Publications by authors named "Angélique Vienot"

18 Publications

  • Page 1 of 1

Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort.

Br J Cancer 2021 Mar 26. Epub 2021 Mar 26.

Department of Hepato-Gastroenterology and Gastrointestinal Oncology, Université de Paris, Paris Descartes University, Hôpital Européen Georges Pompidou, Paris, France.

Background: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group.

Methods: This is a retrospective multicentre study. We included all consecutive patients with non-pre-treated LAPA or BRPA treated with FOLFIRINOX.

Results: We included 330 patients (57.9% male, 65.4% <65 years, 96.4% PS <2). Disease was classified as BRPA in 31.1% or LAPA in 68.9%. Objective response rate with FOLFIRINOX was 29.5% and stable disease 51%. Subsequent CRT was performed in 46.4% of patients and 23.9% had curative intent surgery. Resection rates were 42.1% for BRPA and 15.5% for LAPA. Main G3/4 toxicities were fatigue (15%), neutropenia (12%) and neuropathy (G2/3 35%). After a median follow-up of 26.7 months, median OS (mOS) and PFS were 21.4 and 12.4 months, respectively. For patients treated by FOLFIRINOX alone, or FOLFIRINOX followed by CRT, or FOLFIRINOX + /- CRT + surgery, mOS was 16.8 months, 21.8 months and not reached, respectively (p < 0.0001).

Conclusions: FOLFIRINOX for LAPA and BRPA seems to be effective with a manageable toxicity profile. These promising results in "real-life" patients now have to be confirmed in a Phase 3 randomised trial.
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http://dx.doi.org/10.1038/s41416-021-01341-wDOI Listing
March 2021

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice.

Qual Life Res 2021 Jan 2. Epub 2021 Jan 2.

Methodological and Quality of Life Unit in Oncology, University Hospital of Besançon, 25000, Besançon, France.

Introduction: Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance patient-centered care. We evaluated the feasibility of REMOQOL in the French context in the QOLIBRY study. The primary objective was to assess the patients' compliance with REMOQOL.

Methods: The QOLIBRY study was a single-center, prospective study conducted in the University Hospital of Besançon (France). Eligible patients were those treated with systemic therapies for breast, lung or colorectal cancer at any stage. Patients were invited to complete the EORTC QLQ-C30 questionnaire and cancer-site-specific modules before each visit on tablets and/or computers in the hospital or at home. During the consultation, physicians had real-time access to visual summaries of HRQoL scores. Compliance was assessed as adequate if at least 66% of HRQoL assessments were completed during the 4 months of follow-up.

Results: Between March 2016 and October 2018, 177 patients were included in the QOLIBRY study. Median age was 64 years (IQR 54-71). The proportion of patients with an adequate compliance rate was 95.5% (n = 63) in the breast cancer cohort, 98.2% (n = 55) in the colorectal cancer cohort, and 90.9% (n = 50) in the lung cancer cohort. The physicians checked the HRQoL results in 73.1% of visits and prescribed supportive care and adapted patient management in 8.3% and 5.2% of visits, respectively.

Conclusion & Perspectives: The results of QOLIBRY study suggest that REMOQOL is feasible in the French context. However, information about HRQoL monitoring, training of the physicians in the use of the software, and recommendations for using HRQoL results to guide care are essential and must be improved.
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http://dx.doi.org/10.1007/s11136-020-02721-0DOI Listing
January 2021

Anti-Telomerase CD4 Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials.

Int J Mol Sci 2020 Sep 17;21(18). Epub 2020 Sep 17.

INSERM, EFS BFC, UMR1098, RIGHT, University of Bourgogne Franche-Comté, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25000 Besançon, France.

Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients' clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients' survival.
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http://dx.doi.org/10.3390/ijms21186838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554943PMC
September 2020

FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study.

Oncologist 2020 11 17;25(11):e1701-e1710. Epub 2020 Sep 17.

Oncology Multidisciplinary Research Group (GERCOR), Paris, France.

Background: Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer.

Materials And Methods: This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity.

Results: Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7-20.3) and median PFS1 was 9.4 months (95% CI, 8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0-22.3). The rates of grade 3-4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%).

Conclusion: 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France.

Implications For Practice: FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.
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http://dx.doi.org/10.1634/theoncologist.2020-0577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648331PMC
November 2020

Platelet transfusions in haematologic malignancies in the last six months of life.

Vox Sang 2021 Apr 13;116(4):425-433. Epub 2020 Aug 13.

EFS Bourgogne Franche Comté, Besançon, France.

Background And Objectives: Practices in end-of-life platelet transfusions in haematologic malignancies are variable. Our aim was to describe the platelet transfusion burden and parameters linked to this indication in such a setting and thereby contribute to defining optimal practices.

Materials And Methods: From July 2015 to December 2016, all consecutive deceased adult patients with a haematologic malignancy receiving a platelet transfusion in the last 6 months of their life from the Etablissement Français du Sang Bourgogne Franche-Comté were included retrospectively. The outcome criteria were changes in the number of platelet transfusions, percent platelet recovery, platelet transfusion interval, reported bleeding with its grade and recipient adverse events in the last 6 months of life.

Results: Among the 1125 patients monitored, 119 were included in our study. Bleeding prophylaxis (versus treatment) was the reason for 55% of transfusions. 18% of platelet concentrates (n = 1999) were transfused during the last two weeks of life. As death approached, the transfusion and haemorrhage burden increased (P < 0·0001 in both cases), whereas platelet recovery and transfusion interval decreased (P = 0·02 in both cases). Recipient adverse events were rare (0·6%) and of minor severity.

Conclusion: In end-of-life transfused patients with haematologic malignancies, approaching death is associated with an increased number of platelet transfusions and bleeding events, while platelet recovery and transfusion intervals are reduced. Such findings, together with further evaluations, may contribute to informing best practices for these patients.
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http://dx.doi.org/10.1111/vox.12986DOI Listing
April 2021

Continuum of care for advanced biliary tract cancers.

Clin Res Hepatol Gastroenterol 2020 11 22;44(6):810-824. Epub 2020 Jun 22.

Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University, 35, rue Dailly, 92210 Saint-Cloud, France. Electronic address:

Biliary tract cancers (BTC) are a heterogeneous group of epithelial neoplasms, with a poor prognosis. Advanced BTC remains a challenging, non-curable disease. In this review, we provide an overview of the medical treatment options in advanced BTC and new strategies under development. Gemcitabine plus platinum chemotherapy is the standard first-line therapy in this setting. Recently, 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX) regimen became the only second-line therapy to be prospectively validated beyond failure of gemcitabine plus cisplatin combination in a phase III study, even though chemotherapy yielded modest survival improvement over best supportive care. Anti-epidermal growth factor receptor and antiangiogenic antibodies have not demonstrated any survival benefit in unselected patient populations. In recent years, knowledge about the molecular heterogeneity of BTC has considerably increased with the advent of large-scale genomic and transcriptomic analyses, opening up new perspectives for so-called personalised targeted therapies. Patients with BTC may be particularly good candidates for biomarker-driven strategies in clinical practice. Among current developments, the targeting of fibroblast growth factor receptor and isocitrate dehydrogenase gene alterations are the most promising avenues, and combination immunotherapies are under investigation.
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http://dx.doi.org/10.1016/j.clinre.2020.05.009DOI Listing
November 2020

Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer.

Int J Cancer 2020 12 7;147(11):3177-3188. Epub 2020 Jul 7.

Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France.

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.
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http://dx.doi.org/10.1002/ijc.33146DOI Listing
December 2020

Molecular description of ANGPT2 associated colorectal carcinoma.

Int J Cancer 2020 10 22;147(7):2007-2018. Epub 2020 May 22.

INSERM, EFS BFC, UMR1098, RIGHT, University of Bourgogne Franche-Comté, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaireet Génique, Besançon, France.

Angiopoietin-2 (ANGPT2) is a prognostic factor in metastatic colorectal cancer (CRC). Nevertheless, it remains to be elucidated which molecular characteristics make up the ANGPT2-related poor-prognosis CRC subset. Public transcriptomic datasets were collected from Gene Expression Omnibus GEO and with the TCGAbiolinks R-package for the TCGA. After appropriate normalization, differential expression analysis was performed using Benjamini and Hochberg method for false discovery rate. Plasma from two prospective clinical trials were used to investigate the clinical impact of ANGPT2-related biomarkers. In the 935 samples included in four annotated platforms (GPL) and derived from localized CRC, ANGPT2 expression conferred a worst overall survival (HR = 1.20; p = 0.02). CRC stage, ANGPT2 expression but not Consortium Molecular Subtype (CMS) predict overall survival in multivariate analysis. ANGPT2 expression was not correlated with a specific CMS nor to RAS, RAF, MSI, p53, CIN, CIMP genomic alterations. Gene expression analysis revealed that ANGPT2 CRC subset is characterized by angiogenesis-related gene expression, presence of myeloid cells, stromal organization and resistance to chemotherapy. A prognostic model was proposed using seric levels of ANGPT2, STC1 and CD138 in 97 mCRC patients. Our results provide evidence that ANGPT2 is a prognostic factor in localized CRC and defined a specific CRC subset with potential clinical implementation.
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http://dx.doi.org/10.1002/ijc.32993DOI Listing
October 2020

FOLFOXIRI FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study.

World J Gastrointest Oncol 2020 Mar;12(3):332-346

University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France.

Background: FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer.

Aim: To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.

Methods: Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI ( = 165) or FOLFIRINOX ( = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m), oxaliplatin (85 mg/m), leucovorin (200 mg/m) and 5-fluorouracil (3200 mg/m as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared.

Results: Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; = 0.219) and progression-free survival (hazard ratio = 1.27; = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group 47.8% in the FOLFIRINOX group ( = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort 19.5% in the FOLFIRINOX cohort ( = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens.

Conclusion: FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.
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http://dx.doi.org/10.4251/wjgo.v12.i3.332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081111PMC
March 2020

Immune Therapy for Liver Cancers.

Cancers (Basel) 2019 Dec 27;12(1). Epub 2019 Dec 27.

Department of Medical Oncology, Curie Institute, University of Versailles Saint-Quentin, 35 rue Dailly, 92210 Saint-Cloud, France.

Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) display a poor prognosis with 5-year overall survival rates around 15%, all stages taken together. These primary liver malignancies are often diagnosed at advanced stages where therapeutic options are limited. Recently, immune therapy has opened new opportunities in oncology. Based on their high programmed death-ligand 1 expression and tumor-infiltrating lymphocytes, HCC and BTC are theoretically good candidates for immune checkpoint blockade. However, clinical activity of single agent immunotherapy appears limited to a subset of patients, which is still ill-defined, and combinations are under investigation. In this review, we provide an overview of (i) the biological rationale for immunotherapies in HCC and BTC, (ii) the current state of their clinical development, and (iii) the predictive value of immune signatures for both clinical outcome and response to these therapies.
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http://dx.doi.org/10.3390/cancers12010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016834PMC
December 2019

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan.

Clin Colorectal Cancer 2019 12 4;18(4):e394-e401. Epub 2019 Sep 4.

S.C. Oncologia, Department of Oncology, ASL BI, Biella, Italy.

Background: FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes.

Patients And Methods: We investigated putative prognostic factors among 137 MPC/LAPC patients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275).

Results: Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001).

Conclusion: The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPC patients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.
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http://dx.doi.org/10.1016/j.clcc.2019.08.004DOI Listing
December 2019

[A GERCOR-AERIO national survey of oncology residents in France: Current setting and expectations regarding post-internship and research].

Bull Cancer 2019 May 12;106(5):407-420. Epub 2019 Apr 12.

Institut Curie, université Versailles Saint-Quentin (UVSQ), département d'oncologie médicale, 35, rue Dailly, 92210 Saint-Cloud, France; GERCOR, 151, rue du Faubourg Saint-Antoine, 75011 Paris, France.

Introduction: The demographics of oncology residents has changed since 2010 with the increase in the size of promotions. The evolution of the residents' aspirations towards research and their future exercise in parallel with these demographic changes has not been assessed.

Methods: A questionnaire was developed by a working group from GERCOR (cooperative group in oncology), involving clinicians, researchers, GERCOR members, and residents. It consisted of 62 questions divided into 7 sections: demographics, medical thesis, post-residency, mobility, publication activity, basic research, and clinical/translational research. The national survey was published online by the Association d'enseignement et de recherche des internes en oncologie (AERIO).

Results: In total, 143 residents participated, of which 116 (81.1%) completed the questionnaire entirely. The population was representative of the current demographics, with a majority of women (65.0%), a median age of 28 years, and 39.7% of residents from Paris region. The unsupervised analysis revealed four profiles of residents, including one group strongly committed to research (16.8%), one group with moderate involvement (41.3%) and one group that did not seem interested in research (14.7%). Uncertainty about future position and lack of time and interaction with researchers appeared to be the main barriers to involvement of residents in research.

Discussion: This national survey provided useful information about the residents' perspective to academic research. It may serve as a basis for proposing measures adapted to their expectations.
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http://dx.doi.org/10.1016/j.bulcan.2019.02.009DOI Listing
May 2019

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations.

Eur J Cancer 2019 04 1;111:94-106. Epub 2019 Mar 1.

Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France; Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France. Electronic address:

Background: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting.

Methods: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model.

Results: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392).

Conclusion: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.
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http://dx.doi.org/10.1016/j.ejca.2019.01.019DOI Listing
April 2019

Baseline splenic volume as a surrogate marker of FOLFIRINOX efficacy in advanced pancreatic carcinoma.

Oncotarget 2018 May 22;9(39):25617-25629. Epub 2018 May 22.

Department of Medical Oncology, Center Georges Francois Leclerc, Dijon, France.

Background: The FOLFIRINOX regimen is the standard first-line treatment for advanced pancreatic adenocarcinoma (aPDAC). However, because of its potential toxicity, predictive biomarkers could help clinical decision-making.

Methods: A cohort of 97 aPDAC patients treated with first-line FOLFIRINOX were studied. The association between splenic volume and progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariable Cox analyses. The external validation cohort was composed of 117 patients treated with Gemcitabine and 52 patients treated with FOLFIRINOX.

Results: In the training cohort, the splenic volume of 97 patients was measured at baseline and at the end of therapy. The spleen size increased in 81% of patients, with at least a 50% increase in 27% of patients. Baseline splenomegaly predicted PFS (HR 1.812, 95% CI = [1.036-3.169]; = 0.03) and OS (HR 1.983, 95% CI = [1.085-3.624]; = 0.02) in the training cohort. These results were then validated in an external cohort of patients who were treated with FOLFIRINOX excluding those in the control cohort who were treated with gemcitabine. In a multivariate model based on the CoxBoost method, the following were selected as predictive markers of FOLFIRINOX efficacy (AUC = 0.81): performance status, liver metastasis, baseline Ca199 and CEA levels and baseline splenomegaly. The predictive ability of the model was validated in the external cohort that was also treated with FOLFIRINOX.

Conclusions: Baseline splenomegaly is a predictive marker of a poor response to FOLFIRINOX in aPDAC and remained predictive when associated with other clinical variables.
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http://dx.doi.org/10.18632/oncotarget.25424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986639PMC
May 2018

Enterocolitis in Patients with Cancer Treated with Docetaxel.

Anticancer Res 2018 04;38(4):2443-2446

Department of Medical Oncology, University Hospital of Besançon, Besançon, France.

Background: Enterocolitis is a rare, but serious gastrointestinal complication associated with docetaxel-based chemotherapy in patients with cancer. The incidence, clinical presentation and outcome of enterocolitis in patients with cancer treated with docetaxel-based chemotherapy was assessed in this study Patients and Methods: All patients treated with docetaxel for cancer between January 2010 and December 2014 at the University Hospital of Besançon were identified and their medical records reviewed.

Results: During this period, 1,227 patients received docetaxel chemotherapy and gastrointestinal events occurred in 381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal events was associated with a higher dose of docetaxel (≥75 mg/m) (odds ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65 (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%) patients, respectively; 54 patients (14.2%) were hospitalized. Computed tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients presented radiological signs of enterocolitis. Three deaths (0.8%) related to enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120 patients (31.5%).

Conclusion: Gastrointestinal events in patients treated with docetaxel may be a potential sign of fatal enterocolitis and require particular attention. Dose reduction at the first cycle may reduce the risk of such events.
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http://dx.doi.org/10.21873/anticanres.12497DOI Listing
April 2018

A systematic review of economic evaluation in pancreatic ductal adenocarcinoma.

Eur J Cancer 2017 11 9;86:207-216. Epub 2017 Oct 9.

Department of Pharmacy, University Hospital of Besançon, Besançon, France; INSERM UMR 1098, University of Bourgogne - Franche-Comté, Besançon, France. Electronic address:

Objectives: The economic evaluation (EE) of healthcare interventions has become a necessity. However, high quality needs to be ensured in order to achieve validated results and help making informed decisions. Thus, the objective of the present study was to systematically identify and review published pancreatic ductal adenocarcinoma-related EEs and to assess their quality.

Methods: Systematic literature research was conducted in PubMed and Cochrane to identify published EEs between 2000 and 2015. The quality of each selected EE was assessed by two independent reviewers, using the Drummond's checklist.

Results: Our systematic review was based on 32 EEs and showed a wide variety of methodological approaches, including different perspectives, time horizon, and cost effectiveness analyses. Nearly two-thirds of EEs are full EEs (n = 21), and about one-third of EEs had a Drummond score ≥7, synonymous with 'high quality'. Close to 50% of full EEs had a Drummond score ≥7, whereas all of partial EEs had a Drummond score <7 (n = 11).

Conclusions: Over the past 15 years, a lot of interest has been evinced over the EE of pancreatic ductal adenocarcinoma (PDAC) and its direct impact on therapeutic advances in PDAC. To provide a framework for health care decision-making, to facilitate transferability and to lend credibility to health EEs, their quality must be improved. For the last 4 years, a tendency towards a quality improvement of these studies has been observed, probably coupled with a context of rational decision-making in health care, a better and wider spread of recommendations and thus, medical practitioners' full endorsement.
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http://dx.doi.org/10.1016/j.ejca.2017.08.035DOI Listing
November 2017

Overall Survival Prediction and Usefulness of Second-Line Chemotherapy in Advanced Pancreatic Adenocarcinoma.

J Natl Cancer Inst 2017 10;109(10)

Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.

Background: In advanced pancreatic ductal adenocarcinoma (aPDAC), there is no consensual strategy for second-line chemotherapy (L2). Better discrimination of overall survival (OS) may help clinical decision-making. We aimed to predict OS from the beginning of L2 and to assess the benefit from chemotherapy among the identified risk groups.

Methods: Analyses were derived from all consecutive aPDAC patients treated at Besancon University Hospital, Besancon, France, between January 2003 and December 2013 (n = 462). The association of 50 parameters with OS was evaluated using univariate and multivariable Cox analyses. Based on the final model, a prognostic nomogram and score were developed and externally validated. Patients in the external validation cohort who received L2 (n = 163) were treated at three French institutions between January 2010 and April 2016. All statistical tests were two-sided.

Results: In the development cohort, 395 patients (85.5%) were eligible for L2, of which 261 (66.1%) were treated. Age, smoking status, liver metastases, performance status, pain, jaundice, ascites, duration of first-line, and type of L2 regimen were identified as independent prognostic factors for OS in L2. The score determined three groups with median OS of 11.3 months (95% confidence interval [CI] = 9.1 to 12.9 months), 3.6 months (95% CI = 2.6 to 4.7 months), and 1.4 months (95% CI = 1.2 to 1.7 months), for low-, intermediate-, and high-risk groups, respectively ( P < .001). By applying the score in the population eligible for L2 but untreated, the chemotherapy benefit was statistically significant across all groups, but with a magnitude of the effect decreased statistically significantly from low- to high-risk groups ( P = .001 for treatment and risk groups interaction term). The ability of the score to discriminate OS was confirmed in the external validation cohort.

Conclusions: This prognostic nomogram and score in patients with aPDAC can accurately predict OS before administration of L2 and may help clinicians in their therapeutic decisions.
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http://dx.doi.org/10.1093/jnci/djx037DOI Listing
October 2017

Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP).

Br J Cancer 2016 Jul 12;115(3):281-9. Epub 2016 Jul 12.

Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France.

Background: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP).

Methods: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France.

Results: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001).

Conclusions: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.
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http://dx.doi.org/10.1038/bjc.2016.212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973163PMC
July 2016