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1. Impact of Sarcopenia on Survival in Patients Treated with FOLFIRINOX in a First-Line Setting for Metastatic Pancreatic Carcinoma

Author

Lisa Lellouche, Maxime Barat, Anna Pellat, Juliette Leroux, Felix Corre, Rachel Hallit, Antoine Assaf, Catherine Brezault, Marion Dhooge, Philippe Soyer, and Romain Coriat

Subjects
metastatic pancreatic carcinoma, FOLFIRINOX, sarcopenia, oxaliplatin, Medicine
Abstract

Sarcopenia, defined as decreased muscle mass and strength, can be evaluated by a computed tomography (CT) examination and might be associated with reduced survival in patients with carcinoma. The prognosis of patients with metastatic pancreatic carcinoma is poor. The FOLFIRINOX (a combination of 5-fluorouracil, irinotecan, and oxaliplatin) chemotherapy regimen is a validated first-line treatment option. We investigated the impact of sarcopenia on overall survival (OS) and progression-free survival (PFS) in patients with metastatic pancreatic carcinoma. Clinical data and CT examinations of patients treated with FOLFIRINOX were retrospectively reviewed. Sarcopenia was estimated using baseline CT examinations. Seventy-five patients were included. Forty-three (57.3%) were classified as sarcopenic. The median OS of non-sarcopenic and sarcopenic patients were 15.6 and 14.1 months, respectively (p = 0.36). The median PFS was 10.3 in non-sarcopenic patients and 9.3 in sarcopenic patients (p = 0.83). No differences in toxicity of FOLFIRINOX were observed. There was a trend towards a higher probability of short-term death (within 4 months of diagnosis) in sarcopenic patients. In this study, the detection of sarcopenia failed to predict a longer OS or PFS in selected patients deemed eligible by a physician for triplet chemotherapy and receiving the FOLFIRINOX regimen in a first-line setting, confirming the major importance of a comprehensive patient assessment by physicians in selecting the best treatment option.

Published
2023
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2. Impact of Sarcopenia on Patients with Localized Pancreatic Ductal Adenocarcinoma Receiving FOLFIRINOX or Gemcitabine as Adjuvant Chemotherapy

Author

Victor Mortier, Felix Wei, Anna Pellat, Ugo Marchese, Anthony Dohan, Catherine Brezault, Maxime Barat, David Fuks, Philippe Soyer, and Romain Coriat

Subjects
pancreatic adenocarcinoma, adjuvant chemotherapy, FOLFIRINOX, gemcitabine, sarcopenia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Despite its toxicity, modified FOLFIRINOX is the main chemotherapy for localized, operable pancreatic adenocarcinomas. Sarcopenia is known as a factor in lower overall survival (OS). The purpose of this study was to assess the impact of sarcopenia on OS in patients with localized pancreatic ductal adenocarcinoma (PDAC) who received modified FOLFIRINOX or gemcitabine as adjuvant chemotherapy. Methods: Patients with operated PDAC who received gemcitabine-based (GEM group) or oxaliplatin-based (OXA group) adjuvant chemotherapy between 2008 and 2021 were retrospectively included. Sarcopenia was estimated on a baseline computed tomography (CT) examination using the skeletal muscular index (SMI). The primary evaluation criterion was OS. Secondary evaluation criteria were disease-free survival (DFS) and toxicity. Results: Seventy patients treated with gemcitabine-based (n = 49) and oxaliplatin-based (n = 21) chemotherapy were included, with a total of fifteen sarcopenic patients (eight in the GEM group and seven in the OXA group). The median OS was shorter in sarcopenic patients (25 months) compared to non-sarcopenic patients (158 months) (p = 0.01). A longer OS was observed in GEM non-sarcopenic patients (158 months) compared to OXA sarcopenic patients (14.4 months) (p < 0.01). The median OS was 157.7 months in the GEM group vs. 34.1 months in the OXA group (p = 0.13). No differences in median DFS were found between the GEM group and OXA group. More toxicity events were observed in the OXA group (50%) than in the GEM group (10%), including vomiting (p = 0.02), mucositis (p = 0.01) and neuropathy (p = 0.01). Conclusion: Sarcopenia is associated with a worse prognosis in patients with localized operated PDAC whatever the delivered adjuvant chemotherapy.

Published
2022
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3. Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

Author

Lisa Lellouche, Lola-Jade Palmieri, Solène Dermine, Catherine Brezault, Stanislas Chaussade, and Romain Coriat

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

Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene ( BRCA) can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients’ outcomes in the near future.

Published
2021
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4. Therapeutic Management of Advanced Hepatocellular Carcinoma: An Updated Review

Author

Manon Falette Puisieux, Anna Pellat, Antoine Assaf, Claire Ginestet, Catherine Brezault, Marion Dhooge, Philippe Soyer, and Romain Coriat

Subjects
hepatocellular carcinoma, cirrhosis, prognosis, treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Hepatocellular carcinoma (HCC) usually occurs in the setting of liver cirrhosis and more rarely in a healthy liver. Its incidence has increased in the past years, especially in western countries with the rising prevalence of non-alcoholic fatty liver disease. The prognosis of advanced HCC is low. In the first-line setting of advanced HCC, sorafenib, a tyrosine kinase inhibitor, was the only validated treatment for many years. In 2020, the combination of atezolizumab, an immune checkpoint inhibitor, and bevacizumab showed superiority to sorafenib alone in survival, making it the first-line recommended treatment. Regorafenib and lenvatinib, other multikinase inhibitors, were also validated in the second and first-line settings, respectively. Transarterial chemoembolization can be an alternative treatment for patients with intermediate-stage HCC and preserved liver function, including unresectable multinodular HCC without extrahepatic spread. The current challenge in advanced HCC lies in the selection of a patient for the optimal treatment, taking into account the underlying liver disease and liver function. Indeed, all trial patients present with a Child–Pugh score of A, and the optimal approach for other patients is still unclear. Furthermore, the combination of atezolizumab and bevacizumab should be considered in the absence of medical contraindication. Many trials testing immune checkpoint inhibitors in association with anti-angiogenic agents are ongoing, and primary results are promising. The landscape in advanced HCC management is undergoing profound change, and many challenges remain for optimal patient management in the years to come. This review aimed to provide an overview of current systemic treatment options for patients with advanced unresectable HCC who are not candidates for liver-directed therapy.

Published
2022
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5. Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions

Author

Anna Pellat, Anne Ségolène Cottereau, Lola-Jade Palmieri, Philippe Soyer, Ugo Marchese, Catherine Brezault, and Romain Coriat

Subjects
neuroendocrine neoplasms, well-differentiated grade-3, functional imaging, chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Digestive well-differentiated grade 3 neuroendocrine tumors (NET G-3) have been clearly defined since the 2017 World Health Organization classification. They are still a rare category lacking specific data and standardized management. Their distinction from other types of neuroendocrine neoplasms (NEN) not only lies in morphology but also in genotype, aggressiveness, functional imaging uptake, and treatment response. Most of the available data comes from pancreatic series, which is the most frequent tumor site for this entity. In the non-metastatic setting, surgical resection is recommended, irrespective of grade and tumor site. For metastatic NET G-3, chemotherapy is the main first-line treatment with temozolomide-based regimen showing more efficacy than platinum-based regimen, especially when Ki-67 index

Published
2021
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6. Impact of a dedicated multidisciplinary meeting on the management of superficial cancers of the digestive tract

Author

Solène Dermine, Maximilien Barret, Caroline Prieux, Sophie Ribière, Sarah Leblanc, Marion Dhooge, Catherine Brezault, Vered Abitbol, Benoit Terris, Frédéric Beuvon, Alexandre Rouquette, Bertrand Dousset, Sébastien Gaujoux, Philippe Soyer, Anthony Dohan, Jean-Emmanuel Bibault, Romain Coriat, Frédéric Prat, and Stanislas Chaussade

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

Background The recent development of endoscopic resection for superficial gastrointestinal cancers could justify the need for a dedicated oncological multidisciplinary meeting (MDM). The aim of our study was to evaluate the impact of the dedicated MDM on the management of superficial cancers of the digestive tract. Methods A dedicated MDM was developed at our tertiary referral center. A retrospective review of the MDM conclusions for all patients referred from March 2015 to March 2017 was performed. Outcomes measurements were the outcomes of endoscopic resection, and the concordance rate between the MDM recommendations, European Society of Gastrointestinal Endoscopy (ESGE) guidelines, and final patient management. Results In total, 153 patients with a median age of 69 years were included. Half of the patients had major comorbidities. The mean lesion size was 25 mm, and R0 and curative resection rate were 73.9 % and 56.9 %, respectively. Forty-three patients had an indication for surgery after endoscopic resection. The concordance rate between ESGE guidelines and MDM recommendation was 92.2 %, and 12 patients did not receive the treatment recommended due to comorbidities. Conclusion A MDM dedicated to superficial tumors helped tailor the ESGE guidelines to each patient in order to avoid unnecessary surgery.

Published
2018
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7. Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

Author

Baptiste Camus, Anne-Ségolène Cottereau, Lola-Jade Palmieri, Solène Dermine, Florence Tenenbaum, Catherine Brezault, and Romain Coriat

Subjects
neuroendocrine tumors, neoplasm metastasis, PRRT, peptide receptor radionuclide therapy, gastroenteropancreatic tumor, pulmonary tumor, Medicine
Abstract

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

Published
2021
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8. Organ Preservation after Endoscopic Resection of Early Esophageal Cancer with a High Risk of Lymph Node Involvement

Author

Solène Dermine, Thomas Lévi-Strauss, Einas Abou Ali, Arthur Belle, Sarah Leblanc, Jean-Emmanuel Bibault, Amélie Barré, Lola-Jade Palmieri, Catherine Brezault, Marion Dhooge, Benoit Terris, Anthony Dohan, Philippe Soyer, Arthur Berger, Gabriel Rahmi, Romain Coriat, Stanislas Chaussade, and Maximilien Barret

Subjects
superficial esophageal cancer, endoscopic mucosal resection, endoscopic submucosal dissection, chemoradiotherapy, close follow-up, organ preservation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Esophagectomy is recommended after endoscopic resection of an early esophageal cancer when pejorative histoprognostic criteria indicate a high risk of lymph node involvement. Our aim was to analyze the clinical outcomes of a non-surgical, organ preserving management in this clinical setting. Patients and Methods: This retrospective study was performed in two tertiary centers from 2015 to 2020. Patients were included if they had histologically complete resection of an early esophageal cancer, with poor differentiation, lymphovascular invasion or deep submucosal invasion. Endoscopic resection was followed by chemoradiotherapy or follow-up in case of surgical contraindications or patient refusal. Outcome measures were disease-free survival (DFS), overall survival (OS), cancer specific survival (CSS) and toxicity of chemoradiotherapy. Results: Forty-one patients (36 with squamous cell carcinoma and 5 with adenocarcinomas) were included. The estimated high risk of lymph node involvement was based on poor differentiation (10/41; 24%), lympho-vascular invasion (11/41; 27%), muscularis mucosa invasion or deep sub-mucosal invasion (38/41; 93%). Thirteen patients (13/41; 32%) were closely monitored, and 28 (28/41; 68%) were treated by chemoradiotherapy or radiotherapy alone. In the close follow-up group, DFS, OS and CSS were 92%, 92% and 100%, respectively vs. 75%, 79% and 96%, respectively in the chemoradiotherapy group at the end of the follow-up. Serious adverse events related to chemoradiotherapy occurred in 10% of the patients. There were no treatment-related deaths. Conclusions: Our study shows that close follow-up may be an alternative to systematic esophagectomy after endoscopic resection of early esophageal cancer with a predicted high risk of lymph node involvement.

Published
2020
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9. Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

Author

Lola-Jade Palmieri, Solène Dermine, Amélie Barré, Marion Dhooge, Catherine Brezault, Anne-Ségolène Cottereau, and Romain Coriat

Subjects
pancreatic neuroendocrine tumor, pancreatic neuroendocrine neoplasm, pancreatic neuroendocrine carcinoma, neoadjuvant, palliative, chemotherapy, Medicine
Abstract

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

Published
2020
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10. Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors

Author

Solène Dermine, Lola-Jade Palmieri, Julie Lavolé, Amélie Barré, Antony Dohan, Einas Abou Ali, Anne-Ségolène Cottereau, Sébastien Gaujoux, Catherine Brezault, Stanislas Chaussade, and Romain Coriat

Subjects
neuroendocrine tumors, liver metastasis, surgery, radiofrequency ablation, trans-arterial embolization, trans-arterial chemoembolization, trans-arterial radioembolization, Medicine
Abstract

The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.

Published
2019
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12. Supplementary Tables 1-7 from Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Author

Benoit Terris, Gilles Mentha, Pietro E. Majno, Bertand Dousset, Patrick Descombes, Céline Delucinge-Vivier, Catherine Brezault, Sébastien Tauzin, and Laura Rubbia-Brandt

Abstract

Supplementary Tables 1-7 from Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Published
2023

13. Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)

Author

David Malka, Benoît Dupont, Alain Gratet, Pamela Biondiani, Marion Chauvenet, Dany Gargot, Pierre-Emmanuel Henneresse, Hortense Laharie, Johann Dreanic, Valérie Lebrun Lyat, Catherine Brezault-Bonnet, Morgan Andre, Géraldine Perkins, Philippe Houyau, Yves Rinaldi, Etienne Suc, Dominique Besson, Valérie Boige, Cécile Julien, Julien Taieb, Simon Pernot, Benoît Avisse, Pauline Regnault, Ahmed Bedjaoui, Marie-Pierre Galais, Côme Lepage, Céline Lepère, Mme E. Barbier, Antoine Holllebecque, Anne Escande, Julie Vincent, Sandrine Lavau denes, Marie-Claude Gouttebel, Leila Bengrine Lefevre, Anne Thirot Bidault, Anne-Laure Pointet, Julie Gigout, Faiza Khemissa Akouz, Louis-Marie Dourthe, Frederick Moryoussef, Maxime Lesouef, Vincent Bourgeois, François Ghiringhelli, Patrick Texereau, Samy Louafi, Gildas Phelip, Yann Berge, Jean-François Codoul, Jérôme Chamois, Eric Terrebonne, Karine Bouhier Leporrier, Bidaut Wahiba, X. Artignan, Pr Pierre Michel, Iulia Pripon, David Sefrioui, Pierre-Luc Etienne, Romain Coriat, Aurélie Parzy, Mustapha Atlassi, Aziz Zaanan, Jean-Baptiste Bachet, Philippe Dominici, Jean Martin, Mathilde Martinez, Dominique Genet, Raymond Despax, Karine Le Malicot, Laurent Miglianico, Salvatore Caruso, Bruno Valenza, Nicolas Barriere, and Oana Zveltlana Cojocarasu

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Paclitaxel, Population, Leucovorin, Phases of clinical research, Adenocarcinoma, Neutropenia, Irinotecan, Deoxycytidine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Albumins, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, Aged, education.field_of_study, Drug Substitution, business.industry, Middle Aged, medicine.disease, Gemcitabine, Neoadjuvant Therapy, Progression-Free Survival, Pancreatic Neoplasms, Treatment Outcome, 030104 developmental biology, Oncology, Tolerability, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Camptothecin, Female, Fluorouracil, France, business, Febrile neutropenia, medicine.drug
Abstract

Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.

Published
2020

15. Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

Author

Romain Coriat, Catherine Brezault, Lola-Jade Palmieri, Lisa Lellouche, Stanislas Chaussade, and Solène Dermine

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, Review, Pembrolizumab, chemotherapy, olaparib, Systemic therapy, maintenance, Olaparib, nab-paclitaxel, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Advances in Treatment of Lung Cancer Patients with Targetable Mutations, PARP inhibitors, RC254-282, Chemotherapy, pancreatic carcinoma, business.industry, Microsatellite instability, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic Pancreatic Adenocarcinoma, medicine.disease, Gemcitabine, 030104 developmental biology, quality of life, chemistry, 030220 oncology & carcinogenesis, microsatellite instability, pembrolizumab, business, medicine.drug
Abstract

Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene ( BRCA) can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients’ outcomes in the near future.

Published
2021

16. Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions

Author

Romain Coriat, Anna Pellat, Lola-Jade Palmieri, Catherine Brezault, Ugo Marchese, Philippe Soyer, and Anne-Ségolène Cottereau

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, 030209 endocrinology & metabolism, Review, Neuroendocrine tumors, chemotherapy, well-differentiated grade-3, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Internal medicine, Medicine, RC254-282, functional imaging, Chemotherapy, Temozolomide, Everolimus, neuroendocrine neoplasms, business.industry, Sunitinib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Regimen, 030220 oncology & carcinogenesis, Radionuclide therapy, business, medicine.drug
Abstract

Simple Summary We herein present the latest data on characteristics and therapeutic management of gastro-entero-pancreatic well-differentiated neuroendocrine grade 3 tumors (GEP-NET G-3). Although neuroendocrine neoplasms (NEN) of the digestive tract are rare tumors, progress in diagnosis has allowed their better identification. Since 2017, a new category of NEN showing well-differentiated morphology and high Ki-67 index has been defined, the NET G-3. These tumors show differences not only in morphology but also in genotype, clinical features, and treatment response, compared with classical high-grade NEN. Therefore, they should be managed differently but suffer from lack of data. We find our work important, underlying the need to conduct new rigorous clinical studies in this population. Abstract Digestive well-differentiated grade 3 neuroendocrine tumors (NET G-3) have been clearly defined since the 2017 World Health Organization classification. They are still a rare category lacking specific data and standardized management. Their distinction from other types of neuroendocrine neoplasms (NEN) not only lies in morphology but also in genotype, aggressiveness, functional imaging uptake, and treatment response. Most of the available data comes from pancreatic series, which is the most frequent tumor site for this entity. In the non-metastatic setting, surgical resection is recommended, irrespective of grade and tumor site. For metastatic NET G-3, chemotherapy is the main first-line treatment with temozolomide-based regimen showing more efficacy than platinum-based regimen, especially when Ki-67 index

Published
2021

17. Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica

Author

Antoine Assaf, Benoit Terris, Lola-Jade Palmieri, Alexandre Rouquette, Frédéric Beuvon, Anna Pellat, Einas Abou Ali, Claire Ginestet, Arthur Belle, Dr Marion Dhooge, Dr Catherine Brezault, Rachel Hallit, Anthony Dohan, Stanislas Chaussade, Romain Coriat, and Maximilien Barret

Subjects
Linitis Plastica, Hepatology, Stomach, Gastroenterology, Humans, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Endosonography, Retrospective Studies
Abstract

Gastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3-10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP.We performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP.Between January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies.Gastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.

Published
2022

18. Impact of a dedicated multidisciplinary meeting on the management of superficial cancers of the digestive tract

Author

Sarah Leblanc, Jean-Emmanuel Bibault, Sébastien Gaujoux, Catherine Brezault, Sophie Ribiere, Benoit Terris, Frédéric Prat, Maximilien Barret, Vered Abitbol, Philippe Soyer, Anthony Dohan, Caroline Prieux, Marion Dhooge, Romain Coriat, Stanislas Chaussade, Frédéric Beuvon, Alexandre Rouquette, Bertrand Dousset, and Solène Dermine

Subjects
Curative resection, medicine.medical_specialty, Original article, business.industry, General surgery, Concordance, Unnecessary Surgery, Patient management, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, 030220 oncology & carcinogenesis, medicine, Referral center, 030211 gastroenterology & hepatology, Pharmacology (medical), Endoscopic resection, Digestive tract, lcsh:Diseases of the digestive system. Gastroenterology, lcsh:RC799-869, business
Abstract

Background The recent development of endoscopic resection for superficial gastrointestinal cancers could justify the need for a dedicated oncological multidisciplinary meeting (MDM). The aim of our study was to evaluate the impact of the dedicated MDM on the management of superficial cancers of the digestive tract. Methods A dedicated MDM was developed at our tertiary referral center. A retrospective review of the MDM conclusions for all patients referred from March 2015 to March 2017 was performed. Outcomes measurements were the outcomes of endoscopic resection, and the concordance rate between the MDM recommendations, European Society of Gastrointestinal Endoscopy (ESGE) guidelines, and final patient management. Results In total, 153 patients with a median age of 69 years were included. Half of the patients had major comorbidities. The mean lesion size was 25 mm, and R0 and curative resection rate were 73.9 % and 56.9 %, respectively. Forty-three patients had an indication for surgery after endoscopic resection. The concordance rate between ESGE guidelines and MDM recommendation was 92.2 %, and 12 patients did not receive the treatment recommended due to comorbidities. Conclusion A MDM dedicated to superficial tumors helped tailor the ESGE guidelines to each patient in order to avoid unnecessary surgery.

Published
2018

19. Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review

Author

Lola-Jade Palmieri, Florence Tenenbaum, Solène Dermine, Romain Coriat, Catherine Brezault, Anne-Ségolène Cottereau, and Baptiste Camus

Subjects
Oncology, medicine.medical_specialty, gastroenteropancreatic tumor, Peptide receptor, medicine.medical_treatment, lcsh:Medicine, Review, Neuroendocrine tumors, Octreotide lar, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, neoplasm metastasis, 0302 clinical medicine, Internal medicine, medicine, In patient, peptide receptor radionuclide therapy, pulmonary tumor, Somatostatin receptor, business.industry, lcsh:R, General Medicine, medicine.disease, Radiation therapy, Treatment modality, 030220 oncology & carcinogenesis, Radionuclide therapy, PRRT, neuroendocrine tumors, business
Abstract

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

Published
2021

20. The choice for the optimal therapy in advanced biliary tract cancers: Chemotherapy, targeted therapies or immunotherapy

Author

Romain Coriat, Lola-Jade Palmieri, Marion Dhooge, Julie Lavolé, Solène Dermine, Amélie Barré, Stanislas Chaussade, Catherine Brezault, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Clinical Decision-Making, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Tumor Microenvironment, medicine, Humans, Pharmacology (medical), Molecular Targeted Therapy, Precision Medicine, Pharmacology, Cisplatin, Chemotherapy, business.industry, Immunotherapy, Chemotherapy regimen, Gemcitabine, 3. Good health, Transcriptome Sequencing, Biliary Tract Neoplasms, Treatment Outcome, 030104 developmental biology, Biliary tract, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract

Biliary tract cancers (BTCs) represent a heterogeneous group that includes intrahepatic cholangiocarcinomas (CCAs), perihilar-CCAs or Klatskin tumors, extrahepatic-CCAs, and gallbladder adenocarcinoma. These entities have distinct demographics, risk factors, clinical presentation, and molecular characteristics. In advanced BTCs, the recommendations are mainly supporting a doublet chemotherapy regimen using cisplatin/gemcitabine (CisGem) with a 5-year overall survival rate close to 5% and median overall survival (mOS) of less than a year. The lack of overall efficacy stresses the need for personalized therapies. Recently, whole-genome and transcriptome sequencing highlighted the diversity of BTCs' subtypes. Distinct genetic alterations were retrieved according to the localization, with a high rate of potentially actionable alterations. Targeted therapies and immunotherapy have since then been tested for BTCs, trying to propose a more personalized treatment. This review describes the different therapeutic options, validated and in development, for patients with advanced BTCs.

Published
2020

21. Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

Author

Amélie Barré, Solène Dermine, Anne-Ségolène Cottereau, Marion Dhooge, Romain Coriat, Lola-Jade Palmieri, and Catherine Brezault

Subjects
Oncology, medicine.medical_specialty, Mitotic index, Proliferation index, medicine.medical_treatment, lcsh:Medicine, 030209 endocrinology & metabolism, Review, Neuroendocrine tumors, chemotherapy, pancreatic neuroendocrine tumor, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, palliative, Internal medicine, Medicine, Chemotherapy, business.industry, Incidence (epidemiology), neoadjuvant, pancreatic neuroendocrine carcinoma, lcsh:R, General Medicine, medicine.disease, targeted therapy, Pancreatic Neuroendocrine Neoplasm, Somatostatin, 030220 oncology & carcinogenesis, pancreatic neuroendocrine neoplasm, business
Abstract

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

Published
2020

22. Oral therapies in digestive oncology (Review)

Author

Romain Coriat, Solène Dermine, Catherine Brezault, Caroline Klotz, Stanislas Chaussade, Lola Jade Palmieri, and Julie Lavolé

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, MEDLINE, Administration, Oral, Antineoplastic Agents, Therapeutic education, Digestive System Neoplasms, Targeted therapy, Internal medicine, medicine, Humans, Molecular Targeted Therapy, Medical prescription, Oral therapy, Clinical Trials as Topic, business.industry, Cancer, General Medicine, medicine.disease, Trained nurse, Oncology patients, business, Algorithms
Abstract

Targeted therapy and oral chemotherapy indications are increasing in the realm of digestive oncology. Oral intake of cancer agents is sometimes compulsory (no i.v. equivalent) or is preferred by the patient or the physician. Although oral chemotherapy facilitates the treatment of oncology patients, the treatment diversity, risk of pharmaceutical interactions and monitoring of side effects are potentially challenging and need to be fully acknowledged by the physician. We offer here a literature review of the indications, doses, side effects and monitoring of every oral therapy indicated in Digestive Oncology. We suggest a prescription algorithm including therapeutic education by the physician or a trained nurse, and pharmaceutical counseling.

Published
2020

23. Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors

Author

Einas Abou Ali, Lola-Jade Palmieri, Antony Dohan, Stanislas Chaussade, Anne-Ségolène Cottereau, Romain Coriat, Solène Dermine, Julie Lavolé, Amélie Barré, Catherine Brezault, and Sébastien Gaujoux

Subjects
Oncology, medicine.medical_specialty, Prognostic factor, Radiofrequency ablation, lcsh:Medicine, trans-arterial radioembolization, Review, Neuroendocrine tumors, trans-arterial chemoembolization, 030218 nuclear medicine & medical imaging, Metastasis, law.invention, surgery, 03 medical and health sciences, 0302 clinical medicine, Quality of life, law, Internal medicine, Medicine, Hepatic artery embolization, Non pharmacological, trans-arterial embolization, business.industry, Incidence (epidemiology), lcsh:R, General Medicine, medicine.disease, liver metastasis, 030220 oncology & carcinogenesis, radiofrequency ablation, neuroendocrine tumors, business
Abstract

The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.

Published
2019

24. Les progrès dans la prise en charge des cholangiocarcinomes

Author

Romain Coriat, Sophie-Clémentine Ribiere, Chloé Leandri, Marie-Anne Guillaumot, and Catherine Brezault

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, medicine, 030212 general & internal medicine, General Medicine, business
Abstract

Points essentiels Les cancers des voies biliaires sont une entite rare dont l’incidence augmente en France. La resection chirurgicale du cholangiocarcinome reste la seule therapeutique curative. Le traitement adjuvant par la capecitabine a la dose de 1250 mg/m2, deux fois par jour du premier au 14e jour (cycle de 21 jours) pendant 6 mois est dorenavant le traitement standard apres chirurgie curative. A un stade metastatique, le traitement de reference consiste en l’association d’un sel de platine a la gemcitabine. Aucun biomarqueur n’a ete identifie pour predire la reponse a la chimiotherapie. Le sequencage de l’ADN permet d’identifier des mutations tumorales particulieres dans les cancers des voies biliaires qui sont l’objet d’etudes ciblees.

Published
2018

25. Tumour growth increased following antiangiogenic interruption

Author

Bertrand Brieau, Chloé Leandri, Catherine Brezault, Marie-Anne Guillaumot, Sarra Oumrani, Romain Coriat, Ammar Oudjit, and Stanislas Chaussade

Subjects
Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Bevacizumab, Colorectal cancer, Recombinant Fusion Proteins, medicine.medical_treatment, Leucovorin, Disease, Adenocarcinoma, Neovascularization, 03 medical and health sciences, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Aflibercept, Pharmacology, Neovascularization, Pathologic, business.industry, Growth factor, Middle Aged, medicine.disease, Vascular endothelial growth factor, Receptors, Vascular Endothelial Growth Factor, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Fluorouracil, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract

Vascular endothelial growth factor inhibitors, led by bevacizumab, are considered the cornerstone of the therapy in metastatic colorectal carcinoma. We present the case of a patient with metastatic colorectal cancer who experienced rapid tumour growth with liver broad invasion after the withdrawal of an antivascular endothelial growth factor therapy, aflibercept. The rebound effect caused by the residual tumour inducing a regrowth after an initial controlled disease has already been stressed in mice and metastatic colorectal cancer patients following bevacizumab interruption. The use of liver volume evaluation was consistent with the Response Evaluation Criteria in Solid Tumours 1.1 criteria evaluation and might be a useful tool in patients with more than a half liver invasion. We describe for the first time the case of a major liver disease progression, confirmed by Response Evaluation Criteria in Solid Tumours 1.1 criteria and liver volume evaluation, after an antiangiogenic interruption in second line.

Published
2017

26. Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers

Author

Catherine Brezault, Olivier Mir, Marie Bréchon, Johann Dreanic, Marie-Anne Guillaumot, François Goldwasser, Marie Dior, Romain Coriat, and B Brieau

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Organoplatinum Compounds, Bevacizumab, medicine.medical_treatment, Angiogenesis Inhibitors, GemOx, Deoxycytidine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Progression-free survival, Aged, Pharmacology, Chemotherapy, business.industry, Middle Aged, Progression-Free Survival, Gemcitabine, Oxaliplatin, Regimen, Biliary Tract Neoplasms, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC.

Published
2017

27. Immune Checkpoint Inhibitor-Induced Colitis: Diagnosis and Management

Author

Diane Damotte, Vered Abitbol, Johann Dreanic, Stanislas Chaussade, Catherine Brezault, Marie Dior, Caroline Prieux-Klotz, B Brieau, and Romain Coriat

Subjects
Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Perforation (oil well), Colonoscopy, Inflammatory bowel disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Costimulatory and Inhibitory T-Cell Receptors, Adrenal Cortex Hormones, Neoplasms, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Colitis, medicine.diagnostic_test, biology, business.industry, Antibodies, Monoclonal, medicine.disease, Infliximab, Immune checkpoint, Diarrhea, Oncology, 030220 oncology & carcinogenesis, Immunology, biology.protein, Interdisciplinary Communication, Immunotherapy, medicine.symptom, Antibody, business, medicine.drug
Abstract

Immune checkpoint inhibitors are monoclonal antibodies indicated for an increasing number of malignant diseases. These agents can cause specific side effects, which need to be anticipated while clear patterns of management need to be established. Immune checkpoint inhibitor-mediated gastrointestinal side effects, including diarrhea and colitis, occur in up to 30% of patients. Severe colitis can lead to severe dehydration or intestinal perforation. Endoscopic lesions and histopathological features of immune checkpoint inhibitor-induced colitis are similar to an inflammatory bowel disease (IBD) flare. Patients with immune checkpoint inhibitor-induced diarrhea and colitis are treated with corticosteroids. Infliximab can be used in cases of corticosteroid failure. Rectosigmoïdoscopy or colonoscopy should be performed when severe immune checkpoint inhibitor-induced colitis is suspected, but endoscopic investigations should not delay treatment. Specific patient education as well as co-operation between oncologists and gastroenterologists is essential.

Published
2017

28. Tumeurs neuroendocrines de l’intestin grêle : actualités sur le traitement médical

Author

Catherine Brezault, Romain Coriat, Caroline Prieux-Klotz, B Brieau, Johann Dreanic, and Marie Dior

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Medicine, 030212 general & internal medicine, General Medicine, business
Abstract

Resume Contexte Les tumeurs neuro-endocrines (TNE) de l’intestin grele sont des tumeurs rares dont l’incidence est en augmentation. La chirurgie curative reste le « gold standard » de la prise en charge des TNE de l’intestin grele. Elle doit etre envisagee des que possible et cela meme a un stade metastatique. La prise en charge des TNE de l’intestin grele metastatique bien differenciee non operable a recemment evolue avec la publication d’essais demontrant le benefice des therapies ciblees et de la radiotherapie metabolique, entrainant une modification des pratiques et des recommandations francaises et internationales. Objectif L’objectif de cette revue est de presenter les donnees recentes obtenues, dont trois etudes de phases III, qui modifient la prise en charge des TNE ileales metastatiques bien differenciees et de faire l’etat des lieux sur les options therapeutiques disponibles. Sources documentaires Les sources documentaires utilisees se sont basees sur : PubMed avec recherche par mots cles (neurendocrine tumor, mid gut, treatment), recommandations de la societe europeenne des tumeurs neuro-endocrines (ENETS), essais presentes au congres de l’ESMO 2015 (European Society for Medical Oncology). Selection des etudes Nous avons exclu les etudes sur les TNE extradigestives exclusives, les TNE peu differenciees, les traitements chirurgicaux et les etudes de phase I. Resultats Dans cette revue sont abordes trois essais de phase III randomises, de grande ampleur : les etudes CLARINET, RADIANT et NETTER. Ces etudes demontrent l’efficacite respectivement des analogues de la somatostatine, des inhibiteurs de mTOR et de la radiotherapie metabolique. Conclusion Cette revue met en avant la validation par des etudes randomisees d’un inhibiteur de mTOR, l’everolimus, et de la radiotherapie metabolique dans les TNE digestives non pancreatiques metastatique non operable bien differenciee de grade G1/2 en progression sous analogues de la somatostatine.

Published
2017

29. Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment

Author

C.S. Voican, Catherine Brezault, Marion Dhooge, Stanislas Pol, Romain Coriat, Pierre Loulergue, Stanislas Chaussade, Olivier Mir, and Johann Dreanic

Subjects
Oncology, Hepatitis B virus, medicine.medical_specialty, medicine.medical_treatment, Antineoplastic Agents, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, medicine, Humans, Hepatitis, Chemotherapy, business.industry, virus diseases, Lamivudine, Imatinib, Hematology, Immunotherapy, Hepatitis B, medicine.disease, Chemotherapy regimen, digestive system diseases, Doxorubicin, 030220 oncology & carcinogenesis, Immunology, Virus Activation, 030211 gastroenterology & hepatology, Rituximab, business, medicine.drug
Abstract

Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. The risk is well documented for conventional chemotherapy agents, everolimus and imatinib. HBV screening can be recommended before systemic treatment initiation. In patients with positive HBs antigen, preemptive treatment should be given, using lamivudine. Background Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. Design We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were ‘hepatitis B reactivation’, cross-referenced with ‘chemotherapy’, then ‘hepatitis B’ cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. Results From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. Conclusion Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.

Published
2016

30. Gastric Carcinoma at the Era of Targeted Therapies

Author

Elena Sion, Marion Dhooge, Stanislas Chaussade, Catherine Brezault, Romain Coriat, and Johann Dreanic

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Esophageal Neoplasms, Receptor, ErbB-2, medicine.drug_class, medicine.medical_treatment, Clinical Biochemistry, Antineoplastic Agents, Gastric carcinoma, Pharmacology, Antibodies, Monoclonal, Humanized, Monoclonal antibody, Ramucirumab, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Trastuzumab, Internal medicine, Drug Discovery, Humans, Medicine, Molecular Targeted Therapy, Clinical Trials as Topic, Chemotherapy, biology, business.industry, Antibodies, Monoclonal, Cancer, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Monoclonal, biology.protein, Molecular Medicine, Antibody, business, medicine.drug
Abstract

Gastric and gastro-esophageal cancers (GC/GEJ) appear as the second cancer-related death worldwide. Diagnosis is made at an advanced stage offering a curative attempt in less than 50% of cases. Despite the improvements of the systemic cytotoxic chemotherapy regimens, the prognosis of patients with metastatic GC/GEJ cancer remains poor. Recent insights in biochemical pathways have permitted to identify potential targets. The extracellular domain of HER2 receptors is implicated in cells' proliferation and in the anti-apoptotic process occurring in GC/GEJ cancers. Trastuzumab, a monoclonal antibody targeting HER2, in addition to chemotherapy permitted to obtain more than one year of survival in HER2-positive advanced GC/GEJ cancers. Recently, ramucirumab, a humanized monoclonal antibody targeting VEGFR-2 receptor demonstrated its efficacy as a second line treatment for patients with advanced GC/GEJ cancer. These encouraging results have justified evaluating targeted therapies in GC/GEJ cancers. In this review, we summarize targeted therapies that might present clinical efficacy in the treatment of advanced GC/GEJ cancers.

Published
2016

31. Endoscopic ultrasound efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study

Author

Jean-Marc Gornet, Catherine Brezault, Arnaud Pasquer, Ammar Oudjit, Pascal Artru, Alexandre Rouquette, Nelson Lourenco, Thomas Walter, Stephanie Morgant, and Romain Coriat

Subjects
Endoscopic ultrasound, medicine.medical_specialty, Linitis plastica, medicine.medical_treatment, 030501 epidemiology, Lesion, 03 medical and health sciences, 0302 clinical medicine, medicine, Lymph node, medicine.diagnostic_test, business.industry, Case-control study, Cancer, General Medicine, medicine.disease, digestive system diseases, Peritoneal carcinomatosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Original Article, Gastrectomy, Radiology, medicine.symptom, 0305 other medical science, business
Abstract

BACKGROUND: Endoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to “classical” GC. METHODS: A retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC. RESULTS: Forty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis. CONCLUSIONS: This study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to “classical” GC paving for a broader use of EUS in preoperative settings.

Published
2021

32. Computed tomography scan efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study

Author

Thomas Walter, Stephanie Morgant, Arnaud Pasquer, Catherine Brezault, Romain Coriat, Nelson Lourenco, Jean-Marc Gornet, Alexandre Rouquette, Gérard Lledo, Ammar Oudjit, and Pascal Artru

Subjects
CT scan, medicine.medical_specialty, Linitis plastica, Computed tomography, PTNM stage, Lesion, 03 medical and health sciences, Gastric adenocarcinoma, 0302 clinical medicine, medicine, Lymph node, Original Research, linitis, medicine.diagnostic_test, business.industry, computed tomography, medicine.disease, Peritoneal carcinomatosis, Histological lesion, medicine.anatomical_structure, Oncology, Cancer Management and Research, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Radiology, gastric adenocarcinoma, medicine.symptom, business
Abstract

Stéphanie Morgant,1 Pascal Artru,2 Ammar Oudjit,3 Nelson Lourenco,4 Arnaud Pasquer,5 Thomas Walter,6 Jean-Marc Gornet,4 Alexandre Rouquette,7 Gérard Lledo,2 Catherine Brezault,1 Romain Coriat1 1Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France; 2Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France; 3Radiology Unit, Cochin Teaching Hospital, Paris, France; 4Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France; 5Digestive Surgery Unit, Edouard Herriot Teaching Hospital, Lyon, France; 6Oncology Unit, Edouard Herriot Teaching Hospital, Lyon, France; 7Pathology Department, Cochin Teaching Hospital, Paris, France Background: Computed tomography (CT) scan is a key imaging technique in the staging of gastric adenocarcinoma and therapeutic management of patients. The aim of this study was to evaluate the performance of CT scan in the staging of parietal and metastatic invasion in gastric linitis plastica group. Methods: A retrospective multicentric French study was conducted from January 2006 to December 2015 on patients with no metastatic gastric linitis plastica and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed. Results: Fifty patients were included in the linitis plastica group and 100 in the control group. Patients from the linitis group were significantly different from those from the control group with a lower age at diagnosis, a more advanced histological lesion, a more frequent ­undiagnosed peritoneal carcinomatosis, and a higher risk of R1 resection. Sensitivity and specificity of CT scan for the diagnosis of lymph node involvement were 44% and 75%, respectively, in the linitis plastica group and 55% and 60%, respectively, in the control group. The sensitivity and specificity of CT scan for the T3–T4 parietal invasion were 26% and 100%, respectively, in the linitis group and 40% and 72%, respectively, in the control group. Conclusion: CT scan has an equal sensitivity and specificity for the evaluation of lymph node and parietal involvement in gastric adenocarcinoma, including linitis plastica. CT scan remains the cornerstone of preoperative evaluation in gastric adenocarcinoma, including linitis plastica. However, CT presents a lack of sensitivity to diagnose low-volume peritoneal carcinomatosis. Keywords: computed tomography, CT scan, linitis, gastric adenocarcinoma

Published
2018

33. [Therapeutic advances in the management of biliary tract carcinoma]

Author

Sophie-Clémentine, Ribiere, Chloé, Léandri, Marie-Anne, Guillaumot, Catherine, Brezault, and Romain, Coriat

Subjects
Cholangiocarcinoma, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, France, Medical Oncology, Combined Modality Therapy, Deoxycytidine, Gemcitabine, Capecitabine
Abstract

Cancers of the bile ducts or cholangiocarcinomas are a rare entity whose incidence is increasing in France. Surgical resection of cholangiocarcinoma remains the only curative therapy. Adjuvant therapy with capecitabine at a fixed dose of 1250mg/m

Published
2018

34. Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis

Author

Tessa Tabouret, Olivier Mir, Marion Dhooge, Stanislas Chaussade, Catherine Brezault, Johann Dreanic, Thomas Gregory, and Romain Coriat

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Side effect, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Ischemia, Angiogenesis Inhibitors, Adenocarcinoma, Gastroenterology, Femoral head, Internal medicine, medicine, Humans, Pharmacology (medical), Neoplasm Metastasis, Aged, Retrospective Studies, Pharmacology, Chemotherapy, business.industry, Osteonecrosis, Retrospective cohort study, medicine.disease, Surgery, medicine.anatomical_structure, Oncology, Female, Colorectal Neoplasms, business, medicine.drug
Abstract

Purpose Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a musculo-skeletal disease secondary to cellular death of bone component mainly induced by corticosteroids, alcohol use, or connective tissue disorders. Methods The medical records of patients with metastatic colorectal carcinoma receiving Bevacizumab between January 2006 and November 2013 were retrospectively reviewed and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility were examined by orthopaedist and evaluated by imaging. Results We report on osteonecrosis of humeral and femoral head in patient with metastatic colon adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment (>6 months), lack of other factors predisposing to osteonecrosis. These observations, according to literature, suggests that long exposure to anti VEGF-A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either on the femoral head or the humeral head with an incidence of 4 out of 1000 patients. Conclusions With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms.

Published
2015

35. Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib

Author

Romain Coriat, Olivier Bouché, Frédérick Moryoussef, Catherine Brezault, Christine Hoeffel, Julien Volet, Coralie Barbe, and Marion Dhooge

Subjects
medicine.medical_specialty, GiST, business.industry, medicine.medical_treatment, Imatinib, medicine.disease, Gastroenterology, Targeted therapy, Surgery, Lumbar, hemic and lymphatic diseases, Physiology (medical), Sarcopenia, Internal medicine, Toxicity, medicine, Orthopedics and Sports Medicine, In patient, Stromal tumor, business, neoplasms, medicine.drug
Abstract

Background Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia. Methods Thirty-one patients with advanced (n = 16) or high-risk resected (n = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration. Results Twelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre-treatment sarcopenia was not associated with grades 3–4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p

Published
2015

36. Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients

Author

Catherine Brezault, Olivier Mir, Johann Dreanic, Romain Coriat, Stanislas Chaussade, Maximilien Barret, and Marion Dhooge

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, Cetuximab, Bevacizumab, Performance status, business.industry, Colorectal cancer, medicine.medical_treatment, medicine.disease, Targeted therapy, Surgery, Clinical trial, Interquartile range, Physiology (medical), Internal medicine, medicine, Orthopedics and Sports Medicine, business, medicine.drug
Abstract

Background In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular-targeted agents. Methods From January 2007 to February 2012, patients with metastatic colorectal cancer and poor predictive survival score (mGPS = 2), treated with 5-fluorouracil-based chemotherapy in addition to an anti-epidermal growth factor receptor (EGFR) or anti-vascular epidermal growth factor (VEGF) therapy, were included to assess the interest of targeted therapy within mGPS = 2' patients. Results A total of 27 mGPS = 2' patients were included and received a 5-fluorouracil-based systemic chemotherapy in addition to an anti-EGFR treatment (cetuximab; n = 18) or an anti-VEGF treatment (bevacizumab; n = 9). Median follow-up was 12.1 months (interquartile range 4.9–22). Patients were Eastern Cooperative Oncology Group (ECOG) Performance Status 1, 2, and 3 in 66% (n = 18), 26% (n = 7), and 8% (n = 2), respectively. Comparing anti-EGFR and anti-VEGF groups, median progression-free survival was 3.9 and 15.4 months, respectively, and was significantly different (P = 0.046). Conversely, the median overall survival was not significantly different between the two groups (P = 0.15). Conclusion Our study confirmed the poor survival of patients with mGPS = 2 despite the use of targeted therapy and identified the superiority of an anti-VEGF treatment in progression-free survival, without a significant benefit in the overall survival compared with the anti-EGFR therapy. Our results deserved confirmation by a prospective clinical trial.

Published
2015

37. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset

Author

Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Alois Lang, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Jean-Luc Van Laethem, Eric Van Cutsem, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Hassan RezaieKalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Marc Ychou, Ayman Zawadi, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Eveline Boucher, Julien Taieb, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara MatysiakBudnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Gunnar Folprecht, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans GuenterDerigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Roberto Labianca, Giuseppe Colucci, Dino Amadori, Enrico Mini, Alfredo Falcone, Corrado Boni, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Domenico Cristi Corsi, Stefania Salvagni, Silvana Chiara, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Josep Tabernero, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel ValladaresAyerbes, Jaime FeliuBatlle, Silvia Gil, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis CireraNogueras, BernadoQueralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos PijaumePericay, Manuel ConstenlaFigueiras, InmaculadaGuasch Jordan, Maria Jose GomeReina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio MarcuelloGaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica GuillotMorales, Marta LlanosMuñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel HernandezBusquier, Teresa Checa Ruiz, Adelaida LacastaMuñoa, MiquelNogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio GalanBrotons, Santiago AlbiolRodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita CentellesRuiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, and Leslie Samuel

Subjects
Oncology, Hematology
Published
2015

38. Hereditary Non-polyposis Colorectal Cancer: Prevention and Therapeutic Options

Author

Marion Dhooge, Johann Dreanic, S. Grandjouan, Catherine Brezault, Stanislas Chaussade, and Romain Coriat

Subjects
Oncology, medicine.medical_specialty, Aspirin, Hepatology, business.industry, Colorectal cancer, Genetic counseling, Gastroenterology, Microsatellite instability, medicine.disease, Prophylactic Surgery, digestive system diseases, Lynch syndrome, Colorectal surgery, Chromoendoscopy, Internal medicine, Medicine, business, medicine.drug
Abstract

Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common hereditary colorectal cancer (CRC) syndrome. The first and foremost preventive measure is to identify patients with LS among CRC patients. This requires the screening of colorectal cancer through polymerase chain reaction-based microsatellite instability (MSI) testing or immunohistochemistry to look for a loss of expression of one of the mismatch repair (MMR) proteins and the referral of selected patients to genetic counseling. In LS patients, annual or biannual complete colonoscopy with chromoendoscopy is the only validated way to significantly reduce mortality related to CRC with the greatest quality-adjusted life expectancy benefit compared with prophylactic surgery. In the case of diagnosis of colonic cancer, a subtotal colectomy with an ileo-rectal anastomosis is recommended, in order to decrease the risk of metachronous CRC. However, segmental surgery can be discussed on an individual basis. Chemoprevention with aspirin seems to be efficient in decreasing colorectal cancer risk in LS, but the minimum effective dose and potential adverse events associated with long-term use are not yet known. The option of taking low-dose aspirin might be discussed with mutated gene carriers regarding the benefit and risks of the treatment.

Published
2015

39. The predictive and prognostic value of the Glasgow Prognostic Score in metastatic colorectal carcinoma patients receiving bevacizumab

Author

François Goldwasser, Stanislas Chaussade, Marion Dhooge, Catherine Brezault, Johann Dreanic, Olivier Mir, Marianne Maillet, and Romain Coriat

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Bevacizumab, Colorectal cancer, medicine.drug_class, Irinotecan, Monoclonal antibody, Prognostic score, Epidermal growth factor, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Neoplasm Metastasis, Cytotoxic Therapy, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, business.industry, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Camptothecin, Female, Fluorouracil, Colorectal Neoplasms, business, Value (mathematics), medicine.drug
Abstract

The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC) patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal antibody to vascular epidermal growth factor, improves the overall survival in mCRC. The aim of the present study was to assess the prognostic value of GPS in mCRC patients receiving antivascular epidermal growth factor therapy. From August 2005 to August 2012, consecutive patients with mCRC who received chemotherapy plus bevacizumab were eligible for the present analysis. The clinical stage, C-reactive protein, albumin and the Eastern Cooperative Oncology Group performance status were recorded at the time of initiation of bevacizumab. Patients received 5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the digestive oncology multidisciplinary staff proposal and in line with the French recommendations for the treatment of mCRC. Eighty patients were eligible (colon n = 59, rectum n = 21), with a median follow-up of 14 months (range 1-58 months). Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n = 41, 51%) or irinotecan (n = 27, 34%). At baseline, 56, 31 and 13% of patients had a GPS of 0 (n = 45), 1 (n = 25) and 2 (n = 10), respectively. The median progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P = 0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months, respectively (P = 0.004). Our study confirmed the prognostic value of GPS in mCRC patients receiving chemotherapy plus bevacizumab. Given the poor survival observed in patients with an GPS of 2, studies dedicated to these patients could identify optimal treatment modalities.

Published
2014

40. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author

Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, 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 ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), 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 ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), 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 ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], 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 Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), 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), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), 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), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), 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), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, 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)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.

Published
2017

41. Adénocarcinome gastrique à cellules indépendantes : une entité à part

Author

Marion Dhooge, Romain Coriat, Tessa Tabouret, Catherine Brezault, Frédéric Beuvon, Stanislas Chaussade, and Alexandre Rouquette

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Gastric bypass, Medicine, General Medicine, business, Neoadjuvant therapy
Abstract

Points essentiels L’adenocarcinome gastrique a cellules independantes (ADCI) est une entite de cancer gastrique particuliere. Son incidence est en augmentation. La place de l’anatomopathologiste est centrale dans l’identification de ces lesions. L’histologie correspond a un adenocarcinome avec une composante de cellules independantes majoritaire (> 50 %). L’ADCI a le meme pronostic que l’adenocarcinome gastrique mais apparait plus agressif. Les cellules independantes ont une moindre sensibilite a la chimiotherapie. Cette mise au point a pour objectif de discuter des particularites histologiques, pronostiques et therapeutiques de ce cancer.

Published
2014

42. Self-expandable metal stent through the tumor to treat an intestinal obstruction due to pancreatic squamous cell carcinoma

Author

Frédéric Prat, Heithem Soliman, Catherine Brezault, Johann Dreanic, and Romain Coriat

Subjects
medicine.medical_specialty, business.industry, Self expandable, medicine.medical_treatment, Pancreatic squamous cell carcinoma, Gastroenterology, MEDLINE, Stent, 03 medical and health sciences, 0302 clinical medicine, Text mining, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, Video Case Report, business
Published
2017

43. Tumeurs neuroendocrines pancréatiques bien différenciées : l’apport des thérapies ciblées

Author

Géraldine Perkins, Thibaut Vaysse, Romain Coriat, Stanislas Chaussade, Catherine Brezault, and Marion Dhooge

Subjects
Oncology, Pathology, medicine.medical_specialty, business.industry, Incidence (epidemiology), General Medicine, Disease, medicine.disease, Internal medicine, medicine, Adenocarcinoma, Stage (cooking), Who classification, business
Abstract

The neuroendocrine pancreatic tumors are rare tumors, but their incidence is constantly rising. Even if the management of these tumors has to be surgical as soon as possible, the disease is most often metastatic at the stage of the diagnostic. The prognostic and the therapeutic options differ from pancreatic adenocarcinoma. Available treatments have evolved over the last years with recent publications of studies that bring to light the benefits of targeted therapies in this pathology. This has resulted in modifications of both practices and either French and international guidelines. Therefore, we focus on the management of the grade 1 and grade 2 well-differentiated neuroendocrine pancreatic tumors as classified in new WHO classification of neuroendocrine neoplasms published in 2010.

Published
2013

44. [Mid gut neuroendocrine tumors: News on medical treatment]

Author

Marie, Dior, Johann, Dreanic, Caroline, Prieux-Klotz, Bertrand, Brieau, Catherine, Brezault, and Romain, Coriat

Subjects
Ileal Neoplasms, Neuroendocrine Tumors, Therapies, Investigational, Antineoplastic Combined Chemotherapy Protocols, Intestinal Neoplasms, Intestine, Small, Humans, Chemoradiotherapy, Molecular Targeted Therapy, Combined Modality Therapy
Abstract

Mid gut neuroendocrine tumors (NET) are rare tumors whose incidence is increasing. Curative surgery remains the gold standard for the treatment of NETs of the small intestine. Surgery should be considered as soon as possible even if a metastatic stage is diagnosed. The management of unresectable well-differentiated metastatic NETs of the small intestine recently changed with the publication of trials demonstrating the benefit of targeted therapies and metabolic radiotherapy, leading to a change of practices and update of French and international recommendations.The objective of this review is to present the recent data consisting of three phase III studies, which modify the management of well-differentiated metastatic midgut NETs and make an inventory of the available treatment options.The documentary sources used were gathered through the PubMed website using keyword searching (neurendocrine tumor, mid gut, treatment). We also referred to recommendations of the European Society of neuroendocrine tumors (ENETS) trials presented at ESMO Congress 2015 (European Society for Medical Oncology).We excluded studies of exclusive extra-digestive NETs, poorly differentiated NETs, surgical treatments and phase I studies.We discussed three randomized phase III trials: CLARINET, RADIANT and NETTER studies. These studies demonstrated the efficacy of respectively somatostatin analogues, mTOR inhibitors and metabolic radiotherapy.This review highlights the validation by randomized studies of an mTOR inhibitor and metabolic radiotherapy in metastatic non-pancreatic digestive NETs unresectable well-differentiated grade of G1/2 in progression under somatostatin analogues.

Published
2016

45. Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2

Author

Géraldine Perkins, Pascaline Boudou-Rouquette, Stanislas Chaussade, François Goldwasser, Jean-Philippe Durand, Olivier Mir, Romain Coriat, Marion Dhooge, Catherine Brezault, and Stanislas Ropert

Subjects
Adult, Male, Oncology, Sarcopenia, Cancer Research, medicine.medical_specialty, Palliative care, Drug-Related Side Effects and Adverse Reactions, Organoplatinum Compounds, Cholangitis, Antineoplastic Agents, Deoxycytidine, Severity of Illness Index, Gastroenterology, Disease-Free Survival, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Severity of illness, medicine, Carcinoma, Humans, Pharmacology (medical), Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Performance status, business.industry, Palliative Care, Peripheral Nervous System Diseases, Middle Aged, medicine.disease, Thrombocytopenia, Gemcitabine, Confidence interval, Oxaliplatin, Biliary Tract Neoplasms, Treatment Outcome, Female, business, medicine.drug
Abstract

The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

Published
2012

46. Existe-t-il une alternative à la chimiothérapie adjuvante par FOLFOX dans les cancers coliques de stade III ?

Author

Anouk Esch, Romain Coriat, Géraldine Perkins, Stanislas Chaussade, and Catherine Brezault

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, business.industry, Colorectal cancer, medicine.medical_treatment, Perforation (oil well), Cancer, General Medicine, medicine.disease, digestive system diseases, Regimen, FOLFOX, Internal medicine, medicine, Stage (cooking), business, Mass screening, medicine.drug
Abstract

Being the second cancer for men and the third cancer for women in France, colorectal cancer represents a serious public health issue. Its incidence has increased these last years and despite new therapeutics being developed, it still has a bad prognostic. Thanks in part to Hemoccult national mass screening program, its diagnosis is made possible at an earlier stage, which makes a surgical curative resection and the carrying out of adjuvant chemotherapy possible. For stage III colic cancer that has been surgically removed, adjuvant chemotherapy by FOLFOX 4 has to be offered. Nevertheless, because of its toxicities, the patient's high age, important comorbidities or post-surgical complications, this chemotherapy occasionally cannot be done. What are the colorectal cancer prognostic factors which would guide the chemotherapy? TNM classification, number of examined lymph nodes, MSI status, and presence or not of a perforation or a perinervous, lymphatic or venous invasion is recognized prognostic factors. Also, what are the alternatives of FOLFOX 4 regimen as colorectal cancer adjuvant treatment?

Published
2012

47. Resection of Late Pulmonary Metastases from Pancreatic Adenocarcinoma: Is Surgery an Option?

Author

Maximilien Barret, Johann Dreanic, Alexandre Rouquette, B Brieau, Romain Coriat, Jean-François Regnard, and Catherine Brezault

Subjects
Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Adenocarcinoma, Resection, Recurrence, Pancreatic cancer, medicine, Carcinoma, Humans, Neoplasm Metastasis, Survival rate, Aged, Pancreas adenocarcinoma, Chemotherapy, Lung, business.industry, General Medicine, medicine.disease, Surgery, Pancreatic Neoplasms, Survival Rate, medicine.anatomical_structure, Oncology, business
Abstract

Patients with recurrences from pancreas adenocarcinoma have a poor survival rate despite new chemotherapy treatment options. Recurrences are mainly hepatic metastases or peritoneal dissemination and surgical treatment is not recommended. Late and single metachronous pulmonary recurrences are uncommon and may mimic primary lung carcinoma. We report two patients with late and unique pulmonary metastasis from pancreatic cancer. These two patients underwent surgical resection; three and five years later, they did not experience recurrences. Cases called for a surgical approach in late and unique pulmonary metastases from pancreatic cancer, and paved the way for a prolonged chemotherapy free period.

Published
2015

48. Incidence et physiopathologie de l’endobrachyœsophage

Author

Géraldine Perkins, Romain Coriat, and Catherine Brezault

Subjects
medicine.medical_specialty, education.field_of_study, Pathology, business.industry, Esophageal disease, Population, Reflux, Cancer, General Medicine, medicine.disease, Gastroenterology, digestive system diseases, medicine.anatomical_structure, Dysplasia, Internal medicine, Barrett's esophagus, Medicine, Adenocarcinoma, Esophagus, business, education
Abstract

Key points Barrett's esophagus is a well-known precursor of esophageal adenocarcinoma. Monitoring patients with Barrett's esophagus is recommended for detecting high-grade dysplasia or cancer. Gastroesophageal reflux disease affects approximately 20% of the population in developed countries. About 10–15% of patients with gastroesophageal reflux disease develop Barrett's esophagus, which can progress to adenocarcinoma. The esophagus is normally lined by squamous mucosa. Therefore, it is clear that for an adenocarcinoma, there is a prior sequence of events that lead to normal squamous mucosa transformation.

Published
2011

49. Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Author

Benoit Terris, Laura Rubbia-Brandt, Gilles Mentha, Sébastien Tauzin, Céline Delucinge-Vivier, Bertrand Dousset, Patrick Descombes, Catherine Brezault, and Pietro Majno

Subjects
Cancer Research, MMP2, Organoplatinum Compounds, Vascular Endothelial Growth Factor C/genetics/metabolism, Vascular Endothelial Growth Factor C, Hepatic Veno-Occlusive Disease, Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism, ddc:616.07, Biology, Bioinformatics, Chemokine CCL20/genetics/metabolism, Gene expression, Cluster Analysis, Humans, Interleukin 6, Liver/metabolism/pathology, Chemokine CCL20, ddc:617, Reverse Transcriptase Polymerase Chain Reaction, Microarray analysis techniques, Gene Expression Profiling, Hepatic Veno-Occlusive Disease/chemically induced/genetics, Hypoxia-Inducible Factor 1, alpha Subunit, Microarray Analysis, Immunohistochemistry, Hepatic stellate cell activation, Oxaliplatin, Gene expression profiling, HIF1A, Liver, Oncology, biology.protein, Signal Transduction/genetics, DNA microarray, Signal Transduction
Abstract

Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS. Mol Cancer Ther; 10(4); 687–96. ©2011 AACR.

Published
2011

50. Application of ANAES guidelines for colonoscopy in France: A practical survey

Author

Frédéric Prat, S. Grandjouan, Sarah Leblanc, Marianne Gaudric, R Coriat, Catherine Brezault, U. Chaput, J. Huppertz, and Stanislas Chaussade

Subjects
Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Quality Assurance, Health Care, Screening test, Colorectal cancer, Colonoscopy, Endoscopic mucosal resection, Gastroenterology, Accreditation, Continuing medical education, Surveys and Questionnaires, Internal medicine, Health care, Humans, Medicine, Societies, Medical, medicine.diagnostic_test, business.industry, General surgery, General Medicine, Guideline, medicine.disease, Health Surveys, Colon cancer screening, Practice Guidelines as Topic, France, Guideline Adherence, Colorectal Neoplasms, business
Abstract

In 2004, the French health authorities published guidelines on the indications for colonoscopy. However, no study has evaluated the awareness of healthcare practitioners of these guidelines. The aim of this study was to determine the level of awareness of the ANAES guidelines among French gastroenterologists.A questionnaire comprising 20 multiple choice questions (MCQ) was presented to a group of 79 gastroenterologists between February and June in 2008. The questions covered screening tests for colon cancer (one question), endoscopic mucosal resection (two questions) and the ANAES guidelines (17 questions). According to the number of colonoscopies performed per year (less than 100, 100-500, more than 500), the answers to these questions were analyzed separately.Among the practitioners carrying out less than 100, 100-500 and more than 500 colonoscopies per year, the guidelines for colon cancer screening were known by 33, 50 and 56%, respectively, the quality criteria for endoscopic mucosal resection by 0, 0 and 3.7%, respectively, and the ANAES guideline indications for colonoscopy by 34.3, 51.2 and 48.9%, respectively (P0.001). The ANAES guidelines were significantly better known by practitioners who were performing more than 100 colonoscopies per year, while the indications for control colonoscopy were less often correctly anticipated. No differences were found concerning postponed indications.The ANAES guidelines consists of the following elements: (1) awareness of the ANAES guidelines is poor, with control colonoscopy being correctly anticipated in just over a third of the gastroenterologists; (2) performing more than 100 colonoscopies per year improves knowledge of the ANAES guidelines; and (3) the ANAES guidelines need to be simplified and should be covered by continuing medical education.

Published
2010

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