Publications by authors named "Solene Doat"

10 Publications

  • Page 1 of 1

Prognostic value of the early change in neutrophil-to-lymphocyte ratio in metastatic pancreatic adenocarcinoma.

Clin Res Hepatol Gastroenterol 2020 Oct 11:101541. Epub 2020 Oct 11.

Sorbonne Université, 4 Place Jussieu, 75005, Paris, France; Department of Hepato-Gastroenterology, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital 75013, APHP, Paris, France. Electronic address:

In metastatic pancreatic adenocarcinoma, a high neutrophil-to-lymphocyte ratio (NLR) at diagnosis is a marker of poor prognosis. The prognostic role of baseline NLR and NLR change during first-line chemotherapy were determined. We conducted a retrospective study by using data from a single-center prospective cohort and a randomized open-label, multicenter, randomized trial. Two hundred and twelve patients were analyzed. Baseline NLR>5 was an independent marker of poor prognosis for overall survival (HR=2.01, 95% CI 1.33-3.05; P=0.001) and progression-free survival (PFS; HR=1.80, 95% CI 1.23-2.65; P=0.0026). According to NLR dynamics (n=172), patients with NLR≤5 on days 1 and 15 had a significantly better prognosis than those with NLR≤5 on day 1 and NLR>5 on day 15 (HR=2.23, 95% CI 1.18-4.21; P=0.013), NLR >5 on day 1 and NLR ≤5 on day 15 (HR=3.25, 95% CI 1.86-5.68; P<0.001), and NLR>5 on days 1 and 15 (HR=3.37, 95% CI 1.93-5.90; P<0.001). Over time, bad responders (PFS <6 months) had significantly higher mean NLR than good responders (PFS>6 months; group effect: P<0.0001). Seven out of eight patients with baseline NLR>5 had circulating tumor DNA. This study confirmed the independent prognostic value of baseline NLR >5 in metastatic pancreatic cancer. The change in NLR early during chemotherapy was also a prognostic indicator in patients with NLR ≤5.
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October 2020

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302).

Clin Colorectal Cancer 2020 Dec 12;19(4):285-290. Epub 2020 Jun 12.

Department of Gastroenterology and Digestive Oncology, Hopital European George Pompidou, Paris, France. Electronic address:

Background: FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.

Patients And Methods: Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H: 55% and H= 75%. Data were analyzed in intention to treat.

Results: Forty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.

Conclusion: Although the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.
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December 2020

Reasons for chemotherapy discontinuation and end-of-life in patients with gastrointestinal cancer: A multicenter prospective AGEO study.

Clin Res Hepatol Gastroenterol 2021 Jan 11;45(1):101431. Epub 2020 May 11.

Department of hepatogastroenterology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75013 Paris, France.

Background: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.

Methods: This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.

Results: One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.

Conclusion: Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
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January 2021

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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February 2020

Tumor-size responses to first-line is a predictor of overall survival in metastatic colorectal cancer.

Eur Radiol 2019 Jul 31;29(7):3871-3880. Epub 2019 Jan 31.

Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objectives: Early tumor shrinkage (ETS) has been reported to be associated with survival of metastatic colorectal cancer (mCRC) patients. Our aim was to analyze long-term tumor-size evolution, according to early mCRC best responses during the first-line therapy, to evaluate first best response-survival links.

Methods: Sixty-five patients with unresectable mCRCs, treated between 2010 and 2015, were included retrospectively in this descriptive monocenter study and grouped according to their RECIST 1.1 first-line best responses: progressive disease (PD), stable disease with tumor-size evolution between 0 and + 19% (SD+) or 0 and - 29% (SD-), and partial responders (PRs), who were classed PR with ETS (ETS) or without (PR). Tumor-size evolution and best tumor responses to each chemotherapy line were analyzed.

Results: Tumor loads of ETS or PR mCRCs tended to remain inferior to their initial values: 60% of patients died with target lesion sums below baseline. For first-line SD+ or PD mCRCs, rapid tumor load increases continued during successive lines: > 80% died with target lesion sums above baseline. ETS mCRCs responded better to subsequent lines (37.5% second-line PR), whereas PD mCRCs remained refractory to other therapies (0% second- and third-line PR). Overall survival rates were significantly (p = 0.03) longer for the ETS group (29.9 [95% CI: 12.6-47.1] months) and shorter for the PD group (17.1 [95% CI: 1.5-37.5] months).

Conclusion: Tumors responding to first-line chemotherapy also responded better to subsequent lines, whereas PD mCRCs remained refractory, which may explain the better survival associated with ETS.

Key Points: • Early shrinking tumors under first-line chemotherapy responded better to subsequent lines, maintaining low tumor loads, potentially explaining the link between early tumor shrinkage and overall survival of metastatic colorectal cancer (mCRC) patients. • mCRCs progressing under first-line chemotherapy remained refractory to other therapies and their tumor loads increased rapidly. • Even outside a clinical trial, an early first CT scan reevaluation with RECIST criteria 8 weeks after starting first-line therapy is crucial to determine long-term mCRC evolution.
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July 2019

Prostatitis, other genitourinary infections and prostate cancer risk: Influence of non-steroidal anti-inflammatory drugs? Results from the EPICAP study.

Int J Cancer 2018 10 16;143(7):1644-1651. Epub 2018 Jul 16.

Université Paris-Saclay, Université Paris-Sud, CESP (Center for Research in Epidemiology and Population Health), Inserm, Team Cancer and Environment, Villejuif, France.

Epidemiological studies have suggested that prostatitis may increase the risk of prostate cancer due to chronic inflammation. We studied the association between several genitourinary infections and the risk of prostate cancer based on data from the EPICAP study. EPICAP is a population-based case-control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls have been face to face interviewed using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer, and personal history of genitourinary infections: prostatitis, urethritis, orchi-epididymitis, and acute pyelonephritis. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Overall, 139 (18%) cases and 98 (12%) controls reported having at least one personal history of genitourinary infections (OR = 1.64 [1.23-2.20]). The risk increased with the number of infections (p-trend < 0.05). The association was specifically observed with personal history of chronic prostatitis and acute pyelonephritis (OR = 2.95 [1.26-6.92] and OR = 2.66 [1.29-5.51], respectively) and in men who did not use any non-steroidal anti-inflammatory drugs (OR = 2.00 [1.37-2.91]). Our results reinforce the hypothesis that chronic inflammation, generated by a personal history of genitourinary infections, may play a role in prostate carcinogenesis.
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October 2018

Clinical outcome of portal vein thrombosis in patients with digestive cancers: A large AGEO multicenter study.

Dig Liver Dis 2018 Mar 16;50(3):285-290. Epub 2017 Nov 16.

Department of Oncology, Poitiers University Hospital, Poitiers, France; Department of Gastroenterology, Poitiers University Hospital, Poitiers, France; Laboratory of Inflammation, tissus épithéliaux et cytokines (LITEC), Poitiers University, France.

Introduction: Management of portal vein thrombosis (PVT) in cancer patients remains discussed.

Aims: The objective of this multicenter retrospective study was to investigate the management and outcome of PVT in patients with digestive cancers other than hepatocellular carcinoma (HCC).

Method: Main inclusion criteria were trunk or branch PVT in patients with locally advanced or metastatic digestive cancers. Predictive factors of bleeding and overall survival (OS) were evaluated in univariate and multivariate analysis.

Results: Between 2012 and 2016, 118 patients with PVT and digestive cancers were identified. The majority had a pancreatic cancer (50%). Sixty-six percent of patients had trunk PVT location. Endoscopic screening of portal hypertension was performed in only 7 patients (1%) and 5 had esophageal varices. Gastrointestinal bleeding occurred in 22 patients (19%) and 12 patient deaths (17%) were related to a gastrointestinal hemorrhage. Metastatic disease (HR=2.83 [95%CI 1.47-5.43], p<0.01) and gastrointestinal hemorrhage (HR=1.68 [95%CI 1.01-2.78], p=0.04) were associated with OS in multivariate analysis. Only trunk PVT location was significantly associated with gastrointestinal hemorrhage in multivariate analysis (HR=5.56 [95%CI 1.18-26.32], p=0.03).

Conclusion: A high rate of variceal bleeding leading to death was found in this cohort. Endoscopic screening and the efficacy of prophylactic treatment of variceal bleeding remain to be evaluated in a prospective study.
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March 2018

Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk: results from the EPICAP study.

Cancer Med 2017 Oct 21;6(10):2461-2470. Epub 2017 Sep 21.

CESP (Center for Research in Epidemiology and Population Health), Inserm, Team Cancer and Environment, Université Paris-Saclay, Université Paris-Sud, Villejuif, France.

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population-based case-control study carried out in 2012-2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All-NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61-0.98, especially in men using NSAIDs that preferentially inhibit COX-2 activity (OR 0.48, 95% CI 0.28-0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53-0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27-0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07-0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti-COX-2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed.
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October 2017

Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker.

Clin Cancer Res 2017 Jan 19;23(1):116-123. Epub 2016 Dec 19.

Université Paris Sorbonne Cité, INSERM UMR-S1147 MEPPOT, CNRS SNC5014, Centre Universitaire des Saints-Péres, Paris, France. Equipe labélisée Ligue contre le Cancer.

Purpose: Despite recent therapeutic advances, prognosis of patients with pancreatic adenocarcinoma remains poor. Analyses from tumor tissues present limitations; identification of informative marker from blood might be a promising alternative. The aim of this study was to assess the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma.

Experimental Design: From 2011 to 2015, blood samples were prospectively collected from all consecutive patients with pancreatic adenocarcinoma treated in our center. Identification of ctDNA was done with next-generation sequencing targeted on referenced mutations in pancreatic adenocarcinoma and with picoliter droplet digital PCR.

Results: A total of 135 patients with resectable (n = 31; 23%), locally advanced (n = 36; 27%), or metastatic (n = 68; 50%) pancreatic adenocarcinoma were included. In patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency (MAF) of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (OS; 6.5 vs. 19.0 months; P < 0.001) in univariate and multivariate analyses (HR = 1.96; P = 0.007). To evaluate the impact of ctDNA level, patients were grouped according to MAF tertiles: OS were 18.9, 7.8, and 4.9 months (P < 0.001). Among patients who had curative intent resection (n = 31), 6 had ctDNA detectable after surgery, with an MAF of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs.17.6 months; P = 0.03) and shorter OS (19.3 vs. 32.2 months; P = 0.027).

Conclusions: ctDNA is an independent prognostic marker in advanced pancreatic adenocarcinoma. Furthermore, it arises as an indicator of shorter disease-free survival in resected patients when detected after surgery. Clin Cancer Res; 23(1); 116-23. ©2016 AACR.
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January 2017

Unbalance between plasma levels of Protein Z and protein Z-dependent inhibitor in patients with colorectal and pancreatic cancer: a pilot study.

Thromb Res 2014 Feb 22;133(2):299-300. Epub 2013 Nov 22.

Université Paris-Sud, Laboratoire d'Hématologie, EA 4531, 92290 Châtenay-Malabry, France; Service de Biologie Clinique, Hôpital Foch, 92151 Suresnes, France. Electronic address:

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February 2014