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1. Influence of Covariates on 18F-FDG PET/CT Diagnostic Accuracy for Liver Metastasis

Author

Vincent Habouzit, Anthime Flaus, Jean-Marc Phelip, Sylvain Grange, Bertrand Le Roy, Rémi Grange, and Nathalie Prévot

Subjects
fluorodeoxyglucose F18, positron emission tomography computed tomography, oncology, liver metastasis, Medicine (General), R5-920
Abstract

(1) Background: 18F-FDG PET/CT diagnostic accuracy for liver metastasis (LM) could be influenced by technical parameters, lesion size, and the patient’s covariates. This retrospective study aimed to evaluate these covariates’ impact on PET/CT sensitivity. (2) Methods: Consecutive patients with suspected LMs who underwent 18F-FDG PET/CT scans were included. PET/CT scans were interpreted visually. The reference standard integrated histopathological and imaging follow-up. Logistic regression modeling and average marginal predictions were used to calculate per-lesion diagnostic performance measures with cluster robust 95% confidence intervals and to assess the covariates’ impact on PET/CT sensitivity. (3) Results: We included 192 patients with 330 lesions. 18F-FDG PET/CT exhibited a per-lesion sensitivity, specificity, positive predictive value, and negative predictive value of 86%, 79%, 91%, and 69%, respectively. In multivariate analysis, TOF PET/CT exhibited a higher sensitivity than non-TOF PET/CT (91% vs. 78%, p = 0.02). Sensitivity was reduced for lesions < 10 mm compared to larger lesions (56% vs. 93%, p < 0.001). A 5 kg/m2 increase in BMI led to an average 5% sensitivity reduction (p < 0.001). Age, sex, blood glucose level below 11 mmol/L, and liver density did not significantly impact sensitivity (p > 0.05). (4) Conclusions: 18F-FDG PET/CT sensitivity might be reduced with non-TOF PET, lesions < 10 mm, and higher BMI.

Published
2024
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2. Safety and efficacy of emergency transarterial embolization for mesenteric bleeding

Author

Chloé Extrat, Sylvain Grange, Clément Chevalier, Nicolas Williet, Jean-Marc Phelip, Fabrice-Guy Barral, Bertrand Le Roy, and Rémi Grange

Subjects
Mesentery, Hematoma, Embolization, Bleeding, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Patients with spontaneous or traumatic active mesenteric bleeding cannot be treated endoscopically. Transarterial embolization can serve as a potential alternative to emergency surgery. Literature on transarterial embolization for mesenteric bleeding remains very scarce. The objective of this study was to evaluate the safety and efficacy of transarterial embolization for mesenteric bleeding. We reviewed all consecutive patients admitted for mesenteric bleeding to the interventional radiology department, in a tertiary center, between January 2010 and March 2021. Mesenteric bleeding was defined as mesenteric hematoma and contrast extravasation and/or pseudoaneurysm visible on pre-operative CT scan. We evaluated technical success, clinical success, and complications. Results Among the 17 patients admitted to the interventional department for mesenteric bleeding, 15 presented with active mesenteric bleeding requiring transarterial embolization with five patients with hemodynamic instability. Mean age was 67 ± 14 years, including 12 (70.6%) males. Technical success was achieved in 14/15 (93.3%) patients. One patient with technical failure was treated by percutaneous embolization with NBCA-Lipiodol mixture. Three patients (20%) had early rebleeding: two were treated by successful repeat embolization and one by surgery. One patient (6.7%) had early death within 30 days and two patients (13.3%) had late death after 30 days. Mean length of hospitalization was 12.8 ± 7 days. There were no transarterial embolization-related ischemic complications. Conclusion Transarterial embolization is a safe and effective technique for treating mesenteric bleeding even in patients with hemodynamic instability. Transarterial embolization doesn’t close the door to surgery and could be proposed as first intention in case of mesenteric bleeding.

Published
2022
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3. G-CSF filgrastim biosimilar-Sandoz reduces the incidence of febrile neutropenia in patients receiving chemotherapy regimens with rest periods not exceeding 14 days: A French, multicenter, prospective, non-interventional study

Author

Jean-Marc Phelip, Pierre-Jean Souquet, Maya Hacini, Mohamad Chehimi, Vincent Bourgeois, Ryma Bennoune, and Olivier Tredan

Subjects
Filgrastim biosimilar, Febrile neutropenia, Supportive care, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: The objective of this study was to describe filgrastim biosimilar-Sandoz modalities of use in patients receiving cytotoxic chemotherapy regimens with a rest period of ≤14 days and to investigate the incidence of febrile neutropenia (FN) in routine clinical practice. Methods: This was a French, multicenter, prospective and descriptive, non‐interventional study including patients with breast, lung, gastrointestinal cancer or a lymphoma initiating filgrastim biosimilar-Sandoz treatment and in the context of cytotoxic chemotherapy with a rest period not exceeding 14 days. Data were collected during two routine clinical visits on the modalities of use of filgrastim biosimilar-Sandoz, on the incidence of neutropenia events and on adverse events. Results: Between November 2015 and June 2018, 1080 patients were enrolled in the study in 129 centers. Overall, 941 patients were evaluable for efficacy and 937 for safety. Of the 941 patients, 84.8% had a solid tumor and 15.2% had a lymphoid hemopathy. Filgrastim biosimilar-Sandoz was prescribed as primary prophylaxis in 74.0% of the patients and as secondary prophylaxis in 22.4% of the patients. FN was reported in 1.5% of patients with a solid tumor and 12.6% of patients with a lymphoma. A chemotherapy relative dose intensity of over 85% with regard to the reference dose was achieved by more than 80% of the patients in all tumor localizations. Conclusions: The study showed that filgrastim biosimilar-Sandoz is safe to use and effective in preventing FN and in allowing to maintain the dose intensity of chemotherapy.

Published
2023
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4. Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage II colorectal cancer

Author

Adrien Grancher, Ludivine Beaussire, Sylvain Manfredi, Karine Le Malicot, Marie Dutherage, Vincent Verdier, Claire Mulot, Olivier Bouché, Jean-Marc Phelip, Charles-Briac Levaché, Philippe Deguiral, Sophie Coutant, David Sefrioui, Jean-François Emile, Pierre Laurent-Puig, Frédéric Bibeau, Pierre Michel, Nasrin Sarafan-Vasseur, Côme Lepage, and Frederic Di Fiore

Subjects
circulating tumor DNA, liquid biopsy, colorectal cancer, stage II, next generation sequencing, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Circulating tumor DNA (ctDNA) is reported to be promising in localized colorectal cancer (CRC). The present study aimed to retrospectively evaluate the impact of ctDNA in patients with a resected stage II CRC from the PROGIGE 13 trial with available paired tumor and blood samples. A group of recurrent patients were matched one-to-one with nonrecurrent patients according to sex, tumor location, treatment sequence, and blood collection timing. CtDNA was analyzed by digital PCR according to NGS of tumors. Disease-free survival (DFS) and overall survival (OS) were analyzed based on ctDNA, and the risks of recurrence and death were determined. A total of 134 patients were included, with 67 patients in each group. At least one alteration was identified in 115/134 tumors. Postoperative ctDNA was detected in 10/111 (9.0%) informative samples and was detected more frequently in the recurrent group (16.7% versus 1.8%; p = 0.02). The median DFS of ctDNA+ versus ctDNA- patients was 16.8 versus 54 months (p = 0.002), respectively, and the median OS was 51.3 versus 69.5 months (p = 0.03), respectively. CtDNA was associated with recurrence (ORa = 11.13, p = 0.03) and death (HRa = 3.15, p = 0.01). In conclusion, the presence of postoperative ctDNA is associated with both recurrence and survival in stage II CRC.

Published
2022
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5. Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors

Author

Nicolas Vial, Julien Langrand-Escure, Peng Diao, Max-Adrien Garcia, Omar Jmour, Majed Ben Mrad, Jean-Baptiste Guy, Wiem Abid, Sandrine Sotton, Sophie Espenel, Elodie Guillaume, Amel Rehailia-Blanchard, Grégoire Pigné, Jane-Chloe Trone, Chloe Rancoule, David Kaczmarek, Thierry Muron, Bertrand Le Roy, Jean-Marc Phelip, Alexis Vallard, and Nicolas Magné

Subjects
Medicine
Abstract

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p

Published
2021
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6. Hyperprogressive Disease After Combined Anti-PD-L1 and Anti-CTLA-4 Immunotherapy for MSI-H/dMMR Gastric Cancer: A Case Report

Author

Romain Varnier, Thibaut Garrivier, Emilie Hafliger, Aymeric Favre, Clélia Coutzac, Clément Spire, Pauline Rochefort, Matthieu Sarabi, Françoise Desseigne, Pierre Guibert, Anne Cattey-Javouhey, Pamela Funk-Debleds, Charles Mastier, Adrien Buisson, David Pérol, Oliver Trédan, Jean-Yves Blay, Jean-Marc Phelip, and Christelle de la Fouchardiere

Subjects
gastric cancer, MSI -H, immunotherapy, hyperprogression, durvalumab, tremelimumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Immune checkpoint inhibitors (ICI) have been developed in gastric adenocarcinomas and approved in first-line metastatic setting (in combination with chemotherapy) as well as in pretreated patients. Microsatellite instability-high (MSI-H) tumors are predicted to derive high benefit from ICI but data in gastric locations are limited. Here, we describe the case of a 68-year old patient with stage IV MSI-H gastric adenocarcinoma, referred to our center to receive immunotherapy after failure of standard of care (surgery with perioperative platin-based chemotherapy and paclitaxel plus ramucirumab at disease progression). The patient received one injection of durvalumab and tremelimumab and was hospitalized eighteen days after because of occlusive syndrome. The CT scan showed hyperprogression of the lymph nodes and hepatic lesions, compressing the gastric stump. He died few days later. Molecular analyses did not explain this outcome. To our knowledge, this is one of the first reported cases of hyperprogressive disease after combined ICI for a patient with MSI-H tumor. We review the potential causes and discuss the emerging literature regarding predictive factors of hyperprogression in the particular subset of MSI-H patients. If some data were available in retrospective studies, validation of strong predictive factors is needed to avoid such dramatic evolutions.

Published
2021
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7. First Characterization with Ultrasound Contrast Agent of a Fibrovascular Polyp Before Its Endoscopic Resection: A Case Report (with Videos)

Author

Nicolas Williet, Radwan Kassir, Francois Casteillo, Violaine Yvorel, Cyril Habougit, Xavier Roblin, and Jean-Marc Phelip

Subjects
Esophageal fibrovascular polyp, Ultrasound endoscopy contrast enhancement, Polypectomy, Microvascularization, Internal medicine, RC31-1245, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

We described for the first time the contrast enhancement of a giant fibrovascular esophageal polyp using ultrasound contrast agent, Sonovue® (Bracco, Milan, Italy) during echoendoscopy. Fine Doppler was unsuccessful in showing vascularization due to the mobile characteristic of the tumor. In contrast, via Sonovue®, tissue microcirculation was highlighted inside the entire head of the polyp, leading to better appreciate the risk of bleeding related to its resection. In a second part, we showed the feasibility of classic polypectomy for this giant polyp (5×5 cm) without complication and results of control endoscopy at 3 months. The present case is summarized in a video.

Published
2019
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9. Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

Author

Timothy Price, Chiara Cremolini, Alfredo Falcone, Eric Van Cutsem, Julien Taieb, Jean-Marc Phelip, Jean-Baptiste Bachet, Lucjan Wyrwicz, Fabienne Portales, Ahmet Ozet, Irfan Cicin, Dan Atlan, Martin Becquart, Loick Vidot, and Nadjat Mounedji

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background In RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.Methods In this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results 793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.Conclusions PRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration number NCT03306394.

Published
2020
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10. Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey

Author

Julien Langrand-Escure, Peng Diao, Max-Adrien Garcia, Guoping Wang, Jean-Baptiste Guy, Sophie Espenel, Elodie Guillaume, Amel Rehailia-Blanchard, Grégoire Pigné, Guy de Laroche, David Kaczmarek, Thierry Muron, Jack Porcheron, Jean-Marc Phelip, Alexis Vallard, and Nicolas Magné

Subjects
Medicine, Science
Abstract

Abstract This retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatment characteristics with univariate and multivariate analyses. Data of 593 consecutive non-metastatic rectal cancer patients were analyzed. Median follow-up was 41 months. Median OS was 9 years. Radiotherapy was delivered in pre-operative (n = 477, 80.5%), post-operative (n = 75, 12.6%) or exclusive (n = 41, 6.9%) setting. In the whole set of patients, age, nutritional condition, tumor stage, tumor differentiation, and surgery independently influenced OS. For patients experiencing surgery, OS was influenced by age, tumor differentiation and nodal status. Surgical resection is the cornerstone treatment for locally-advanced rectal cancer. Poor tumor differentiation and node involvement were identified as major predictive factor of poor OS. The research in treatment intensification and in identification of radioresistance biomarkers should therefore probably be focused on this particular subset of patients.

Published
2018
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11. Folfirinox gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

Author

Nicolas Williet, Angélique Saint, Anne-Laure Pointet, David Tougeron, Simon Pernot, Astrid Pozet, Dominique Bechade, Isabelle Trouilloud, Nelson Lourenco, Vincent Hautefeuille, Christophe Locher, Jérome Desrame, Pascal Artru, Anne Thirot Bidault, Bertrand Le Roy, Denis Pezet, Jean-Marc Phelip, and Julien Taieb

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

Published
2019
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12. Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials

Author

Aurélien de Reyniès, Claire Mulot, Laetitia Dahan, Jean-Baptiste Bachet, Shu-Fang Wang-Renault, Valérie Taly, Jean-Marc Phelip, Pierre Laurent-Puig, Daniel Pietrasz, Yves Rinaldi, Julien Taieb, Jerome Durand-Labrunie, Hélène Blons, Solene Doat, Mathilde Postel, Karine Le Malicot, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Fédération Francophone de Cancérologie Digestive (FFCD), Equipe EPICAD (LNC - U1231), 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)-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), Epigenetec, Centre de Ressources Biologiques (CRB), Hôpital Européen [Fondation Ambroise Paré - Marseille], CHU Saint-Etienne, 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), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), and TALY, Valerie

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Multivariate analysis, Post hoc, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Circulating Tumor DNA, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Metastatic pancreatic cancer, Biomarkers, Tumor, Humans, Medicine, Prospective Studies, Neoplasm Metastasis, Aged, Chemotherapy, Plasma samples, business.industry, Hazard ratio, DNA Methylation, Middle Aged, Metastatic Pancreatic Adenocarcinoma, Prognosis, Pancreatic Neoplasms, Survival Rate, Clinical trial, Mutation, Female, business
Abstract

International audience; Objective: The prognostication of metastatic pancreatic adenocarcinoma (mPDAC) patients remains uncertain, mainly based on carbohydrate antigen 19-9 (CA19-9), with limited utility. Circulating tumour DNA (ctDNA) has been suggested as a prognostic factor, but its added value has been poorly explored. The objective was to determine whether ctDNA is an independent factor for the prognostication of mPDAC.Design: Translational study based on two prospective collections of plasma samples of mPDAC patients naïve for chemotherapy. One used as a test series and the other as validation series coming from two randomised trials (Prodige 35 and Prodige 37). CtDNA was assessed by digital droplet PCR targeting two methylated markers (HOXD8 and POU4F1) according to a newly developed and validated method. Univariate and multivariate analyses were performed according to ctDNA status.Results: Of 372 plasma samples available, 354 patients were analyzed for survival. In the validation series, 145 of 255 patients were found ctDNA positive (56.8%), Median PFS and OS were 5.3 and 8.2 months in ctDNA-positive and 6.2 and 12.6 months in ctDNA-negative patients, respectively. ctDNA positivity was more often associated with young age, high CA19-9 level and neutrophils lymphocytes ratio. In multivariate analysis including these previous markers, ctDNA was confirmed as an independent prognostic marker for PFS (adjusted hazard ratio (HR) 1.5, CI 95% [1.03-2.18], p = 0.034) and OS (HR 1.62, CI 95% [1.05-2.5], p = 0.029).Conclusions: In this first ctDNA assessment in a large series of mPDAC derived from clinical trials, ctDNA was detectable in 56.8% of patients and confirmed as an independent prognostic marker.

Published
2022
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13. Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial

Author

Clélia Coutzac, Frederic Bibeau, Meher Ben Abdelghani, Thomas Aparicio, Romain Cohen, Elodie Coquan, Olivier Dubreuil, Ludovic Evesque, François Ghiringhelli, Stefano Kim, Samuel Lesourd, Cindy Neuzillet, Jean-Marc Phelip, Guillaume Piessen, Philippe Rochigneux, Emmanuelle Samalin, Emilie Soularue, Yann Touchefeu, David Tougeron, Aziz Zaanan, Christelle de la Fouchardière, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Paul Strauss, CRLCC Paul Strauss, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Eugène Marquis (CRLCC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut du Cancer de Montpellier (ICM), Institut Mutualiste de Montsouris (IMM), Nantes Université (Nantes Univ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Amgen, Bristol-Myers Squibb, BMS, Pfizer, AstraZeneca, Bayer, Roche, Sanofi, Meso Scale Diagnostics, MSD, Les Laboratories Pierre Fabre, MSD France, Ministère des Affaires Sociales et de la Santé, Institut National Du Cancer, INCa: PHRC-K 2019 Inca-DGOS_14333, PRT-K 2020–15324, Servier, Institut Servier, CC declares a consulting and advisory board for Amgen, Servier, and received honoria from Servier, Amgen. TA received honoraria from Servier, Pierre fabre, Amgen, AstraZeneca and declares consulting for Bioven, Servier, SIRTEC, MSD. RC received honoraria from MSD Oncology, Pierre Fabre, and Bristol-Myers Squibb, declares consulting from Exeliom Biosciences, Enterome Bioscience and received research funding from Servier Institute. OD received honoraria from Amgen, Sanofi, Merck Serono, MSD, Servier, Ipsen, Keocyt and declares consulting for Merck Serono, Sanofi, MSD, AstraZeneca, Novartis. LE declares consulting for BMS and Servier. FG declares research grant from Roche, AstraZeneca and consulting for Astrazenca, Roche, Sanofi, BMS, MSD, Merck-Serono, Amgen. EL declares consulting for Roche, Servier, Ipsen, Bayer, BTG, MSD. CN received honoraria from Amgen, AstraZeneca, Baxter, Bristol-Myers Squibb, Fresenius Kabi, Incyte Biosciences, Merck, MSD, Mylan, Novartis, Nutricia, Pierre Fabre, Roche, Sanofi, Servier and research funding from Roche. ES received honoraria from Servier, Amgen, Merck Serono, MSD, Pierre Fabre Oncology BMS, Sanofi, Research funding from Bayer, and declares consulting for Pierre Fabre Oncology. YT declares honoraria from MSD, Astra Zeneca, Bayer, Amgen, Servier, Ipsen, Pierre Fabre, AAA and consulting for Merck. DT received honoraria from Amgen, Roche, Sanofi, Bristol-Myers Squibb, Merck Serono, MSD, Bristol-Myers Squibb, Servier/Pfizer, Ipsen, research funding from AstraZeneca, SERVIER, Roche, MSD, BTG, and declares consulting for Sanofi, MSD, Pierre Fabre, and AstraZeneca. A.Z. declares consulting and/or advisory boards for Amgen, Lilly, Merck, Roche, Sanofi, Servier, Baxter, MSD, Pierre Fabre, Havas Life, Alira Health, Zymeworks, and Daiichi. CDLF received honoraria from Amgen, Astra- Zeneca, Bayer, Bristol-Myers Squibb, Eisai, Incyte Biosciences, Ipsen, Lilly, Merck Serono, MSD, Pierre Fabre Oncologie, Pfizer, Roche, Sanofi-Aventis, Servier. FB, MBZ, SK, EC, PR and ES declares no conflicts of interests., and This study is supported by a grant from the French Ministry of Health and the French National Cancer Institute (PHRC-K 2019 Inca-DGOS_14333 and PRT-K 2020–15324). It is also carried out with the support of MSD France. The opinions expressed in this article are those of the authors and do not necessarily reflect those of MSD France.

Subjects
Hepatology, MSI/dMMR, [SDV]Life Sciences [q-bio], Gastroenterology, Immune checkpoint inhibitor, DNA Mismatch Repair, Colorectal cancer, Perioperative immunotherapy, Antineoplastic Agents, Immunological, Endometrial cancer, Neoplasms, Humans, Immunologic Factors, Microsatellite Instability, Immunotherapy, Prospective Studies, Colorectal Neoplasms, Gastric cancer, Immune Checkpoint Inhibitors
Abstract

International audience; Background: Immune checkpoint inhibitors (ICI) targeting Programmed death-1 (PD-1) have shown their efficacy in advanced MSI/dMMR (microsatellite instability/deficient mismatch repair) tumors. The MSI/dMMR status predicts clinical response to ICI. The promising results evaluating ICI in localized MSI/dMMR tumors in neoadjuvant setting need to be confirmed in MSI/dMMR solid tumors. The aim of the IMHOTEP trial is to assess the efficacy of neoadjuvant anti-PD-1 treatment in MSI/dMMR tumors regarding the pathological complete response rate. Methods: This study is a prospective, multicenter, phase II study including 120 patients with localized MSI/dMMR carcinomas suitable for curative surgery. A single dose of pembrolizumab will be administered before the surgery planned 6 weeks later. Primary objective is to evaluate the efficacy of neoadjuvant pembrolizumab according to pathological complete tumor response. Secondary objectives are to assess safety, recurrence-free survival and overall survival. Ancillary studies will assess molecular and immunological biomarkers predicting response/resistance to ICI. First patient was enrolled in December 2021. Discussion: The IMHOTEP trial will be one of the first clinical trial investigating perioperative ICI in localized MSI/dMMR in a tumor agnostic setting. Assessing neoadjuvant anti-PD-1 is mandatory to improve MSI/dMMR patient's outcomes. The translational program will explore potential biomarker to improve our understanding of immune escape and response in this ICI neoadjuvant setting.

Published
2022
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14. Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology

Author

Josep M. Llovet, Peter R. Galle, Paolo Abada, Sara Lonardi, Jiri Tomasek, Su Jin Koh, Guido Stirnimann, Richard S. Finn, Masatoshi Kudo, Jean-Marc Phelip, Tae-You Kim, Ryan C. Widau, Mark Karwal, Tsai Sheng Yang, Kenyon D. Ogburn, Denis Pezet, Andrew X. Zhu, Yann Touchefeu, Chunxiao Wang, and Kun Liang

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, 610 Medizin, 610 Medicine & health, Chronic liver disease, Antibodies, Monoclonal, Humanized, Gastroenterology, Ramucirumab, 03 medical and health sciences, Liver disease, 0302 clinical medicine, 610 Medical sciences, Internal medicine, Medicine, Humans, 030304 developmental biology, 0303 health sciences, Hepatology, business.industry, Liver Neoplasms, Hepatitis C, Hepatitis B, medicine.disease, digestive system diseases, 3. Good health, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Liver function, business, Viral load
Abstract

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. METHODS Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). RESULTS Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value = .23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55-0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55-1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40-0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. CONCLUSIONS Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.

Published
2021
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15. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL)

Author

Zev A. Wainberg, David Ferry, Ravindranath Patel, Denis Pezet, Elzbieta Wojcik, Kazumasa Fujitani, Vera Gorbounova, Fernando Cabanillas, Bela Piko, Fidel David Huitzil Melendez, Agnes Ruzsa, Jean-Marc Phelip, Madhuri Bajaj, J.T. Beck, Elizabeth Won, Alexander Luft, Sara Lonardi, Peter C. Enzinger, Maen A. Hussein, Bohuslav Melichar, Daisuke Sakai, Angel Gomez Villanueva, A Madi, Georgina Garnica Jaliffe, Carlo Barone, Guillermo Mendez, Marina N. Nechaeva, György Bodoky, Hubert Ayala, Francesco Di Costanzo, Julien Taieb, David H. Ilson, Leslie Samuel, Ronald L. Burkes, Mayukh Das, Marc Van den Eynde, Charles S. Fuchs, Scott M. Berry, Ji Lin, Shuichi Hironaka, Christina Maria Gomez, Thierry Alcindor, Eric Van Cutsem, James A. Jr Reeves, Katriina Peltola, Timothy R. Asmis, Christine Brezden-Masley, Udit Verma, Javier Gallego Plazas, Isabelle Sinapi, Peter Bono, Nozomu Machida, Cynthia Coo Chua, Francisco Javier Ramirez Godinez, Annemieke Cats, Raija Kallio, Alex Beny, Hiroki Hara, Cardellino Giovanni Gerardo, Diego Lucas Kaen, Wasat Mansoor, Miguel Angel Escudero, Andràs Csilla, Akihito Tsuji, Ralf-Dieter Hofheinz, Jana Pribylova, Marianne Nordsmark, Daniel Dammrich, Maria Alejandra Bartoli, Joanna Pikiel, Robert Andrew Dichmann, Maria Di Bartolomeo, Ricardo Villalobos Valencia, Jill Lacy, Raymond Jang, Carlos Alberto Hernandez, Giuseppe Aprile, Nina A. Karaseva, Jonathan Wadsley, Ian Chau, Svetlana Protsenko, Jana Prausová, Maria Błasińska-Morawiec, Salah-Eddin Al-Batran, Hélène Senellart, Stephen Leong, Francisco Gutiérrez Delgado, Johanna C. Bendell, Laurent Mineur, M.I. Grootscholten, Hugo Ford, Russell D. Petty, Laura Visa Turmo, Roberto Carlesi, Hector Velez-Cortez, Maria Alsina, Jiri Petera, Seigo Yukisawa, Federico Longo Munoz, Mette Karen Yilmaz, Pilar Garcia Alfonso, Baruch Brenner, Irfan Firdaus, William E. Lawler, Sylvie Lorenzen, Moustapha Tehfe, Kohei Shitara, Naotoshi Sugimoto, Karen Geboes, A.J. Ten Tije, Walid Shaib, Shigenori Kadowaki, Nicolas Robert Maisey, H.M.W. Van Laarhoven, Radka Obermannova, F.L.G. Erdkamp, Rubén Dario Kowalyszyn, Joanna Wojcik-Tomaszewska, Peter Istvan Acs, Crystal S. Denlinger, Ravit Geva, Srinivasan Madhusudan, Brian Anthony DiCarlo, Ferdinando De Vita, Alejandro Molina Alavez, Gunnar Folprecht, Kensei Yamaguchi, Moses Sundar Raj, Judit Kocsis, Susanna Hegewisch-Becker, Joana Vidal Barrull, Daisuke Takahari, Tomasz Sarosiek, Luis Fein, Mohamed Hebbar, Tibor Csoszi, Manish A. Shah, Alfredo Falcone, Hugo Hool, Michel Ducreux, Per Pfeiffer, Einat Shacham-Shmueli, Howard J. Lim, Taito Esaki, Oncology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and Quality of Life, and AGEM - Re-generation and cancer of the digestive system

Subjects
Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Esophageal Neoplasms, Adenocarcinoma, Antibodies, Monoclonal, Humanized, Placebo, Sudden death, Gastroenterology, Ramucirumab, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, medicine, Clinical endpoint, Humans, Progression-free survival, Aged, Intention-to-treat analysis, Performance status, business.industry, Hazard ratio, Middle Aged, Vascular Endothelial Growth Factor Receptor-2, Progression-Free Survival, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, Esophagogastric Junction, Fluorouracil, Cisplatin, business
Abstract

Summary Background VEGF and VEGF receptor 2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether the addition of ramucirumab, a VEGFR-2 antagonist monoclonal antibody, to first-line chemotherapy improves outcomes in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma. Methods For this double-blind, randomised, placebo-controlled, phase 3 trial done at 126 centres in 20 countries, we recruited patients aged 18 years or older with metastatic, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Eligible patients were randomly assigned (1:1) with an interactive web response system to receive cisplatin (80 mg/m2, on the first day) plus capecitabine (1000 mg/m2, twice daily for 14 days), every 21 days, and either ramucirumab (8 mg/kg) or placebo on days 1 and 8, every 21 days. 5-Fluorouracil (800 mg/m2 intravenous infusion on days 1–5) was permitted in patients unable to take capecitabine. The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients. We did a sensitivity analysis of the primary endpoint, including a central review of CT scans. Overall survival was a key secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02314117. Findings Between Jan 28, 2015, and Sept 16, 2016, 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidine and cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319). Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607–0·935, p=0·0106; median progression-free survival 5·7 months [5·5–6·5] vs 5·4 months [4·5–5·7]). A sensitivity analysis based on central independent review of the radiological images did not corroborate the investigator-assessed difference in progression-free survival (HR 0·961, 95% CI 0·768–1·203, p=0·74). There was no difference in overall survival between groups (0·962, 0·801–1·156, p=0·6757; median overall survival 11·2 months [9·9–11·9] in the ramucirumab group vs 10·7 months [9·5–11·9] in the placebo group). The most common grade 3–4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group. The most common serious adverse events were vomiting (14 [4%] in the ramucirumab group vs 21 [7%] in the placebo group) and diarrhoea (11 [3%] vs 19 [6%]). There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events. In the ramucirumab group, these adverse events were acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, and sudden death (n=1 of each). In the placebo group, these adverse events were cerebrovascular accident (n=1), multiple organ dysfunction syndrome (n=2), pulmonary embolism (n=2), sepsis (n=1), and small intestine perforation (n=1). Interpretation Although the primary analysis for progression-free survival was statistically significant, this outcome was not confirmed in a sensitivity analysis of progression-free survival by central independent review, and did not improve overall survival. Therefore, the addition of ramucirumab to cisplatin plus fluoropyrimidine chemotherapy is not recommended as first-line treatment for this patient population. Funding Eli Lilly and Company.

Published
2019
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16. Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial

Author

Romain Coriat, Nicolas Loménie, Côme Lepage, Thierry Lecomte, Violaine Randrian, Camille Kurtz, Jean-Louis Legoux, Jean-Marc Phelip, Astrid Lièvre, Pierre Laurent-Puig, Julien Taieb, Jean-François Emile, Carole Monterymard, David Tougeron, Harry Sokol, Jérémie Bez, Laurent Mineur, Claire Gallois, Laetitia Dahan, Stefano Kim, Vincent Hautefeuille, Claude Capron, Marine Gilabert, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Ambroise Paré [AP-HP], Hôpital JeanMinjoz, 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Sainte Catherine [Avignon], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Informatique Paris Descartes (LIPADE (URP_2517)), Université de Paris (UP), HalioDX and the 'Ligue nationale contre le cancer', 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 de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Jonchère, Laurent, École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, DNA Mismatch Repair, 03 medical and health sciences, Antineoplastic Agents, Immunological, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Checkpoint blockade, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Humans, Medicine, Immune Checkpoint Inhibitors, Chemotherapy, Hepatology, business.industry, Tumour-infiltrating lymphocytes, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Oxaliplatin, Clinical trial, 030220 oncology & carcinogenesis, Microsatellite Instability, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, medicine.drug
Abstract

International audience; Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high";. The first patient was included on April 20, 2021.

Published
2021
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17. The Screening and COnsensus Based on Practices and Evidence (SCOPE) Program–Results of a Survey on Daily Practice Patterns for Patients with mCRC

Author

Harpreet Wasan, Fernando Rivera, Gerald W. Prager, Daniele Santini, Jean Marc Phelip, Claus-Henning Köhne, and Juan Manuel O’Connor

Subjects
medicine.medical_specialty, Consensus, Colorectal cancer, KRAS-wildtype mCRC, Article, KRAS-mutated mCRC, metastatic colorectal cancer, practice patterns, regorafenib, trifluridine-tipiracil, antineoplastic combined chemotherapy protocols, consensus, humans, surveys and questionnaires, colorectal neoplasms, quality of life, chemistry.chemical_compound, Quality of life, Regorafenib, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Adverse effect, RC254-282, Scope (project management), business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Guideline, medicine.disease, Oxaliplatin, Clinical trial, chemistry, Emergency medicine, Quality of Life, business, Colorectal Neoplasms, medicine.drug
Abstract

The SCOPE project aimed to better understand practice patterns, identify drivers for treatment goals, and determine third- and fourth-line treatment choices for patients with metastatic colorectal cancer (mCRC). The survey was developed by an expert panel of gastrointestinal oncologists. Questions concerned general practice patterns, and treatment decisions for three hypothetical patient case scenarios. Participants had to routinely manage patients with mCRC. We present results from 629 participants who provided input on patient treatment scenarios (data cutoff: 17/01/2020). Prolonging overall survival (OS, 51%) was the main aim in first line. In third line, quality of life (QOL) was the primary goal (34%). Forty-three percent also cited efficacy-focused goals, 18% and 13% noted prolonging OS and improving progression-free survival as main aims, respectively. For fit and active patients, 89% of respondents considered trifluridine-tipiracil an appropriate third-line treatment, regorafenib (31%) or clinical trial enrollment (29%) were the fourth-line options. For patients with comorbidities and limited caregiver support, trifluridine-tipiracil was the preferred third-line treatment (70%). For KRAS-mutated patients with comorbidities and adverse events who received prior oxaliplatin, 90% considered oxaliplatin rechallenge an unsuitable third-line treatment, mainly due to the risk of cumulative toxicity (75%). In the third/fourth-line settings, trifluridine-tipiracil followed by regorafenib was the most common option (54%), 17% chose regorafenib followed by trifluridine-tipiracil. Efficacy coupled with QOL are important goals in third-line treatment. Daily practice patterns reflect the guideline recommendations in third- and fourth-line settings, with a trend toward using trifluridine-tipiracil versus regorafenib in KRAS-wildtype and KRAS-mutant tumors.

Published
2021
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18. Gemcitabine/nab-paclitaxel versus folfirinox in locally advanced pancreatic cancer: A European multicenter study

Author

Julien Taieb, Angelica Petrillo, Anthony Lopez, Jean-Marc Phelip, Michele Ghidini, Lucie Weislinger, Audrey Thoor, Nicolas Williet, Gaël S. Roth, Ferdinando De Vita, Mila Petrova, J. Forestier, Williet, N., Petrillo, A., Roth, G., Ghidini, M., Petrova, M., Forestier, J., Lopez, A., Thoor, A., Weislinger, L., De Vita, F., Taieb, J., and Phelip, J. M.

Subjects
Cancer Research, Abdominal pain, medicine.medical_specialty, FOLFIRINOX, Predictors of response, Prognostic factors, Gastroenterology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pancreatic cancer, Internal medicine, medicine, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Retrospective cohort study, medicine.disease, Gemcitabine/nab-paclitaxel, Gemcitabine, medicine.anatomical_structure, Oncology, Paclitaxel, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, medicine.symptom, Pancreas, business, Chemoradiotherapy, medicine.drug
Abstract

Background: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). Methods: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan–Meier method. Results: A total of 147 patients (GN: n = 60, FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%, p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8–13.5) vs. 12.1 months (95% CI: 10.1–14.6, p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6–20.2) and 16.7 months (95% CI: 14.8–20.4, p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 &gt, 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%, p &lt, 0.001), was not predictive. Conclusion: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.

Published
2021

19. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author

Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], 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, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Published
2020
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20. 337 Pembrolizumab in combination with xelox bevacizumab in patients with microsatellite stable (MSS) metastatic colorectal cancer and a high immune infiltrate: a proof of concept study. FFCD 1703 POCHI

Author

Julien Taieb, Jean-François Emile, Claude Capron, David Tougeron, Romain Coriat, Stephano Kim, Jean-Marc Phelip, Laetitia Dahan, Violaine Randrian, Jean Louis Legoux, Marine Gilabert, Vincent Hautefeuille, Claire Gallois, Pierre Laurent-Puig, Laurent Mineur, Harry Sokol, Bez Jérémie, Carole Monterymard, Côme Lepage, Thierry Lecomte, and Astrid Lièvre

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Tumor-infiltrating lymphocytes, Pembrolizumab, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Primary tumor, lcsh:RC254-282, Oxaliplatin, Capecitabine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, medicine.drug
Abstract

Background Immune checkpoint inhibitors (ICI) are very effective in deficient DNA mismatch-repair system (dMMR)/microsatellite instable (MSI) metastatic colorectal cancer (mCRC). About 15% of MSS/pMMR CRCs are highly infiltrated by tumor infiltrating lymphocyte (TIL) with a good prognosis. Some immune scores based on CD3+ and/or CD8+ T-cells infiltration are validated and reproducible, especially TuLIS1 and Immunoscore®.2 No data are available concerning efficacy of ICI in this subpopulation of mCRC. Pembrolizumab, an anti-PD1 (programmed death-1) monoclonal antibody has been recently reported very effective in patients with MSI/dMMR mCRC. Immunogenic cell death induced by chemotherapy, such as oxaliplatin, could increase the efficacy of ICI. We formulated the hypothesis that patients with a pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin-based chemotherapy. Methods POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of pembrolizumab in combination with chemotherapy as first-line treatment of pMMR mCRC with a high immune infiltrate. Primary objective is PFS at 10 months, i.e. number of patients alive and without radiological and/or clinical progression at 10 months evaluated by the investigator. Main secondary objectives are overall survival, secondary resection rate, depth of response and early tumour shrinkage. Main inclusion criteria are pMMR mCRC untreated for metastatic disease and with at least one measurable metastatic target according to RECIST v1.1 criteria. Patients must have resected primary tumor to evaluate two different immune scores (Immunoscore® and TuLIS) and patients are eligible if one score is ‘high’. Patients will receive combination of pembrolizumab (200 mg), bevacizumab (7.5 mg/kg), oxaliplatin (130 mg/m²) and capecitabine (2000 mg/m²/day, on day 1 to 14). Treatment will be repeated every 3 weeks until disease progression or unacceptable toxicity. The clinical hypotheses are to increase PFS at 10 months from 50% to 70%. With a one-sided type error of 5%, power of 85%, 10% rate of patients lost to follow-up or not evaluable, 55 patients have to be included. If 32 patients or more are alive and without progression at 10 months, the treatment will be considered as effective. Thus, with 15% ‘high’ immune score, about 400 patients must be tested in order to include 55 patients in POCHI trial. The ancillary study will consist to identify predictive biomarkers of response and included expression of PD-L1, circulating lymphocytes circulating tumour DNA, mutational load and gut microbiota. Inclusions will start in September 2020 and theoretical end of recruitment is 2023. Results N/A Conclusions N/A Acknowledgements We thank all the cooperative groups (FFCD – UNICANCER GI– GERCOR) for their contribution and participation to the present trial. We thank MSD and HalioDX for their support. Trial Registration NCT04262687 Ethics Approval This study was approved by ‘Agence Nationale de Securite du Medicament et des produits de sante (ANSM)’ on 24/03/2020; approval number MEDAECNAT-2020-01-00038_2019-002407-18.’ Consent N/A References Emile JF, et al., Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX. Eur J Cancer 2017 Sep;82:16–24 Pages, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 2018 May 26;391(10135):2128–2139.

Published
2020

21. Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

Author

Loick Vidot, Julien Taieb, Irfan Cicin, Ahmet Ozet, Martin Becquart, Fabienne Portales, Timothy J. Price, Chiara Cremolini, Dan Atlan, Jean-Marc Phelip, Jean-Baptiste Bachet, Nadjat Mounedji, Eric Van Cutsem, Alfredo Falcone, Lucjan Wyrwicz, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Queen Elizabeth Hospital, University of Pisa - Università di Pisa, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Gazi University, Trakya Universitesi [Edirne], Institut de Recherches Internationales Servier [Suresnes] (IRIS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), 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), Gestionnaire, Hal Sorbonne Université, 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, Vascular Endothelial Growth Factor A, Cancer Research, Pyrrolidines, Colorectal cancer, [SDV]Life Sciences [q-bio], Trifluridine, trifluridine tipiracil, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, colorectal cancer, metastatic, quality of life, safety, Original Research, 0303 health sciences, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Nausea, Placebo, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, Adverse effect, 030304 developmental biology, Tipiracil, Aged, business.industry, medicine.disease, chemistry, business, Thymine
Abstract

BACKGROUND: In RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil. METHODS: In this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL). RESULTS: 793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03-14.72). There was no clinically relevant change from baseline in QoL. CONCLUSIONS: PRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment. TRIAL REGISTRATION NUMBER: NCT03306394. ispartof: ESMO OPEN vol:5 issue:3 ispartof: location:England status: published

Published
2020
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22. Treatment guidelines of metastatic colorectal cancer in older patients from the French Society of Geriatric Oncology (SoFOG)

Author

Gilles Albrand, Tristan Cudennec, Leila Bengrine-Lefevre, Camille Petri, Anne-Marie Bouvier, Eric Francois, Elena Paillaud, Jean-Marc Phelip, Elisabeth Carola, Bérengère Couturier, Florence Canoui-Poitrine, Philippe Caillet, Thomas Aparicio, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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), and Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé)

Subjects
medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Context (language use), Targeted therapy, Metastasis, 03 medical and health sciences, chemistry.chemical_compound, Older patient, 0302 clinical medicine, Regorafenib, Medicine, Humans, Chemotherapy, Neoplasm Metastasis, Intensive care medicine, Societies, Medical, Aged, Neoplasm Staging, Hepatology, Performance status, business.industry, Gastroenterology, medicine.disease, Combined Modality Therapy, 3. Good health, Geriatric oncology, chemistry, 030220 oncology & carcinogenesis, Quality of Life, 030211 gastroenterology & hepatology, France, business, Colorectal Neoplasms, medicine.drug
Abstract

International audience; Background: Several guidelines dedicated to metastatic colorectal cancer (mCRC) are available. Since 2013 no recent guidelines are specifically dedicated to older patients and based on a systematic review. Materials and methods: A multidisciplinary Task Force with digestive oncologists, geriatricians and methodologists from the SoFOG was formed in 2016 to update recommendations on medical treatment of mCRC based on a systematic review of publications from 2000 to 2018. Search strategy has followed a standardized protocol from the formulation of clinical questions and definition of a search algorithm to the selection of complete articles for recommendations. Results: The four selected key questions were: For which older patients with mCRC can we considered: (1) Any chemotherapy, (2) Mono or poly-chemotherapy, (3) Anti-angiogenic therapy, (4) Other targeted therapy. Main recommendations for older patients are: (1) Omission of chemotherapy should be discussed with a geriatrician for patients with severe comorbidities, advanced dementia, uncontrolled psychiatric disorder or severe loss of autonomy. (2) If tumor response is not the main aim, a mono-chemotherapy with 5-fluorouracil combined with bevacizumab is recommended as first-line. (3) For patients with symptoms related to metastases or with a planned metastasis ablation, a doublet chemotherapy combined with bevacizumab or anti-EGFR antibody in the context of a RAS wild type tumor is recommended as first-line. Preliminary data suggest that regorafenib may be used, in its registered indication, in patients under 80 with a performance status of 0 and no autonomy alterations and that trifluridine-tipiracil may be used with a tight supervising of hematological function.

Published
2020
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23. First Characterization with Ultrasound Contrast Agent of a Fibrovascular Polyp Before Its Endoscopic Resection: A Case Report (with Videos)

Author

Radwan Kassir, Francois Casteillo, Cyril Habougit, Jean-Marc Phelip, Nicolas Williet, Xavier Roblin, and Violaine Yvorel

Subjects
lcsh:Internal medicine, medicine.medical_specialty, media_common.quotation_subject, medicine.medical_treatment, Esophageal fibrovascular polyp, Medicine (miscellaneous), Case Report, Resection, 03 medical and health sciences, 0302 clinical medicine, Medicine, Contrast (vision), Radiology, Nuclear Medicine and imaging, Endoscopic resection, lcsh:RC799-869, lcsh:RC31-1245, media_common, Ultrasound endoscopy contrast enhancement, medicine.diagnostic_test, business.industry, Ultrasound, Gastroenterology, Polypectomy, Endoscopy, Giant Fibrovascular Esophageal Polyp, Microvascularization, 030220 oncology & carcinogenesis, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Radiology, business, Complication
Abstract

We described for the first time the contrast enhancement of a giant fibrovascular esophageal polyp using ultrasound contrast agent, Sonovue® (Bracco, Milan, Italy) during echoendoscopy. Fine Doppler was unsuccessful in showing vascularization due to the mobile characteristic of the tumor. In contrast, via Sonovue® , tissue microcirculation was highlighted inside the entire head of the polyp, leading to better appreciate the risk of bleeding related to its resection. In a second part, we showed the feasibility of classic polypectomy for this giant polyp (5×5 cm) without complication and results of control endoscopy at 3 months. The present case is summarized in a video.

Published
2018

24. Intensification of induction chemotherapy before consolidation chemoradiotherapy improves progression-free survival and time without treatment in patients with locally advanced pancreatic cancers

Author

Xavier Roblin, Nicolas Williet, Thomas Di Bernardo, Chloé Vernet, Nicolas Magné, Léa Saban Roche, Jean-Marc Phelip, and Thierry Muron

Subjects
Oncology, medicine.medical_specialty, Performance status, pancreatic carcinoma, FOLFIRINOX, business.industry, medicine.medical_treatment, Induction chemotherapy, GemOx, survival, Gemcitabine, Radiation therapy, Internal medicine, locally advanced, parasitic diseases, medicine, Progression-free survival, business, Chemoradiotherapy, induction chemotherapy, radiotherapy, medicine.drug, Research Paper
Abstract

Aims To assess the interest of induction chemotherapy (ICT) intensification before chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer. Methods Charts of patients treated between February 2010 and November 2016 with consolidation capecitabin based-CRT were retrospectively reviewed in this bicentric study. Patients who underwent Gemcitabine as ICT (Group G) were compared to patients treated with intensive ICT (group I). Primary objectives were progression-free survival (PFS), defined as the time from the first day of ICT to progression or last follow-up, and Time without treatment (TWT), as the time from the last day of CRT to progression. Results Patients' characteristics were balanced between group I (Folforinox: n = 24; GemOx: n = 6) and group G (n = 16) including mean age (63.7 vs 68.1 years), and performance status (PS 0-1 :90% vs 93.7%). Median PFS (17.8 months vs 12 months; p = 0.02) and TWT (7.4 months vs 2.5 months p = 0.01) were statistically better in group I vs group G. These results remained statistically and clinically significant by comparing Folfirinox subgroup to Gemcitabine. A trend to a better median overall survival was observed in group I (20.4 months) vs group G (18.3 months; p = 0.07). After adjusting for ICT duration, PS, and CA19.9 level, ICT intensification remains independently prognostic. Toxicity profile was in accordance with Literature. Conclusion This study shows ICT intensification before CRT is an interesting approach in patients with locally advanced pancreatic cancer. Further studies are needed to confirm these results, and to assess the specific role of CRT in this setting.

Published
2018

25. Outcome and prognostic factors in 593 non-metastatic rectal cancer patients: a mono-institutional survey

Author

G. Pigne, Alexis Vallard, Amel Rehailia-Blanchard, M.-A. Garcia, Nicolas Magné, Jack Porcheron, Thierry Muron, Elodie Guillaume, Julien Langrand-Escure, Guoping Wang, Jean-Baptiste Guy, David Kaczmarek, P. Diao, Sophie Espenel, Jean-Marc Phelip, and Guy de Laroche

Subjects
Male, Oncology, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, Aftercare, Radiation Tolerance, 0302 clinical medicine, 030212 general & internal medicine, Aged, 80 and over, Proctectomy, Multidisciplinary, Age Factors, Chemoradiotherapy, Middle Aged, Prognosis, Neoadjuvant Therapy, Progression-Free Survival, 030220 oncology & carcinogenesis, Medicine, Female, Adult, medicine.medical_specialty, Science, Antineoplastic Agents, Adenocarcinoma, Article, 03 medical and health sciences, Radioresistance, Internal medicine, medicine, Humans, Non metastatic, Progression-free survival, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Rectal Neoplasms, business.industry, Rectum, Retrospective cohort study, medicine.disease, Survival Analysis, Radiation therapy, Radiotherapy, Adjuvant, Neoplasm Recurrence, Local, business
Abstract

This retrospective study was undertaken to provide more modern data of real-life management of non-metastatic rectal cancer, to compare therapeutic strategies, and to identify prognostic factors of overall survival (OS) in a large cohort of patients. Data on efficacy and on acute/late toxicity were retrospectively collected. Patients were diagnosed a non-metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. OS was correlated with patient, tumor and treatment characteristics with univariate and multivariate analyses. Data of 593 consecutive non-metastatic rectal cancer patients were analyzed. Median follow-up was 41 months. Median OS was 9 years. Radiotherapy was delivered in pre-operative (n = 477, 80.5%), post-operative (n = 75, 12.6%) or exclusive (n = 41, 6.9%) setting. In the whole set of patients, age, nutritional condition, tumor stage, tumor differentiation, and surgery independently influenced OS. For patients experiencing surgery, OS was influenced by age, tumor differentiation and nodal status. Surgical resection is the cornerstone treatment for locally-advanced rectal cancer. Poor tumor differentiation and node involvement were identified as major predictive factor of poor OS. The research in treatment intensification and in identification of radioresistance biomarkers should therefore probably be focused on this particular subset of patients.

Published
2018

26. Difficult endoscopic diagnosis of a pancreatic plasmacytoma: Case report and review of literature

Author

Nicolas Williet, Jean-Marc Phelip, Karine Augeul-Meunier, Olivier Dumas, Michèle Cottier, Radwan Kassir, Xavier Roblin, Muriel Cuilleron, and Leslie Rinaldi

Subjects
endocrine system, medicine.medical_specialty, business.industry, Case Report, Review, medicine.disease, 03 medical and health sciences, Ultrasound endoscopy, 0302 clinical medicine, medicine.anatomical_structure, Oncology, immune system diseases, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Diagnosis, medicine, Plasmacytoma, 030211 gastroenterology & hepatology, Radiology, Pancreas, business, neoplasms
Abstract

A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis. Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later. This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission. A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography. In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search.

Published
2017

27. Histopathological and molecular study from EUS fine-needle biopsy of a programmed cell death ligand 1 positive, KRAS mutated pancreatic metastasis

Author

Sophie Bayle-Bleuez, Jean-Marc Phelip, Quentin Tournier, Nicolas Williet, and Francois Casteillo

Subjects
Pancreatic metastasis, Hepatology, business.industry, Gastroenterology, medicine, Cancer research, Radiology, Nuclear Medicine and imaging, KRAS, medicine.disease_cause, business, Programmed cell death ligand 1, Fine needle biopsy, Images and Videos
Published
2020

28. Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

Author

Julien Taieb, Isabelle Trouilloud, Jean-Marc Phelip, David Tougeron, Christophe Locher, Simon Pernot, Vincent Hautefeuille, Anne Thirot Bidault, Pascal Artru, Bertrand Le Roy, Astrid Pozet, Angélique Saint, Nelson Lourenco, Anne-Laure Pointet, Dominique Béchade, Jérôme Desramé, Nicolas Williet, Denis Pezet, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Département de gastro-entérologie et d'oncologie digestive [HEGP - APHP], Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'oncologie digestive, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Center Jean Mermoz, Clinique Saint Jean, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Gastroentérologie et hépatologie, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, FOLFIRINOX, survival, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, First line therapy, Internal medicine, Metastatic pancreatic cancer, medicine, pancreatic adenocarcinoma, In patient, lcsh:RC799-869, ComputingMilieux_MISCELLANEOUS, Nab-paclitaxel, business.industry, gemcitabine/nab-paclitaxel, Gastroenterology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gemcitabine, 3. Good health, metastatic, 030104 developmental biology, 030220 oncology & carcinogenesis, Propensity score matching, Folfirinox, lcsh:Diseases of the digestive system. Gastroenterology, business, medicine.drug
Abstract

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

Published
2019
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29. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial

Author

Inmaculada Ales, Hakan Harputluoglu, Marc Peeters, Jean-Marc Phelip, G. Pelletier, Zsuzsanna Kahan, Alice Gangloff, Fadi Farhat, Imam Waked, Luc Lasser, René Gerolami, Giovanni Luca, Thomas Berg, Julie Le Boulicaut, Jean-Pierre Zarski, Ivan Borbath, Wolfgang Sieghart, Ozlem Ata, Howard Ozer, Julie Vincent, Thierry Fontanges, Bartomeu Massuti, Christos Galanopoulos, Mohammed El Kassas, Audrey Molé, Imam Wakid, Philippe Merle, Nasr El Lahlouby, Andreas Maieron, Marilyne Debette-Gratien, Antonio Cubillo, György Bodoky, Sylvain Manfredi, Faiza Khemissa-Akouz, Jawad Makarem, Jean-Frédéric Blanc, Ahmet Coker, Carmen Guillén, Massimo Colombo, Michael Schultheiß, Joerg Trojan, Yann Touchefeu, Isabelle Ollivier-Hourmand, François Habersetzer, Vlad Ratziu, Amr Abdel, Amr S Saad, Miguel Marín, Magdolna Dank, Mohamed Bouattour, Hélène Regnault, Jean-Didier Grangé, Pierluigi Toniutto, Hanaa Kohail, Sameh Shamaa, Carine Richou, Erdem Goker, Eric Nguyen-Khac, Oscar Alabiso, G.-P. Pageaux, Andrea Casadei-Gardini, Moses Raj, Alexander Zipprich, Henning Wege, Ilkay Tugba, Aurore Baron, Victor Navarro, Domenico Amoroso, Issam Chehade, Nashat Gabrail, Pierre Attali, Barbara Dauvois, Stefano Tamberi, Driffa Moussata, Angela Buonadonna, Emiliano Tamburini, Muhammet Ali, Armand Abergel, Albert Tran, Suayib Yalcin, Ursula Ehmer, Hermini Manzano, Jean Delwaide, Andrés Muñoz, Carlos López, Jean-Pierre Bronowicki, Zsolt Horváth, Alper Sevinc, Gloria Sánchez, Ralph Hauke, Gabriele Luppi, Bérangère Vasseur, Nelson S. Yee, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, P., Blanc, J. -F., Phelip, J. -M., Pelletier, G., Bronowicki, J. -P., Touchefeu, Y., Pageaux, G., Gerolami, R., Habersetzer, F., Nguyen-Khac, E., Casadei-Gardini, A., Borbath, I., Tran, A., Wege, H., Saad, A. S., Colombo, M., Abergel, A., Richou, C., Waked, I., Yee, N. S., Mole, A., Attali, P., Le Boulicaut, J., Vasseur, B., Moussata, D., Grange, J. -D., Ratziu, V., Khemissa-Akouz, F., Regnault, H., Dauvois, B., Zarski, J. -P., Ollivier-Hourmand, I., Manfredi, S., Debette-Gratien, M., Gangloff, A., Fontanges, T., Baron, A., Bouattour, M., Vincent, J., Sieghart, W., Maieron, A., Peeters, M., Delwaide, J., Lasser, L., Berg, T., Schultheiss, M., Zipprich, A., Trojan, J., Ehmer, U., Luppi, G., Luca, G., Tamberi, S., Amoroso, D., Alabiso, O., Buonadonna, A., Toniutto, P., Tamburini, E., Cubillo, A., Munoz, A., Guillen, C., Sanchez, G., Manzano, H., Navarro, V., Ales, I., Massuti, B., Dank, M., Bodoky, G., Kahan, Z., Horvath, Z., Gabrail, N., Ozer, H., Galanopoulos, C., Hauke, R., Raj, M., Harputluoglu, H., Sevinc, A., Goker, E., Coker, A., Yalcin, S., Ali, M., Ata, O., Tugba, I., Elkassas, M., Abdel, A., Wakid, I., Shamaa, S., El, N., Kohail, H., Makarem, J., Chehade, I., Farhat, F., Lopez, C., and Marin, M.

Subjects
Male, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Treatment Failure, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Antibiotics, Antineoplastic, Liver Neoplasms, Middle Aged, Sorafenib, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Female, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, Population, Antineoplastic Agents, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Carcinoma, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Adverse effect, Aged, Hepatology, Dose-Response Relationship, Drug, business.industry, medicine.disease, Thrombocytopenia, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Doxorubicin, Asthenia, Nanoparticles, business
Abstract

Summary Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT01655693 . Findings Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2–34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1–10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1–11·8) in the control group (HR 1·00 [95% CI 0·78–1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. Interpretation Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. Funding Onxeo.

Published
2019
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30. JOURNAL OF CLINICAL ONCOLOGY Volume: 37 Issue: 15 Supplement: S Meeting Abstract: 4136 Published: MAY 20 2019

Author

Daniel Pietrasz, Laetitia Dahan, Pierre Laurent-Puig, Shu-Fang Wang-Renault, Solene Doat, Jean-Marc Phelip, Jean-Baptiste Bachet, Karine Le Malicot, Julien Taieb, Y. Rinaldi, Valérie Taly, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Descartes - Paris 5 (UPD5), Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Européen [Fondation Ambroise Paré - Marseille], 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), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], 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), and TALY, Valerie

Subjects
Cancer Research, Prognostic factor, business.industry, [SDV]Life Sciences [q-bio], Metastatic Pancreatic Adenocarcinoma, 3. Good health, Highly sensitive, [SDV] Life Sciences [q-bio], 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, Circulating tumor DNA, 030220 oncology & carcinogenesis, Cancer research, Medicine, Prognostic biomarker, business, Gene, DNA, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract

4136 Background: Circulating tumor DNA has emerged as prognostic biomarker in oncology. Many different genes can be mutated within a tumor, complicating procedures, even with highly sensitive next-generation sequencing (NGS). DNA methylation in promotor of specific genes is an early key epigenetic change during oncogenesis. Specific methylated genes could be a potential relevant cancer biomarker that may substitute for NGS panels. The aim of this study was to assess the prognostic value of Met-DNA in mPAC. Methods: Prognostic value of Met-DNA was assessed in a prospective cohort (PLAPAN) of mPAC (training cohort), correlated with NGS, then in two prospective independent validation cohorts from two randomized phase II trials (PRODIGE 35 and 37). Plasma samples were collected before chemotherapy on EDTA-coated tubes. Met-DNA was quantified using two specific markers of pancreatic DNA methylation by digital droplet PCR and correlated with prospectively registered patient (pts) characteristics and oncologic outcomes (progression free survival (PFS) and overall survival (OS)). Results: 330 patients (pts) were enrolled. 60% (n = 58) of the 96 pts of the training cohort had at least one Met-DNA marker. The correlation with NGS assessment was R = 0.93 (Pearson; p < 0.001). 59.5% (n = 100/168) and 59% (n = 39/66) of pts had detectable Met-DNA in the 2 validation cohorts. In the training cohort, Met-DNA was correlated with poor OS (HR = 1.82; 95%CI 1.07-2.42; p = 0.026). In validation cohorts, Met-DNA was a prognostic factor of PFS (HR = 1.62; 95%CI 1.17-2.25, p = 004) and OS (HR = 1.79; 95%CI 1.28-2.49, p < 0.001) in PRODIGE 35, as in PRODIGE 37: PFS HR = 1.79 (95%CI 1.07-2.99; p = 0.026) and OS HR = 2.08 (95%CI [1.18-3.68], p = 0.01), respectively. In multivariate analysis adjusted on gender, age, CA19-9 > 40UI.mL, treatment arm, number of metastatic sites and stratified on center, Met-DNA was independently associated with poor OS in both trials: HR = 1.81 (95%CI 1.10-2.98; p = 0.02) and HR = 3.62 (95%CI: 1.32-9.93; p = 0.01). Conclusions: This study demonstrates that Met-DNA is a strong independent prognostic factor in mPAC. These results argue for patient’s stratification on ctDNA status for further randomized trials. Clinical trial information: NCT02827201 and NCT02352337.

Published
2019

31. Modified FOLFIRINOX versus CisGem first-line chemotherapy for locally advanced non resectable or metastatic biliary tract cancer (AMEBICA)-PRODIGE 38: Study protocol for a randomized controlled multicenter phase II/III study

Author

Sylvain Manfredi, Prodige Investigators, Pierre Michel, Jérôme Desramé, Julien Edeline, Jean-Frédéric Blanc, Cindy Neuzillet, Jean-Marc Phelip, Vincent Bourgeois, David Malka, Emilie Barbier, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Eugène Marquis (CRLCC), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Fédération Francophone de la Cancérologie Digestive, FFCD, Equipe EPICAD (LNC - U1231), 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)-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), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Duchenne, CH Boulogne sur Mer, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital privé Jean Mermoz, and 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 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

Subjects
Male, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, Modified folfirinox, Leucovorin, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Advanced biliary cancer, Irinotecan, Deoxycytidine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Humans, Medicine, Neoplasm Invasiveness, Neoplasm Staging, Chemotherapy, Hepatology, business.industry, Gallbladder, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Gemcitabine, Primary tumor, 3. Good health, Oxaliplatin, medicine.anatomical_structure, Bile Duct Neoplasms, Biliary tract, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, France, Cisplatin, Drug Monitoring, business, medicine.drug
Abstract

IF 3.287 (2017); International audience; IntroductionCombination of cisplatine and Gemcitabine (CisGem) is the reference 1st line Chemotherapy in patients with advanced biliary cancer. FOLFIRINOX demonstrated an overall survival superiority when compared to gemcitabine in 1st line for patients with metastatic pancreatic adenocarcinoma. Because of similarities between pancreatic and biliary cancers, we proposed a randomized trial comparing mFOLFIRINOX and CisGEm.AimPRODIGE38-AMEBICA is a phase II/III trial evaluating efficacy of modifed FOLFIRINOX (D1 bolus removed) or CisGEm on patients with locally advanced non resectable or metastatic biliary tract cancer.Patients and methodsMain inclusion criteria are histologically or cytologically proven biliary tract tumor (intra or extra hepatic or hilar or gallbladder carcinoma), measurable disease (metastases and/or primary tumor), Bilirubin

Published
2019
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32. 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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33. Adenoma detection with blue-water infusion colonoscopy: a randomized trial

Author

Marc O’Brien, Olivia Scalone, D. Pere-Verge, Sandrine Baubet, Claire Billioud, Karine Stroeymeyt-Martin, Driffa Moussata, Christine Chambon-Augoyard, Guillermo Aguero Garcete, Stéphane Degeorges, Sandrine Touzet, Adriane Lesne, Thierry Ponchon, Jérôme Rivory, Audrey Pasquion, Claire Cruiziat, Sylvaine Chalumeau, Florence Léger-Nguyen, S. Poupon-Bourdy, Jean-Marc Phelip, Philippe Brulet, Benjamin Hamel, J. C. Souquet, Thierry Fontanges, Laurent Magaud, Fabien Petit-Laurent, Julien Scanzi, Laurent Poincloux, Angélique Denis, Marion Chauvenet, Mathieu Pioche, Olivier Rouquette, Gwenaelle Tourlonias, Elsa Thimonier, Emmanuelle Graillot, CHU Estaing [Clermont-Ferrand], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Gastro-enterology department, CHU Clermont-Ferrand, Hepato-Gastroenterology, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastro-entérologie, CH Pierre Oudot Bourgoin-Jallieu, Hôpital de la Croix-Rousse [CHU - HCL], Hôpital Villefranche sur Saône, Université Panthéon-Sorbonne ( UP1 ), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Application des ultrasons à la thérapie ( LabTAU ), 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 Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris 1 Panthéon-Sorbonne (UP1), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Application des ultrasons à la thérapie (LabTAU), 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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM), and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adenoma, Male, medicine.medical_specialty, medicine.medical_treatment, Operative Time, Color, Colonoscopy, Adenocarcinoma, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Intubation, Cecum, Intubation, Gastrointestinal, ComputingMilieux_MISCELLANEOUS, Aged, medicine.diagnostic_test, business.industry, Fecal occult blood, Water, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Colorectal Neoplasms, business
Abstract

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 – 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known.Clinical trials registration: EudraCT 2012-A00548 – 35; NCT01937429.

Published
2017
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34. Laparoscopy could be the best approach to treat colorectal cancer in selected patients aged over 80 years: Outcomes from a multicenter study

Author

Brice Gayet, Jean-Marc Phelip, Xavier Roblin, David Fuks, Léa Clavel, Jack Porcheron, Leslie Rinaldi, Mehdi Ouaissi, Nicolas Williet, Anderson Loundou, Igor Sielezneff, Gabriele Barabino, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, 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), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Department of Digestive Surgery, University Medical Hospital, Service d'Hépato-gastroentérologie [CHU Saint-Etienne], CHU Amiens-Picardie, Departement medico-chirurgical de pathologie digestive, Institut Mutualiste de Montsouris (IMM), Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées (LINA-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Male, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030230 surgery, Metastasis, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Humans, 10. No inequality, Laparoscopy, Survival rate, Colectomy, Survival analysis, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Aged, 80 and over, Hepatology, medicine.diagnostic_test, business.industry, Age Factors, Gastroenterology, Retrospective cohort study, Length of Stay, medicine.disease, Survival Analysis, 3. Good health, Surgery, Survival Rate, Treatment Outcome, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Multivariate Analysis, Female, France, Colorectal Neoplasms, Elective Surgical Procedure, business
Abstract

The efficacy and safety of treating elderly patients with colorectal cancer (CRC) is of concern. This study aimed to compare the short- and long-term outcomes of elective laparoscopic vs. open surgery to treat CRC in very elderly patients.All patients aged80 years and who had undergone a colectomy for CRC without metastasis between July 2005 and April 2012 were considered for inclusion. Demographic, clinical, operative, and postoperative data, plus overall and disease-free survival rates, were retrospectively collected and compared between two groups of patients that underwent an open procedure (OP group) or laparoscopy (LG).123 patients were enrolled (55 OPG, 68 LG). Median age was similar between the groups (84 vs. 83 years, respectively; NS). Duration of surgery was significantly lower in OPG (170 vs. 200min; p=0.030). Overall mortality at 3 months was 8.3%: it tended to be greater in the OPG (16.5% vs. 1.5%, NS). Morbidity was significantly greater in the OPG compared to the LG (52.7% vs. 27.5%; p=0.021), resulting in significantly longer hospital stay (12 vs. 8 days, respectively; p0.001). Pathological findings were similar between the two groups. Cumulative overall survival rates at 3 and 5 years were significantly greater after laparoscopy (85% and 72%) compared to open surgery (58.2% and 48%, respectively; p0.001).Our study suggests that laparoscopy is safe and could increase overall survival compared to open surgery in elderly patients suffering from CRC.This retrospective study compared the short- and longer-term outcomes of patients aged80 years and undergoing elective laparoscopic or open surgery for CRC between 2005 and 2012.

Published
2017
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35. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author

Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, 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), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), 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), Service d'oncologie médicale [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), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Published
2016
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36. Compound heterozygous PKHD1 variants cause a wide spectrum of ductal plate malformations

Author

Julien Thevenon, Christel Thauvin-Robinet, Yannis Duffourd, Jean-Baptiste Rivière, Laurent Morisse, Anne Minello, Fabienne Prieur, Nadège Gigot, Boris Guiu, Jean-Pierre Cerceuil, Laurence Faivre, Alain Beurdeley, Daniel Meynard, Denis Massenet, Judith St-Onge, Emmanuel Jacquemin, Claire Vanlemmens, Patrick Hillon, Laurence Michel-Calemard, Jean-Marc Phelip, Christiane Mousson, Flore Lacassin, Jean-Benoît Courcet, Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), CHU Saint-Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Agence de Santé des îles Wallis & Futuna, Centre hospitalier territorial Gaston-Bourret [Nouméa], CHU Dijon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de néphrologie (CHU de Dijon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Université de Montpellier (UM), Service d'hépato-gastro-entérologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, Heterozygote, Caroli disease, Receptors, Cell Surface, PKHD1, Bile Duct Diseases, Biology, Compound heterozygosity, Young Adult, autosomal recessive polycystic kidney disease, Genetics, medicine, Humans, Exome, Genetic Predisposition to Disease, Child, Genetics (clinical), Exome sequencing, Polycystic Kidney, Autosomal Recessive, [SDV.GEN]Life Sciences [q-bio]/Genetics, High-Throughput Nucleotide Sequencing, Heterozygote advantage, Middle Aged, medicine.disease, Prognosis, Major gene, Autosomal Recessive Polycystic Kidney Disease, 3. Good health, Pedigree, Ductal Plate Malformation, Bile Ducts, Intrahepatic, Phenotype, Mutation, ductal plate malformation, Female
Abstract

International audience; Ductal plate malformations (DPM) present with a wide phenotypic spectrum comprising Von Meyenburg complexes (VMC), Caroli disease (CD), Caroli syndrome (CS), and autosomal recessive polycystic kidney disease (ARPKD). Variants in PKHD1 are responsible for ARPKD and CS with a high inter- and intra-familial phenotypic variability. Rare familial cases of CD had been reported and exceptional cases of CD are associated with PKHD1 variants. In a family of three siblings presenting with a wide spectrum of severity of DPM, we performed whole exome sequencing and identified two PKHD1 compound heterozygous variants (c.10444G>A; p.Arg3482Cys and c.5521C>T; p.Glu1841Lys), segregating with the symptoms. Two compound heterozygous PKHD1 variants, including one hypomorphic variant, were identified in two other familial cases of DPM with at least one patient presenting with CD. This report widens the phenotypic variability of PKHD1 variants to VMC, and others hepatic bile ducts malformations with inconstant renal phenotype in adults and highlights the important intra-familial phenotypic variability. It also showed that PKHD1 might be a major gene for CD. This work adds an example of the contribution of exome sequencing, not only in the discovery of new genes but also in expanding the phenotypic spectrum of well-known disease-associated genes, using reverse phenotyping.

Published
2015
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37. Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue

Author

Valérie Forest, Delphine Boudard, Xavier Roblin, Lara Leclerc, Jean-Marc Phelip, Michèle Cottier, Gabriele Barabino, Dimitrios Bitounis, Jérémie Pourchez, Gwendoline Sarry, Leslie Rinaldi, Jean-Philippe Klein, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées (LINA-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Centre Ingénierie et Santé (CIS-ENSMSE), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Acid digestion, Colorectal cancer, Colon, Biopsy, Context (language use), colorectal cancer, environmental risk, Adenocarcinoma, magnesium, Tumour tissue, Environmental risk, Medicine, Distribution (pharmacology), Humans, Colorectal adenocarcinoma, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Aged, Aged, 80 and over, Hepatology, business.industry, Spectrophotometry, Atomic, Gastroenterology, Rectum, elemental analysis, Middle Aged, medicine.disease, 3. Good health, Metals, Colorectal tissue, Case-Control Studies, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, Colorectal Neoplasms
Abstract

International audience; Background: Colorectal cancer is considered to be an environmental disease. In this context, the study of environmental risk factors associated with the presence of chemical elements is important, as well as improving our knowledge of the elemental fingerprint of tumor tissuecompared to non-cancer tissue.Aims: The objective was to evaluate the element distribution in colorectal adenocarcinoma biopsies, adjacent non-tumor tissues, and healthy controls (non-cancer colorectal biopsies including occlusion or ischemic colons).Methods: The study is a case-control study which compared the element distribution in colon biopsies from two groups of patients: with colorectal cancer and without colorectal cancer. Patients with colorectal cancer provided 2 different groups of samples: colorectal cancer biopsies and adjacent non-tumor tissues. 15 metal concentrations (Al, B, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Se, Si, Ti, V, and Zn) in colorectal biopsies were quantified by using acid digestion procedures and then inductively coupled plasma (ICP) atomic emission spectrometry.Results: A total of 104 patients were included. 76 patients in the colorectal cancer group (i.e. tumor and adjacent non-tumor tissues) and 28 patients in the healthy control group (i.e. noncancer colorectal biopsies). Among the 15 elements analyzed by ICP spectrometry, only boron, chromium, zinc, silicon, and magnesium were found in colorectal tissue at clearly detectable concentrations. Our data indicated that colorectal tumor biopsies have significantly elevated concentrations of magnesium as compared to adjacent non-tumor or healthy tissues. Zinc concentration followed the same trend but differences were not statistically significant. In addition, silicon appears to be more accumulated in colorectal cancer tissue than in healthy non-cancer tissue, while chromium was mostly found in adjacent non-tumor tissue. Conclusion: Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in colorectal tumor. Their potential role in colorectal carcinogenesis should be explored.

Published
2015
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38. Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

Author

Xavier Roblin, Emilie Del Tedesco, Christian Genin, Laurent Peyrin Biroulet, Hubert Marotte, Melanie Rinaudo, Jean-Marc Phelip, Stéphane Paul, Amélie Moreau, Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Rhumatologie [Saint-Etienne], CHU Saint-Etienne-Hôpital de Bellevue, Service d'immunologie [CHU Saint-Etienne], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Rhumatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service d'immunologie - Suivi des biothérapies [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Centre International de Recherche en Infectiologie (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Serum, Crohn’s disease, [SDV]Life Sciences [q-bio], Crohn's Disease Activity Index, TNF, Inflammatory bowel disease, Gastroenterology, Severity of Illness Index, UC, Maintenance therapy, adalimumab, ROC, Intestinal Mucosa, skin and connective tissue diseases, AAA, Outcome, Response to Therapy, Crohn's disease, biology, AUROC, CDAI, Prognostic Factor, Middle Aged, Ulcerative colitis, 3. Good health, CD, Treatment Outcome, CRP, medicine.drug, Adult, musculoskeletal diseases, medicine.medical_specialty, likelihood ratio, tumor necrosis factor, IBD, LHR, Antibodies, Monoclonal, Humanized, C-reactive protein, mucosal healing, Young Adult, Anti-Adalimumab, inflammatory bowel disease, Internal medicine, Adalimumab, medicine, Humans, Immunologic Factors, receiver-operating characteristic, ulcerative colitis, MH, Hepatology, antibodies against adalimumab, business.industry, area under the receiver-operating characteristic curve, Endoscopy, medicine.disease, Inflammatory Bowel Diseases, Surgery, ADA, Cross-Sectional Studies, biology.protein, Trough level, business
Abstract

International audience; BACKGROUND & AIMS:Little is known about the association between pharmacokinetic features of adalimumab and mucosal healing in patients with inflammatory bowel disease (IBD).METHODS:We conducted a cross-sectional study of 40 patients with Crohn's disease (CD) or ulcerative colitis (UC) who received adalimumab maintenance therapy and underwent endoscopic evaluation of disease activity and pharmacokinetic analysis (measurements of trough levels and antibodies against adalimumab). Patients in clinical remission were identified based on CD activity index scores less than 150 or Mayo scores less than 3 (for those with UC). Patients with mucosal healing were identified based on Mayo endoscopic scores less than 2 (for UC) or the disappearance of all ulcerations (for CD).RESULTS:The median trough level of adalimumab was higher in patients in clinical remission (6.02 μg/mL) than in patients with active disease (3.2 μg/mL; P = .012). Trough levels of adalimumab were also higher in patients with mucosal healing (6.5 μg/mL) than in patients without (4.2 μg/mL; P

Published
2014
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39. Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire en Oncologie phase II study

Author

Olivier Dupuis, Emmanuel Touboul, Christophe Louvet, Gérard Lledo, Laurence Moureau-Zabotto, Jacques Balosso, Laurent Mineur, Véronique Vendrely, Jean-Marc Phelip, Pauline Afchain, Thierry André, Florence Huguet, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Sainte Catherine [Avignon], Centre Hospitalier Universitaire Saint André, Université Bordeaux Segalen - Bordeaux 2, Clinique Saint-Jean, Centre de Radiothérapie, Collaboration, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Serduc, Raphael

Subjects
Male, Cancer Research, MESH: Combined Modality Therapy, Organoplatinum Compounds, Gastroenterology, Deoxycytidine, 0302 clinical medicine, MESH: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Medicine, Infusions, Intravenous, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Organoplatinum Compounds, Middle Aged, Combined Modality Therapy, 3. Good health, Oxaliplatin, Survival Rate, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Fluorouracil, MESH: Pancreatic Neoplasms, medicine.drug, Adult, medicine.medical_specialty, MESH: Survival Rate, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, GemOx, Adenocarcinoma, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, education, MESH: Infusions, Intravenous, Survival rate, 030304 developmental biology, Aged, MESH: Humans, Performance status, business.industry, MESH: Adenocarcinoma, MESH: Deoxycytidine, Induction chemotherapy, MESH: Adult, Gemcitabine, MESH: Male, Surgery, Pancreatic Neoplasms, Concomitant, Feasibility Studies, business, MESH: Feasibility Studies, MESH: Female, MESH: Fluorouracil
Abstract

Background According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy. Patients and Methods Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m2 on day 1 and oxaliplatin 100 mg/m2 on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m2 FU as a continuous infusion and 60 mg/m2of oxaliplatin weekly. Results Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%). Conclusion Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.

Published
2008
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40. MacDuffie syndrome and primary sclerosing cholangitis: an exceptional association

Author

Frédéric Heluwaert, Jean-Marc Phelip, Bruno Bonaz, Marie Noelle Hilleret, Jean-Pierre Zarski, Nathalie Sturm, Xavier Roblin, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, and Sinniger, Valérie

Subjects
medicine.medical_specialty, Physiology, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Transplant surgery, MESH: Diagnosis, Differential, Internal medicine, medicine, MESH: Syndrome, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, MESH: Humans, MESH: Middle Aged, business.industry, MESH: Vasculitis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Cholangitis, Sclerosing, MESH: Male, 3. Good health, 030211 gastroenterology & hepatology, business, Biliary tract disease
Abstract

International audience; No abstract

Published
2006
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41. 6-tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine

Author

Jean-Luc Faucheron, Alain A. Chartier, Gaëlle Hardy, Bruno Bonaz, F. Helluwaert, Xavier Roblin, Jean-Marc Phelip, Germain Bessard, Françoise Serre-Debeauvais, Sinniger, Valérie, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Laboratoire de Pharmacologie (HP2), CHU Grenoble-Hôpital Michallon, Département de chirurgie générale et digestive, and CHU Grenoble

Subjects
Male, Azathioprine, Gastroenterology, Tioguanine, 0302 clinical medicine, Crohn Disease, Pharmacology (medical), Prospective Studies, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Thiopurine methyltransferase, biology, Mercaptopurine, Inflammatory Bowel Diseases, MESH: Follow-Up Studies, Middle Aged, Ulcerative colitis, 3. Good health, Phenotype, Treatment Outcome, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, MESH: Immunosuppressive Agents, MESH: 6-Mercaptopurine, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, MESH: Colitis, Ulcerative, MESH: Phenotype, Antimetabolite, 03 medical and health sciences, Internal medicine, medicine, Humans, Erythrocyte Mean Corpuscular Volume, Active metabolite, MESH: Azathioprine, Aged, MESH: Adolescent, MESH: Humans, Hepatology, MESH: Crohn Disease, business.industry, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH: Prospective Studies, Surgery, biology.protein, Colitis, Ulcerative, business, MESH: Female, Follow-Up Studies
Abstract

International audience; BACKGROUND: 6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine. AIM: The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine. METHODS: Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients. RESULTS: A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission. CONCLUSIONS: Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).

Published
2005
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44. The Screening and COnsensus Based on Practices and Evidence (SCOPE) Program–Results of a Survey on Daily Practice Patterns for Patients with mCRC

Author

Gerald Prager, Claus-Henning Köhne, Juan Manuel O’Connor, Fernando Rivera, Daniele Santini, Harpreet Wasan, and Jean Marc Phelip

Subjects
metastatic colorectal cancer, practice patterns, trifluridine-tipiracil, regorafenib, KRAS-mutated mCRC, KRAS-wildtype mCRC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The SCOPE project aimed to better understand practice patterns, identify drivers for treatment goals, and determine third- and fourth-line treatment choices for patients with metastatic colorectal cancer (mCRC). The survey was developed by an expert panel of gastrointestinal oncologists. Questions concerned general practice patterns, and treatment decisions for three hypothetical patient case scenarios. Participants had to routinely manage patients with mCRC. We present results from 629 participants who provided input on patient treatment scenarios (data cutoff: 17/01/2020). Prolonging overall survival (OS; 51%) was the main aim in first line. In third line, quality of life (QOL) was the primary goal (34%). Forty-three percent also cited efficacy-focused goals; 18% and 13% noted prolonging OS and improving progression-free survival as main aims, respectively. For fit and active patients, 89% of respondents considered trifluridine-tipiracil an appropriate third-line treatment; regorafenib (31%) or clinical trial enrollment (29%) were the fourth-line options. For patients with comorbidities and limited caregiver support, trifluridine-tipiracil was the preferred third-line treatment (70%). For KRAS-mutated patients with comorbidities and adverse events who received prior oxaliplatin, 90% considered oxaliplatin rechallenge an unsuitable third-line treatment, mainly due to the risk of cumulative toxicity (75%). In the third/fourth-line settings, trifluridine-tipiracil followed by regorafenib was the most common option (54%); 17% chose regorafenib followed by trifluridine-tipiracil. Efficacy coupled with QOL are important goals in third-line treatment. Daily practice patterns reflect the guideline recommendations in third- and fourth-line settings, with a trend toward using trifluridine-tipiracil versus regorafenib in KRAS-wildtype and KRAS-mutant tumors.

Published
2021
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45. 337 Pembrolizumab in combination with xelox bevacizumab in patients with microsatellite stable (MSS) metastatic colorectal cancer and a high immune infiltrate: a proof of concept study. FFCD 1703 POCHI

Author

Come Lepage, Harry Sokol, Julien Taieb, Thierry Lecomte, Vincent Hautefeuille, Romain Coriat, David Tougeron, Laétitia Dahan, Pierre Laurent-Puig, Jean Francois Emile, Stephano Kim, Carole Monterymard, Marine Gilabert, BEZ Jérémie, Astrid Lievre, Laurent Mineur, Jean Louis Legoux, Jean marc Phelip, Claude Capron, Claire Gallois, and Violaine Randrian

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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46. Reply to M. Salati et al.

Author

Phelip JM and Malka D

Abstract

Competing Interests: Jean Marc PhelipHonoraria: Merck Serono, Roche, Sanofi, Amgen, Lilly, Servier, BayerConsulting or Advisory Role: Roche, Merck Serono, Amgen, Servier, Bayer, SanofiResearch Funding: Roche, Merck SeronoTravel, Accommodations, Expenses: Roche, Merck Serono, Bayer, Servier, Sanofi, Amgen David MalkaHonoraria: Roche, Amgen, Bayer, Merck Serono, Servier, Sanofi, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO Pharma, Incyte, AgiosConsulting or Advisory Role: Roche, Sanofi, Merck Serono, MSD, Servier, Bayer, Incyte, Amgen, Agios, Bristol Myers SquibTravel, Accommodations, Expenses: Roche, Bayer, Sanofi, Merck Serono, Amgen, Servier, Pierre FabreNo other potential conflicts of interest were reported.

Published
2022
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47. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9).

Author

Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, Phelip JM, François E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, and Bennouna J

Subjects
Aged, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease-Free Survival, Female, Humans, Induction Chemotherapy, Male, Middle Aged, Neoplasm Metastasis, Time Factors, Antineoplastic Agents, Immunological therapeutic use, Bevacizumab therapeutic use, Colorectal Neoplasms drug therapy
Abstract

Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.

Published
2018
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48. Difficult endoscopic diagnosis of a pancreatic plasmacytoma: Case report and review of literature.

Author

Williet N, Kassir R, Cuilleron M, Dumas O, Rinaldi L, Augeul-Meunier K, Cottier M, Roblin X, and Phelip JM

Abstract

A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis. Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later. This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission. A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography. In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search., Competing Interests: Conflict-of-interest statement: None.

Published
2017
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