods, then increased steadily thereafter reaching 59% during the last period (p0.001). Median relative survival increased from 5.9 months during the 1976-96 period to 10.2 months during the 1997-2004 period but, despite the availability of targeted therapies, remained at 9.5 months during the 2005-09 period. During the last study period, less than 10% of elderly patients received targeted therapies compared to more than 40% for younger patients. Their median relative survival was 5.0 months compared to 15.6 months in younger patients.There was an improvement in survival in relation with the increased use of more effective medical treatment. However, at a population-based level, patients are not all treated equally and most of them, especially the elderly, do not benefit from the most up-to-date treatment options.
Published: 2013
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35. Biweekly docetaxel, fluorouracil, leucovorin, oxaliplatin (TEF) as first-line treatment for advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: safety and efficacy in a multicenter cohort

Author: Julien Taieb, Jean-Nicolas Vaillant, Emmanuelle Samalin, Emmanuel Mitry, Laetitia Dahan, Hajer Turki, Jean-François Seitz, Philippe Rougier, Céline Lepère, Bruno Landi, Aziz Zaanan, Cécile Dalban, Simon Pernot, Marc Ychou, and Thibault Mazard
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, Leucovorin, Docetaxel, Adenocarcinoma, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, neoplasms, Survival rate, Aged, Neoplasm Staging, Cisplatin, Chemotherapy, business.industry, Gastroenterology, General Medicine, Prognosis, medicine.disease, digestive system diseases, Oxaliplatin, Survival Rate, stomatognathic diseases, Fluorouracil, Female, Taxoids, Esophagogastric Junction, business, therapeutics, Follow-Up Studies, medicine.drug
Abstract: Docetaxel-cisplatin-5-FU chemotherapy is superior to 5-FU-cisplatin in terms of response rate and survival in advanced gastric cancer (AGC), but is more toxic. Oxaliplatin is better tolerated than cisplatin, which it can effectively replace in this setting. We hypothesize that incorporating docetaxel into a simplified FOLFOX regimen should be a tolerable and effective option in first-line treatment of AGC.Data were collected at six French centers from patients with metastatic or local AGC who received docetaxel, fluorouracil, leucovorin, or oxaliplatin (TEF) as first-line treatment. TEF was administered as follows: docetaxel (50 mg/m(2)), oxaliplatin (85 mg/m(2)), and leucovorin (40 mg/m(2)) on day 1, and 5-FU continuous infusion for 48 h (2400 mg/m(2)) every 2 weeks.Forty-one patients were enrolled. Performance status was grade 0 and 1 in respectively 27 and 58 % of patients; 17 patients had adenocarcinoma of the gastroesophageal junction; 37 patients had metastatic disease, 22 had a poorly differentiated or diffuse type. Objective response rate was 66 %, with a complete response in two patients (5 %). Median progression-free survival and overall survival were respectively 6.3 and 12.1 months. Tolerability was acceptable with no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (30 %) and neuropathy (12.5 %). Curative intent surgery after response to TEF was performed in seven patients (17 %).TEF is an effective first-line treatment with an acceptable toxicity profile for patients with AGC. It may allow curative resection in initially unresectable patients. TEF should now be evaluated in prospective randomized trials.
Published: 2013
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36. Role of microsatellite instability in the management of colorectal cancers

Author: Wulfran Cacheux, Astrid Lièvre, Etienne Rouleau, Bruno Buecher, Emmanuel Mitry, and Barbara Dieumegard
Subjects: Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, Leucovorin, Germline, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Hepatology, business.industry, Gastroenterology, Microsatellite instability, Prognosis, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Lynch syndrome, Oxaliplatin, Treatment Outcome, Chemotherapy, Adjuvant, Fluorouracil, Microsatellite Instability, DNA mismatch repair, Colorectal Neoplasms, business, medicine.drug
Abstract: Microsatellite instability is the consequence of a deficient mismatch repair system. It has a key role in the diagnostic strategy of Lynch syndrome, where tumours are all characterized by the presence of this phenotype. Microsatellite instability is therefore essential in the selection of colorectal cancer patients in whom a germline analysis of Mismatch Repair genes is possibly indicated. Moreover, microsatellite instability tumours are associated with a good prognosis and a resistance to fluorouracil-based adjuvant chemotherapy, which has a clinical application mainly in stage II colon cancer patients in whom adjuvant chemotherapy has a less beneficial effect than in stage III and outcome in presence of microsatellite instability is excellent. Recent data suggest that impact of microsatellite instability on benefit to fluorouracil-based adjuvant chemotherapy is dependent of the molecular mechanism involved in this genetic instability since an improved survival has been reported with adjuvant fluorouracil in microsatellite instability colorectal cancers of germline origin but not in sporadic cases. Predictive value of microsatellite instability on response to fluorouracil/oxaliplatin adjuvant chemotherapy has been less evaluated but recent studies suggest that the favorable outcome of Microsatellite instability tumours is maintained in patients receiving FOLFOX.
Published: 2013
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37. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials

Author: Tim Maughan, Philippe Rougier, Ute Schubert, Eric Van Cutsem, Gunnar Folprecht, Richard Stephens, Emmanuel Mitry, Jean-Yves Douillard, Hartmut Hecker, Leonard B. Saltz, Claus-Henning Köhne, and Matthew T. Seymour
Subjects: Male, Cancer Research, medicine.medical_specialty, Combination therapy, Colorectal cancer, medicine.drug_class, Leucovorin, Kaplan-Meier Estimate, Irinotecan, Gastroenterology, Antimetabolite, Disease-Free Survival, Folinic acid, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Odds Ratio, Humans, Aged, Neoplasm Staging, Proportional Hazards Models, Randomized Controlled Trials as Topic, Aged, 80 and over, business.industry, Hazard ratio, Age Factors, Cancer, Confounding Factors, Epidemiologic, Middle Aged, medicine.disease, Surgery, Logistic Models, Treatment Outcome, Oncology, Clinical Trials, Phase III as Topic, Fluorouracil, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: Purpose Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC). Patients and Methods Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age ≥ 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients. Results Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and ≥ 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable. Conclusion Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
Published: 2016
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38. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation

Author: Philippe Ruszniewski, Frederico Costa, Waldemar Szpak, Ola Nilsson, Göran Åkerström, Ashley B. Grossman, Günter Klöppel, Marianne Pavel, Ramon Salazar, Rachida Lebtahi, Babs Taal, Joseph Davar, Reza Kianmanesh, Anne Marie McNicol, Massimo Falconi, David J. Gross, Anne Couvelard, Dik J. Kwekkeboom, Ursula Plöckinger, Dermot O'Toole, Ulrich Frank Pape, Bruno Annibale, Emilio Bajetta, Klemens Scheidhauer, Paul Komminoth, Marie Pierre Vullierme, Yuan Jia Chen, Aldo Scarpa, Diego Ferone, Bjorn I. Gustafsson, D. Ivan, Gregory Kaltsas, Beata Kos-Kudła, Emmanuel Mitry, Jaroslava Barkmanova, Mauro Papotti, Guido Rindi, Kjell Öberg, Barbro Eriksson, Ulrich Knigge, Wouter W. de Herder, Jean-Yves Scoazec, Marco Platania, Aurel Perren, Anders Sundin, Rudolf Arnold, Val Lewington, Rudolf Hyrdel, Bertram Wiedenmann, Gianfranco Delle Fave, Juan Manuel O'Connor, Pavel Vítek, R., Arnold, Y., Chen, F., Costa, Falconi, Massimo, D., Gro, A. B., Grossman, R., Hyrdel, B., Kos Kudła, R., Salazar, U., Plöckinger, Åkerström, G., Annibale, B., Bajetta, E., Barkmanova, J., Couvelard, A., Davar, J., De Herder, W., Delle Fave, G., Eriksson, B., Ferone, D., Gustafsson, B., Ivan, D., Kaltsas, G., and Kianmanesh, R.
Subjects: Endocrinology, Diabetes and Metabolism, appendix tumor, hypophysis, Neuroendocrine tumors, insulinoma, Medical Records, Benign tumor, computer assisted tomography, Documentation, Follow-Up Studies, Humans, Medical History Taking, Neoplasm Staging, Neuroendocrine Tumors, Endocrinology, benign tumor, cancer diagnosis, nuclear magnetic resonance imaging, conference paper, medicine.diagnostic_test, Medical record, genetic screening, priority journal, cancer grading, cancer surgery, neuroendocrine tumor, medicine.medical_specialty, diagnostic imaging, disease classification, parathyroid gland, Cellular and Molecular Neuroscience, pentetreotide, endoscopic surgery, Internal medicine, tumor marker, cancer staging, echography, follow up, human, liver metastasis, medical documentation, practice guideline, tumor volume, world health organization, medicine, Insulinoma, Tumor marker, Cancer staging, Endocrine and Autonomic Systems, business.industry, Poorly differentiated, medicine.disease, Endoscopy, business, human activities
Abstract: Summary of follow-up recommendations in patients with benign and malignant neuroendocrine tumorsFollow-upyes/no endoscopy US/CT/MRI Octreoscan CgABenign insulinoma noType 1 gastric carcinoid yes yearlyRectal carcinoid no (if completely resected)Appendiceal carcinoid T1 noAppendiceal carcinoid T2 ? (see text)Resectable tumor (uncertain behavior)G1 every 6–12 months yes(gastric carc.)yes every 2 years 2 yes 1 Resectable malignant tumor with/without nodal involvementG1 every 6–12 months yes every 2 years 2 yes 1 G2 every 6 months yes yearly 2 yes 1 G3 every 3 months yes yearly 2 yes 3 Non-resectable malignant tumor with/without nodal involvement and/or liver and other metastasesG1 every 6–12 months yes every 2 years 2 yesG2 every 6 months yes yearly 2 yesG3 every 3 months yes yearly 2 yes 31 Only in the presence of a visible tumor. 2 Recommendations regarding the time frames of Octreoscan should be adjusted to the individual situation. 3 In poorly differentiated tumors and negative CgA NSE may act as a suitable marker.
Published: 2016

39. Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients

Author: Faiza Khemissa, Jean-François Seitz, J. Cretin, Olivier Bouché, Laurent Teillet, Dominique Genet, Jean-Baptiste Bachet, Jean-Louis Jouve, Olivier Boulat, Dany Gargot, Thierry Lecomte, Céline Lepère, Mohamed Ramdani, Gilles Breysacher, Christophe Locher, Iradj Sobhani, Emilie Maillard, Emmanuel Mitry, Thomas Aparicio, Dominique Auby, Roger Faroux, Mohamed Gasmi, Laetitia Stefani, Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpitaux Civils Colmar, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service Hépato-gastroentérologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de Médecine, Centre Hospitalier Libourne, Centre Hospitalier Départemental Les Oudairies, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastro-Entérologie [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 de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Curie [Paris], Lipides - Nutrition - Cancer [Dijon - U1231] (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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre hospitalier de Libourne, Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de gastro-entérologie - Hôpital Henri Mondor, Institut Curie, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre d'Investigation Clinique [Rennes] ( CIC ), 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 ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Prognostic factors, Irinotecan, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Elderly, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Karnofsky Performance Status, Neoplasm Metastasis, Prospective cohort study, Geriatric Assessment, Aged, Aged, 80 and over, Chemotherapy, biology, business.industry, medicine.disease, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, biology.protein, Quality of Life, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: IF 6.163; International audience; AIM:Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis.METHOD:Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).RESULTS:From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL.CONCLUSION:The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.
Published: 2016
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40. Colorectal neuroendocrine carcinomas and adenocarcinomas share oncogenic pathways. A clinico-pathologic study of 12 cases

Author: Hélène Blons, Emmanuel Mitry, Frédérique Penault-Llorca, Raymond Karkouche, Jean-François Emile, Jean-Baptiste Bachet, Christophe Penna, Jean-Paul Saint André, Philippe Rougier, Jean-François Côté, Jeremy Sandrini, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Ambroise Paré [AP-HP], Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, 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), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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: Male, Time Factors, Oncogene Proteins, Fusion, endocrine system diseases, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, DNA Mutational Analysis, malignant tumor, medicine.disease_cause, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, In Situ Hybridization, Cancer, 0303 health sciences, rectal disease, Gastroenterology, Middle Aged, 3. Good health, colorectal adenocarcinoma, Phenotype, Treatment Outcome, 030220 oncology & carcinogenesis, Disease Progression, Female, KRAS, Colorectal Neoplasms, intestinal disease, neuroendocrine tumor, Adenoma, Adult, Proto-Oncogene Proteins B-raf, In situ hybridization, Adenocarcinoma, colonic disease, BRAF, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, colorectal carcinoma, oncogenesis, Proto-Oncogene Proteins, medicine, Carcinoma, Humans, Endocrine system, Genetic Predisposition to Disease, RNA, Messenger, neoplasms, Aged, Retrospective Studies, 030304 developmental biology, Chemotherapy, Hepatology, business.industry, Histology, medicine.disease, digestive system diseases, Carcinoma, Neuroendocrine, Mutation, ras Proteins, Cancer research, Digestive diseases, business, V600E
Abstract: International audience; OBJECTIVE:Neuroendocrine carcinomas (NECs) are rare neoplasms with an increasing incidence. Oncogenetic pathways of colorectal NEC are still poorly understood, and no treatment standards are available for these rare tumors.METHODS:We analyzed retrospectively the clinical records and histology of 12 patients with colorectal NEC. KRAS and BRAF mutations were investigated after the dissection of exoendocrine and neuroendocrine components. ALK alterations and EML4-ALK transcripts were detected by in-situ hybridization and determination of fusion transcripts, respectively.RESULTS:At the time of diagnosis, the mean age of the patients was 60 years (40-79) and 10 patients had synchronous metastases. A transient response occurred in two patients and one patient treated with cisplatin-etoposide or fluoropyrimidine-oxaliplatin, respectively. Tumor progression-related death occurred in 11 of 12 patients. Ten tumors contained an exocrine component, accounting for 5-70% of the tumor, and the other two contained an amphicrine component. BRAF/KRAS mutations were found in six of 10 tumors, corresponding to BRAF(V600E) (n=2) or KRAS(G12D) (n=2), KRAS(G12V) or KRAS(G13D). DNA was obtained from both exocrine and endocrine components in seven cases, and the BRAF/KRAS status was identical in all cases. Split of the ALK locus was detected in a minority of tumor cells in two of eight cases, but EML4-ALK transcripts were absent.CONCLUSION:The association of an exocrine component in all cases and the similar profile of BRAF/KRAS mutations indicate that colorectal NEC may correspond to a high-grade transformation of colorectal carcinoma. New chemotherapy regimens using targeted therapies should be assessed in these tumors.
Published: 2012
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41. Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study

Author: Eveline Nueesch, Bogdana Balas, Joonghyun Ahn, Solange Peters, S-H.I. Ou, Emmanuel Mitry, D-W. Kim, Tony Mok, R. Camidge, Rafal Dziadziuszko, Rafael Rosell, Maurice Pérol, Alice T. Shaw, Ali Zeaiter, and S. Gadgeel
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Crizotinib, business.industry, Hematology, Therapy naive, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Intensive care medicine, business, medicine.drug
Published: 2017
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42. Chimiothérapie de l'adénocarcinome du pancréas métastatique : défis et espoirs

Author: Thierry Conroy and Emmanuel Mitry
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Performance status, business.industry, FOLFIRINOX, medicine.medical_treatment, Hematology, General Medicine, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Gemcitabine, Regimen, Internal medicine, Pancreatic cancer, medicine, Radiology, Nuclear Medicine and imaging, Folfirinox Regimen, business, medicine.drug
Abstract: The outcome for patients with metastatic pancreatic ductal adenocarcinoma is dismal. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on phase III randomized studies. Single-agent gemcitabine, the reference treatment since 1995, offers only slight benefit. Numerous trials using gemcitabine in combination with different cytotoxic agents have resulted in no major improvement compared to gemcitabine alone. Only the gemcitabine-erlotinib combination has shown a small, but statistically improvement in survival. In selected patients with good performance status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the Folfirinox regimen, when compared to gemcitabine as single agent, was associated with more toxicities, but also with significant increased survival and delay in the degradation of quality of life. So, Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.
Published: 2011
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43. Chromogranin a Measurement in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma: Screening for False Positives and a Prospective Follow-Up Study

Author: Joël Guigay, Agnès Laplanche, Guillaume Cadiot, Michèle d’Herbomez, Françoise Borson-Chazot, Sophie Leboulleux, Philippe Ruszniewski, Emmanuel Mitry, Michel Ducreux, Eric Baudin, Thomas Walter, Catherine Lombard-Bohas, Jean-Luc Raoul, Clarisse Dromain, and Delphine Vezzosi
Subjects: Adult, Male, 0301 basic medicine, Oncology, endocrine system, Cancer Research, medicine.medical_specialty, Pathology, Clinical Biochemistry, Pathology and Forensic Medicine, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Biomarkers, Tumor, Carcinoma, medicine, False positive paradox, Humans, False Positive Reactions, Neoplasm Metastasis, Prospective cohort study, Aged, Gastrointestinal Neoplasms, Neoplasm Staging, biology, business.industry, Surrogate endpoint, Follow up studies, Cancer, Chromogranin A, Middle Aged, medicine.disease, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, business, Follow-Up Studies
Abstract: Background Multiple causes of false-positive chromogranin A (CgA) measurement have been reported that may affect its impact as a surrogate marker of RECIST progression in well-differentiated gastroenteropancreatic neuroendocrine tumors (WDGEPNET). Aims 1) To evaluate the frequency of false-positive CgA results. 2) To prospectively compare CgA variations with RECIST morphological changes in patients without known causes of false-positive CgA measurements. Methods First, the conditions responsible for potentially false-positive CgA measurements were screened in 184 consecutive patients with metastatic WDGEPNET. Secondly, a variation in CgA at a 6-month interval was compared to RECIST results at 6 months in 46 patients. Results Among 184 patients, elevated CgA was found in 130 cases (71%) including 99 patients with at least one cause of a false-positive result. Impaired kidney function as well as medication with proton pump inhibitors were found to be the 2 major causes of false-positive results. The sensitivity and specificity of CgA measurements compared with morphological tumor changes according to the RECIST criteria were 71% and 50%, respectively, at 6 months. Conclusion Routine screening for the causes of false-positive CgA measurements is mandatory in WDGEPNET patients. Our study does not validate the use of CgA as a surrogate marker of tumor progression.
Published: 2011
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44. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment

Author: A. Kramar, P. Afchain, Rosine Guimbaud, M. Ychou, Thomas Aparicio, Emmanuelle Samalin, Françoise Desseigne, Antoine Adenis, Fadi Abbas, Emmanuel Mitry, Julien Edeline, Simon Thezenas, Yves Becouarn, Olivier Bouché, O. Romano, and Etienne Dorval
Subjects: Adult, Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Esophageal Neoplasms, Adenocarcinoma, Neutropenia, Irinotecan, Gastroenterology, Folinic acid, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, FOLFIRI Regimen, Humans, Medicine, Aged, Retrospective Studies, Aged, 80 and over, Hepatology, business.industry, Middle Aged, medicine.disease, Antineoplastic Agents, Phytogenic, Surgery, Docetaxel, Fluorouracil, FOLFIRI, Camptothecin, Female, Esophagogastric Junction, business, medicine.drug, Epirubicin
Abstract: Summary Objectives The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. Methods Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m 2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400 mg/m 2 i.v. over two hours followed by 5-FU 400 mg/m 2 i.v. bolus then 5-FU 2400 mg/m 2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. Results There was no difference between chemonaive and not chemonaive pts treated as first-line in terms of response rate 37% (95% CI: 25–50) vs 44% (95% CI: 21–69), median PFS, 6.7 (95% CI: 5.5–9.9) vs 5.3 months (95% CI: 3.6–6.9) ( P = 0.25), and OS, 13.1 (95% CI: 11.7–18.7) vs 8.8 months (95% CI: 7.3–15.6) ( P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8–39) vs 22% (95% CI: 6–48), median PFS, four months (95% CI: 2.8–5.4) vs 3.5 months (95% CI: 2.3–4.5) ( P = 0.56), and OS, 10.4 months (95% CI: 5.4–14.4) vs 5.3 months (95% CI: 3.5–11.3) ( P = 0.58), respectively. The global grade 3–4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). Conclusions This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.
Published: 2011
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45. Primary results of ALESIA: Phase III, randomised open-label study of alectinib (ALC) vs crizotinib (CRZ) in Asian patients (pts) with treatment-naïve ALK+ advanced non-small-cell lung cancer (NSCLC)

Author: Peter N. Morcos, C. Zhou, Emmanuel Mitry, L. Bu, Zhi Ming Li, Sang We Kim, Soohyeon Lee, Li Yang, Thanyanan Reungwetwattana, Ying Cheng, Jiaojiao Zhou, C. Wang, Jing He, Tingting Xu, J.-J. Yang, Yiping Zhang, and Y. Lu
Subjects: Alectinib, Oncology, 030213 general clinical medicine, medicine.medical_specialty, Crizotinib, business.industry, non-small cell lung cancer (NSCLC), Hematology, medicine.disease, Therapy naive, 03 medical and health sciences, 0302 clinical medicine, Open label study, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, medicine.drug
Published: 2018
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46. Primary results of ALESIA: A randomised, phase III, open-label study of alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced NSCLC

Author: Peter N. Morcos, L. Bu, Soohyeon Lee, Ying Cheng, Y. Lu, Li Yang, Jiaojiao Zhou, L. Zhang, Emmanuel Mitry, Tingting Xu, C. Wang, Jing He, Sang We Kim, Ting Liu, J.-J. Yang, Yiping Zhang, Thanyanan Reungwetwattana, and C. Zhou
Subjects: Alectinib, Oncology, 030213 general clinical medicine, medicine.medical_specialty, Randomization, Crizotinib, business.industry, Hematology, Therapy naive, 03 medical and health sciences, 0302 clinical medicine, Open label study, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, medicine.drug
Published: 2018
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47. Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study

Author: Ting Liu, D.R. Camidge, Alice T. Shaw, Emmanuel Mitry, Solange Peters, Tony Mok, Johannes Noe, Rafal Dziadziuszko, and Malgorzata Nowicka
Subjects: Alectinib, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Oncology, business.industry, 030220 oncology & carcinogenesis, Cancer research, Medicine, Hematology, business
Published: 2018
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48. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301)

Author: Laurent Bedenne, Emmanuel Mitry, Jean-Marc Phelip, Jean-Luc Raoul, Philippe Rougier, Jean-François Seitz, Pascal Hammel, Bruno Chauffert, Marc Ychou, Pierre Michel, F. Bonnetain, Jean-Louis Legoux, Laetitia Dahan, Mohamed Gasmi, and Stéphane Cattan
Subjects: Adult, Male, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Leucovorin, Adenocarcinoma, Deoxycytidine, Antimetabolite, Drug Administration Schedule, Folinic acid, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Aged, 80 and over, Chemotherapy, Performance status, business.industry, Gastroenterology, Middle Aged, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Survival Analysis, Gemcitabine, Surgery, Pancreatic Neoplasms, Treatment Outcome, Fluorouracil, Disease Progression, Female, France, Cisplatin, business, medicine.drug
Abstract: Purpose Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. Methods Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0–2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%). Results 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0–1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). Conclusion This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.
Published: 2010
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49. Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma

Author: Pascal Hammel, Laurent Bedenne, Jean-Louis Legoux, Laetitia Dahan, Jean-François Seitz, Franck Bonnetain, Emilie Maillard, Emmanuel Mitry, Marc Ychou, and Philippe Rougier
Subjects: Male, Cancer Research, medicine.medical_specialty, Time Factors, Emotions, Pain, Kaplan-Meier Estimate, Adenocarcinoma, law.invention, Randomized controlled trial, Quality of life, law, Surveys and Questionnaires, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Longitudinal Studies, Neoplasm Metastasis, Fatigue, Proportional hazards model, business.industry, Surrogate endpoint, Minimal clinically important difference, Metastatic Pancreatic Adenocarcinoma, medicine.disease, humanities, Surgery, Pancreatic Neoplasms, Clinical trial, Oncology, Quality of Life, Female, business
Abstract: Background The Federation Francophone de Cancerologie Digestive phase III trial in patients with metastatic pancreatic adenocarcinoma comparing 5FU, folinic acid and cisplatin combination followed by gemcitabine (Arm A) versus the opposite sequence (Arm B) failed to demonstrate a benefit in overall survival. To longitudinally compare the quality of life (QoL) we explored different definitions of time until definitive deterioration (TUDD) of QoL scores according to minimal clinically important difference (MCID) cut-offs. Methods QoL was evaluated using the EORTC QLQ-C30 every 8 weeks until death. The following scores were analysed: global health, emotional functioning, physical functioning, fatigue and pain. TUDD was defined as the time interval between randomisation and the first occurrence of a decrease in QLQ-C30 score ⩾5 points without any further improvement in QoL score ⩾5 points or any further available QoL data. Analyses were repeated using a 10 point MCID and/or including death as event. Results From 08/2003 to 05/2006, 102 patients in Arm A and 100 in Arm B were included. Using a 5 and a 10 point MCID, TUDD curves of the 5 scores did not differ according to treatment arm., The median TUDD of global health was 5.2 months (4.3–6.2) in Arm A and 6.1 months (5.1–8.5) in Arm B (log-rank p = 0.50) including death as an event for a 5 point MCID. Multivariate Cox model showed that tumour localisation and progression were independently associated with TUDD (p Conclusions The strategy of chemotherapy did not influence the deterioration of QoL. The TUDD approach seems to provide meaningful clinical results that are adapted to metastatic pancreatic adenocarcinoma trials.
Published: 2010
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50. Abstract 1642: Alectinib in treatment-naïve anaplastic lymphoma kinase-positive (ALK+) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA)

Author: Katherine S. MacGilchrist, Parneet Cheema, Emmanuel Mitry, Vlatka Smoljanovic, Rachel Rosenthal, Anna Steenrod, Michelle Orme, and Juliane Schaefer
Subjects: Alectinib, Oncology, Cancer Research, medicine.medical_specialty, education.field_of_study, Ceritinib, Crizotinib, business.industry, Population, Cancer, medicine.disease, law.invention, Pemetrexed, Randomized controlled trial, law, Internal medicine, medicine, business, Lung cancer, education, medicine.drug
Abstract: Background: The standard of care for treatment-naïve ALK+ mNSCLC patients (pts) is an ALK tyrosine kinase inhibitor (TKI). Pts treated with crizotinib generally experience disease progression within 1 year, often within the central nervous system (CNS). As such, there is a high unmet need for CNS-active ALK TKIs. Phase III data from 2 ALK TKIs, alectinib and ceritinib, showed improved efficacy vs crizotinib and chemotherapy, respectively; however, no studies have directly compared these TKIs. We report a NMA to compare the efficacy/safety of these therapies. Methods: A SLR was conducted to identify ALK+ mNSCLC randomized controlled trials (RCTs) in treatment-naïve pts. Efficacy/safety endpoints were extracted and the feasibility of using the data in a NMA was assessed. Data were analyzed using a fixed effect analysis in WinBUGs following NICE guidelines. Results: 1194 citations were identified, of which 4 RCTs were in treatment-naïve pts (ALEX [NCT02075840], ASCEND-4 [NCT01828099], PROFILE 1014 [NCT01154140] and PROFILE 1029 [NCT01639001]). All were open-label, phase III RCTs and pts were similar in terms of age, ECOG PS, disease stage, sex and smoking status. More pts had baseline CNS metastasis (mets) in ALEX (40%) vs the other trials (26-32%). PROFILE 1029 was conducted in East Asian pts and only included in a sensitivity analysis. Chemotherapy arms differed in that pemetrexed maintenance was included in ASCEND-4 but not in the PROFILE studies. Key efficacy/safety results are shown in the Table. Data from the sensitivity analyses were similar. Conclusion: Alectinib significantly improved progression-free survival compared with other treatments in the ITT population including in pts with baseline CNS mets. Alectinib showed significantly fewer grade 3-4 AEs than ceritinib. The difference in chemotherapy arms of the 2 trials may have impacted the NMA efficacy results. Table. NMA results in treatment-naïve ALK+ mNSCLC patientsComparisonEfficacy/Safety Endpoints PFS by IRC* HR (95% CrI)Subgroup CNS Mets at Baseline* PFS by IRC HR (95% CrI)OS* HR (95% CrI)Grade 3 or 4 AEs§OR (95% CrI)Alectinib vs chemotherapy0.23 (0.15-0.34)0.21 (0.10-0.44)0.63 (0.34-1.15)0.81 (0.44-1.52)Alectinib vs crizotinib0.50 (0.36-0.70)0.37 (0.22-0.63)0.76 (0.49-1.20)0.65 (0.41-1.04)Alectinib vs ceritinib0.41 (0.25-0.67)0.31 (0.13-0.71)0.85 (0.42-1.73)0.36 (0.17-0.79)Crizotinib vs chemotherapy0.45 (0.35-0.58)0.57 (0.35-0.93)0.82 (0.54-1.24)1.24 (0.81-1.91)Ceritinib vs chemotherapy0.55 (0.42-0.72)0.70 (0.44-1.11)0.73 (0.50-1.06)2.25 (1.42-3.61)Ceritinib vs crizotinib1.22 (0.84-1.79)1.22 (0.62-2.43)0.90 (0.52-1.57)1.82 (0.96-3.44)Statistically significant differences indicated in bold based on 95% CrI; *Hazard ratio Citation Format: Anna Steenrod, Michelle Orme, Katherine S. MacGilchrist, Rachel Rosenthal, Juliane Schaefer, Vlatka Smoljanovic, Emmanuel Mitry, Parneet K. Cheema. Alectinib in treatment-naïve anaplastic lymphoma kinase-positive (ALK+) metastatic non-small-cell lung cancer (mNSCLC): Systematic literature review (SLR) and network meta-analysis (NMA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1642.
Published: 2018
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