Publications by authors named "Pierre Michel"

136 Publications

Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19.

Ann Hepatol 2021 Feb 20:100334. Epub 2021 Feb 20.

Service de Médecine Vasculaire, GHRMSA, Hôpital Emile Muller, 20, Rue du Dr Laennec, 68051 Mulhouse, France.

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http://dx.doi.org/10.1016/j.aohep.2021.100334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896488PMC
February 2021

Management of digestive cancers during the COVID-19 second wave: A French intergroup point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR).

Dig Liver Dis 2021 03 17;53(3):306-308. Epub 2020 Dec 17.

Digestive Oncology Department, Reims University Hospital, Reims, France.

Introduction: The COVID-19 pandemic has major impact of healthcare systems, including cancer care pathways. The aim of this work is to discuss in a multidisciplinary approach the therapeutic and/or strategies adaptations for patients treated for a digestive cancer during the European second wave of COVID-19 pandemic.

Methods: A collaborative work was performed by several French societies to answer how to preserve digestive cancer care with no loss of chance during the second wave of COVID-19. In this context, all recommendations are graded as expert's agreement according to level evidence found in literature until October 2020 and the experience of the first wave of the COVID-19 pandemic.

Results: As far as possible, no therapeutic modification should be carried out. If necessary, therapeutic adjustments may be considered if they do not constitute a loss of chance for patients. Considering the level of evidence all therapeutic modifications need to be discussed in multidisciplinary tumor board meeting and with patient consent. By contrast to first wave cancer prevention, cancer screening, supportive care and clinical trials should be continued.

Conclusion: Recommendations proposed could limit cancer excess mortality due to the COVID-19 pandemic but should be adapted according to the situation in each hospital.
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http://dx.doi.org/10.1016/j.dld.2020.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836265PMC
March 2021

Systematic Duplex Ultrasound Screening in Conventional Units for COVID-19 Patients with Follow-up of 5 Days.

J Vasc Surg Venous Lymphat Disord 2020 Dec 2. Epub 2020 Dec 2.

Service de Médecine Vasculaire , GHRMSA ,Hôpital Emile Muller, Mulhouse,France.

Objective: COVID-19 patients may develop coagulopathy which is associated with poor prognosis and high risk of thrombosis. The objective of this work was to evaluate the prevalence of deep venous thrombosis of lower limbs (DVT) through ultrasonography in patients infected with COVID-19 admitted to hospital in conventional units with 5 days monitoring. The secondary objective was to determine if D-dimer levels body mass index (BMI) and C-reactive ; protein (CRP) were associated with DVT.

Materials And Methods: 72 patients with a mean age of 65±12.3 years infected with COVID-19 were admitted to three conventional units at our institution ,28 patients were women. A COVID-19 diagnosis was made by transcriptase polymerase chain reaction by means of nasopharyngeal swab or by chest computer tomography (CT) without iodine contrast media. Demographics ,co-morbidities characteristics and laboratory parameters were collected . A preventive anticoagulation treatment was established on admission with low molecular weight heparin (LMWH) . A complete venous duplex ultrasound (DU) test of lower limbs was performed on Day (D) 0 and D5 .A pulmonary CT angiograms with iodine contrast media (CTPA) was required when was ; suspected pulmonary embolism (PE).

Results: On D0 the DU showed acute DVT in seven patients (9.75%).A CTPA was performed in 12 patients (16.65%) ,3 of whom with an acute PE (25 %). On D0 acute DVT was not significantly associated with CRP (mean 101±98.6 in the group without DVT versus 67.6±58.4 mg/l p=0.43) or BMI ( 27.7 ±5.04 versus 28.1 ± 2.65 Kg/m2 p=0.54 ).However we found a significant association between acute DVT and D-dimer levels (1536±2347 versus 9652 ±10205 ng/ml p <0.01).Among the patients included on D0 only 32 had a DU on D5.Forty of them (55.55%) were not examined for the following reasons : 7 were previously diagnosed with VTE on D0 (9.7%) and therefore had been excluded on D5 8 (11%) had been transferred to the intensive care unit (ICU) 10 (14%) discharged from the hospital 5 (7%) died and 10 ( 13.9%) due to technical issues. On D5 5 patients had acute DVT (15.6%) in addition to those found on D0 3 were distal and 2 proximal despite preventive anticoagulation with LMWH.

Conclusions: Hospitalized non ICU patients with COVID-19 pneumonia have a high frequency of venous thrombotic events justifying screening with duplex ultrasound.
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http://dx.doi.org/10.1016/j.jvsv.2020.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709786PMC
December 2020

Comparison of physical activity and quality of life in home haemodialysis (HHD) patients versus conventional in-centre haemodialysis (ICHD) patients: the observational, longitudinal, prospective, international, multicentric SeCoIA study protocol.

BMC Nephrol 2020 11 23;21(1):500. Epub 2020 Nov 23.

Physidia SAS, Saint-Barthélémy-d'Anjou, France.

Background: Home haemodialysis (HHD), has shown improved clinical outcomes, as well as a better quality of life, compared to conventional in-centre haemodialysis (ICHD) but still has a global low prevalence among end-stage renal disease patients. Haemodialysis (HD) patients tend to be sedentary but only few studies, mainly in North American ICHD patients, have evaluated the level of activity in HD patients.

Methods: SeCoIA is an observational, longitudinal, prospective, international, multicentric, study, conducted in metropolitan France and Belgium. The main objective of the study is to quantify the physical activity measured by the total daily number of steps, in HHD patients compared to ICHD patients. The SeCoIA study will include 80 HHD patients and 80 ICHD patients,. Secondary objectives will be to characterize the HHD population and to confirm HHD efficiency on clinical parameters, as well as quality of life (QoL), in current practice. Physical activity will be measured by a 3-axis accelerometer. Accelerometers have been shown to provide accurate information, on both physical activity and sedentary behaviour. Patients will be instructed to wear the device and complete a patient diary 7 consecutive days after inclusion and the first week of each month for 12 months. Decision to undergo HDD or ICHD is independent of the study and follow-up frequency remains at the discretion of the physician/centre. QoL and quality of sleep will be respectively assessed by the Kidney Disease Quality of Life 1.2 (KDQOL™) and the Pittsburg Sleep Quality index (PSQI) questionnaires at inclusion, 6- and 12-month visits. Patients presenting a restless leg syndrome (RLS) will also complete the International Restless Legs Syndrome rating scale (IRLS) questionnaire.

Discussion: The SeCoIA study will be the first large cohort study (160 patients) evaluating physical activity, objectively measured with a 3-axis accelerometer, in HHD versus ICHD patients. The present study will also include a comparison of QoL with a focus on RLS between HHD and ICHD. It is anticipated that HHD patients will have an improved physical activity and QoL which should encourage physicians to further promote HHD.

Trial Registration: Clinical trial NCT03737578 study registered on November 9, 2018 (Retrospectively registered).
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http://dx.doi.org/10.1186/s12882-020-02127-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682091PMC
November 2020

What is the Best Therapeutic Strategy for Metachronous Resectable Colorectal Liver Metastases After Adjuvant Oxaliplatin-Based Chemotherapy? A Multidisciplinary Inter-Group Survey.

World J Surg 2021 Mar 18;45(3):822-830. Epub 2020 Nov 18.

Department of Digestive Surgery and Surgical Oncology, Bicêtre Hospital, APHP, Le Kremlin Bicêtre, France.

Background: To report the current clinical practice of French physicians for metachronous resectable liver metastasis (LM) occurring after a FOLFOX adjuvant chemotherapy for primary cancer.

Methods: Twenty four clinical situations were proposed to a panel of experts via 4 learned societies. Clinical situations varied according time of recurrence (early between 6 and 12 month or > 12 month), extension of LM (limited ≤ 2 or extended > 2 lesions), presence of a neuropathy or not, and of a RAS or BRAF mutation.

Results: A total of 157 physicians participated in this study. A consensus was reached in 17 (71%) clinical situations. For an early limited recurrence, whatever presence of neuropathy, the preferred therapeutic approach (45%) was upfront surgery. For an early extended recurrence, whatever presence of neuropathy, there was a consensus (64%) for a preoperative chemotherapy by FOLFIRI + biologic agent. For a late recurrence without neuropathy, there was a consensus (50%) for a preoperative FOLFOX chemotherapy, whatever the extension of LM. For a late recurrence with neuropathy, upfront surgery was chosen (52%) for limited LM, and preoperative chemotherapy by FOLFIRI + biologic agent (73%) for extended LM. No response was influenced by the RAS mutation status. There was a strong consensus for intensified preoperative chemotherapy in all clinical situations for BRAF-mutated LM.

Conclusions: This national survey provides an overview of the practice patterns in the treatment of LM occurring after adjuvant FOLFOX for primary. It could be a basis to establish expert's recommendations for the clinical practice.
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http://dx.doi.org/10.1007/s00268-020-05837-zDOI Listing
March 2021

Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19.

Ann Hepatol 2021 Mar-Apr;21:100274. Epub 2020 Oct 30.

Service de Médecine Vasculaire, GHRMSA, Hôpital Emile Muller, 20, Rue du Dr Laennec, 68051 Mulhouse, France.

Introduction And Objectives: Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of venous thromboembolic (VTE) events and elevated aminotransferases (AT).The objective of this work was to evaluate the incidence of aminotransferases disorders in patients infected with COVID-19 and to manage the VTE events associated with elevated AT.

Patients Or Materials And Methods: We report a retrospective study of 46 patients admitted for COVID-19 infection. Venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using low molecular weight heparin with Enoxaparin. Demographics, comorbidities and laboratory parameters were collected and analyzed.

Results: Elevated AT were reported in 28 patients (61%). 10 had acute VTE events of which eight (17.4%) had aminotransferases disorders. They had been treated with curative Enoxaparin. After a follow-up of 15 and/or 30 days, six of them were controlled, and treated with direct oral anticoagulant (DOACs) after normalization of aminotransferases.

Conclusions: The incidence of aminotransferases disorders associated with acute VTE events in patients infected with COVID-19 is significant. The use of DOACs appear pertinent in these patients. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.
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http://dx.doi.org/10.1016/j.aohep.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833905PMC
October 2020

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

Eur J Cancer 2020 12 8;141:62-81. Epub 2020 Oct 8.

Department of Gastroenterology, Saint Louis Hospital, APHP, Université de Paris, Paris, FFCD, France.

Background: Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated.

Patients And Methods: In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and 11th June 2020. The primary end-point was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary end-points.

Results: From April 4 to 11th June 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except for cytotoxic chemotherapy in the subgroup of patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment (such as chemotherapy, targeted or immune therapy) interrupted or stopped following diagnosis of COVID-19.

Conclusions: Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.
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http://dx.doi.org/10.1016/j.ejca.2020.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543792PMC
December 2020

Maintenance treatment with fluoropyrimidine plus bevacizumab versus fluoropyrimidine alone after induction chemotherapy for metastatic colorectal cancer: The BEVAMAINT - PRODIGE 71 - (FFCD 1710) phase III study.

Dig Liver Dis 2020 10 31;52(10):1143-1147. Epub 2020 Jul 31.

University hospital Saint Louis, APHP, Paris, France.

Background: Maintenance treatments with fluoropyrimidine alone or combined with bevacizumab after induction chemotherapy are two standard options in first-line metastatic colorectal cancer (mCRC). However, no trial has compared these two maintenance regimens.

Methods: BEVAMAINT is a multicenter, open-label, randomized phase III trial comparing fluoropyrimidine alone or plus bevacizumab as maintenance treatment after induction polychemotherapy in mCRC. The primary endpoint is the time-to-treatment failure (TTF), calculated from date of randomization to first radiological progression, death, start of a new chemotherapy regimen (different from induction or maintenance chemotherapy) or end of maintenance treatment without introduction of further chemotherapy. We expect a 2-month TTF improvement from 6 months in the monotherapy arm to 8 months in the combination arm (hazard ratio [HR], 0.75). Based on a two-sided α risk of 5% and a power of 80%, using Schoenfeld method, 379 events are required (planned enrolment, 400 patients). Patients with mCRC, whose disease is measurable according to RECIST 1.1 criteria and controlled (objective response or stable disease) - but remains unresectable - after 4 to 6 months of induction polychemotherapy (doublet or triplet chemotherapy with or without anti-EGFR or bevacizumab), and who have recovered from limiting adverse events of induction polychemotherapy are eligible for randomization. Randomization is stratified according to center, response to induction chemotherapy (objective response vs stable disease), ECOG performance status (0-1 vs 2), maintenance fluoropyrimidine (5-fluorouracil vs capecitabine) and primary tumor status (resected vs not). Capecitabine or bolus and infusional 5-fluorouracil plus folinic acid (simplified LV5FU2 regimen) are both accepted for maintenance chemotherapy, at investigator's discretion. Clinical evaluation, tumor imaging, carcinoembryonic antigen and circulating tumor DNA dosages are planned at enrolment and every 9 weeks. The maintenance treatment will be discontinued in the event of unbearable toxicity, progression or patient refusal. After maintenance discontinuation, reintroduction of induction polychemotherapy is recommended; otherwise a second-line treatment is started. The enrolment has begun in January 2020.
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http://dx.doi.org/10.1016/j.dld.2020.06.034DOI Listing
October 2020

The Day after Tomorrow: How Should We Address Health System Organization to Treat Cancer Patients after the Peak of the COVID-19 Epidemic?

Oncology 2020 17;98(12):827-835. Epub 2020 Jul 17.

Department of Digestive Surgery, Rouen University Hospital, Rouen, France.

On March 11, 2020, the WHO director general declared COVID-19 a pandemic. This pandemic evolves in successive phases, i.e., phase 1 (the start phase), phase 2 ("the storm"), and phase 3 (the recession). To date, oncology and surgery groups have only given instructions for addressing phases 1 and 2. To prevent excess cancer mortality, health care systems (HCS) need to be restructured. Our aim is to detail the specificities of each epidemic phase and discuss several methods of organization to optimize cancer patient flow during the COVID-19 pandemic, particularly during phase 3. Hospitals must be reorganized in order to create a cancer hub that is free of infection, allowing for the safe treatment of patients. Hospital structures are different, but all allow for the creation of virus-free areas. Screening programs are critical and need to be applied to all people entering the virus-free zone, including health care workers. Some reorganization proposals are internal to a hospital, while others require interhospital collaboration. The heterogeneity and complexity of HCS will make interhospital management difficult. The ministry of health has an important role in managing the cancer crisis. Cancer management should be declared a priority. Oncological and surgical societies must coordinate their efforts to facilitate this prioritization. The anticipation of oncological management during phase 3 of the pandemic is necessary because it requires a complete readjustment of HCS. This adaptation should allow for the continuation of cancer care to prevent excess cancer mortality, as the virus will still be present for a currently undetermined period of time.
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http://dx.doi.org/10.1159/000509650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445382PMC
December 2020

Application of Functional Data Analysis to Identify Patterns of Malaria Incidence, to Guide Targeted Control Strategies.

Int J Environ Res Public Health 2020 06 11;17(11). Epub 2020 Jun 11.

Aix Marseille Université, Assistance Publique-Hôpitaux de Marseille(APHM), INSERM, IRD, SESSTIM, Hop Timone, BioSTIC, Biostatistic and ICT, 13005 Marseille, France.

We introduce an approach based on functional data analysis to identify patterns of malaria incidence to guide effective targeting of malaria control in a seasonal transmission area. Using functional data method, a smooth function (functional data or curve) was fitted from the time series of observed malaria incidence for each of 575 villages in west-central Senegal from 2008 to 2012. These 575 smooth functions were classified using hierarchical clustering (Ward's method), and several different dissimilarity measures. Validity indices were used to determine the number of distinct temporal patterns of malaria incidence. Epidemiological indicators characterizing the resulting malaria incidence patterns were determined from the velocity and acceleration of their incidences over time. We identified three distinct patterns of malaria incidence: high-, intermediate-, and low-incidence patterns in respectively 2% (12/575), 17% (97/575), and 81% (466/575) of villages. Epidemiological indicators characterizing the fluctuations in malaria incidence showed that seasonal outbreaks started later, and ended earlier, in the low-incidence pattern. Functional data analysis can be used to identify patterns of malaria incidence, by considering their temporal dynamics. Epidemiological indicators derived from their velocities and accelerations, may guide to target control measures according to patterns.
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http://dx.doi.org/10.3390/ijerph17114168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312547PMC
June 2020

COVID-19 epidemic: Proposed alternatives in the management of digestive cancers: A French intergroup clinical point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR).

Dig Liver Dis 2020 06 14;52(6):597-603. Epub 2020 May 14.

Department of Hepatogastroenterology, Normandie Université, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, F 76000 Rouen, France. Electronic address:

Introduction: Patients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic.

Methods: French societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients' risk of contamination while continuing to treat their cancer. All recommendations are graded as experts' agreement according to the level of evidence found in the literature until March 2020.

Results: A proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent.

Conclusion: COVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.
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http://dx.doi.org/10.1016/j.dld.2020.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255323PMC
June 2020

Correction to: Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).

BMC Cancer 2020 03 3;20(1):168. Epub 2020 Mar 3.

Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Paul Brousse Hospital, Villejuif, France.

Following publication of the original article [1], the authors reported an error in the "Samples size calculation and statistical considerations" section.
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http://dx.doi.org/10.1186/s12885-020-6678-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053072PMC
March 2020

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Rapid Nanopore Whole-Genome Sequencing for Anthrax Emergency Preparedness.

Emerg Infect Dis 2020 02;26(2):358-361

Human anthrax cases necessitate rapid response. We completed Bacillus anthracis nanopore whole-genome sequencing in our high-containment laboratory from a human anthrax isolate hours after receipt. The de novo assembled genome showed no evidence of known antimicrobial resistance genes or introduced plasmid(s). Same-day genomic characterization enhances public health emergency response.
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http://dx.doi.org/10.3201/eid2602.191351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986837PMC
February 2020

Patients' perception and attitude to totally implantable venous access for urologic or digestive cancer: A cross-sectional study.

Bull Cancer 2019 Nov 14;106(11):959-968. Epub 2019 Oct 14.

Rouen University Hospital, Research group "Dynamics and Events of Care Pathways", 76000 Rouen, France.

Introduction: Totally implanted venous access (TIVA) improves the safety and welfare of patients treated with cancer chemotherapy (CCT). We aimed to evaluate patients' perception of TIVA placement, TIVA use, and information on TIVA, and to assess the association between patients' perception and their attitude regarding a potential TIVA re-implantation.

Methods: We conducted a single center cross-sectional survey in a university hospital in Northern France. Patients included were consecutive urologic or digestive cancer inpatients admitted for a CCT cycle via TIVA between April 9th and May 9th 2014. We analyzed patients' satisfaction, experience, and attitude, especially when requiring potential TIVA re-implantation under local anesthesia (LA), using a standardized questionnaire and medical records. We analyzed risk factors for refusing potential TIVA re-implantation under LA using multivariate logistic regression.

Results: Eighty-one patients were interviewed (no refusals), including 57 with a TIVA device placed under LA in our university hospital. Among them, 52/57 (91%) reported satisfactory TIVA placement, but respectively 21/57 (37%) and 18/57 (32%) complained of painful or uncomfortable TIVA placement; 51/57 (89%) were satisfied with care provided during CCT cycles. Risk factors for refusing potential re-implantation under LA were: TIVA placement considered painful (P=0.012) or uncomfortable (P=0.038) and dissatisfaction with care provided during CCT cycles (P=0.028).

Discussion: We show that despite good overall satisfaction regarding TIVA, some aspects were less positive and warrant improvement actions. It suggests that these actions could not only improve patients' experience of TIVA use but could also facilitate continuation of treatment in the long term.
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http://dx.doi.org/10.1016/j.bulcan.2019.09.004DOI Listing
November 2019

[Olaparib and pancreatic cancer: A challenging Lesson].

Bull Cancer 2019 Sep 6;106(9):715-716. Epub 2019 Aug 6.

Hôpital universitaire de Rouen, Normandie université, service d'hépato-gastroentérologie, UNIROUEN, Inserm 1245, IRON group, 76000 Rouen, France.

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http://dx.doi.org/10.1016/j.bulcan.2019.07.002DOI Listing
September 2019

Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR).

Dig Liver Dis 2019 10 15;51(10):1357-1363. Epub 2019 Jul 15.

Department of Digestive Oncology, University Hospital of Reims, Reims, France.

Introduction: This document is a summary of the French intergroup guidelines regarding the management of metastatic colorectal cancer (mCRC) published in January 2019, and available on the French Society of Gastroenterology website (SNFGE) (www.tncd.org).

Methods: This collaborative work was realized by all French medical and surgical societies involved in the management of mCRC. Recommendations are graded in three categories (A, B and C), according to the level of evidence found in the literature, up until December 2018.

Results: The management of metastatic colorectal cancer has become complex because of increasing available medical, radiological and surgical treatments alone or in combination. The therapeutic strategy should be defined before the first-line treatment, mostly depending on the presentation of the disease (resectability of the metastases, symptomatic and/or threatening disease), of the patient's condition (ECOG PS, comorbidities), and tumor biology (RAS, BRAF, MSI). The sequence of targeted therapies also seems to have an impact on the outcome (angiogenesis inhibition beyond progression). Surgical resection of metastases was the only curative intent treatment to date, joined recently by percutaneous tumor ablation tools (radiofrequency, microwave). Localized therapies such as hepatic intra-arterial infusion, radioembolization and hyperthermic intraperitoneal chemotherapy, also have seen their indications specified (liver-dominant disease and resectable peritoneal carcinomatosis). New treatments have been developed in heavily pretreated patients, increasing overall survival and preserving quality of life (regorafenib and trifluridine/tipiracil). Finally, immune checkpoint inhibitors have demonstrated high efficacy in MSI mCRC.

Conclusion: French guidelines for mCRC management are put together to help offer the best personalized therapeutic strategy in daily clinical practice, as the mCRC therapeutic landscape is complexifying. These recommendations are permanently being reviewed and updated. Each individual case must be discussed within a multidisciplinary team (MDT).
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http://dx.doi.org/10.1016/j.dld.2019.05.035DOI Listing
October 2019

[Dihydropyrimidine dehydrogenase deficiency screening for management of patients receiving a fluoropyrimidine: Results of two national practice surveys addressed to clinicians and biologists].

Bull Cancer 2019 Sep 25;106(9):759-775. Epub 2019 Jun 25.

Laboratoire d'oncopharmacologie, centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice cedex 2, France. Electronic address:

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.
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http://dx.doi.org/10.1016/j.bulcan.2019.04.013DOI Listing
September 2019

Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer.

Mol Cancer Ther 2019 06 29;18(6):1137-1148. Epub 2019 Mar 29.

Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T, Lille, France.

Besides the detection of somatic receptor tyrosine kinases (RTK) mutations in tumor samples, the current challenge is to interpret their biological relevance to give patients effective targeted treatment. By high-throughput sequencing of the 58 RTK exons of healthy tissues, colorectal tumors, and hepatic metastases from 30 patients, 38 different somatic mutations in RTKs were identified. The mutations in the kinase domains and present in both tumors and metastases were reconstituted to perform an unbiased functional study. Among eight variants found in seven RTKs (EPHA4-Met726Ile, EPHB2-Val621Ile, ERBB4-Thr731Met, FGFR4-Ala585Thr, VEGFR3-Leu1014Phe, KIT-Pro875Leu, TRKB-Leu584Val, and NTRK2-Lys618Thr), none displayed significantly increased tyrosine kinase activity. Consistently, none of them induced transformation of NIH3T3 fibroblasts. On the contrary, two RTK variants (FGFR4-Ala585Thr and FLT4-Leu1014Phe) caused drastic inhibition of their kinase activity. These findings indicate that these RTK variants are not suitable targets and highlight the importance of functional studies to validate RTK mutations as potential therapeutic targets.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-0582DOI Listing
June 2019

Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial.

Expert Rev Pharmacoecon Outcomes Res 2019 Oct 15;19(5):601-608. Epub 2019 Feb 15.

Department of Biostatistic and Epidemiology, Gustave Roussy , Villejuif , France.

: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). : Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. : In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. : The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.
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http://dx.doi.org/10.1080/14737167.2019.1580573DOI Listing
October 2019

The Patient-Reported Experience Measure for Improving qUality of care in Mental health (PREMIUM) project in France: study protocol for the development and implementation strategy.

Patient Prefer Adherence 2019 21;13:165-177. Epub 2019 Jan 21.

Aix-Marseille University, School of Medicine, CEReSS - Health Service Research and Quality of Life Center - EA 3279 Research Unit, Marseille, France, Email

Background: Measuring the quality and performance of health care is a major challenge in improving the efficiency of a health system. Patient experience is one important measure of the quality of health care, and the use of patient-reported experience measures (PREMs) is recommended. The aims of this project are 1) to develop item banks of PREMs that assess the quality of health care for adult patients with psychiatric disorders (schizophrenia, bipolar disorder, and depression) and to validate computerized adaptive testing (CAT) to support the routine use of PREMs; and 2) to analyze the implementation and acceptability of the CAT among patients, professionals, and health authorities.

Methods: This multicenter and cross-sectional study is based on a mixed method approach, integrating qualitative and quantitative methodologies in two main phases: 1) item bank and CAT development based on a standardized procedure, including conceptual work and definition of the domain mapping, item selection, calibration of the item bank and CAT simulations to elaborate the administration algorithm, and CAT validation; and 2) a qualitative study exploring the implementation and acceptability of the CAT among patients, professionals, and health authorities.

Discussion: The development of a set of PREMs on quality of care in mental health that overcomes the limitations of previous works (ie, allowing national comparisons regardless of the characteristics of patients and care and based on modern testing using item banks and CAT) could help health care professionals and health system policymakers to identify strategies to improve the quality and efficiency of mental health care.

Trial Registration: NCT02491866.
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http://dx.doi.org/10.2147/PPA.S172100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345324PMC
January 2019

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

Dig Liver Dis 2019 02 28;51(2):318-320. Epub 2018 Nov 28.

Hôpital privé Jean Mermoz, Lyon, France.

Introduction: Combination of cisplatine and Gemcitabine (CisGem) is the reference 1st line Chemotherapy in patients with advanced biliary cancer. FOLFIRINOX demonstrated an overall survival superiority when compared to gemcitabine in 1st line for patients with metastatic pancreatic adenocarcinoma. Because of similarities between pancreatic and biliary cancers, we proposed a randomized trial comparing mFOLFIRINOX and CisGEm.

Aim: PRODIGE38-AMEBICA is a phase II/III trial evaluating efficacy of modifed FOLFIRINOX (D1 bolus removed) or CisGEm on patients with locally advanced non resectable or metastatic biliary tract cancer.

Patients And Methods: Main inclusion criteria are histologically or cytologically proven biliary tract tumor (intra or extra hepatic or hilar or gallbladder carcinoma), measurable disease (metastases and/or primary tumor), Bilirubin <1,5 N and transaminases <5 N. The randomization (ratio 1:1) will be stratified on center, stage of the disease, tumor localization and previous adjuvant treatment. The Phase II trial has an objective of 73% patients alive and without progression at 6 months for Folfirinox (versus 59% for Gemcis). 128 additional patients should be added in the phase III trial with an objective of overall survival improvement of 4 months in favor of mFOLFIRINOX.

Conclusion: The study is opened in France (EudraCT no.: 2015-002282-35). All the patients (188) of the phase II part are currently randomized.
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http://dx.doi.org/10.1016/j.dld.2018.11.018DOI Listing
February 2019

CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts.

HPB (Oxford) 2019 05 20;21(5):582-588. Epub 2018 Nov 20.

Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Digestive Oncology Unit and Department of Medical Oncology, Henri Becquerel Centre, Rouen, F 76000, Rouen, France. Electronic address:

Background: Although carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring.

Methods: This was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort.

Results: A total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14-0.44).

Conclusions: A CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.
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http://dx.doi.org/10.1016/j.hpb.2018.09.006DOI Listing
May 2019

Totally implanted venous access-associated adverse events in oncology: Results from a prospective 1-year surveillance programme.

Bull Cancer 2018 Nov 12;105(11):1003-1011. Epub 2018 Oct 12.

Rouen University Hospital, Research Group "Dynamics and Events of Care Pathways", 1, rue de Germont, 76031 Rouen cedex, France.

Introduction: During the last decade, most studies on totally implanted venous access-associated adverse events (TIVA-AE) were conducted retrospectively and/or were based on a limited sample size. The aim of our survey was two-fold: to estimate the incidence of TIVA-AE and to identify risk factors in patients with cancer.

Methods: Data from our routine surveillance of TIVA-AE were collected prospectively between October 2009 and January 2011 in two oncology referral centers in Northern France. The open cohort under surveillance during the same time period was reconstituted retrospectively using data from the hospital information systems. Incidences of first TIVA-AE per 1000 TIVA-days were calculated. Risk factors were identified using multivariate logistic regressions.

Results: We included 2286 cancer patients, corresponding to 582,347 TIVA-days. Among the 133 first TIVA-AE observed (incidence 0.23 per 1000 TIVA-days [0.19-0.27]), there were 50 infectious AE (incidence 0.09 [0.06-0.11]) and 83 non-infectious AE (incidence 0.14 [0.11-0.17]). Compared to non-metastatic solid cancers, metastatic cancers (aOR=2.3 [0.9-6.0]), and hematologic malignancies (aOR=3.2 [1.1-8.8]) tended to be associated with a higher risk of infectious TIVA-AE (P=0.087). Solid cancer type was associated with non-infectious TIVA-AE (P=0.030), especially digestive cancers.

Discussion: We report accurate estimations of TIVA-AE incidences in one of the largest populations among previously published studies. As in previous studies, metastatic cancers and hematologic malignancies tended to be associated with a higher risk of infectious TIVA-AE. Further studies are warranted to confirm the effect of digestive cancers.
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http://dx.doi.org/10.1016/j.bulcan.2018.09.005DOI Listing
November 2018

Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).

BMC Cancer 2018 Jul 24;18(1):762. Epub 2018 Jul 24.

Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Paul Brousse Hospital, Villejuif, France.

Background: At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC.

Methods: PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence.

Discussion: The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.

Trial Registration: ClinicalTrials.gov , NCT02959879 . Trial registration date: November 9, 2016.
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http://dx.doi.org/10.1186/s12885-018-4663-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057099PMC
July 2018

Computerized adaptive testing with decision regression trees: an alternative to item response theory for quality of life measurement in multiple sclerosis.

Patient Prefer Adherence 2018 19;12:1043-1053. Epub 2018 Jun 19.

Aix-Marseille Univ, School of Medicine, CEReSS - Health Service Research and Quality of Life Center, Marseille, France.

Background: The aim of this study was to propose an alternative approach to item response theory (IRT) in the development of computerized adaptive testing (CAT) in quality of life (QoL) for patients with multiple sclerosis (MS). This approach relied on decision regression trees (DRTs). A comparison with IRT was undertaken based on precision and validity properties.

Materials And Methods: DRT- and IRT-based CATs were applied on items from a unidi-mensional item bank measuring QoL related to mental health in MS. The DRT-based approach consisted of CAT simulations based on a minsplit parameter that defines the minimal size of nodes in a tree. The IRT-based approach consisted of CAT simulations based on a specified level of measurement precision. The best CAT simulation showed the lowest number of items and the best levels of precision. Validity of the CAT was examined using sociodemographic, clinical and QoL data.

Results: CAT simulations were performed using the responses of 1,992 MS patients. The DRT-based CAT algorithm with minsplit = 10 was the most satisfactory model, superior to the best IRT-based CAT algorithm. This CAT administered an average of nine items and showed satisfactory precision indicators (R = 0.98, root mean square error [RMSE] = 0.18). The DRT-based CAT showed convergent validity as its score correlated significantly with other QoL scores and showed satisfactory discriminant validity.

Conclusion: We presented a new adaptive testing algorithm based on DRT, which has equivalent level of performance to IRT-based approach. The use of DRT is a natural and intuitive way to develop CAT, and this approach may be an alternative to IRT.
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http://dx.doi.org/10.2147/PPA.S162206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016264PMC
June 2018

Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO).

Dig Liver Dis 2018 Aug 6;50(8):768-779. Epub 2018 Jun 6.

Department of Hepato-gastroenterology and Digestive Oncology, CHU Rouen, Rouen, France.

Introduction: This document is a summary of the French Intergroup guidelines regarding the management of gastric cancer published in October 2016, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org), updated in October 2017.

Methods: This collaborative work was realized under the auspices of several French medical societies involved in management of gastric cancer. Recommendations are graded in three categories (A-C), according to the amount of evidence found in the literature until July 2017.

Results: There are several known risk factors for gastric cancer, including Helicobacter pylori and genetic predispositions, both requiring a specific screening for patients and their relatives. The diagnosis and staging evaluation are essentially based on gastroscopy plus biopsies and computed tomography scan. The endoscopic ultrasonography can be used for superficial tumors in case of discussion for endoscopic resection (T1N0). For local disease (N+ and/or T > T1), the strategic therapy is based on surgery associated with perioperative chemotherapy. In the absence of preoperative treatment (for any raison), the postoperative chemoradiotherapy (or chemotherapy) should be discussed for patients with stage II or III tumor. For metastatic disease, the treatment is based on "palliative" chemotherapy consisting in a doublet or triplet regimens depending of age, performance status and HER2 tumor status. For patients with limited metastatic disease, surgical resection could be discussed in multidisciplinary meeting in case of stable disease after chemotherapy.

Conclusion: These guidelines in gastric cancer are done to help decision for daily clinical practice. These recommendations are permanently being reviewed. Each individual case must be discussed within a multidisciplinary team.
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http://dx.doi.org/10.1016/j.dld.2018.04.025DOI Listing
August 2018

Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials.

Eur J Cancer 2018 07 26;98:1-9. Epub 2018 May 26.

Digestive Oncology Department, CHU La Timone, APHM, Aix-Marseille Univ, Marseille, France.

Background: Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.

Patients And Methods: A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy.

Results: The rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991-1999 period) to 41.5% (2000-2006 period) and 44.8% (2007-2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80-0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01-1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87-1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients.

Conclusion: Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.
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http://dx.doi.org/10.1016/j.ejca.2018.03.031DOI Listing
July 2018

Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

Dig Liver Dis 2018 Apr 1;50(4):408-410. Epub 2018 Mar 1.

Department of Medical Oncology, Mutualiste Montsouris Institute, Paris, France.

Introduction: In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m q3w) to cisplatin (75 mg/m q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated.

Aim: GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity.

Materials And Methods: Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions.

Results: The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index.

Conclusion: This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432).
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http://dx.doi.org/10.1016/j.dld.2018.01.119DOI Listing
April 2018

Aspirin versus placebo in stage III or high-risk stage II colon cancer with PIK3CA mutation: A French randomised double-blind phase III trial (PRODIGE 50-ASPIK).

Dig Liver Dis 2018 Mar 30;50(3):305-307. Epub 2017 Dec 30.

French Federation of Digestive Oncology (FFCD), INSERM LCN UMR 1231 EPICAD, Dijon, France.

Oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. Two recent retrospective studies strongly suggested that low-dose aspirin used (100 mg/d) after surgical resection of colorectal cancer with a PIK3CA mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. We propose a double-blind randomized phase III study to evaluate aspirin (100 mg/d during 3 years or until recurrence) versus placebo. Main inclusion criteria are patients aged 18 or 20, stage III or high risk stage II. The primary endpoint of the study is 3-year disease-free survival (DFS). Hypotheses are to improve 3-years DFS from placebo: 72% to aspirin: 83% (HR = 0.56). 94 events and 264 patients with PIK3CA mutation are required. The secondary endpoints are DFS at 5 years, the overall survival rate at 5 years, grade 3-4 severe bleeding.
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http://dx.doi.org/10.1016/j.dld.2017.12.023DOI Listing
March 2018