Publications by authors named "Hervé Perrier"

23 Publications

  • Page 1 of 1

Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study.

J Clin Oncol 2021 Oct 18:JCO2100679. Epub 2021 Oct 18.

Gustave Roussy, Université Paris Saclay, Villejuif, France.

Purpose: Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown.

Methods: In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected).

Results: A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one).

Conclusion: mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
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http://dx.doi.org/10.1200/JCO.21.00679DOI Listing
October 2021

Expected outcomes and patients' selection before chemoembolization-"Six-and-Twelve or Pre-TACE-Predict" scores may help clinicians: Real-life French cohorts results.

World J Clin Cases 2021 Jun;9(18):4559-4572

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France.

Background: Careful selection of hepatocellular carcinoma (HCC) patients prior to chemoembolization treatment is a daily reality, and is even more necessary with new available therapeutic options in HCC.

Aim: To propose two new models to better stratify patients and maximize clinical benefit: "6 and 12" and "pre/post-TACE-predict" (TACE, transarterial chemoembolization).

Methods: We evaluated and compared their performance in predicting overall survival with other systems {Barcelona Clinic Liver Cancer (BCLC), Albumin-Bilirubin (ALBI) and NIACE [Number of tumor(s), Infiltrative HCC, alpha-fetoprotein, Child-Pugh (CP), and performance status]} in two HCC French cohorts of different stages enrolled between 2010 and 2018.

Results: The cohorts included 324 patients classified as BCLC stages A/B (cohort 1) and 137 patients classified as BCLC stages B/C (cohort 2). The majority of the patients had cirrhosis with preserved liver function. "Pre-TACE-predict" and "6 and 12" models identified three distinct categories of patients exhibiting different prognosis in cohort 1. However, their prognostic value was no better than the BCLC system or NIACE score. Liver function based on CP and ALBI grades significantly impacted patient survival. Conversely, the "post-TACE-predict" model had a higher predictive value than other models. The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient (cohort 2).

Conclusion: The newly proposed "Pre-TACE-predict" and "6 and 12" models offer an interesting stratification into three categories in a recommended TACE population, as they identify poor candidates, those with partial control and durable response. The models' contribution was reduced in a population with advanced stage HCCs.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223847PMC
June 2021

Performance of Self-Collected Saliva Testing Compared with Nasopharyngeal Swab Testing for the Detection of SARS-CoV-2.

Viruses 2021 05 12;13(5). Epub 2021 May 12.

Laboratory "Health Systemic Process", EA4129, University Lyon 1, 69008 Lyon, France.

The aim of this study was to determine whether self-collected pure saliva (SCPS) is comparable to nasopharyngeal (NP) swabs in the quantitative detection of SARS-CoV-2 by RT-PCR in asymptomatic, mild patients with confirmed COVID-19. Thirty-one patients aged from 18 to 85 years were included between 9 June and 11 December 2020. A SCPS sample and a NP sample were taken for each patient. Quantitative PCR was performed to detect SARS-CoV-2 viral load. Results of SCPS vs. NP samples testing were compared. Statistical analyses were performed. Viral load was significantly correlated ( = 0.72). The concordance probability was estimated at 73.3%. In symptomatic adults, SCPS performance was similar to that of NP swabs (Percent Agreement = 74.1%; = 0.11). Thus, the salivary test based on pure oral saliva samples easily obtained by noninvasive techniques has a fair agreement with the nasopharyngeal one in asymptomatic, mild patients with a confirmed diagnosis of COVID-19.
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http://dx.doi.org/10.3390/v13050895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150338PMC
May 2021

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial.

Clin Microbiol Infect 2021 Oct 24;27(10):1494-1501. Epub 2021 May 24.

Laboratory "Systemic Health Care", EA4129, University of Lyon, University Claude Bernard Lyon 1, Lyon, France.

Objectives: To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.

Methods: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.

Results: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log copies/mL; IQR 0-4.19), compared with placebo (3.31 log copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis.

Conclusions: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.
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http://dx.doi.org/10.1016/j.cmi.2021.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142805PMC
October 2021

Avelumab versus standard second line treatment chemotherapy in metastatic colorectal cancer patients with microsatellite instability: The SAMCO-PRODIGE 54 randomised phase II trial.

Dig Liver Dis 2021 03 25;53(3):318-323. Epub 2020 Dec 25.

Gastroenterology Department and Medical Oncology Department, Poitiers University Hospital, Poitiers, France.

Immune checkpoint inhibitors have failed in treating metastatic colorectal cancer (mCRC) patients except those with dMMR/MSI tumors. However, until very recently we had only non-comparative promising data in this population with anti-programmed cell death 1/ programmed cell death ligand 1 (PD1/PD-L1) antibodies alone or combined with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies. This comparative phase II trial (NCT03186326), conducted in more than 100 centers in France, will include dMMR/MSI mCRC patients with progression after a first-line treatment with chemotherapy ± targeted therapies, to evaluate efficacy and safety of the anti-PDL1 Avelumab versus a standard second-line treatment. Main inclusion criteria were patients aged 18 to 75 years, ECOG performance status ≤2, dMMR/MSI mCRC and failure of a standard first-line regimen. Patient will be randomised to receive Avelumab 10 mg/kg versus standard second-line doublet chemotherapy plus a targeted agent according to tumor RAS status. Patients will be followed for 4 years. A gain of 5 months in median PFS is expected in favour of the Avelumab arm (12 vs 7 months; HR=0.58). Secondary endpoints include objective response rate, overall survival, quality of life and toxicity. In addition, circulating tumour DNA and microbiota will be explored to test their potential prognostic and predictive values. The study was opened in March 2018.
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http://dx.doi.org/10.1016/j.dld.2020.11.031DOI Listing
March 2021

Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study.

Clin Res Hepatol Gastroenterol 2021 Mar 21;45(2):101464. Epub 2020 Jun 21.

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

Background: Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection.

Aims: We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure.

Methods: Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated.

Results: No bleeding complication was reported. One and two liver failures were respectively observed in sunitinib and placebo patients. Compliance to sunitinib treatment was acceptable. Sunitinib dose reduction occurred in 37% of patients due to acute toxicity. Main grade 3-4 toxicities were: thrombocytopenia, neutropenia, increased bilirubin, increased ALT and asthenia. In the sunitinib group, the median PFS and OS were 9.05 [5.81;11.63] and 25.0 [13.5;36.8] months, respectively. In the placebo group, the median PFS and OS were 5.51 [4.14;7.79] and 20.5 [15.1;30.6] months, respectively.

Conclusions: TACE plus sunitinib in the first-line therapy for patients with HCC not suitable for surgical resection was feasible. CLINICALTRIALS.

Gov Number: NCT01164202.
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http://dx.doi.org/10.1016/j.clinre.2020.05.012DOI Listing
March 2021

Drastic Reduction of Turnaround Time After Implementation of a Fully Automated Assay for RAS-BRAF Mutations in Colorectal Cancer: A Pilot Prospective Study in Real-life Conditions.

Pathol Oncol Res 2020 Oct 22;26(4):2469-2473. Epub 2020 Jun 22.

Rouen University Hospital, Rouen, France.

In some situations, there is a need for rapid mutation tests for guiding clinical decisions and starting targeted therapies with minimal delays. In this study we evaluated the turnaround time before and after the implementation of a fully automated multiplex assay for KRAS and NRAS/BRAF mutation tests (Idylla™ platform, Biocartis) in metastatic colorectal cancer. The objective of this project was to compare the turnaround times in 2017-2018 with the fully automated multiplex assay to the 2016 results with previous methods. Centers with a number of tests for metastatic colorectal cancer > 100 yearly and a usual turnaround time ≥ 3 weeks for mutation detection were selected. Results of 505 KRAS tests and 369 NRAS/BRAF tests were transmitted by 10 centers. The mean turnaround time from test prescription to reception of results was reduced from 25.8 days in 2016 to 4.5 days in 2017-2018. In conclusion, this pilot project shows that the Idylla™ platform for testing KRAS and NRAS/BRAF mutations allows an optimized turnaround time from test prescription to reception of results.
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http://dx.doi.org/10.1007/s12253-020-00818-yDOI Listing
October 2020

Small bowel adenocarcinoma: Results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients.

Int J Cancer 2020 08 22;147(4):967-977. Epub 2020 Jan 22.

Department of Oncology, Saint Antoine Hospital, APHP, Paris, France.

Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23-90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz-Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin-based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54-months median follow-up, the 5-year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA-resected tumours, the prognostic factors for OS were grade and T stage.
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http://dx.doi.org/10.1002/ijc.32860DOI Listing
August 2020

Sorafenib: Experience and Better Manage-ment of Side Effects Improve Overall Survival in Hepatocellular Carcinoma Patients: A Real-Life Retrospective Analysis.

Liver Cancer 2019 Nov 27;8(6):457-467. Epub 2019 Mar 27.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Marseille, France.

Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this translates into a better prognosis.

Methods: This was a retrospective study of advanced HCC patients treated with sorafenib between 2007 and 2017.

Results: 188 advanced HCC patients received > 4 weeks of sorafenib. Median treatment duration was 5.4 months and median overall survival (mOS) 10 months (95% confidence interval 15-27). Sorafenib was initiated in 65 patients in 2007-2012 and 123 in 2013-2017. Both groups were comparable except for Barcelona Clinic liver cancer class. Tumor progression, disease control (DC) rate, and incidence of toxicity were similar in the 2 periods, but the duration of treatment (4.3 vs. 5.9 months; < 0.01) and mOS (8 vs. 12 months; < 0.002) differed. Among progressive disease patients, mOS was similar (7 months) but for those who had DC at 8 weeks, mOS was longer in the recent period (13 vs. 27 months; < 0.0001). In the univariate analysis of OS, the period of treatment had a prognostic value.

Conclusion: When comparing 2 periods of treatment in advanced HCC patients under sorafenib, duration of treatment and mOS were higher in the recent period. While mOS did not differ for patients who progressed, it was 2-fold higher in the recent period for those who had tumor control. Improvements in the use of sorafenib seem to be associated with better outcomes limited to patients with DC.
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http://dx.doi.org/10.1159/000497161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883434PMC
November 2019

Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study.

Gut 2020 04 28;69(4):681-690. Epub 2019 Nov 28.

Département d'oncologie médicale, Georges-Francois Leclerc Centre, Dijon, Bourgogne-Franche-Comté, France

Objective: Diagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.

Design: We have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.

Results: Within the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated 'DGMuneS', outperformed Immunoscore when used in estimating patients' prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk.

Conclusion: These findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients' prognosis.
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http://dx.doi.org/10.1136/gutjnl-2019-319292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063404PMC
April 2020

FOLFOX alone or combined with rilotumumab or panitumumab as first-line treatment for patients with advanced gastroesophageal adenocarcinoma (PRODIGE 17-ACCORD 20-MEGA): a randomised, open-label, three-arm phase II trial.

Eur J Cancer 2019 07 23;115:97-106. Epub 2019 May 23.

Department of Hepatogastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges Pompidou, Paris, Sorbonne Paris Cité, Paris Descartes University, France.

Background: Epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (MET) pathways, which promote tumour growth and proliferation, are often deregulated in advanced gastroesophageal adenocarcinomas. We assessed whether adding panitumumab (an EGFR inhibitor) or rilotumumab (a HGF inhibitor) to first-line fluoropyrimidine-based and platinum-based chemotherapy (modified oxaliplatin, leucovorin and fluorouracil [mFOLFOX6]) benefits to patients with advanced gastroesophageal adenocarcinoma.

Patients And Methods: This phase II, open-label, randomised, three-arm study enrolled patients ≥18 years, with advanced gastroesophageal adenocarcinoma, Eastern Cooperative Oncology Group performance status 0-1 and no known HER2 overexpression. Patients were randomly assigned (1:1:1) mFOLFOX6 (oxaliplatin 85 mg/m, leucovorin 400 mg/m, 5-fluorouracil 400 mg/m bolus then 2400 mg/m over 46 h) alone or combined with panitumumab (6 mg/kg) or rilotumumab (10 mg/kg) every 2 weeks until limiting toxicity, patient's refusal or disease progression. The primary end-point was the 4-month progression-free survival (PFS) rate. Secondary end-points included overall survival (OS) and tolerance.

Results: The study enrolled 162 patients in 29 French centres. The median follow-up was 23.6 months (interquartile range = 16.4-29.0). The 4-month PFS rate was 71% (95% confidence interval [CI] = 57-82) with chemotherapy alone, 57% (95% CI = 42-71) combined with panitumumab and 61% (95% CI = 47-74) combined with rilotumumab. Median OS was 13.1 months (95% CI = 8.7-16.9) with chemotherapy alone, 8.3 months (95% CI = 6.2-13.2) combined with panitumumab and 11.5 months (95% CI = 7.9-17.1) combined with rilotumumab. Adverse events grade ≥III occurred less frequently with chemotherapy alone (62%) than with panitumumab (83%) and rilotumumab (89%).

Conclusions: We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients.

Trial Registration: European Clinical Trials Database, number 2009-012797-12.
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http://dx.doi.org/10.1016/j.ejca.2019.04.020DOI Listing
July 2019

Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort.

Eur J Gastroenterol Hepatol 2019 Nov;31(11):1414-1423

Department of Gastroenterology and Hepatology.

Background: Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management.

Patients And Methods: A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival.

Results: Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage.

Conclusion: HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.
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http://dx.doi.org/10.1097/MEG.0000000000001420DOI Listing
November 2019

Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case-control study.

Eur J Gastroenterol Hepatol 2018 Apr;30(4):368-375

Departments of Hepato-Gastroenterology.

Background: Direct-acting antivirals (DAAs) therapy against hepatitis C viral (HCV) infection has markedly improved the sustained viral response. However, recent studies have suggested an unsuspected high rate of hepatocellular carcinoma (HCC) recurrence.

Patients And Methods: A retrospective case-control study was carried out to investigate the impact of DAAs on tumor recurrence in patients with complete response to HCC treatment within our HCV-related cirrhosis cohort. Patients who received [group 1 (G1), n=22] or not [group 2 (G2), n=49] a DAAs therapy were matched 1 : 2 for age, sex, liver function, HCC stage, and treatment.

Results: Initial HCC were mostly Barcelona Clinic Liver Cancer stage A (95% G1, 94% G2). Sustained viral response with DAAs was achieved in 86% of patients. After a similar median overall follow-up time with similar radiologic surveillance after HCC treatment, 41% of patients developed radiologic tumor recurrence in G1 versus 35% of patients in G2 (P=0.7904). There was no significant difference in time to progression between the two groups [12 (9-16) months G1 vs. 14 (8-21) months G2, P=0.7688], or Barcelona Clinic Liver Cancer stage at recurrence. However, the interval between HCC treatment and antiviral therapy was significantly different among DAAs patients with recurrence and those without recurrence [7.0 (2.5-9.0) months vs. 36.0 (9.0-58.0) months, P=0.0235, respectively].

Conclusion: In our case-control study, HCV therapy with DAAs does not accelerate or prevent early HCC recurrence compared with untreated patients. The rate of recurrence, time to progression, and HCC pattern are similar. Early DAAs treatment (<12 months) after HCC cure should be discouraged considering the HCC recurrence rate during this period.
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http://dx.doi.org/10.1097/MEG.0000000000001082DOI Listing
April 2018

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort.

World J Gastroenterol 2017 Apr;23(14):2545-2555

Xavier Adhoute, Hervé Perrier, Paul Castellani, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, 13008 Marseille, France.

Aim: To compare the performances of the Barcelona clinic liver cancer (BCLC) nomogram and others systems (BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma (HCC) French cohort.

Methods: Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion (AIC) and C-index were compared among scoring systems.

Results: The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis (81%), child-Pugh A (73%), alcohol-related (41%), HCV-related (27%). HCC were multinodular (59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A (17%), B (16%), C (60%) and D (7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups ( < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful.

Conclusion: In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.
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http://dx.doi.org/10.3748/wjg.v23.i14.2545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394518PMC
April 2017

NIACE score for hepatocellular carcinoma patients treated by surgery or transarterial chemoembolization.

Eur J Gastroenterol Hepatol 2017 Jun;29(6):706-715

aDepartment of Hepato-Gastroenterology bDepartment of Hepatobiliary Surgery cDepartment of Radiology, Hôpital Saint-Joseph dAlphaBio Laboratory eDepartment of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette fDepartment of Hepatobiliary Surgery, Centre Hospitalo-Universitaire Timone, Marseille gDepartment of Hepato-Gastroenterology, Centre Hospitalo-Universitaire de Nancy hINSERM U954, Université de Lorraine, CHU de Nancy, Vandoeuvre les Nancy, France.

Background And Aims: Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child-Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations.

Patients And Methods: This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery (n=207) or by chemoembolization (n=168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system.

Results: The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55-81) months versus 35 (21-56) months (P=0.0004) and 20 (17-24) months versus 13 (7-17) months (P=0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score.

Conclusion: In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.
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http://dx.doi.org/10.1097/MEG.0000000000000852DOI Listing
June 2017

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments.

World J Hepatol 2016 Jun;8(17):703-15

Xavier Adhoute, Paul Castellani, Hervé Perrier, Marc Bourlière, Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, 13008 Marseille, France.

Therapeutic management of hepatocellular carcinoma (HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer (BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.
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http://dx.doi.org/10.4254/wjh.v8.i17.703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911504PMC
June 2016

Prognosis of advanced hepatocellular carcinoma: a new stratification of Barcelona Clinic Liver Cancer stage C: results from a French multicenter study.

Eur J Gastroenterol Hepatol 2016 Apr;28(4):433-40

Departments of aHepato-Gastroenterology bHepatobiliary Surgery cRadiology, Hôpital Saint-Joseph dAlphaBio Laboratory eDepartment of Hepato-Gastroenterology and Digestive Oncology, Institut Paoli-Calmette, Marseille fDepartment of Hepato-Gastroenterology, Centre Hospitalo-Universitaire, Saint-André Bordeaux, Bordeaux gDepartment of Hepato-Gastroenterology and Digestive Oncology, Centre Eugène Marquis, Rennes hDepartment of Hepato-Gastroenterology iINSERM U954, Université de Lorraine, CHU de Nancy, Vandoeuvre les Nancy, France.

Background: Advanced hepatocellular carcinoma (HCC) includes a wide spectrum of tumors and patients' prognosis after treatment is highly variable. Moreover, therapeutic options based on the Barcelona Clinic Liver Cancer (BCLC) staging system algorithm are restricted to one systemic therapy.

Aim Of The Study: To refine the stratification among BCLC C HCC patients by establishing a new simple prognostic score.

Patients And Methods: A regression model based on a BCLC stage C population and validated with an external cohort of BCLC C HCC patients defined the score. It was therefore validated among three external cohorts of BCLC C HCC patients treated with sorafenib.

Results: Five variables had independent prognostic values: the number of nodules, the infiltrating nature of the HCC, α-fetoprotein serum level, Child-Pugh score, and Eastern Cooperative Oncology Group Performance Status grade. They were integrated into a new score named NIACE ranging from 0 to 7, well correlated with survival. With the use of one threshold value, this score enables defining of two populations with different survivals among BCLC C patients and specifically among those treated with sorafenib.

Conclusion: The NIACE score defines different prognostic subgroups after palliative treatment of HCC. It could be an additional tool for BCLC C HCC before inclusion in clinical trials or for the management of patients. These results must be validated in a prospective study.
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http://dx.doi.org/10.1097/MEG.0000000000000558DOI Listing
April 2016

Recommendations for the use of chemoembolization in patients with hepatocellular carcinoma: Usefulness of scoring system?

World J Hepatol 2015 Mar;7(3):521-31

Xavier Adhoute, Paul Castellani, Herve Perrier, Marc Bourliere, Department of Hepatology, Hopital Saint-Joseph, 13285 Marseille, France.

Several hepatocellular carcinoma (HCC) staging systems have been established, and a variety of country-specific treatment strategies are also proposed. The barcelona - clinic liver cancer (BCLC) system is the most widely used in Europe. The Hong Kong liver Cancer is a new prognostic staging system; it might become the reference system in Asia. Transarterial chemoembolization (TACE) is the most widely used treatment for HCC worldwide; but it showed a benefit only for intermediate stage HCC (BCLC B), and there is still no consensus concerning treatment methods and treatment strategies. In view of the highly diverse nature of HCC and practices, a scoring system designed to assist with decision making before the first TACE is performed or prior to repeating the procedure would be highly useful.
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http://dx.doi.org/10.4254/wjh.v7.i3.521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381174PMC
March 2015

Retreatment with TACE: the ABCR SCORE, an aid to the decision-making process.

J Hepatol 2015 Apr 21;62(4):855-62. Epub 2014 Nov 21.

Department of Hepato-Gastroenterology, Hôpital Saint-Joseph Marseille, France. Electronic address:

Background & Aims: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) and it is the most commonly used treatment for HCC worldwide. However, no prognostic indices, designed to select appropriate candidates for repeat conventional TACE, have been incorporated in the guidelines.

Methods: From January 2007 to April 2012, 139 consecutive HCC patients, mainly with an alcohol- or viral-induced disease, were treated with TACE. Using a regression model on the prognostic variables of our population, we determined a score designed to help for repeat TACE and we validated it in two cohorts. We also compared it to the ART score.

Results: In the multivariate analysis, four prognostic factors were associated with overall survival: BCLC and AFP (>200 ng/ml) at baseline, increase in Child-Pugh score by ⩾2 from baseline, and absence of radiological response. These factors were included in a score (ABCR, ranging from -3 to +6), which correlates with survival and identifies three groups. The ABCR score was validated in two different cohorts of 178 patients and proofed to perform better than the ART score in distinguishing between patients' prognosis.

Conclusions: The ABCR score is a simple and clinically relevant index, summing four prognostic variables endorsed in HCC. An ABCR score ⩾4 prior to the second TACE identifies patients with dismal prognosis who may not benefit from further TACE sessions.
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http://dx.doi.org/10.1016/j.jhep.2014.11.014DOI Listing
April 2015

Uracil-tegafur/leucovorin and mitomycin C salvage therapy in patients with advanced colorectal cancer: a phase II study.

J Chemother 2012 Aug;24(4):207-11

Department of Medical Oncology, Antoine Lacassagne Cancer Research Center, Nice, France.

We investigated the efficacy and safety of oral Uracil/tegafur (UFT) with leucovorin and mitomycin C (MMC) as third-line treatment for patients with extensively pretreated metastatic colorectal cancer (mCRC). This was a multicenter, prospective phase II study. Patients received MMC 7 mg/m² on day 1 and UFT 300 mg/m² with leucovorin 90 mg, both divided into three daily doses, on days 1-28 every 5 weeks. All patients had failed prior treatment with irinotecan, oxaliplatin, fluoropyrimidine, bevacizumab, and cetuximab. The primary endpoint was tumor control rate evaluated after 2 cycles. Twenty-one patients were included: median age was 66 years (41.1-87.8 years). Tumor control rate was observed in 26.7% of the 15 patients evaluable for response. Median overall survival was 6.4 months. Grade 3 adverse events were asthenia, anorexia, and vomiting. In patients with mCRC who have progressed after as many as two prior therapies, the combination of UFT/leucovorin and MMC is safe and may produce a short stabilization of disease in approximately 25% of patients.
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http://dx.doi.org/10.1179/1973947812Y.0000000021DOI Listing
August 2012

Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents.

Br J Haematol 2012 Mar 23;156(5):619-25. Epub 2011 Dec 23.

Hématologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France.

Lenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis-stimulating agents (ESA) is not known. We report on 31 consecutive lower-risk non-del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion-dependent (RBC-TD) patients, who became transfusion-independent (RBC-TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion-free after 11(+)-31(+) months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC-TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies.
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http://dx.doi.org/10.1111/j.1365-2141.2011.08979.xDOI Listing
March 2012

[Sarcoidosis following pegylated interferon therapy: two cases].

Gastroenterol Clin Biol 2006 Apr;30(4):615-9

Service d'Hépato-Gastroentérologie, Hôpital Saint Joseph, Marseille.

One side effect of the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report two new cases and offer an exhaustive review of the literature. A 39-year-old man with type C chronic active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 7 months of treatment with pegylated interferon. The evolution was favourable after stopping treatment. The second patient developed cutaneous lesions after 6 months of treatment. Resolution occurred after the discontinuation of the treatment. In these two cases ribavirin was stopped before the first signs of sarcoidosis.
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http://dx.doi.org/10.1016/s0399-8320(06)73238-9DOI Listing
April 2006
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