Publications by authors named "Stephane Obled"

8 Publications

  • Page 1 of 1

Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis.

Hepatol Int 2021 Feb 9;15(1):93-104. Epub 2021 Jan 9.

Centre Eugène Marquis, Rennes, France.

Background And Aims: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis.

Methods: PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS).

Results: 160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib.

Conclusion: In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib.

Clinical Trial Registration: The study was referenced in clinicaltrials.gov (NCT01357486).
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http://dx.doi.org/10.1007/s12072-020-10120-3DOI Listing
February 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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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Outcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients.

Clin Res Hepatol Gastroenterol 2020 06 19;44(3):286-294. Epub 2019 Sep 19.

Digestive and Mini-invasive Surgery unit, Department of Digestive Surgery and Transplantation, St Eloi Hospital, centre hospitalier universitaire, 80, avenue Augustin-Fliche, 34295 Montpellier, France; Université de Montpellier-Nîmes, 641, avenue du Doyen-Gaston-Giraud, 34090 Montpellier, France; Department of Medical Oncology, université de Montpellier-Nîmes, centre hospitalier universitaire, 641, avenue du Doyen-Gaston-Giraud, 34090 Montpellier, France; Department of Digestive Surgery, University of Montpellier-Nîmes, Carémeau Hospital, place du professeur Debré, 30900 Nîmes, France; Department of Endocrinology, université de Montpellier-Nîmes, centre hospitalier universitaire, 641, avenue du Doyen-Gaston-Giraud, 34090 Montpellier, France; Department of Radiology, université de Montpellier-Nîmes, centre hospitalier universitaire, 641, avenue du Doyen-Gaston-Giraud, 34090 Montpellier, France; Department of Gastroenterology, University of Montpellier-Nîmes, Carémeau Hospital, place du professeur Debré, 30900 Nîmes, France; Oncology, université de Montpellier-Nîmes, institut du cancer de Montpellier (ICM), parc Euromédecine, 208, rue des Apothicaires, 34298 Montpellier, France; Department of Pathology, université de Montpellier-Nîmes, centre hospitalier universitaire, 641, avenue du Doyen-Gaston-Giraud, 34090 Montpellier, France; Digestive & Oncologic Surgery, université de Montpellier-Nîmes, institut du cancer de Montpellier (ICM), parc Euromédecine, 208, rue des Apothicaires, 34298 Montpellier, France.

Aim: The aim of this study was to evaluate the new World Health Organization (WHO) 2017 grading system and the others clinicopathological factors in pancreatic neuroendocrine tumor (panNET) operated patients.

Methods: Histological staging was based on the WHO 2017 grading system. Outcome after surgery and predictors of overall survival (OS) and disease free survival (DFS) were evaluated.

Results: A total of 138 patients underwent surgical resection with a severe morbidity and mortality rates of 14.5% and 0.7% respectively. Five years OS differed according to WHO 2017: 95% among 58 patients with NETG1, 82% in 68 patients with NETG2, 35% in 7 patients with NETG3 and 0% in 5 patients with NECG3 (P<0.0001). Independent predictors of worse OS were age>60 y.o (P=0.014), synchronous metastasis (P=0.005) and WHO 2017 with significant differences between NETG1 versus NETG2 (P=0.005), NETG3 (P<0.001) and NECG3 (P<0.001). Independent predictors of worse DFS were symptomatic NET (P=0.038), pN+ status (P=0.027) and WHO 2017 with significant differences between NETG1 versus NETG3 (P=0.014) and NECG3 (P=0.009).

Conclusion: The WHO 2017 grading system is a useful tool for patient prognosis after panNET resection and the tailoring of therapeutic strategy. Surgery could provide good results in NETG3 patients.
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http://dx.doi.org/10.1016/j.clinre.2019.08.010DOI Listing
June 2020

[Chemotherapy for colorectal cancer: Pragmatic assessment of prescription changes and relative dose intensity].

Bull Cancer 2017 Sep 1;104(9):714-720. Epub 2017 Jun 1.

Centre hospitalier universitaire Carémeau, pharmacie, place du Pr-Robert-Debré, 30029 Nîmes cedex 9, France. Electronic address:

Introduction: Chemotherapy induced toxicities can generate changes in prescribing and relative dose intensity which have an impact on therapeutic efficacy.

Method: This is a prospective observational study performed in hepato-gastroenterology department for 6 months. All patients treated for colorectal cancer and beginning a protocol with at least one parenteral drug have been included.

Results: Among the 48 patients enrolled, 85.4% of them had at least one prescription change, which concerned 30.3% of 238 cycles. Of the 766 analyzed prescription lines, 16.6% of them were postponed and/or 6.7% had modified dosage and/or 5.6% were stopped prematurely. Grades 2 to 4 adverse reactions were responsible for at least one change prescribing to 64.6% of patients and 17.6% of cycles. Toxicity induced prescription changes were mainly due to clinical toxicities (79.3%). The rate of patients with a relative dose intensity greater than 70% was 92.9% in adjuvant state, 66.7% and 62.5% in metastatic state first line and second and subsequent line.

Conclusion: High-grade clinical toxicities are the main chemotherapy prescription change pattern in colorectal cancer. Knowledge of toxicities before the patient's arrival is expected to target patients for which the drug preparation can be anticipated and for which a cycle postponement, dose adjustment or discontinuation is necessary.
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http://dx.doi.org/10.1016/j.bulcan.2017.04.006DOI Listing
September 2017

Care pathway of patients with metastatic pancreatic cancer in daily practice in France: Results from the REPERE national survey.

Bull Cancer 2017 Apr 11;104(4):321-331. Epub 2017 Jan 11.

Jean-Minjoz University Regional Hospital (CHRU), 3, boulevard Fleming, 25030 Besançon, France.

Data in the literature regarding the care pathway of pancreatic cancer patients are limited. The objective of the REPERE survey was to identify and describe the initial stages of the care pathway of pancreatic patients in the metastatic phase. From May to October 2015, 62 oncologists (ON) or gastroenterologists specialized in digestive oncology (GESDO) and 300 general practitioners (GP) completed an electronic questionnaire on the pathway of 728 patients recently diagnosed with metastatic pancreatic adenocarcinoma. Of these patients, 200 completed a questionnaire given by a specialized physician (ON/GESDO). Weight loss (65%), fatigue (53%) or anorexia (49%) were the main signs/symptoms that motivated the patients to seek medical advice. For 87% of patients, the general practitioner was the first medicine doctor they consulted. According to the respondents (patient, general practitioner or specialist), the median delay between the onset of the first symptoms and the final diagnosis of pancreatic cancer was between 41 and 65 days. This time lapse tended to decrease with associated jaundice (-15 days on average, standard deviation=8, P<0.1 NS) or with patient concerns triggered by the first symptoms (-11 days on average, standard deviation=6, P<0.05). On the contrary, the time lapse was longer (+14 days on average, standard deviation=6, P<0.05) when the general practitioner prescribed symptomatic treatment. In conclusion, diagnostic management of patients with metastatic pancreatic cancer should be accelerated with efforts to raise practitioners' awareness.
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http://dx.doi.org/10.1016/j.bulcan.2016.11.022DOI Listing
April 2017

Feasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer.

Clin Colorectal Cancer 2016 09 2;15(3):250-6. Epub 2015 Dec 2.

Multidisciplinary Oncology Research Group (Groupe Coopérateur Multidisciplinaire en Oncologie), Paris, France; Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France; Université Pierre et Marie Curie Paris 6, Paris, France. Electronic address:

Background: 5-Fluorouracil and leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (XELOX) is a standard adjuvant treatment for patients with stage III colon cancer (CC). Capecitabine is an oral fluoropyrimidine, and administration of oxaliplatin does not necessarily require the insertion of a central venous access device (CVAD). We evaluated the feasibility of XELOX without a CVAD as adjuvant treatment in patients with stage III CC.

Patients And Methods: We retrospectively studied prospectively collected data from patients with stage III CC treated with XELOX in the International Duration Evaluation of Adjuvant Chemotherapy French trial. Patients were divided into 2 groups: those with a CVAD and those with peripheral venous access (PVA), including patients who had and had not had a CVAD at the first cycle of chemotherapy. Chemotherapy without a CVAD was considered feasible if the patient received all cycles of adjuvant therapy without it.

Results: A total of 203 patients were included: 86 (43%) in the PVA group and 116 (57%) in the CVAD group. Of the 85 patients in the PVA group (1 patient was not treated), 69 (81.2%) did not require the insertion of a CVAD. However, 16 (18.8%) required CVAD insertion owing to systematic delay of the initially planned CVAD before the second cycle of chemotherapy in 7, complications related to PVA usage in 5, a switch to the modified FOLFOX6 regimen in 2, and other reasons in 2. The oxaliplatin dose was similar in both groups regardless of the chemotherapy duration. XELOX without a CVAD was feasible for 81.2% of the patients for whom a CVAD had not been planned before chemotherapy and for 88.4% of patients for whom chemotherapy was planned without the use of a CVAD.

Conclusion: XELOX chemotherapy without a CVAD is a feasible approach for treating patients with stage III CC in the adjuvant setting.
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http://dx.doi.org/10.1016/j.clcc.2015.11.004DOI Listing
September 2016

Patient information for liver biopsy: impact of a video movie.

Gastroenterol Clin Biol 2007 Mar;31(3):274-8

Service d'Hépato-Gastroentérologie, CHU Nîmes, Cedex.

Aims: The information given to patients before a medical procedure is usually delivered verbally and in the form of a written document. Viewing a video movie about the procedure might be helpful in improving the quality of patient information and thus contributed to reduce patient anxiety. The aim of this prospective study on the methods used to deliver information to patients scheduled for liver biopsy was to determine, in comparison with standard information delivery, the impact on anxiety and understanding of additional information provided by a video movie.

Methods: Patients included in this study were scheduled for liver biopsy. Three days before the procedure, a physician informed the patients about liver biopsy and gave them a written information document. After this standard information delivery, the patients were randomly assigned to two groups, to view or not a video movie illustrating liver biopsy and recalling the information provided in the information document. Anxiety was measured after the information visit and just before the biopsy procedure using Spielberger's self-administered STAI-Y questionnaire. Patient understanding of and satisfaction with the information received were evaluated respectively before and after the procedure.

Results: Among the 67 patients retained for analysis, 33 viewed the information video and 34 did not. The level of anxiety measured at the information visit and before liver biopsy was similar in the two groups (38.8 and 37.4 with video versus 38.9 and 40.1 without video). The patients had an excellent understanding of the information received (12.3/14 with video; 12.7/14 without video) and were well satisfied with the information received.

Conclusion: The patients understood and were well satisfied with the information received about liver biopsy. Complementary information in the form of a video movie had no effect on patient anxiety.
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http://dx.doi.org/10.1016/s0399-8320(07)89372-9DOI Listing
March 2007

Activation of XII motoneurons and premotor neurons during various oropharyngeal behaviors.

Respir Physiol Neurobiol 2005 Jul;147(2-3):159-76

Laboratoire de Physiologie Neurovégétative, UMR CNRS 6153 INRA 1147, Université Paul Cézanne Aix-Marseille III, Av. Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France.

Neural control of tongue muscles plays a crucial role in a broad range of oropharyngeal behaviors. Tongue movements must be rapidly and accurately adjusted in response to the demands of multiple complex motor tasks including licking/mastication, swallowing, vocalization, breathing and protective reflexes such as coughing. Yet, central mechanisms responsible for motor and premotor control of hypoglossal (XII) activity during these behaviors are still largely unknown. The aim of this article is to review the functional organization of the XII motor nucleus with particular emphasis on breathing, coughing and swallowing. Anatomical localization of XII premotor neurons is also considered. We discuss results concerned with multifunctional activity of medullary and pontine populations of XII premotor neurons, representing a single network that can be reconfigured to produce different oromotor response patterns. In this context, we introduce new data on swallowing-related activity of XII (and trigeminal) motoneurons, and finally suggest a prominent role for the pontine Kölliker-Fuse nucleus in the control of inspiratory-related activity of XII motoneurons supplying tongue protrusor and retrusor muscles.
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http://dx.doi.org/10.1016/j.resp.2005.03.015DOI Listing
July 2005