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1. A real-world analysis on the efficacy and tolerability of liposomal irinotecan plus 5-fluorouracil and folinic acid in metastatic pancreatic ductal adenocarcinoma in Belgium

Author

Lise Verbruggen, Lisa Verheggen, Greetje Vanhoutte, Catherine Loly, Willem Lybaert, Ivan Borbath, Philippe Vergauwe, Koen Hendrickx, Celine Debeuckelaere, Amy de Haar-Holleman, Jean-Luc Van Laethem, and Marc Peeters

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

Background: Currently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients. Objectives: To provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk–benefit ratio of the intervention. Methods: Medical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan–Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively. Results: A total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/m² (range 49.24 mg/m²) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6–8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as later-line treatment was, respectively, 6.8 months (95% CI: 5.9–7.0 months) and 5.6 months (95% CI: 4.2– no upper limit ). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4–4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8–4.8 months) while this was 2.4 months (95% CI: 1.9–9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4. Conclusion: Nal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC. Trial details: Retrospective study on the efficacy and tolerability of liposomal irinotecan (NALIRI); ClinicalTrials.gov Identifier: NCT0509506 ( https://clinicaltrials.gov/ct2/show/NCT05095064?term=naliri&draw=2&rank=2 ).

Published
2023
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2. Fortnightly or fractionated weekly docetaxel–cisplatin–5‐FU as first‐line treatment in advanced gastric and gastroesophageal junction adenocarcinoma: The randomized phase II DoGE study

Author

Amélie Deleporte, Marc Van den Eynde, Frédéric Forget, Stéphane Holbrechts, Thierry Delaunoit, Ghislain Houbiers, Hassan R. Kalantari, Stéphanie Laurent, Erik Vanderstraeten, Marc De Man, Philippe Vergauwe, Marylene Clausse, Jacques Van Der Auwera, Lionel D’Hondt, Pascal Pierre, Bjorn Ghillemijn, Angelique Covas, Marianne Paesmans, Lieveke Ameye, Ahmad Awada, Francesco Sclafani, and Alain Hendlisz

Subjects
5‐FU, cisplatin, docetaxel, fortnightly, gastric cancer, gastroesophageal cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background While docetaxel/cisplatin/5‐fluorouracil (DCF) outperforms CF in first‐line gastric adenocarcinoma, toxicity remains an issue. Methods This multicenter phase II trial randomized chemonaïve metastatic gastric adenocarcinoma patients to fractionated weekly DCF (D 40 mg/m2, C 35 mg/m², F 1800 mg/m² over 24 h, on days 1 and 8 every 3 weeks, arm (1) or fortnightly DCF (D 50 mg/m2, C 50 mg/m², F 2000 mg/m² over 48 h every 2 weeks, arm (2). Prophylactic granulocyte colony‐stimulating factor (G‐CSF) was not allowed. The primary endpoint was the rate of febrile neutropenia within the first six treatment weeks (early FN). Results A total of 106 eligible patients were recruited. The early and overall FN rates were 9.5% and 17% in arm 1, respectively, and 5.9% and 8% in arm 2, respectively. Grade ≥3 toxicities occurred in 81% of patients in arm 1 and 90% of patients in arm 2, the most common being neutropenia (33% vs. 61%), fatigue (27% vs. 25%), vomiting (21% vs. 12%), anorexia (19% vs. 18%), and diarrhea (17% vs. 10%). Median progression‐free survival and overall survival were 5.1 (95% CI, 3.2–6.5) and 8.2 months (95% CI, 6.0–14.5), respectively, in arm 1 and 5.2 (95% CI, 3.0–6.9) and 11.9 months (95% CI, 7.4–15.9), respectively, in arm 2. Conclusions Fractionated weekly and fortnightly DCF regimens are associated with a low risk of early FN, and a better hematological toxicity profile as compared to historical DCF without compromising efficacy. Both regimens offer greater convenience removing the need for systematic use of prophylactic G‐CSF.

Published
2021
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3. Acupuncture as a Complementary Therapy for Cancer Care: Acceptability and Preferences of Patients and Informal Caregivers

Author

Laura Tack, Tessa Lefebvre, Virginie Blieck, Lieselot Cool, Hans Pottel, Koen Van Eygen, Sofie Derijcke, Philippe Vergauwe, Patricia Schofield, Rebecca Chandler, Pauline Lane, Tom Boterberg, and Philip R. Debruyne

Subjects
acupuncture, cancer, informal caregiver, complementary therapy, cancerrelated side effect, Other systems of medicine, RZ201-999
Abstract

Background : Acupuncture can effectively manage cancer-related side effects, for both patients undergoing treatment and for cancer survivors. It may also be effective in managing physiological and psychological symptoms common among informal caregivers of cancer patients. Objectives: The aim of this survey was to explore the acceptability and preferences of cancer patients, cancer survivors, and their informal caregivers in relation to acupuncture. Methods : The survey was conducted from 20th November to 27th November 2018. The questionnaire was developed to explore acceptability and preferences, including motivation, symptoms to be addressed, and practical issues (location, cost, etc.), in relation to acupuncture. Results : The survey response rate was 94.5% in cancer patients and cancer survivors and 100% in caregivers. Acceptability of acupuncture was 34.5% (n = 40/116) and 48.0% (n = 26/54) in cancer patients and caregivers, respectively. About 52.5% (n = 21/40) of patients preferred to undergo acupuncture at the day center clinic, whereas caregivers had no specific preference. Patients and cancer survivors would use acupuncture for symptoms of fatigue (60%), listlessness (57.5%), and pain (47.5%). Informal caregivers expressed an interest in using acupuncture for their pain, stress, and sleeping difficulties 48.0% (n = 26/54). Conclusion : Cancer patients, cancer survivors, and informal caregivers would accept acupuncture as a complementary therapy. This openness and preference to acupuncture provide the foundations for this complementary therapy to be incorporated into holistic and supportive cancer care, both for patients and those supporting them.

Published
2021
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4. CTCs as a prognostic and predictive biomarker for stage II/III Colon Cancer: a companion study to the PePiTA trial

Author

Françoise Rothé, Marion Maetens, Ghizlane Rouas, Marianne Paesmans, Marc Van den Eynde, Jean-Luc Van Laethem, Philippe Vergauwe, Guido Deboever, Yacine Bareche, Caroline Vandeputte, Michail Ignatiadis, and Alain Hendlisz

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

Abstract Background Adjuvant therapy improves the prognosis of stage II & III colon cancer patients. Unfortunately, most patients do not benefit from this treatment. PePITA (NCT00994864) is a prospective, multicenter, non-randomized study whose primary objective is to predict the outcome of adjuvant therapy in colon cancer. Methods The primary objective was to determine the prognostic and predictive value of circulating tumor cell (CTC) detection before therapy and after one course of preoperative FOLFOX. Results Out of the 58 first patients accrued in PePiTA trial, 36 patients participated in the CTC companion study, of whom 32 had at least one evaluable sample. Only 5 patients (14, 95% CI = 5–30%) had ≥1 CTC/22.5 ml blood in at least one of the two timepoints with 2 patients having ≥1 CTC/22.5 ml at baseline (6, 95% CI: 1–19%). The detection rate of patients with CTCs at baseline being lower than expected, the inclusion of patients in the PePiTA CTC substudy was stopped. The limited sample size did not allow us to investigate the prognostic and predictive value of CTCs in locally advanced colon cancer. Conclusions Our data illustrate the need for further standardized studies in order to find the most reliable prognostic/predictive biomarker in early-stage colon cancer. Trial registration This trial was prospectively registered at Jules Bordet institute (NCT00994864) on the October 14, 2009.

Published
2019
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5. A double‐blind randomized, multicenter, placebo‐controlled study of itopride in functional dyspepsia postprandial distress syndrome

Author

Florencia Carbone, Alain Vandenberghe, Lieselot Holvoet, Hubert Piessevaux, Joris Arts, Philippe Caenepeel, Dirk Staessen, Philippe Vergauwe, Philippe Maldague, Thierry De Ronde, Fabien Wuestenberghs, Vincent Lamy, Veronique Lefebvre, Pascale Latour, Tim Vanuytsel, Michael Jones, and Jan Tack

Subjects
Male, Endocrine and Autonomic Systems, Physiology, Benzamides, Benzyl Compounds, Stomach Diseases, Gastroenterology, Humans, Female, Dyspepsia, Postprandial Period, Abdominal Pain
Abstract

Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient-reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome).Patients with PDS, with or without non-predominant EPS symptoms, were enrolled in an 8-week double-blind placebo-controlled multi-center trial with itopride (100 mg t.i.d.). Patients completed LPDS diaries and questionnaires to assess treatment response. Mann-Whitney test and mixed models were used.One hundred patients (79% females, 39.1 ± 1.5 yo) were included. No significant difference was observed between treatment arms (p = 0.6). Compared to baseline, itopride treatment significantly improved the LPDS score (p = 0.001) and all individual symptoms (p 0.0001). In the placebo arm, this was only the case for belching and epigastric pain (p 0.05). In an exploratory analysis, outcomes in "pure" PDS (n = 45) and overlapping PDS/EPS (n = 55) patients were assessed and showed that the latter subgroup has the largest benefit with itopride compared to placebo (p = 0.03).Using the LPDS score in a pilot controlled trial in FD, itopride shows no therapeutic benefit over placebo after 8 weeks of treatment. In an exploratory post hoc analysis, itopride but not placebo was associated with improvement of symptoms compared to baseline, and this was most prominent in patients with overlapping PDS/EPS. The efficacy of itopride in this subgroup needs to be evaluated in a large study using the same outcome measure. (clinialtrials.org ref.: NCT04647955).

Published
2022
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6. Developing and evaluating a participatory arts programme for cancer patients and their caregivers

Author

Tessa Lefebvre, Philippe Vergauwe, Pauline Lane, Lieselot Cool, Karin Stellamans, Koen Van Eygen, Sofie Derijcke, Hilde Vanneste, Marlies Meersman, Rebecca Chandler, Tom Boterberg, Jos De Backer, Laura Tack, and Philip R. Debruyne

Subjects
medicine.medical_specialty, IMPACT, macromolecular substances, The arts, FATIGUE, 03 medical and health sciences, 0302 clinical medicine, DISTRESS, Neoplasms, Surveys and Questionnaires, medicine, Medicine and Health Sciences, Humans, cancer, 030212 general & internal medicine, caregiver, business.industry, satisfaction, Physical health, Cancer, Citizen journalism, General Medicine, medicine.disease, Distress, Caregivers, 030220 oncology & carcinogenesis, Family medicine, Participatory arts programme, patient, business
Abstract

Objectives Cancer patients, survivors and caregivers often encounter severe distress, having significant consequences to wellbeing, functionality and physical health. This study developed and evaluated a participatory arts programme to determine if such could help to improve the wellbeing of cancer patients and their caregivers. Methods To inform the development of a participatory arts programme, cancer patients and their caregivers at an Organisation of European Cancer Institute (OECI)-designated cancer centre were asked which activities they would wish to engage in (anonymous survey one). A programme was then developed and trialled for 1 year. Following participation, we explored the satisfaction and any benefits of taking part (anonymous survey two). Results Survey one had a participation rate of 70%. In this survey, participants indicated they preferred group-based activities (61%) over an individual approachto take place on a monthly basis (46%). The developed programme ran from December 2018 to December 2019, with 435 patients and caregivers taking part. Two hundred and eighteen completed survey two and revealed a positive response to both the structure and content of the programme and its impact on the wellbeing of patients and caregivers. The majority indicated they felt (much) betterfrom participating in the participatory arts programme. Conclusion This study points out the interest and potential value of a participatory arts programme to the perceived wellbeing. This suggests such programmes could be incorporated into cancer care provision, to serve as psychosocial support. The latter is particularly relevant for improving the lives, wellbeing and health of cancer patients and those supporting them.

Published
2022

7. Circulating DNA in the neoadjuvant setting of early stage colon cancer

Author

Giacomo Bregni, Andrea Pretta, Chiara Senti, Elena Acedo Reina, Caroline Vandeputte, Elena Trevisi, Paraskevas Gkolfakis, Pashalina Kehagias, Amélie Deleporte, Jean-Luc Van Laethem, Philippe Vergauwe, Marc Van den Eynde, Guido Deboever, Jos Janssens, Gauthier Demolin, Stephane Holbrechts, Marylene Clausse, Thierry De Grez, Marc Peeters, Lionel D'Hondt, Karen Geboes, Tatiana Besse-Hammer, Françoise Rothé, Patrick Flamen, Alain Hendlisz, Francesco Sclafani, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'oncologie médicale

Subjects
neoadjuvant treatment, circulating tumour DNA, Hematology, General Medicine, Prognosis, Neoadjuvant Therapy, Circulating Tumor DNA, Colon cancer, cell-free DNA, Oncology, Colonic Neoplasms, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Human medicine, Cell-Free Nucleic Acids
Abstract

Background While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial. Material and Methods Samples were collected at baseline, 2 weeks and surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA, and analysed with ddPCR technology. ROC curves were applied for cut-off points, and outcome measures included 5-year disease-free survival (DFS) and 6-year overall survival (OS). Results After a median follow-up of 52.5 months, baseline circulating-free (cf) DNA was an independent prognostic factor for DFS (HR 3.35, 95% CI: 1.15-9.77, p = .03), and a trend towards a similar association was observed for relative cfDNA changes between baseline and surgery (HR 2.57, 95% CI: 0.94-7.05, p = .07). Among 60 ctDNA assessable patients, 25 (42%) had detectable ctDNA at baseline. While detection of ctDNA at any pre-operative timepoint was not associated with outcome, patients with ctDNA increase (change of the worst trending methylation marker >= 11%, or mean ctDNA change of NPY and WIF1 >= 0%) between baseline and surgery showed a trend towards worse 5-year DFS (HR 3.66, 95% CI: 0.81-16.44, p = .09). Conclusion This is the first study of ctDNA in the neoadjuvant setting of early-stage colon cancer. Results are hypothesis-generating and should be confirmed in larger series.

Published
2022

8. Randomized Phase 2 Study Comparing Pathological Responses of Resected Colorectal Cancer Metastases after Bevacizumab with mFOLFOX6 or FOLFIRI (BEV-ONCO Trial)

Author

Pamela Baldin, Javier Carrasco, Gabriela Beniuga, Anne Jouret-Mourin, Gauthier Demolin, Sandrine Roland, Lionel D’Hondt, Philippe Vergauwe, Daniel Van Daele, Marie Mailleux, Isabelle Sinapi, Astrid De Cuyper, Noëlla Blétard, Brigitte Massart, Monique Delos, Marie-Laure Castella, Aline van Maanen, Marc Van den Eynde, UCL - (MGD) Service d'anatomie pathologique, UCL - (MGD) Service d'oncologie médicale, UCL - SSS/IREC/MORF - Pôle de Morphologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne

Subjects
Cancer Research, Oncology, bevacizumab, chemotherapy, colorectal liver metastases, pathological response, histological growth pattern, tumoral homogeneity
Abstract

Retrospective studies reported that preoperative oxaliplatin-based chemotherapy increased pathological response (PR) in patients resected for colorectal liver metastases (CRLM). This multicenter prospective randomized (1/1) phase II trial evaluated PR on resected CRLM after preoperative mFOLFOX6 (arm A) or FOLFIRI (arm B) + bevacizumab. The primary endpoint was the major pathological response rate (MPRR), defined as the percentage of patients presenting CRLMs with mean tumor regression grade (TRG) < 3. Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Out of 65 patients, 57 patients (28 and 29 in arm A/B) were resected for CRLM (one patient with lung metastases). Clinical and treatment characteristics were similar in both arms. One-month postoperative complications were 39.3%/31.0% in arm A/B (p = 0.585). MPRR and complete PR were 32.1%/20.7% (p = 0.379) and 14.3%/0.0% (p = 0.052) in arm A/B, respectively. PFS and OS were not different. Patients with PR among all CRLMs (max TRG ≤ 3; 43.8% of patients) had a lower risk of relapse (PFS: HR = 0.41, 95%CI = 0.204–0.840, p = 0.015) and a tendency towards better survival (OS: HR = 0.34, 95%CI = 0.104–1.114, p = 0.075). The homogeneity of PR was associated with improved PFS/OS. This trial fails to demonstrate a significant increase in MPRR in patients treated with mFOLFOX6-bevacizumab but confirms PR as an important prognostic factor.

Published
2021

9. Effects of Rome IV Definitions of Functional Dyspepsia Subgroups in Secondary Care

Author

Dirk Staessen, Florencia Carbone, Jan Tack, Philippe Vergauwe, Imke Masuy, Guy Van Roey, Joris Arts, Fabien Wuestenberghs, Karen Van den Houte, Ariane Gerkens, Pascale Latour, Nick Goelen, Philip Caenepeel, Hubert Piessevaux, Jolien Schol, Alain Vandenberghe, Philippe Maldague, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie

Subjects
Adult, Male, medicine.medical_specialty, Rome, behavioral disciplines and activities, Secondary Care, Secondary care, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Bloating, Overlapping PDS-EPS, Internal medicine, Humans, Medicine, In patient, Statistical analysis, Dyspepsia, Fisher's exact test, Hepatology, business.industry, Dyspeptic Patients, digestive, oral, and skin physiology, Gastroenterology, food and beverages, Postprandial Burning, Nausea, Postprandial Period, Rome iii, humanities, digestive system diseases, Postprandial Pain, Abdominal Pain, Distress, Gastroduodenal Questionnaire, Postprandial, 030220 oncology & carcinogenesis, “Adapted” PDS Group, symbols, population characteristics, Female, 030211 gastroenterology & hepatology, business
Abstract

BACKGROUND & AIMS: Functional dyspepsia (FD) is subdivided into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) according to the Rome III consensus. In clinical practice, there is a major overlap between these subgroups. The Rome IV criteria included postprandially occurring symptoms in the PDS subgroup. We aimed to analyze the effects of the Rome IV criteria, compared with Rome III, on FD subgroups in patients recruited from secondary care. METHODS: Patients with FD (n = 224; mean age, 43 ± 1 y; 77% women) were recruited from secondary-care units in Belgium and filled out symptom questionnaires, allowing subdivision according to Rome III and Rome IV criteria and identification of postprandial symptoms. Symptom patterns and demographics were compared between the subgroups. Statistical analysis was performed using the t test and the Fisher exact test. RESULTS: According to the Rome III criteria, 25% of participants had PDS, 8% had EPS, and 67% had an overlap. Postprandial fullness, early satiation, and bloating were present in significantly more patients in the PDS and overlap groups than the EPS group (P < .0001). A higher proportion of patients in the overlap group showed symptoms such as postprandial epigastric pain and nausea than in the EPS group (both P ≤ .02). With the Rome IV criteria, the overlap group was reduced to 35%; 57% of patients were considered to have PDS and 8% to have EPS. Postprandial pain was significantly more prevalent in the PDS than in the EPS group (P ≤ .002), and postprandial nausea was significantly more prevalent in the PDS group than the overlap group (P = .007). CONCLUSIONS: Compared with Rome III criteria, the Rome IV criteria significantly reduces the overlap between PDS and EPS groups. Studies are needed to determine if Rome IV subgroups are associated differently with psychological comorbidities and treatment responses. ispartof: Clin Gastroenterol Hepatol vol:19 issue:8 pages:1620-1626 ispartof: location:United States status: published

Published
2021

10. Sex and Regorafenib Toxicity in Refractory Colorectal Cancer: Safety Analysis of the RegARd-C Trial

Author

Caroline Vandeputte, Thierry Delaunoit, Jean-Charles Goeminne, Thomas Guiot, Jean-Luc Van Laethem, Patrick Flamen, Jos Janssens, Gauthier Demolin, Pashalina Kehagias, Amélie Deleporte, Andrea Pretta, Javier Carrasco, Marc Peeters, Francesco Sclafani, Elena Acedo Reina, Karen Geboes, Giacomo Bregni, Camille Van Bogaert, Chiara Senti, Paraskevas Gkolfakis, Philippe Vergauwe, Lionel D'Hondt, Alain Hendlisz, and Stéphane Holbrechts

Subjects
Oncology, Male, medicine.medical_specialty, Colorectal cancer, Pyridines, chemistry.chemical_compound, Regorafenib, Internal medicine, medicine, Humans, Dosing, Prospective Studies, Adverse effect, business.industry, Standard treatment, Phenylurea Compounds, Gastroenterology, medicine.disease, Rash, Clinical trial, chemistry, Toxicity, Quality of Life, Female, Human medicine, medicine.symptom, business, Colorectal Neoplasms
Abstract

Predictive factors for adverse events in metastatic colorectal cancer patients treated with regorafenib are currently lacking. In this safety analysis of a prospective phase II clinical trial, we assess the association between several clinical, laboratory, and imaging parameters and the occurrence of adverse events. Our results show that female sex is an independent risk factor for increased toxicity. Background: Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking. Materials and Methods: We assessed the association between a number of baseline clinical, laboratory and imaging parameters and the occurrence of TRAEs in 136 patients who had received regorafenib (160 mg/day, 3-weeks-on/1-week-off) in a prospective phase II clinical trial. Results: Grade >= 2 TRAEs during the first cycle of treatment (84% vs. 60%, P=.002) and grade >= 3 TRAEs throughout the whole treatment (71% vs. 53%, P=.035) occurred more frequently in females, with sex being the only independent predictive factor of early and any-time toxicity (OR 3.4; 95% CI: 1.2-11.1, P=.02 and OR 2.1; 95% CI: 1.0-4.4, P=.045, respectively). Fatigue, anorexia, hypertension, and rash were reported significantly more frequently by females than males (P

Published
2021

11. Rationale and design of REGINA, a phase II trial of neoadjuvant regorafenib, nivolumab, and short-course radiotherapy in stage II and III rectal cancer

Author

Giacomo Bregni, Elena Trevisi, Chiara Senti, Gabriel Liberale, Lionel D'Hondt, Karen Geboes, Pashalina Kehagias, Caroline Vandeputte, Marc Buyse, Philippe Vergauwe, Yeter Gokburun, Francesco Sclafani, Jean-Luc Van Laethem, Marc Peeters, Maria Antonietta Bali, Camille Anastasia Chapot, Patrick Flamen, Alain Hendlisz, Javier Carrasco, Pieter Demetter, Marc Van den Eynde, Elena Acedo Reina, Andrea Pretta, Amélie Deleporte, Luigi Moretti, UCL - (MGD) Service d'oncologie médicale, and UCL - SSS/IREC/MONT - Pôle Mont Godinne

Subjects
Oncology, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Stage ii, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Regorafenib, medicine, Radiology, Nuclear Medicine and imaging, business.industry, Standard treatment, Généralités, Hematology, General Medicine, medicine.disease, Total mesorectal excision, Radiation therapy, chemistry, 030220 oncology & carcinogenesis, Human medicine, Nivolumab, business, Chemoradiotherapy
Abstract

SCOPUS: le.j, info:eu-repo/semantics/published

Published
2021

12. 505TiP REGINA: A phase II trial of neoadjuvant regorafenib (rego) in combination with nivolumab (nivo) and short-course radiotherapy (SCRT) in intermediate-risk, stage II-III rectal cancer (RC)

Author

Karel Geboes, Gabriel Liberale, Javier Carrasco, M. Van den Eynde, Giacomo Bregni, Chiara Senti, Amélie Deleporte, Yeter Gokburun, P. Demetter, Alain Hendlisz, E. Acedo Reina, Monika Peeters, Francesco Sclafani, A. Veron, Luigi Moretti, Philippe Vergauwe, Paraskevas Gkolfakis, Marc Buyse, J-L. van Laethem, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'oncologie médicale, and UCL - (SLuc) Service d'hépato-gastro-entérologie

Subjects
Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Hematology, Stage ii, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, Regorafenib, Medicine, Nivolumab, business, Intermediate risk, Short course radiotherapy
Abstract

Background Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and downregulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Trial design REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes). The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pTRG, event-free survival, and overall survival. The study follows a Simon’s two-stage design (null hypothesis pCR=12%, alternative hypothesis pCR=24%; α=5%, β=20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. Clinical trial information: NCT04503694.

Published
2021

13. Acupuncture as a complementary therapy for cancer care: acceptability and preferences of patients and informal caregivers

Author

Rebecca Chandler, Sofie Derijcke, Tom Boterberg, Philip R. Debruyne, Tessa Lefebvre, Koen Van Eygen, Hans Pottel, Lieselot Cool, Pauline Lane, Pat Schofield, Laura Tack, Philippe Vergauwe, and Virginie Blieck

Subjects
medicine.medical_specialty, Cancer-related side effect, 0211 other engineering and technologies, Acupuncture Therapy, Pain, Social Sciences, Complementary therapy, 02 engineering and technology, Integrative & Complementary Medicine, INTEGRATIVE ONCOLOGY, complementary therapy, 03 medical and health sciences, Other systems of medicine, 0302 clinical medicine, Neoplasms, Surveys and Questionnaires, 021105 building & construction, informal caregiver, Acupuncture, Medicine and Health Sciences, Medicine, Humans, cancer, cancerrelated side effect, Cancer, OUTCOMES, Science & Technology, business.industry, PAIN, ADULTS, General Medicine, ALTERNATIVE MEDICINE, medicine.disease, 030205 complementary & alternative medicine, Anesthesiology and Pain Medicine, Informal caregiver, Caregivers, Complementary and alternative medicine, Physical therapy, Sleeping difficulties, business, Life Sciences & Biomedicine, acupuncture, RZ201-999
Abstract

Background: Acupuncture provides a possible complementary therapy which can be used alongside or following cancer treatment to relieve side-effects for cancer patients and survivors, such as pain and depression. Equally, it can provide relief from symptoms such as anxiety and sleep disturbance, which are recognised as significant issues among caregivers of those with cancer. The aim of this study was to explore the acceptability and preferences of cancer patients, disease survivors and their informal caregivers in relation to acupuncture.Methods: A questionnaire was developed to explore acceptability and preferences of cancer patients, disease survivors and their caregivers in relation to acupuncture, including motivations to use acupuncture, preferred symptoms to be addressed, and practical issues (location; cost).Results: A participation rate of 94.5% was obtained, with 116 participating patients and survivors, and 54 caregivers. Acceptability of acupuncture was around 1/3 for patients (34.5%; 40/116) and almost half for informal caregivers (48.0%; 26/54). In terms of preferences, the day care clinic was the favoured location for patients (52.5%; 21/40) to undergo acupuncture, while there was no specific preference on location observed for caregivers. A large number of patients indicated they would be willing to pay to receive the complementary therapy (60%; 24/40). Symptoms of fatigue, feeling listless, and pain were most often identified as complaints patients and survivors would use acupuncture for (60.0%, 57.5%, and 47.5% respectively). For informal caregivers, 48.0% (26/54) expressed an interest in using acupuncture for their pain, stress and sleeping difficulties.Conclusions: This study indicates that many cancer patients, disease survivors and informal caregivers would accept acupuncture as a complementary therapy. They could further identify many symptoms they felt this therapy could relieve. This openness to acupuncture, and expressed preferences provide the foundations for this complementary therapy to be incorporated into holistic and supportive cancer care, both for patients and those supporting them.

Published
2020
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14. REGINA: A phase II trial of neoadjuvant regorafenib (Rego) in combination with nivolumab (Nivo) and short-course radiotherapy (SCRT) in intermediate-risk, stage II-III rectal cancer (RC)

Author

Giacomo Bregni, Chiara Senti, Elena Acedo Reina, Paraskevas Gkolfakis, Luigi Moretti, Ana Veron, Pieter Demetter, Gabriel Liberale, Javier Carrasco, Karen Paula Geboes, Yeter Gokburun, Marc Peeters, Marc Van Den Eynde, Jean-Luc Van Laethem, Philippe Vergauwe, Marc E. Buyse, Amélie Deleporte, Alain Hendlisz, and Francesco Sclafani

Subjects
Cancer Research, Oncology
Abstract

TPS226 Background: Despite recent improvements, management of locally advanced rectal cancer (LARC) remains challenging, and many patients (pts) still experience recurrence. In preclinical models, combining Rego with an anti-PD-1 inhibitor led to superior tumour growth suppression as compared with either treatment alone. In a phase I clinical trial, remarkable results were reported for the combination of Rego and Nivo in advanced MSS colorectal cancer. This synergistic effect is thought to be secondary to the anti-angiogenic effects of Rego and its potential to reduce TAMs, promote M1 macrophage conversion, and down-regulate expression of immunosuppressive factors. Building on these data, we designed a trial of Rego-Nivo with standard SCRT in the neoadjuvant setting of RC. Methods: REGINA is an academic, multicentre, single-arm, phase II trial sponsored by Institut Jules Bordet. Eligible patients are treated according to the following plan: induction phase (Nivo 240 mg IV D1&15, and Rego 80 mg PO D1-14), SCRT (D22-26), consolidation phase (Nivo 240 mg IV D29,43&57, and Rego 80 mg PO D29-49), and surgery (7-8 weeks after SCRT). Key eligibility criteria include age ≥18 years, ECOG PS ≤1, adenocarcinomas below the peritoneal reflection, intermediate-risk, stage II-III tumour (ie, cT3/T4aNany or cT1-2N+, no involvement/threatening of the mesorectal fascia, no involvement of lateral pelvic lymph nodes) irrespective of microsatellite instability status. The primary endpoint is pathological complete response (pCR). Secondary endpoints include, among others, toxicity, compliance to treatment, pathological tumour regression grade, event-free survival, and overall survival. Subjects will be followed for recurrence and survival for 5 years after end of treatment visit. The study follows a Simon’s two-stage design (null hypothesis pCR = 12%, alternative hypothesis pCR = 24%; α= 5%, β= 20%) with a maximum of 60 pts to be enrolled. A safety interim analysis is planned after the first 6 pts have completed treatment. Serial collection of tumour, blood, and stool samples is mandatory at pre-specified time points for exploratory correlative biomarker analyses. The trial is planned to be run at 8-10 centres across Belgium. Study recruitment started in Q1 2021 and is anticipated to complete in Q3 2023. The study is funded by Bayer. Clinical trial information: NCT04503694.

Published
2022
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15. P-276 Sex and regorafenib toxicity in refractory colorectal cancer: A safety analysis of the RegARd-C trial

Author

Javier Carrasco, Thomas Guiot, Philippe Vergauwe, Giacomo Bregni, Caroline Vandeputte, K. Geboes, Thierry Delaunoit, L. D'Hondt, J. C. Goeminne, Amélie Deleporte, Patrick Flamen, G. Paraskevas, Pashalina Kehagias, Jozef Janssens, Francesco Sclafani, Alain Hendlisz, Monika Peeters, Gauthier Demolin, Stéphane Holbrechts, and J.-L. Van Laethem

Subjects
Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Hematology, medicine.disease, chemistry.chemical_compound, Refractory, chemistry, Internal medicine, Regorafenib, Toxicity, Medicine, business
Published
2021
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16. The use of uHear™ to screen for hearing loss in older patients with cancer as part of a comprehensive geriatric assessment

Author

Philippe Clarysse, Ingeborg Dhooge, Patrick Werbrouck, Hans Pottel, Sofie Derijcke, Michelle Lycke, Koen Van Eygen, Tom Boterberg, Philip R. Debruyne, Tessa Lefebvre, Lore Ketelaars, Evi Martens, Philippe Vergauwe, Karin Stellamans, and Patricia Schofield

Subjects
Male, medicine.medical_specialty, Hearing loss, Audiology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Ototoxicity, Older patients, Neoplasms, otorhinolaryngologic diseases, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Hearing Loss, Geriatric Assessment, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Cancer, Geriatric assessment, General Medicine, Gold standard (test), medicine.disease, Acoustic Impedance Tests, 030220 oncology & carcinogenesis, Female, medicine.symptom, Audiometry, business
Abstract

Objective: We previously validated uHear™ to screen for hearing loss in older patients with cancer without a known hearing loss, as part of a comprehensive geriatric assessment (CGA). In view of low specificity, we tested a new modified uHear™ scoring system as described by Handzel. Methods: Patients, aged ≥70 years, were evaluated by uHear™ and conventional audiometry, which is considered the gold standard, as part of a CGA. The pass or fail screening cut-off for uHear™ was defined as having ≥2 consecutive hearing grades starting from the moderate– severe threshold zone ranging from 0.5 to 2.0 kHz (modified Handzel-uHear™ scoring system). To accept the modified Handzel-uHear™ as screening tool, it was predefined that the combined sensitivity (S) and specificity (Sp) of the test (S + Sp/2) was at least 80% and that an actual combined (S + Sp)/2 of 90% would be found. Results: Ninety ears (45 subjects) were tested. Of those ears, 24.4% were identified as impaired by conventional audiometry. Modified Handzel-uHear™ identified 26.7% of tested ears as impaired. The combined (S + Sp)/2 of the modified Handzel-uHear™ was calculated as 77.5%, while in previous cohort, this was retrospectively calculated as 94.6%. A new uHear™ scoring system was proposed and tested in current and previous cohort. A (S + Sp)/2 of 80.2 and 78.8%, respectively, were obtained. Conclusion: uHear™ is a feasible tool for use within the CGA and shows promising results. However, further research is warranted to optimize the cut-off method before it could be routinely implemented within geriatric oncology.

Published
2017
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17. The distress thermometer predicts subjective, but not objective, cognitive complaints six months after treatment initiation in cancer patients

Author

Laurence Goethals, Koen Van Eygen, Tessa Lefebvre, Karin Stellamans, Lore Ketelaars, Philip R. Debruyne, Patricia Schofield, Philippe Vergauwe, Tom Boterberg, Patrick Werbrouck, Lies Pottel, Michelle Lycke, and Hans Pottel

Subjects
Adult, Male, medicine.medical_specialty, media_common.quotation_subject, Anxiety, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Humans, Mass Screening, Verbal fluency test, Cognitive Dysfunction, 030212 general & internal medicine, Neuropsychological assessment, Fatigue, Applied Psychology, Depression (differential diagnoses), Aged, media_common, Aged, 80 and over, medicine.diagnostic_test, Depression, Reproducibility of Results, Cognition, Middle Aged, Psychiatry and Mental health, Distress, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Physical therapy, Female, medicine.symptom, Worry, Psychology, Psychosocial, Stress, Psychological, Clinical psychology
Abstract

Objectives: Research has indicated that cancer-related cognitive impairments (CRCI) may be influenced by psychosocial factors such as distress, worry and fatigue. Therefore, we aimed to validate the distress thermometer (DT) as a screening tool to detect CRCI six months post-treatment-initiation in a group of general cancer patients. Methods: Patients (≥18 years, n = 125) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated at baseline (T0) and six months post-treatment-initiation (T1) for CRCI by a neuropsychological assessment, including patient-reported outcome measures (PROMs). Assessed cognitive domains included premorbid intelligence, attention, processing speed, flexibility, verbal and visual episodic memory and verbal fluency. PROMs entailed distress (DT, cut-off ≥4, range 0–10), anxiety and depression, fatigue (FACIT-fatigue scale) and subjective cognitive complaints. Results: At T0, 60.4% of patients showed a DT score of ≥4, whereas 50% met this criterion at T1. According to the definition of the International Cognition and Cancer Task Force, 25.5% and 28.3% of patients presented with a CRCI at T0 and T1, respectively. When evaluating the DT as a screening tool for CRCI at T1, data showed an inverse relationship between the DT and CRCI. ROC-curve analysis revealed an AUC

Published
2017
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18. Underrepresentation of vulnerable older patients with cancer in phase II and III oncology registration trials: A case-control study

Author

Michelle Lycke, Philippe Vergauwe, Laura Tack, Koen Van Eygen, Jolien De Zutter, Patrick Werbrouck, Lies Pottel, Philip R. Debruyne, Patricia Schofield, Tom Boterberg, Lieselot Cool, Karin Stellamans, Evi Martens, Tessa Lefebvre, Hans Wildiers, Lore Ketelaars, and Hans Pottel

Subjects
Oncology, medicine.medical_specialty, Population, CLOCK DRAWING TEST, Subgroup analysis, Medical Oncology, 03 medical and health sciences, AGE, 0302 clinical medicine, INTERNATIONAL-SOCIETY, Older patients, Internal medicine, Neoplasms, Cancer centre, Medicine and Health Sciences, TOOL, Medicine, Humans, 030212 general & internal medicine, education, ELDERLY-PATIENTS, Geriatric Assessment, Aged, Retrospective Studies, education.field_of_study, business.industry, COMPREHENSIVE GERIATRIC ASSESSMENT, Case-control study, Cancer, ADULTS, PERFORMANCE, medicine.disease, SCREENING, Clinical trial, Exact test, 030220 oncology & carcinogenesis, Case-Control Studies, Geriatrics and Gerontology, business, CLINICAL-TRIALS, TASK-FORCE
Abstract

OBJECTIVES: We aimed to determine the proportion of "fit" versus "vulnerable" older patients with cancer included in phase II and III oncology registration trials, as compared to the proportions in a real life oncology setting. METHODS: Trial and patient characteristics of older (≥70years) patients treated at the OECI-designated clinical cancer centre in Kortrijk and included in a phase II or III oncology registration trial were collected retrospectively. These patients were matched individually with randomly-selected patients from the general oncology setting, based on gender, age, tumour type, tumour stage, and treatment intent. Patients' fitness, based on routine Geriatric-8 (G8) screening, was retrieved from prospectively constructed databases. RESULTS: Between November 2012 and October 2018, 218 older patients with cancer were included in a phase II or III oncology registration trial. Of those, 41 cases with a mean age of 76.0years were included in the analyses. A Fisher's Exact Test revealed a statistical significant difference between cases and matched controls, with a higher proportion of "fit" patients included in phase II or III oncology registration trials compared to the proportion in the matched control group (respectively 70.7% and 41.5%, p

Published
2019

19. Subjective, but not objective, cognitive complaints impact long-term quality of life in cancer patients

Author

Koen Van Eygen, Michelle Lycke, Lieselot Cool, Karin Stellamans, Tessa Lefebvre, N. Liefhooghe, Patricia Schofield, Lies Pottel, Hans Pottel, Philip R. Debruyne, Tom Boterberg, Lore Ketelaars, Patrick Werbrouck, and Philippe Vergauwe

Subjects
Adult, Male, Anxiety depression, Early detection, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Survivorship curve, Neoplasms, Quantitative research, Medicine, Humans, Cognitive Dysfunction, Longitudinal Studies, Patient Reported Outcome Measures, Applied Psychology, Aged, Aged, 80 and over, 030504 nursing, business.industry, Cancer, Cognition, Middle Aged, medicine.disease, Self Concept, Term (time), Psychiatry and Mental health, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, 0305 other medical science, business, Clinical psychology
Abstract

Cognitive complaints, of objective or subjective nature, may negatively impact cancer patients' quality of life (QoL). Further, the early detection of cognitive alterations may lead to an improved QoL. However, the content of such screening is yet unclear. This paper presents long-term QoL data of cancer patients treated with curative intent and its relation with objective and subjective cognitive complaints, and patient-reported outcome measures (PROMs).QoL data, measured by the EORTC QLQ C-30, were obtained at baseline, 6 (T1), 12 (T2), and 24 months (T3) after treatment start, and compared between patients with and without objective and subjective cognitive complaints. The predictive value of PROMs was also examined.QoL data at baseline was collected in 125 patients. Response rates at T1, T2, and T3 were 84.7%, 81.5%, and 83.1%, respectively. Eighty-nine patients returned their QoL questionnaires at all times. Baseline subjective cognitive complaints had a stronger association with worse scores on patients' overall QoL and QoL subscale scores than objective cognitive complaints. An exploratory analysis into the value of PROMs in predicting long-term QoL at T3 revealed a significant effect for the Hospital Anxiety and Depression Scale-Depression and FACIT Fatigue scale.Self-perceived cognitive alterations are negatively associated with patients' overall QoL. As these troubles may already be present at baseline, oncology nurses should screen for the early signs of subjective cognitive complaints by use of PROMs, in order to refer the patient to proper intervention programs which may lead to an improved long-term QoL and faster reintegration into society.

Published
2019

20. Abstract 28: Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC)

Author

Françoise Rothé, Giacomo Bregni, Elena Trevisi, Pashalina Kehagias, Caroline Vandeputte, Chiara Senti, Jean-Luc Van Laethem, Gauthier Demolin, Francesco Sclafani, Paraskevas Gkolfakis, Marylene Clausse, Karen Geboes, Alexis Buggenhout, T. Besse-Hammer, Marc Van den Eynde, Elena Acedo Reina, L. D'Hondt, Stéphane Holbrechts, Guido Deboever, Philippe Vergauwe, Thierry De Grez, Jos Janssens, Amélie Deleporte, Marc Peeters, Andrea Pretta, Patrick Flamen, and Alain Hendlisz

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Stage colon cancer, business.industry, Cell free, chemistry.chemical_compound, chemistry, Internal medicine, Medicine, business, Baseline (configuration management), Value (mathematics), DNA
Abstract

Introduction Circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy. No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with neoadjuvant chemotherapy. We sought to evaluate the prognostic value of baseline and early, on-treatment changes of cfDNA and ctDNA in stage II-III CC pts who were treated with one cycle of neoadjuvant FOLFOX chemotherapy followed by surgery +/- adjuvant FOLFOX chemotherapy in the PePiTA trial. Methods PePITA was a multicentre, single-arm, prospective phase II trial aiming to test in vivo tumour chemosensitivity as assessd by metabolic response using 18F-FDG PET/CT scan of early stage CC and to evaluate its association with survival outcome (NCT00994864). Plasma samples were prospectively collected at baseline and 2 weeks (ie, after one cycle of neoadjuvant FOLFOX chemotherapy). cfDNA was isolated with the QIAmp circulating nucleic acid kit (Qiagen), and quantified with the Qubit fluorometer (Life-Technologies). cfDNA samples were bisulfite converted using the EZ DNA Methylation-Gold™ Kit (Zymo Research), with NPY and WIF1 being selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft V1.6 software (BioRad). The primary outcome measure was 3-year disease-free survival (DFS). Receiver operating characteristics curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with the SPSS for MacOS version 25.0 (SPSS Inc). Results 80 pts were included (ypStage I-II 56%, ypStage III 44%). After a median follow-up of 52.5 months, 3-year DFS was 80% (95%CI 71.2-90.8) and 5-year OS 84% (95%CI 75.2-94.9). Pts with high (≥1.2 ng/µl) baseline cfDNA level had worse 3-year DFS (48% vs 80%; HR 2.72, 95%CI 1.02-7.25; p=0.036) and 5-year OS (71% vs 90%; HR 5.36, 95%CI 1.14-25.28; p=0.017) than those with low baseline cfDNA level. In a multivariable analysis (including sex, ypStage and CEA), baseline cfDNA was the only factor showing a trend towards statistical significance (HR DFS 2.6, 95%CI 0.96-7.01; p=0.059; HR OS 4.65, 95%CI 0.97-22.32; p=0.055). Early changes of cfDNA (Δ ≥11%) after one cycle of neoadjuvant FOLFOX chemotherapy failed to predict survival (HR DFS 1.08, 95%CI 0.42-2.81; p=0.873; HR OS 0.68, 95%CI 0.19-2.39; p=0.543). ctDNA analyses are ongoing and will be presented at the meeting. Conclusions For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with neoadjuvant chemotherapy. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from neoadjuvant, FOXTROT-like, treatment strategies. Citation Format: Giacomo Bregni, Elena Trevisi, Chiara Senti, Andrea Pretta, Caroline Vandeputte, Pashalina Kehagias, Elena Acedo Reina, Amélie Deleporte, Paraskevas Gkolfakis, Jean-Luc Van Laethem, Philippe Vergauwe, Marc Van den Eynde, Guido Deboever, Jos Janssens, Gauthier Demolin, Stephane Holbrechts, Marylene Clausse, Thierry De Grez, Marc Peeters, Lionel D'Hondt, Karen Geboes, Tatiana Besse-Hammer, Alexis Buggenhout, Françoise Rothé, Patrick Flamen, Alain Hendlisz, Francesco Sclafani. Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 28.

Published
2021
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21. Prognostic value of baseline and early changes of circulating-free (cf) and circulating tumor (ct) DNA in the neoadjuvant (NA) setting of early stage colon cancer (CC)

Author

Jos Janssens, Giacomo Bregni, Patrick Flamen, Chiara Senti, Lionel D'Hondt, Marylene Clausse, Stéphane Holbrechts, Karen Geboes, Thierry De Grez, Francesco Sclafani, Caroline Vandeputte, T. Besse-Hammer, Alain Hendlisz, Philippe Vergauwe, Jean-Luc Van Laethem, Paraskevas Gkolfakis, Françoise Rothé, Marc Van den Eynde, Elena Acedo Reina, and Gauthier Demolin

Subjects
Cancer Research, medicine.medical_specialty, Prognostic factor, Stage colon cancer, Oncology, business.industry, Adjuvant chemotherapy, Internal medicine, medicine, Stage (cooking), business, Minimal residual disease, Gastroenterology
Abstract

3600 Background: ctDNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy (CT). No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with NACT. We sought to evaluate the prognostic value of baseline and early changes of cf/ctDNA in stage II-III CC pts who were treated with one cycle of NA FOLFOX CT followed by surgery +/- adjuvant FOLFOX CT in the PePiTA trial. Methods: PePiTA was a multicentre, single-arm, prospective phase II trial testing in vivo tumour chemosensitivity of early stage CC (as assessed by 18F-FDG PET/CT-based metabolic response to one cycle of NA FOLFOX) and its association with long-term outcome (NCT00994864). Plasma samples were prospectively collected at baseline, 2 weeks after one cycle of NA FOLFOX CT, and before surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft v1.6 software (Bio-Rad). Survival outcome measures were 5-year disease-free survival (DFS) and 6-year overall survival (OS). ROC curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with SPSS v25.0 (SPSS Inc.). Results: 80 pts were included (44 ypStage I-II and 36 ypStage III). After a median follow-up of 52.5 months, 5-year DFS and 6-year OS were 68% (95%CI 52-84) and 84% (95%CI 74-94), respectively. Pts with high (≥1600 ng/ml) baseline cfDNA had worse 6-year OS (HR 6.45, 95%CI 1.61-25.84; p = 0.008). Early changes of cfDNA after one cycle of NA FOLFOX CT failed to predict survival (HR DFS 0.96, 95%CI 0.38-2.43; p = 0.92; HR OS 0.62, 95%CI 0.16-2.50; p = 0.50). At baseline, 25 out of 60 (42%) ctDNA-assessable patients were positive. Detectable ctDNA at baseline (HR DFS 2.06, 95%CI 0.65-6.49; p = 0.22; HR OS 3.11, 95%CI 0.57-16.99; p = 0.19) or at any timepoint before surgery (HR DFS 1.65, 95%CI 0.54-5.04; p = 0.38; HR OS 2.80, 95%CI 0.54-14.44; p = 0.22) was not significantly associated with survival. A trend toward a significant association between ctDNA increase at surgery and 5-year DFS was found (HR 3.66, 95%CI 0.81-16.44; p = 0.09). Data on the correlation between early changes of cf/ctDNA and 18F-FDG PET/CT-based metabolic response will be presented at the meeting. Conclusions: For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with NACT. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from FOxTROT-like, NACT treatment strategies. While analysis of ctDNA in this setting did not appear useful to predict prognosis, these results might be secondary to the small sample size.

Published
2021
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22. Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment

Author

Patricia Schofield, Koen Van Eygen, Philippe Vergauwe, Philip R. Debruyne, Laurence Goethals, Lies Pottel, Patrick Werbrouck, Hans Pottel, Lore Ketelaars, Karin Stellamans, Michelle Lycke, and Tom Boterberg

Subjects
medicine.medical_specialty, Intelligence quotient, medicine.diagnostic_test, business.industry, Experimental and Cognitive Psychology, medicine.disease, Surgery, 03 medical and health sciences, Psychiatry and Mental health, Distress, 0302 clinical medicine, Breast cancer, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, Verbal fluency test, Anxiety, Neuropsychological assessment, medicine.symptom, business, Psychosocial, 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract

Introduction: Recent research in the field of cancer-related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors. Methods: Patients (>= 18 years) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated with a baseline neuropsychological assessment including Patient-Reported Outcome Measures (PROMs). PROMs entailed distress, anxiety and depression, fatigue, and cognitive complaints. The neuropsychological assessment comprised several cognitive domains such as premorbid IQ, attention, processing speed, flexibility, verbal and visual episodic memory, and verbal fluency. Results: Cross-sectional data of 125 patients were collected. Patients had a mean age of 60.9 years (range: 30.0-85.0) and comprised primarily females (65.6%). Patients presented with cancer of following sites: breast (44.0%), digestive (28.8%), urological (11.2%), gynecologic (8.0%), hematologic malignancy (4.8%), and lung (3.2%). Patients presented with a premorbid IQ of 105.3 (range: 79.0-124.0). In 29.6% of patients, a CRCI was detected. Binary logistic regression analyses showed that a lower premorbid IQ (beta = -.084, P < .01) and a higher level of fatigue (beta = -.054, P < .05) predicted baseline CRCI. Premorbid IQ also predicted performance on individual cognitive domains. Some domains were also influenced by age, gender, having a breast cancer diagnosis, and an active treatment for hypertension. Conclusion: Premorbid IQ and fatigue are important predictors of baseline CRCI. Therefore, we advise researchers to implement a short IQ test when conducting clinical trials on CRCI.

Published
2016
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23. 449P Randomized phase II study comparing pathological responses of resected colorectal cancer metastases (CRCM) after bevacizumab (BEV) with FOLFOX or FOLFIRI (BEV-ONCO trial)

Author

Anne Jouret-Mourin, M-L. Castella, A. van Maanen, G. Beniuga, S. Roland, Pamela Baldin, N. Bletard, Javier Carrasco, Philippe Vergauwe, L. D'Hondt, B. Massart, Gauthier Demolin, M. Mailleux, M. Van den Eynde, A. De Cuyper, D. Vandaele, I. Sinapi, Monique Delos, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, UCL - (SLuc) Service d'oncologie médicale, and UCL - (SLuc) Service d'anatomie pathologique

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Phases of clinical research, Hematology, medicine.disease, FOLFOX, Internal medicine, medicine, FOLFIRI, business, Pathological, medicine.drug
Abstract

Background Pathological response (PR) of resected CRCM after preop treatment is a recognized prognostic factor. Retrospective studies reported that BEV + oxaliplatin-based chemotherapy increased PR compared to irinotecan-based chemotherapy. In this trial, we aim to demonstrate that preop BEV + FOLFOX would increase PR. Methods BEV-ONCO (NCT01858649) is a multicenter prospective randomized (1/1) phase II trial evaluating PR on resected CRCM after 3 to max 6 cycles of mFOLFOX (ARM A) or FOLFIRI (ARM B) + BEV (5mg/kg/2 weeks). Primary endpoint is the major pathological response rate (MPRR) defined as the % of patients presenting CRCMs with a mean tumor regression grade (TRG)

Published
2020
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24. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial

Author

S Mullamitha, P Potemski, JB Ahn, Gavin Marx, David Cunningham, CG Ponce, James A. Jr Reeves, Cathy Eng, J Cultrera, Rachel Kerr, Neil H. Segal, Josep Tabernero, Marwan Fakih, J-L Canon, Salvatore Siena, JO Streb, YJ Cha, A Smolin, Javier Sastre Valera, S Begbie, Anne Uyei, Alberto Sobrero, Andrew Strickland, S Dowden, Ruth Vera Garcia, N Segal, AS Lee, Evaristo Maiello, E Chmielowska, S Badarinath, Niall C. Tebbutt, Tae Won Kim, K King, J Lee, B Lesperance, Ko Lam, M Van den Eynde, Vinod Ganju, B Tan, R. Young, K Chang, Brigette B.Y. Ma, Mark Kozloff, TY Kim, M Dvorkin, Maria Di Bartolomeo, Jo Park, Nick Pavlakis, M Kozloff, Philippe Vergauwe, Yibing Yan, E. Van Cutsem, M Wroblewska, M Womack, Michael M Vickers, Fortunato Ciardiello, Alfredo Falcone, A Chaudhry, Gabriele Luppi, J Kortmansky, Johanna C. Bendell, Ilsung Chang, John Marshall, RG Carbone, PJ Cuyle, R Mandanas, M Nechaeva, Félix Couture, Andrés Cervantes, Guillem Argiles, Scott M. Berry, Sherif Raouf, E Szutowicz-Zielinska, D Chu, SH Cho, John Davies, J. Asselah, S Baijal, Louise Roberts, Eng, Cathy, Kim, Tae Won, Bendell, Johanna, Argilés, Guillem, Tebbutt, Niall C, Di Bartolomeo, Maria, Falcone, Alfredo, Fakih, Marwan, Kozloff, Mark, Segal, Neil H, Sobrero, Alberto, Yan, Yibing, Chang, Ilsung, Uyei, Anne, Roberts, Louise, Ciardiello, Fortunato, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'hépato-gastro-entérologie, and UCL - (SLuc) Service d'oncologie médicale

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Pyridines, Perforation (oil well), Phases of clinical research, Salvage therapy, Antibodies, Monoclonal, Humanized, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Atezolizumab, Internal medicine, Regorafenib, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Survival rate, Aged, Salvage Therapy, Cobimetinib, business.industry, Phenylurea Compounds, Liver Neoplasms, Middle Aged, Prognosis, Survival Rate, Editorial Commentary, 030104 developmental biology, chemistry, Oncology, 030220 oncology & carcinogenesis, Azetidines, Female, Colorectal Neoplasms, business, Follow-Up Studies
Abstract

Background Microsatellite-stable metastatic colorectal cancer is typically unresponsive to immunotherapy. This phase 3 study was designed to assess atezolizumab plus cobimetinib in metastatic colorectal cancer. Here, we report the comparison of atezolizumab plus cobimetinib or atezolizumab monotherapy versus regorafenib in the third-line setting. Methods IMblaze 370 is a multicentre, open-label, phase 3, randomised, controlled trial, done at 73 academic medical centres and community oncology practices in 11 countries. Patients aged at least 18 years with unresectable locally advanced or metastatic colorectal cancer, baseline Eastern Cooperative Oncology Group performance status of 0–1, and disease progression on or intolerance to at least two previous systemic chemotherapy regimens were enrolled. We used permuted-block randomisation (block size four) to assign patients (2:1:1) via an interactive voice and web response system to atezolizumab (840 mg intravenously every 2 weeks) plus cobimetinib (60 mg orally once daily for days 1–21 of a 28-day cycle), atezolizumab monotherapy (1200 mg intravenously every 3 weeks), or regorafenib (160 mg orally once daily for days 1–21 of a 28-day cycle). Stratification factors were extended RAS status (wild-type vs mutant) and time since diagnosis of first metastasis (

Published
2019

25. An observational pilot study to evaluate the feasibility and quality of oncological home-hospitalization

Author

Jana Missiaen, Lieselot Cool, Pieter Jan De Jonghe, Koen Van Eygen, Philippe Vergauwe, Tessa Lefebvre, Michelle Lycke, Veerle Foulon, Dominique Vandijck, Philip R. Debruyne, and Hans Pottel

Subjects
Male, medicine.medical_specialty, Psychological intervention, Pilot Projects, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Quality of life, Intervention (counseling), Neoplasms, Medicine, Humans, Aged, Quality of Health Care, 030504 nursing, Oncology (nursing), business.industry, General Medicine, Middle Aged, Home Care Services, 030220 oncology & carcinogenesis, Health Care Surveys, Ambulatory, Cohort, Physical therapy, Quality of Life, Feasibility Studies, Observational study, Female, 0305 other medical science, business, Cohort study
Abstract

PURPOSE: The objective of this pilot study was to evaluate the feasibility of oncological home-hospitalization and to compare its quality with standard ambulatory hospital care in terms of patient-reported quality of life and related endpoints by means of a set of validated patient-reported outcome measures (PROMs). METHODS: An observational cohort study (clinicaltrials.gov identifier: NCT03073499) was conducted, allocating patients to (partial) home-hospitalization or standard ambulatory hospital care. PROMs were completed by both cohorts at start of treatment and eight weeks later. An additional study-specific questionnaire was presented to the intervention cohort at study-end assessing their satisfaction with and preferences for the provided homecare. RESULTS: Thirty patients received home-hospitalization, corresponding to 116 interventions. For twenty-eight patients, this comprised all assessments required prior to administration of treatment, which resulted in a significant reduction of waiting time for treatment administration at the hospital in comparison with the control cohort (n = 24) (average reduction of 1:12 h, p 0.05). 29/30 patients of the intervention cohort were satisfied with the provided homecare and preferred to have it continued, 22/25 patients declared to feel at home at least as safe as in the hospital. No serious safety concerns were reported. CONCLUSION: The results of this pilot study suggest that (partial) oncological home-hospitalization is feasible, safe and statistically not affecting patient-reported quality of life. Furthermore, this care model was acceptable and preferred by a substantial number of cancer patients. ispartof: EUROPEAN JOURNAL OF ONCOLOGY NURSING vol:40 pages:44-52 ispartof: location:Scotland status: published

Published
2018

26. 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
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27. Long-Term Outcome of Early Combined Immunosuppression Versus Conventional Management in Newly Diagnosed Crohn's Disease

Author

Filip Baert, Geert R. D'Haens, Philip Caenepeel, Daniel W. Hommes, Judith A. Stibbe, North-Holland Gut Club, Marc A. Benninga, Daniël R. Hoekman, Severine Vermeire, Martine De Vos, Philippe Vergauwe, Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Paediatric Gastroenterology, and Gastroenterology and Hepatology

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Fistula, Colonoscopy, Newly diagnosed, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Crohn Disease, Adrenal Cortex Hormones, Internal medicine, Azathioprine, medicine, Clinical endpoint, Intestinal Fistula, Humans, Intestinal Mucosa, Retrospective Studies, Crohn's disease, Biological Products, Wound Healing, medicine.diagnostic_test, business.industry, Mercaptopurine, Tumor Necrosis Factor-alpha, Medical record, Gastroenterology, Immunosuppression, General Medicine, medicine.disease, Symptom Flare Up, Infliximab, Endoscopy, Hospitalization, Methotrexate, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, Follow-Up Studies
Abstract

Background and aims Long-term outcomes of early combined immunosuppression [top-down] compared to conventional management [step-up] in recently diagnosed Crohn's disease [CD] are unknown. We aimed to investigate long-term outcomes of participants of the Step-up/Top-down-trial. Methods Trial participants' medical records were reviewed retrospectively. For 16 semesters following the 2-year trial, we recorded: clinical activity, medication use, flares, hospitalization, surgery and fistulas. Colonoscopy reports were scored as: endoscopic remission, aphthous/small ulcers or large ulcers. The primary endpoint was the proportion of semesters in remission. Results Data were available from 119/133 patients [step-up n = 60]. During a median follow-up of 8 years, clinical remission rates were similar (70% vs 73% [p = 0.85] in step-up and top-down patients, respectively). A shorter time to flare was observed in step-up patients [median five vs nine semesters, p = 0.01]. Cumulatively, 62% of step-up patients used corticosteroids compared to 41% of top-down patients [p = 0.02]. Anti-tumour necrosis factor [anti-TNF] use was higher in the step-up group [73% vs 54%, p = 0.04]. No differences were found in to time to CD hospitalization [respectively 13 vs 14 semesters, p = 0.30], new fistula [14 vs 15 semesters, p = 0.20] or CD surgery [14 vs 15 semesters, p = 0.25]. Mucosal healing 2 years after treatment was associated with a reduced anti-TNF use, but not with differences in other long-term outcomes. Endoscopic remission occurred at similar rates between groups. Conclusions Top-down treatment did not result in increased clinical remission during long-term follow-up, compared to step-up treatment. However, lower relapse rates and a reduced use of anti-TNF agents and corticosteroids were observed. No difference was found in rates of endoscopic remission, hospitalization, surgery or new fistulas.

Published
2018

28. 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
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29. Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment

Author

Laurence Goethals, Marleen Borms, Lies Pottel, Sofie Derijcke, Hans Pottel, Michelle Lycke, Koen Van Eygen, David Debruyne, Philippe Vergauwe, Patrick Werbrouck, Hans Wildiers, Lore Ketelaars, Philip R. Debruyne, Véronique Ghekiere, and Tom Boterberg

Subjects
Gerontology, medicine.medical_specialty, Mini–Mental State Examination, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Cancer, Experimental and Cognitive Psychology, Cognition, Gold standard (test), medicine.disease, Test (assessment), Psychiatry and Mental health, Oncology, Internal medicine, Medicine, Dementia, business, Clock drawing test
Abstract

Objective: We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in-depth cognitive evaluation within a comprehensive geriatric assessment (CGA). Methods: Patients aged 70 years or older with a histologically confirmed diagnosis of cancer were evaluated with a full CGA, including CDT and Folstein Mini Mental State Examination (MMSE) as gold standard. Validation of the Freund CDT was defined in terms of diagnostic accuracy of the test through receiver operating characteristics (ROC)-analysis. To accept the Freund CDT as a screening tool, we estimated that the area under the ROC curve (AUC) had to differ significantly from 0.70 with an AUC of at least 0.85. Results: Two hundred elderly cancer patients with a mean age of 79.0 years were included. Four patients were excluded from the analyses because of invalid results. Potential cognitive impairment (MMSE ≤23) was observed in 27.0% of patients. Based on of the AUC±SE, the Freund CDT showed excellent diagnostic performance (0.95±0.17). Furthermore, it provided excellent sensitivity (94.3%) and high specificity (87.4%). Conclusions: Our results indicate that the Freund CDT can be used as an initial screening tool to detect elderly cancer patients in need of a more in-depth cognitive assessment within CGA, instead of the MMSE. Copyright © 2014 John Wiley & Sons, Ltd.

Published
2014
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30. Preoperative chemosensitivity testing as predictor of treatment benefit in adjuvant stage III colon cancer: Preliminary analysis of the PePiTA study

Author

Patrick Flamen, Marianne Paesmans, Amélie Deleporte, Jean-Luc Van Laethem, Philippe Vergauwe, Alain Hendlisz, Karen Geboes, Thierry De Grez, Jozef Janssens, T. Besse-Hammer, Alexis Buggenhout, Rafael Caparica, Marylene Clausse, Guido Deboever, Joanna Vermeij, Stéphane Holbrechts, Martine Piccart, Gauthier Demolin, L. D'Hondt, and Marc Van den Eynde

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Adjuvant chemotherapy, business.industry, medicine.medical_treatment, Stage III Colon Cancer, Preliminary analysis, carbohydrates (lipids), 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Adjuvant, Chemosensitivity assay, 030215 immunology
Abstract

3610 Background: Although being the standard-of-care for stage III colon cancer, no biomarkers can identify patients (pts) who benefit from adjuvant chemotherapy. In metastatic pts, the lack of metabolic response (mR) in FDG-PET/CT after 1 chemotherapy cycle predicts the absence of treatment benefit. The PePiTA study aims to evaluate if the absence of mR after 1 cycle of pre-operative chemotherapy is predictive of recurrence in non-metastatic colon cancer pts. Herein, we report a preliminary analysis on surgical outcomes, adverse events and mR assessment after 1 cycle of pre-operative chemotherapy after completing the study accrual objective. Methods: Colon cancer pts eligible for curative resection and ECOG ≤1 received 1 cycle of mFOLFOX followed by surgery in this prospective, multicentre, non-randomized trial. FDG-PET/CT was performed at baseline and after 1 cycle of mFOLFOX. Adjuvant mFOLFOX was administered for up to 12 cycles for stage III pts, whereas for stage II pts the decision to pursue adjuvant chemotherapy was at investigator’s discretion. A decrease ≥15% in SUVmax after 1 cycle of chemotherapy was defined as mR (EORTC criteria) at central review. Results: mR was assessable on the primary tumor in 204/240 pts (85%). In 11 pts (4.6%), staging was modified by the baseline FDG-PET/CT, which detected metastatic disease or other tumors. Pre-operative mFOLFOX was administered to 218 pts, of which 14 (6%) had a grade ≥3 adverse event. Surgery was performed in 218 pts, with a median delay of 20 days (6 to 59) after chemotherapy. Surgical complications occurred in 28 (13%) pts, however no deaths occurred. The median SUVmax decrease between baseline and 2nd FDG-PET/CT was 24%. A mR was observed in 65.2% of the pts, whereas 34.8% showed no mR, including 3% who had progressive disease. Conclusions: One cycle of pre-operative mFOLFOX followed by a mR assessment has shown to be a feasible and safe strategy, raising interest on the potential of neoadjuvant chemotherapy in colon cancer. The early mR assessment identified pts that may not benefit from chemotherapy and might have a worse prognosis. The substantiation of this hypothesis is expected with the study’s long-term results. Clinical trial information: NCT00994864.

Published
2019
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31. PD-030Prospective non-interventional study to collect data on the use of bevacizumab and conventional chemotherapy for the treatment of previously untreated metastatic colorectal cancer in patient's ≥70 years

Author

B. Naessens, Hans Prenen, Guy Lambrecht, Ghislain Houbiers, Cindy Kenis, E Monsaert, V. Moons, E. Van De Walle, E. Van Cutsem, L. Opstaele, Philippe Vergauwe, M De Man, L. Decoster, and Hans Wildiers

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, business.industry, Hematology, medicine.disease, Chemotherapy regimen, 03 medical and health sciences, Abstracts, 030104 developmental biology, 0302 clinical medicine, Text mining, 030220 oncology & carcinogenesis, Internal medicine, Non interventional, medicine, Conventional chemotherapy, In patient, business, medicine.drug
Published
2016

32. Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment

Author

Michelle, Lycke, Lies, Pottel, Hans, Pottel, Lore, Ketelaars, Karin, Stellamans, Koen, Van Eygen, Philippe, Vergauwe, Patrick, Werbrouck, Laurence, Goethals, Patricia, Schofield, Tom, Boterberg, and Philip R, Debruyne

Subjects
Adult, Aged, 80 and over, Male, Depression, Breast Neoplasms, Anxiety, Middle Aged, Neuropsychological Tests, Young Adult, Cognition, Cross-Sectional Studies, Memory, Humans, Cognitive Dysfunction, Female, Aged
Abstract

Recent research in the field of cancer-related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors.Patients (≥18 years) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated with a baseline neuropsychological assessment including Patient-Reported Outcome Measures (PROMs). PROMs entailed distress, anxiety and depression, fatigue, and cognitive complaints. The neuropsychological assessment comprised several cognitive domains such as premorbid IQ, attention, processing speed, flexibility, verbal and visual episodic memory, and verbal fluency.Cross-sectional data of 125 patients were collected. Patients had a mean age of 60.9 years (range: 30.0-85.0) and comprised primarily females (65.6%). Patients presented with cancer of following sites: breast (44.0%), digestive (28.8%), urological (11.2%), gynecologic (8.0%), hematologic malignancy (4.8%), and lung (3.2%). Patients presented with a premorbid IQ of 105.3 (range: 79.0-124.0). In 29.6% of patients, a CRCI was detected. Binary logistic regression analyses showed that a lower premorbid IQ (β = -.084, P .01) and a higher level of fatigue (β = -.054, P .05) predicted baseline CRCI. Premorbid IQ also predicted performance on individual cognitive domains. Some domains were also influenced by age, gender, having a breast cancer diagnosis, and an active treatment for hypertension.Premorbid IQ and fatigue are important predictors of baseline CRCI. Therefore, we advise researchers to implement a short IQ test when conducting clinical trials on CRCI.

Published
2016

33. A two arm phase II study of FOLFIRI in combination with standard or escalating dose of cetuximab as first line treatment for metastatic colorectal cancer: Everest 2 final results

Author

María Luisa Limón, G. Chiritescu, Sabine Tejpar, M.A. Fridrik, Philippe Vergauwe, T. Macarulla Mercade, Richard Greil, Jozef Janssens, Kristoffel R. Dumon, V. Moons, E. Vanderstraeten, Xavier Sagaert, Fernando Rivera, Koen Hendrickx, Marc Ferrante, E. Van Cutsem, István Láng, J.-L. Van Laethem, M. Van den Eynde, C. Santos Vivas, A. Cervantes, Julien Taieb, M. Pracht, Z. Papai, K. Geboes, and Ewald Wöll

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Cetuximab, business.industry, Colorectal cancer, Phases of clinical research, Hematology, medicine.disease, First line treatment, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, FOLFIRI, Medicine, business, medicine.drug
Published
2018
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34. High levels of cell-free DNA (cfDNA) at baseline (BL) and increase of at least one mutation at day 14 (D14) as independent prognostic biomarkers for patients (pts) with advanced colorectal cancer (aCRC) under regorafenib

Author

Marc Peeters, Jozef Janssens, Jean-Charles Goeminne, Amélie Deleporte, Caroline Vandeputte, Jean-Luc Van Laethem, Thierry Delaunoit, L. D'Hondt, Philippe Vergauwe, Stéphane Holbrechts, Ghanem Elias Ghanem, Lieveke Ameye, Hakim El Housni, Marianne Paesmans, Karen Geboes, Javier Carrasco, Pashalina Kehagias, Alain Hendlisz, Gauthier Demolin, and Patrick Flamen

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Advanced colorectal cancer, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Cell-free fetal DNA, chemistry, 030220 oncology & carcinogenesis, Internal medicine, Regorafenib, Mutation (genetic algorithm), Medicine, sense organs, business
Abstract

3532Background: BL-cfDNA combined with plasmatic changes in tumor-specific mutations after 14 days of therapy are explored as independent determinants of outcome in pts with aCRC. Methods: Archival...

Published
2018
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35. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial

Author

Severine Vermeire, Paul Rutgeerts, Fazia Mana, Hans Tuynman, Gert Van Assche, Philippe Vergauwe, Filip Baert, Brian G. Feagan, Sander J. H. van Deventer, Philippe Van Hootegem, Philip Caenepeel, Janneke van der Woude, Guy Lambrecht, Larry Stitt, Daniel W. Hommes, Frank J. Van de Mierop, Geert R. D'Haens, Allan Donner, Ad A. van Bodegraven, Martine De Vos, Jean-Charles R Coche, Thomas Ochsenkühn, Medical Microbiology & Infectious Diseases, Other departments, 01 Internal and external specialisms, Gastroenterology and hepatology, and Other Research

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Azathioprine, Inflammatory bowel disease, Management of Crohn's disease, Statistics, Nonparametric, Belgium, Crohn Disease, Adrenal Cortex Hormones, Germany, Internal medicine, medicine, Humans, Netherlands, Crohn's disease, Chi-Square Distribution, Intention-to-treat analysis, business.industry, Antibodies, Monoclonal, Immunosuppression, General Medicine, Bowel resection, medicine.disease, Infliximab, Surgery, Methotrexate, Treatment Outcome, Female, business, Immunosuppressive Agents, medicine.drug
Abstract

Summary Background Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab. Methods We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710. Findings Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60·0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35·9%) of 64 controls, for an absolute difference of 24·1% (95% CI 7·3–40·8, p=0·0062). Corresponding rates at week 52 were 40/65 (61·5%) and 27/64 (42·2%) (absolute difference 19·3%, 95% CI 2·4–36·3, p=0·0278). 20 of the 65 patients (30·8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25·3%) controls (p=1·0). Interpretation Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

Published
2008
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36. Baseline cell-free DNA (cfDNA) and metabolic tumor volume (MTV) independently predict outcome in metastatic chemorefractory colorectal cancer (mCRC)

Author

L. D'Hondt, Caroline Vandeputte, Stéphane Holbrechts, Jean-Luc Van Laethem, Lieveke Ameye, Thierry Delaunoit, Philippe Vergauwe, Karen Geboes, Javier Carrasco, Tarek Kamoun, Alain Hendlisz, Patrick Flamen, Gauthier Demolin, Jos Janssens, Pashalina Kehagias, Erwin Woff, Jean-Charles Goeminne, Thomas Guiot, Marc Peeters, and Marianne Paesmans

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, business.industry, Metabolic tumor volume, medicine.disease, chemistry.chemical_compound, chemistry, Cell-free fetal DNA, Regorafenib, Internal medicine, medicine, Prognostic biomarker, business
Abstract

11569 Background: No validated prognostic biomarker is currently available for mCRC. This trial assessed cfDNA and MTV before treatment with regorafenib as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS) in mCRC. Methods: After signed informed consent, mCRC patients were enrolled in a prospective non-randomized trial aiming to define unlikelihood to benefit from regorafenib (EudraCT number: 2012-005655-16) and assessed for cfDNA and FDG PET/CT MTV at baseline. cfDNA was extracted from 3mL of plasma and quantified using the Qubit 2.0 fluorometer. All target lesions were delineated on FDG PET/CT using a PERCIST-based threshold and their volumes were summed to obtain total MTV. MTV and cfDNA optimal cutoffs for OS and PFS prediction were determined by the Contal and O’Quigley’s method. MTV, cfDNA, age, gender, Body Mass Index (low, normal, high, obese), ECOG PS, number of chemotherapy lines (NCL), previous use of bevacizumab and presence of a KRAS mutation were included in a multivariate analysis. Results: MTV and cfDNA of 132 evaluable/141 eligible patients were well correlated (Spearman’s correlation coefficient = 0.70; p < 0.001) and risk groups for both PFS and OS were identified on the basis of cfDNA (cfDNA < 1 µg/mL; cfDNA≥1 µg/mL) and MTV (MTV < 100 cm³; 100-300 cm³; > 300 cm³). The multivariate analysis retained cfDNA, MTV, NCL, and obesity as independent parameters for PFS prediction, and cfDNA, MTV, NCL, BMI, and previous use of bevacizumab as independent parameters for OS prediction. Prognostic scores for PFS and OS were developed based on regression coefficients from the final Cox proportional hazards models. Prognostic scores for PFS (1.8 vs 5.3 months, HR: 3.15 for score ≥-3 vs < -3, (95% CI, 2.08-4.76); p < 0.001) and for OS (4.2 vs 13.9 months, HR: 4.59 for score ≥-6 vs < -6: (95% CI, 2.92-7.21); p < 0.001) both identified patients with much contrasted outcomes. Conclusions: Baseline cfDNA and MTV along with BMI parameters predict outcome in patients with mCRC before regorafenib onset. These parameters not related to treatment should be considered, if validated in further studies, as stratification factors in future clinical trials. Clinical trial information: 2012-005655-16.

Published
2017
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37. AVAPLUS: Impact of geriatric assessment on first-line treatment duration (TD) and progression free survival (PFS) in mCRC patients ≥ 70 years

Author

H. Wildiers, Ghislain Houbiers, L. Decoster, G. Lambecht, V. Moons, Hans Prenen, E. Beutels, C. Kenis, B. Naessens, E Monsaert, E. Van Cutsem, D. Frijns, Philippe Vergauwe, and M De Man

Subjects
Oncology, First line treatment, medicine.medical_specialty, business.industry, Internal medicine, medicine, Geriatric assessment, Hematology, Progression-free survival, Duration (project management), business
Published
2016
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38. Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study

Author

David Azria, Jean-Luc Van Laethem, Pascal Hammel, Philippe Vergauwe, Laurence Collette, Marc Polus, Murielle Mauer, Volker Budach, Geertjan van Tienhoven, Karin Haustermans, M. Praet, Eric Van Cutsem, Marc Peeters, Françoise Mornex, Manfred B. Lutz, CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
Adult, Diarrhea, Male, Oncology, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, Kaplan-Meier Estimate, Deoxycytidine, Drug Administration Schedule, Pancreatic cancer, Internal medicine, Original Reports, medicine, Humans, Fatigue, Aged, Chemotherapy, business.industry, Nausea, Middle Aged, medicine.disease, Combined Modality Therapy, Gemcitabine, Surgery, Pancreatic Neoplasms, Radiation therapy, Regimen, Treatment Outcome, Tolerability, Chemotherapy, Adjuvant, Feasibility Studies, Female, Radiotherapy, Adjuvant, business, Chemoradiotherapy, medicine.drug
Abstract

Purpose The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Patients and Methods Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). Results Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%). Conclusion Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.

Published
2010

39. Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015

Author

Muriel Debois, D. Braumann, L. Müller, Harry Bleiberg, Hansjochen Wilke, E. Späth-Schwalbe, J. Van den Brande, J. de Greve, H. Link, P. Reimer, Joerg T. Hartmann, Eric Joosens, E. Van Cutsem, Carsten Bokemeyer, István Láng, U. Bethe, Karl-Friedrich Becker, Jozef Janssens, C.-H. Köhne, Philippe Vergauwe, and Laboratory for Medical and Molecular Oncology

Subjects
Male, IRINOTECAN, Leucovorin, Gastroenterology, Deoxycytidine, PROGNOSTIC-FACTORS, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, ORAL CAPECITABINE, OXALIPLATIN, CELECOXIB, Infusions, Intravenous, Sulfonamides, Anti-Inflammatory Agents, Non-Steroidal, Hematology, Middle Aged, Shock, Septic, Oncology, Fluorouracil, FOLFIRI, Female, Colorectal Neoplasms, medicine.drug, Adult, Diarrhea, medicine.medical_specialty, CAPECITABINE, Adenocarcinoma, Capecitabine, Folinic acid, Double-Blind Method, FIRST-LINE, CYCLOOXYGENASE-2 INHIBITOR, Internal medicine, COLORECTAL, medicine, Humans, Progression-free survival, 5-FU, Aged, XELIRI, Cyclooxygenase 2 Inhibitors, business.industry, Survival Analysis, PHASE-III, FLUOROURACIL, Surgery, Irinotecan, Celecoxib, Pyrazoles, Camptothecin, ADENOMATOUS POLYPOSIS, business, Pulmonary Embolism
Abstract

BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). CONCLUSION: Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.

Published
2008
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40. Retrieval of a migrated esophagojejunal stent by using the double-balloon enteroscope

Author

Hans Orlent, Pierre Laukens, and Philippe Vergauwe

Subjects
medicine.medical_specialty, medicine.medical_treatment, Treatment outcome, Balloon, Risk Assessment, Endoscopy, Gastrointestinal, Esophagus, Postoperative Complications, Device removal, Foreign-Body Migration, Gastrectomy, Stomach Neoplasms, medicine, Humans, Radiology, Nuclear Medicine and imaging, Device Removal, Aged, Oesophagojejunal, business.industry, Anastomosis, Surgical, Gastroenterology, Follow up studies, Stent, Endoscopes, Gastrointestinal, Jejunum, Treatment Outcome, Fluoroscopy, Female, Stents, Radiology, business, Follow-Up Studies
Published
2007

41. 924 Long-Term Outcomes of Top-Down Versus Step-up Treatment in Newly Diagnosed Crohn's Disease: Final Data

Author

Filip Baert, Severine Vermeire, Daniël R. Hoekman, Judith A. Stibbe, Philippe Vergauwe, Martine De Vos, Philip Caenepeel, Geert R. D'Haens, and Adriaan A. van Bodegraven

Subjects
medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Incidence (epidemiology), Gastroenterology, medicine.disease, Ulcerative colitis, law.invention, Randomized controlled trial, law, Internal medicine, Cohort, Long term outcomes, Medicine, Medical prescription, business, Abdominal surgery
Abstract

G A A b st ra ct s variables, healthcare utilization, comorbidities and baseline immunosuppressive medication use, to assess the relative effectiveness and safety of IFX and ADA. Results: Our cohort comprised 1869 biologic-naive UC pts (age, 42.3±16.0y; 50.8% males) who were prescribed IFX (n=1470) or ADA (n=399) as first-line anti-TNF agents, and followed over median of 1.7 years (IQR, 0.9-3.0). Baseline demographics, healthcare utilization (outpatient, inpatient or emergency room visits; imaging and endoscopic procedures), comorbidities and prior medication exposure was comparable between the two groups (Table 1). As compared to ADA, pts treated with IFX were significantly less likely to require IBD-related hospitalization and new steroid prescription, after adjusting for baseline demographic variables, healthcare utilization, comorbidities and baseline immunosuppressive medication use (Table 2). There was no significant difference in the risk of abdominal surgery, though the number of events was small. Persistence on therapy at 6 months was significantly higher for IFX (61.4%) compared to ADA (14.8%). The incidence of serious infections was comparable between IFXand ADA-treated pts (incidence rate per 100 patient years: IFX vs. ADA, 1.49 vs. 2.25). Conclusion: In a large cohort of biologic-naive UC pts, IFX appears superior to ADA as first-line anti-TNF agent for important clinically relevant outcomes, without increased risk of serious infections. This requires further validation in randomized trials. Baseline characteristics of biologic-naive patients with ulcerative colitis.

Published
2015
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42. PD-0568 PHASE II STUDY OF NEO ADJUVANT TREATMENT WITH AVASTIN, XELODA AND ELOXATIN IN RECTAL CANCER (AXE BEAM)

Author

E. Van Cutsem, M. Verstraete, K. Haustermans, Kristoffel R. Dumon, G. Chiritescu, Xavier Sagaert, Philippe Vergauwe, J-P. Machiels, Annelies Debucquoy, and F. Penninckx

Subjects
medicine.medical_specialty, Oncology, business.industry, Colorectal cancer, Medicine, Phases of clinical research, Radiology, Nuclear Medicine and imaging, Hematology, Neo adjuvant, business, Nuclear medicine, medicine.disease, Surgery
Published
2012
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43. Final Results of a Randomized Phase Ii Study with Neo-Adjuvant Triplet or Doublet Therapy, Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer: Axe Beam

Author

F. Mardjuadi, Marc Polus, Yves Humblet, Xavier Sagaert, Annelies Debucquoy, J.-L. Van Laethem, G. Chiritescu, Philippe Vergauwe, J. Decaestecker, J.F. Daisne, J. Arts, Len Verbeke, Karin Haustermans, E. Van Cutsem, André D'Hoore, Kristoffel R. Dumon, and M. Verstraete

Subjects
medicine.medical_specialty, Bevacizumab, business.industry, Surrogate endpoint, Urology, Phases of clinical research, Hematology, Total mesorectal excision, Surgery, Oxaliplatin, Capecitabine, Oncology, Clinical endpoint, medicine, business, Chemoradiotherapy, medicine.drug
Abstract

Aim: To assess the activity and safety of bevacizumab (A) with capecitabine (X) and radiotherapy (RT) with or without oxaliplatin (E) in the preoperative treatment (thx) of locally advanced rectal cancer (LARC). To identify biomarkers for early response prediction. Methods: Patients (pts) with LARC were randomized to RT (1.8Gy/day) with the triplet A (5mg/kg), X (1650mg/m2/day) and E (50mg/m2) in Arm A or the doublet A + X without E in Arm B. Chemoradiotherapy (CRT) started at 2 weeks after 1st infusion of A and continued for 5 weeks. Total mesorectal excision (TME) was planned at 6-8 weeks post CRT. Pathological complete response (pCR) rate in Arm A was the primary endpoint. Safety profile and identification of biomarkers for early response prediction were secondary endpoints. Immunohistochemical staining for the functionality of blood vessels, proliferation and hypoxia as well as Luminex analyses to assess changes in circulating VEGF ligands are performed on tissues and blood samples from consenting pts. Results: Eighty-four pts with median age 61 completed thx, 81 including surgery, with a relative dose intensity of 98% for A and X and 93% for E. During CRT, serious adverse events (SAEs) were more frequent in Arm A vs Arm B: fever (4 vs 0), diarrhea (3 vs 0), infection (4 vs 1). Postoperative SAEs (wound infections, leaks) occurred in 17 pts, 10 in Arm A and 7 in Arm B. Five pts deceased post-study, 3 due to distant disease progression, 2 to postoperative complications. Post-surgery data are available for 81 pts. pCR was seen in 18 pts, 33% (14/43) in Arm A and 10% (4/41) in Arm B in an intent-to-treat analysis (ITT). The rate of good responders (Dworak TRG 3, 4) was higher in Arm A 29/43 vs Arm B 16/41 in ITT. Changes of the pericyte coverage of the blood vessels were observed. The decrease of plasma concentration of PDGF-AA and PDGF-BB correlated with pCR (p = 0.04 and 0.03 respectively). Conclusions: Both triplet and doublet combination showed acceptable safety profiles. The addition of E to X and A with RT seemed beneficial in terms of pCR rates in this patient population, with a slight increase of toxicity. The main endpoint has been reached with 14/43 pCRs in Arm A. PDGF may be a predictor of response in this setting. Final data after a blind central review of the main endpoint and translational research data will be available at the conference. Support from Roche and Sanofi Aventis. Disclosure: K. Haustermans: The author declares an educational grant from Roche for this study. No further conflict of interest; E. Van Cutsem: The author received research funding from Roche and Sanofi, paid to the university. All other authors have declared no conflicts of interest.

Published
2014
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44. Weekly Versus Biweekly Combination of Docetaxel (D)-Cisplatin (C)-5Fu (F) in Advanced Gastric Cancer and Esogastric Junction Adenocarcinoma (Agc): Doge Study

Author

Frédéric Forget, L. D'Hondt, Lieveke Ameye, Thierry Delaunoit, H. Rezaei Kalantari, Marianne Paesmans, E. Vanderstraeten, Alain Hendlisz, Stéphanie Laurent, Amélie Deleporte, A. Covas, Ghislain Houbiers, Marylene Clausse, M. Van den Eynde, Stéphane Holbrechts, Philippe Vergauwe, P. Pierre, B. Ghillemijn, J. Vanderauwera, and M. De Man

Subjects
medicine.medical_specialty, business.industry, Surrogate endpoint, Standard treatment, Phases of clinical research, Hematology, Neutropenia, medicine.disease, Gastroenterology, Surgery, Folinic acid, Regimen, Oncology, Docetaxel, Internal medicine, medicine, business, Febrile neutropenia, medicine.drug
Abstract

Aim: Triweekly DCF is a standard treatment in aGC, but is, however, associated with a bleak 30% febrile neutropenia (FN) incidence requiring prophylactic administration of granulocyte-colony stimulating factor (G-CSF). The DoGE study aims to define efficient but less toxic alternate DCF combinations. Methods: Chemonaive patients (pts) with aGC, age ≥ 18, PS ≤1 and normal organ function were randomized in a multicentric phase II trial (EudraCT 2008-000551-10) between a weekly (D 40 mg/m2,C 35 mg/m2, folinic Acid (FA) 400 mg/m2, F 1800 mg/m2 24 h infusion on days 1 and 8 every 3 weeks (wks), arm 1) and a biweekly regimen (D 50 mg/m2, C 50 mg/m2, FA 400 mg/m2, F 2000 mg/m2 48 h infusion every 2 wks, arm 2). G-CSF was allowed only as secondary prevention. The tumors were assessed every 6 wks. A Briant & Day two -teps design with toxicity and rate of non-progressive disease as primary endpoints was used. Insufficient efficacy was defined as 6 wks-disease control rate (DCR) 25% FN (b = 10% and a = 10% for activity, 15% for toxicity). Results: Between Oct 2008 and Oct 2013, 106 pts were recruited in 15 centers: 76 males (71.7%), PS 0/1: 60 (57%)/46 (43%), median age 62(33-85). Early study closure due to slow accrual led to a reduced 80% power. Among the 103 pts who received the study medications (52 arm 1 and 51 arm 2), 77% and 86% experienced grade III-IV toxic reactions, mainly neutropenia (21%,95% CI 12-34 in arm 1 vs 59%, 95% CI 45-71 in arm 2), and similar fatigue (27% vs 25%), anorexia (19% vs 18%) and diarrhea (15% vs 12%) in both arms. The 6 wks-DCR was 83%, 95% CI 71-91 in arm 1 and 79%, 95% CI 67-88 in arm 2. The pts' outcomes are reported hereunder. Regimen Grade III-IV toxicities * FN at 6 wks * Toxic deaths * mOS¶ mPFS¶ Weekly (arm1) 77 (64-86) 9.6 (4-21) 9 (4-20) 8.2 (6.0-14.5) 5.1 (3.2-6.5) Biweekly (arm2) 86 (74-93) 6 (2-16) 4 (1-13) 11.9 (7.4-15.9) 5.2 (3.0-6.9) * in % (95% CI); ¶ in months (95% CI) Conclusions: Weekly and biweekly DCF meet the study's safety requirements with less than 10% FN rate without G-CSF support. Both regimens have adequate efficacy according to the study design, consistent with the literature findings on the triweekly regimen, and represent valuable alternatives for further clinical development. Disclosure: All authors have declared no conflicts of interest.

Published
2014
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45. AXE Beam: Neo-Adjuvant Triplet Versus Doublet Therapy with Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer – A Randomized Phase II Study at the End of Recruitment

Author

Philippe Vergauwe, J. Decaestecker, G. Chiritescu, Xavier Sagaert, J.F. Daisne, J. Arts, Len Verbeke, Kristoffel R. Dumon, M. Verstraete, Karin Haustermans, J.-L. Van Laethem, André D'Hoore, Marc Polus, E. Van Cutsem, Annelies Debucquoy, Yves Humblet, and F. Mardjuadi

Subjects
medicine.medical_specialty, business.industry, Colorectal cancer, Locally advanced, Phases of clinical research, Hematology, Neo adjuvant, medicine.disease, Total mesorectal excision, Surgery, Pharmaceutical Adjuvants, Oncology, Rectal carcinoma, medicine, business
Published
2014
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46. Su1123 Top-Down Versus Step-Up Treatment in Newly Diagnosed Crohn's Disease: No Difference in Long-Term Outcome

Author

Judith A. Stibbe, Daniël R. Hoekman, Filip Baert, Geert R. D'Haens, Severine Vermeire, Martine De Vos, Philip Caenepeel, and Philippe Vergauwe

Subjects
Crohn's disease, Pediatrics, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine, Newly diagnosed, medicine.disease, business, Outcome (game theory), Term (time)
Published
2014
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47. Preoperative (preop) chemosensitivity testing as predictor of treatment benefit in adjuvant stage III colon cancer (CC): Interim analysis of the PEPITA study

Author

André Efira, Amélie Deleporte, Joanna Vermeij, M Gomez Galdon, Alexis Buggenhout, Philippe Vergauwe, Lionel D'Hondt, Camilo Garcia, Van Den Eynde, A. Hendlisz, Jozef Janssens, Patrick Flamen, J.-L. Van Laethem, Gauthier Demolin, Stéphane Holbrechts, Martine Piccart-Gebhart, Stéphanie Laurent, Marylene Clausse, and Guido Deboever

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Adjuvant chemotherapy, Colorectal cancer, medicine.medical_treatment, medicine.disease, Interim analysis, Surgery, Internal medicine, medicine, Stage (cooking), business, Chemosensitivity assay, Adjuvant
Abstract

385 Background: Adjuvant chemotherapy (CT) improves stage III CC outcome but is not effective for all patients (pts). PePiTA’s main hypothesis is that absence of metabolic response (MR) of the primary tumor after 1 preop CT course predicts absence of benefit from adjuvant CT (at 3-year DFS). This strategy's aim is to spare pts from useless toxicities, improve healthcare resource allocation, and guide translational research. This interim analysis was performed for safety and feasibility of MR assessment (MRA). Methods: Pts ≥ 18 years, with PS ≤ 1, diagnosed with CC considered for curative resection are eligible, after signed consent. Baseline PET is repeated after 1 CT cycle, followed by surgery. PET quality insurance and MRA are performed centrally and the result is blinded for investigators. Results: From 2010 to 2013, 114 pts—M/F (55%/45%), median age 66 (26-81), ECOG 0/1(92%/8%)—were included in 15 Belgian centers. 11 pts were excluded from analysis: 2 hyperglycemia at baseline PET; 2 withdrew consent; 6 PET-revealed stage IV CC; and 1 second cancer. Preop CT was associated with 5% grade (gr) 3-4 neutropenia, 1% gr 3 diarrhea, 1% gr 3 hypokaliemia, 1% peritonitis and 1% gr 3 thromboembolic events. Colectomies were performed in all pts after a median of 20 days (interquartile interval 18-21): 32 right (31%), 69 left (67%), and 2 procedures not detailed. Pathology showed stages 0 (1%), I (13%), II (34%), III (47%), IV (7%), without lymph node downstaging. Postoperative morbidity is 9% (95%CI 5-16%) and includes fistulas (4%), transient ischemic attack (1%), ileus (2%), and evisceration (1%), but no death. Technical or methodological reasons prevented MRA in 19/103 pts. Median SUVmax was 14.4 (4.9-47.8) at baseline, and 10.9 (0-39.3) on day 14. 2 pts presented with complete MR. For the others, median delta SUVmax was -22% (-60 to +31%). MR was observed in 60% of pts, and was absent in 40%, with equal distribution for stages II and III (p = 1.00). Conclusions: 1 course of CT is feasible before curative surgery for CC, without inducing excessive toxicity, delay or surgical morbidity. MRA indicated metabolic signs of chemoresistance in 40% of the primary tumors. Clinical trial information: NCT00994864.

Published
2014
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48. Axe Beam: Encouraging Early Results of a Neo-Adjuvant Bevacizumab, Capecitabine +/- Oxaliplatin and Radiation Multimodality Regimen for Locally Advanced Rectal Cancer

Author

M. Verstraete, E. Van Cutsem, J. Arts, Kristoffel R. Dumon, Philippe Vergauwe, Karin Haustermans, Xavier Sagaert, André D'Hoore, G. Chiritescu, and Annelies Debucquoy

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, business.industry, Colorectal cancer, Phases of clinical research, Hematology, medicine.disease, Oxaliplatin, Capecitabine, Regimen, Internal medicine, medicine, business, Chemoradiotherapy, Febrile neutropenia, medicine.drug
Abstract

In an academic multicentric phase II study, patients (pts) with locally advanced rectal cancer are randomized to receive bevacizumab (5mg/kg), capecitabine (1650mg/m2/day) and radiotherapy (1.8Gy/day) with (Arm A) or without (Arm B) oxaliplatin (50mg/m2). Chemoradiotherapy (CRT) starts at 2 weeks after 1st infusion of bevacizumab and continues for 5 weeks. Total mesorectal excision is planned at 6-8 weeks post CRT. Immunohistochemical staining to study the functionality of blood vessels and Luminex analyses to assess the changes in circulating VEGF ligands are performed on tissues and blood samples from consenting pts. Pathological complete response (pCR) rate, safety profile and identification of biomarkers for early response prediction are the main endpoints. Results Sixty five pts with median age 60 have been enrolled to date. Fifty seven pts completed the full protocol scheme, with a relative dose intensity of 97% for bevacizumab, 95% for capecitabine and 93% for oxaliplatin. Preliminary safety data from 60 evaluable pts show that the regimen is generally well tolerated. Most severe adverse events were post-operative (wound infections, leaks) in 9 pts, equally distributed between arms. During CRT, grade 3 toxicities were more frequent in Arm A: fatigue (1), diarrhea (2), infection (2), febrile neutropenia (1), sensory neuropathy (1). Two pts deceased due to disease progression and one due to lung embolism post-surgery. Fifty two pts are evaluable for response. pCR was seen in 11 pts, 30% (8/26) in Arm A and 12% (3/26) in Arm B (p = 0.08). The rate of good responders (Dworak TRG 3,4) was higher in Arm A 18/26 versus Arm B 10/26 (p = 0.05). Changes in the pericyt coverage of the blood vessels, proliferation of the tumour cells and plasma concentrations of PDGF-AA, PDGF-BB and VEGF were observed and will be further assessed. Conclusions Chemoradiotherapy in combination with bevacizumab showed an acceptable safety profile in this patient population. Adding oxaliplatin determined a slight increase of toxicity but might enhance the percentage of responders. PDGF may be a predictor of response in this setting. Further analyses are ongoing. Conducted with support from Roche and Sanofi Aventis. Disclosure K. Haustermans: The author has received research funding from Roche. E. Van Cutsem: The author has received research funding by Roche and Sanofi Aventis. All other authors have declared no conflicts of interest.

Published
2012
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49. Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: A phase II study of the Belgian Group of Digestive Oncology

Author

Stéphanie Laurent, Ivan Borbath, Anne Demols, E. Van Cutsem, J.-L. Van Laethem, Amélie Deleporte, A. Ceratti, Thierry Delaunoit, Chris Verslype, and Philippe Vergauwe

Subjects
Oncology, Cancer Research, medicine.medical_specialty, biology, Cetuximab, business.industry, Incidence (epidemiology), Gallbladder, Phases of clinical research, Gemcitabine, medicine.anatomical_structure, Internal medicine, medicine, biology.protein, Clinical endpoint, In patient, Epidermal growth factor receptor, business, medicine.drug
Abstract

245 Background: Cholangiocarcinomas (CCK) are uncommon tumors with an increasing incidence and a poor prognosis. Epidermal growth factor receptor (EGFR) expression and activation in CCK have been demonstrated. Methods: We conducted a multicenter phase II trial combining cetuximab (Ctx), an anti-EGFR chimerized IgG1 monoclonal antibody, to gemcitabine (Gem). Patients with either locally advanced (LA) or metastatic (M) CCK (excluding gallbladder) were included; no prior systemic therapy was allowed. Ctx was administrated at the initial dose of 400 mg/m2 and further injections at 250 mg/m2 every 7 days, and Gem was administrated at 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. A Simon 2-stage design was used. We hypothesized that Gem/Ctx would improve 6 month-PFS rate from 20% to 40%. We needed 3 patients with PFS ≥ 6 months from the first 13 to further include a total of 43 patients. Results: Forty-four patients with advanced CCK (41% LA/59%M) were enrolled from 09/2008 to 01/2010. Median age was 61.5 years (range 40-86) and baseline ECOG PS was 0 for 68% and 1 for 32% of the patients. Forty-three percent of the patients had prior surgery. Forty-six percent of the patients were free from progression at 6 months. Median PFS was 5.8 months (95% CI, 4.4-7.4 m) and median overall survival was 11.6 months (95% CI, 8.7-14.6 m). Nine patients (20.9%) had partial response with a median duration of 5 months (range 2-10 m). Disease control rate (PR + SD > 8 weeks) was 81.4%. The most common grades 3/4 related-toxicities were haematological abnormalities (47.7%), skin rash (13.6%) and fatigue (11.3%). Due to toxicity, 6 patients discontinued study treatment; 14 and 3 patients had a Gem and Ctx dose reduction respectively. Among the nine responders, 8 experienced a skin rash of at least grade 2, suggesting a relationship between skin toxicity and efficacy. Conclusions: Our study met its endpoint, i.e., a PFS rate of 46% at 6 months, suggesting that Gem-Ctx combination had promising activity with a manageable toxicity profile in advanced CCK. Adding Ctx to the new standard of care Gem-cisplatin deserves further investigations in CCK. [Table: see text]

Published
2011
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50. W1133 Mucosal Healing Predicts Sustained Clinical Remission in Early Crohn's Disease

Author

Philippe Vergauwe, Liesbeth Moortgat, Gert A. Van Assche, Geert R. D'Haens, Filip Baert, Philip Caenepeel, Brian G. Feagan, Paul Rutgeerts, Severine Vermeire, Pieter C. F. Stokkers, Daniel W. Hommes, and Martine De Vos

Subjects
Crohn's disease, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Mucosal healing, Gastroenterology, medicine, medicine.disease, business
Published
2008
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