Publications by authors named "Matthieu Sarabi"

13 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-021-01341-wDOI Listing
March 2021

Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancer.

J Immunother Cancer 2021 Feb;9(2)

Sorbonne Université; Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, Paris, France.

Metastatic colorectal cancers (mCRC) harboring microsatellite instability (MSI) are sensitive to immune checkpoint inhibitors (ICIs), but the mechanisms of resistance to ICIs remain unclear. Dissociated responses in patients with ICI-treated cancer suggest that certain organs may serve as sanctuary sites due to the tumor microenvironment. This case series describes five patients with ICI-treated MSI mCRC with disease progression limited to the adrenal glands. At ICI initiation, three patients were free of metastasis in the adrenal glands. Four patients experienced objective response per RECIST (Response Evaluation Criteria in Solid Tumors) while treated with ICI. ICI treatment was discontinued due to progressive disease limited to the adrenal glands (n=3) or toxicity (n=2). The time between ICI initiation and progression in the adrenal glands ranged from 11 to 39 months. Adrenalectomy (n=3) and stereotactic body radiation therapy (n=2) were performed. At the last follow-up, all patients were alive and progression free. Molecular analyses were performed in one patient. A significant impairment of the antigen presentation pathway was observed in the ICI-resistant lesion of the adrenal gland, which could be explained by the presence of glucocorticoids in the adrenal gland microenvironment. We also detected an overexpression of , a glucocorticoid-target gene that functions as a mediator of anti-inflammation and immunosuppression. This case series suggests that the adrenal glands may be the sanctuary sites for ICI-treated MSI mCRC through the glucocorticoid-induced impairment of the antigen presentation machinery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-001903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883858PMC
February 2021

Neutrophil Heterogeneity in Cancer: From Biology to Therapies.

Front Immunol 2019 20;10:2155. Epub 2019 Sep 20.

Department of Immunity, Virus, and Inflammation (IVI), Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.

Neutrophils have been extensively described in the pathophysiology of autoimmune and infectious diseases. Accumulating evidence also suggests the important role of neutrophils in cancer progression through their interaction with cancer and immune cells in blood and in the tumor microenvironment (TME). Most studies have described neutrophils as key drivers of cancer progression, due to their involvement in various tumor promoting functions including proliferation, aggressiveness, and dissemination, as well as in immune suppression. However, such studies were focusing on late-stages of tumorigenesis, in which chronic inflammation had already developed. The role of tumor-associated neutrophils (TANs) at early stages of tumor development remains poorly described, though recent findings indicate that early-stage TANs may display anti-tumor properties. Beyond their role at tumor site, evidence supported by NLR retrospective studies and functional analyses suggest that blood neutrophils could also actively contribute to tumorigenesis. Hence, it appears that the phenotype and functions of neutrophils vary greatly during tumor progression, highlighting their heterogeneity. The origin of pro- or anti-tumor neutrophils is generally believed to arise following a change in cell state, from resting to activated. Moreover, the fate of neutrophils may also involve distinct differentiation programs yielding various subsets of pro or anti-tumor neutrophils. In this review, we will discuss the current knowledge on neutrophils heterogeneity across different tissues and their impact on tumorigenesis, as well as neutrophil-based therapeutic strategies that have shown promising results in pre-clinical studies, paving the way for the design of neutrophil-based next generation immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.02155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764113PMC
October 2020

Use's assessment of geriatric variables in the older patient with cancer's multidisciplinary team meeting.

J Geriatr Oncol 2020 04 25;11(3):536-539. Epub 2019 Jul 25.

Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgo.2019.07.015DOI Listing
April 2020

Long-Term Survivors in Metastatic Pancreatic Ductal Adenocarcinoma: A Retrospective and Matched Pair Analysis.

Oncologist 2019 12 4;24(12):1543-1548. Epub 2019 Jun 4.

Department of Medical Oncology, Centre Leon Bérard, Lyon, France.

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an aggressive malignancy with a median overall survival (OS) of between 8 and 11 months. However, a significant number of patients experience a longer survival, more than 18 months. The aim of this study was to describe the "long-term survivor" population and to evaluate clinical and pathological factors that might affect survival.

Materials And Methods: All patients with mPDAC diagnosed in the Centre Leon Bérard (Lyon, France) between January 2010 and June 2015 and who survived more than 18 months were identified. They were compared with a control cohort matched on age, sex, performance status, stage at diagnosis, primary tumor localization, treatment, and liver metastasis. Their clinical features, treatment modalities, and outcomes were analyzed.

Results: A total of 94 patients were included, 47 in each cohort. Both cohorts had identical characteristics as follows: women (51%), performance status ≤1 (95.7%), median age at diagnosis (60 years), and metastasis at diagnosis (83%). Median OS was 26.87 months (95% confidence interval [CI] 23-31.08) in the long-term survivor group (LS group) and 9.79 months (95% CI 5.75-11.86) in the control group (C group). Potential factors of long-term survival were explored with a logistic model (LS group vs. C group). Three factors were identified as significant prognostic factors in the univariate analysis: lymphopenia (odds ratio [OR] = 0.26), neutrophil-to-lymphocyte ratio (NLR; OR = 0.31), and peritoneal carcinomatosis (OR = 0.40). NLR was the only remaining factor in our backward selection procedure.

Conclusion: A significant subset of patients with mPDAC can achieve long-term survival (≥18 months) in 2018. We identified low NLR as a significant prognostic factor associated with long-term survival in mPDAC.

Implications For Practice: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the most lethal types of cancer. A subset of patients with mPDAC can achieve long-term survival (≥18 months) with a modern chemotherapy regimen, such as FOLFIRINOX or gemcitabine/nab-paclitaxel. We identified low neutrophil-to-lymphocyte ratio (NLR) as a significant prognostic factor associated with long-term survival in mPDAC. Prognostic factors such as NLR might allow accurate selection of patients with mPDAC in order to consider individual therapeutic approaches. NLR should be used as a stratification factor in clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2018-0786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975934PMC
December 2019

Primary malignant melanoma of the esophagus, treated with immunotherapy: a case report.

Immunotherapy 2018 08;10(10):831-835

Department of Medical Oncology, Centre Leon Berard, Claude Bernard University, Lyon, France.

Primary malignant melanoma of the esophagus is rare, accounting for less than 0.1-0.2% of all esophageal malignancies. It is associated with a poor outcome due to late detection and high metastatic potential. Here, we report a case of esophageal cancer, which was initially diagnosed as an adenocarcinoma and finally was confirmed as a primary malignant melanoma. This 75-year-old Caucasian male had a history of dysphagia and recent lingering abdominal pain. First biopsy showed a poorly-differentiated adenocarcinoma. He was then treated with neoadjuvant radiochemotherapy. Biopsies were repeated because of an incomplete tumor response, evaluated by endoscopic and imaging studies. The final diagnosis was a malignant melanoma. The patient has been treated with immune-checkpoint inhibitor, nivolumab, an anti-PD1 antibody.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2018-0011DOI Listing
August 2018

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study.

Oncotarget 2017 Nov 8;8(60):101383-101393. Epub 2017 Sep 8.

Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Introduction: Trastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression.

Methods: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method and compared using log-rank test. The prognostic variables with values ≤ 0.05 in univariate analysis were eligible for the Cox multivariable regression model.

Results: From May 2010 to December 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; ECOG performance status [PS] 0-1, 71.2%). The continuation (n=39) versus discontinuation (n=65) of trastuzumab beyond progression was significantly associated with an improvement of median PFS (4.4 versus 2.3 months; =0.002) and OS (12.6 versus 6.1 months; =0.001. In the multivariate analysis including the ECOG PS, number of metastatic sites and measurable disease, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.56; 95% CI, 0.35-0.89; =0.01) and OS (HR, 0.47; 95% CI, 0.28-0.79; =0.004).

Conclusion: This study suggests that continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer. These results deserve a prospective randomized validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.20711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731882PMC
November 2017

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma.

Oncol Lett 2017 Jun 20;13(6):4917-4924. Epub 2017 Apr 20.

Department of Medical Oncology, Centre Léon Bérard, 69008 Lyon, France.

There is a lack of prospective data about second-line treatments for metastatic pancreatic ductal adenocarcinoma patients. This is partially due to recent changes in first-line chemotherapy treatments. Despite this dearth of information, 50.0% of the patients who experience failure with first-line folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (folfirinox) treatment are eligible for additional chemotherapy. In this setting, gemcitabine is widely used without any standard recommendations available. The present study evaluated 42 patients who received gemcitabine subsequent to a first-line treatment of folfirinox between January 2008 and December 2012 at the Centre Léon Bérard (Lyon, France). Clinical data, biological data and tumor characteristics were retrospectively analyzed to identify prognostic factors for successful treatment with gemcitabine. In total, 11 patients (26.2%) experienced control of their cancer with gemcitabine treatment. However, there was no predictive marker for their response to the drug. The median overall survival was 3.6 months from gemcitabine initiation [95% confidence interval (CI), 2.1-5.1]. The median length of gemcitabine treatment was 1.5 months (95% CI, 0.3-13.3). Among the 11 patients who were successfully treated with gemcitabine, 6 were resistant to first-line folfirinox treatment. Patients who were non responsive to folfirinox had a higher probability of success with gemcitabine compared with patients that responded to folfirinox (54.5 vs. 21.4%, respectively; P=0.061). The present study did not identify any clinical or biological marker with a predictive value for successful gemcitabine treatment. Furthermore, successful gemcitabine treatment was not correlated with patients' response to first-line folfirinox treatment. This suggests an absence of cross-resistance in the chemotherapy protocols and provides evidence for effective cancer treatment with the second-line gemcitabine therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.6061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453056PMC
June 2017

Psychoactive drugs influence brain-derived neurotrophic factor and neurotrophin 4/5 levels in the serum of colorectal cancer patients.

Biomed Rep 2017 Jan 7;6(1):89-94. Epub 2016 Nov 7.

Department of Digestive, General and Endocrinal Surgery, University of Limoges Teaching Hospital, F-87042 Limoges Cedex, France; Laboratory EA 3842, Cellular Homeostasis and Pathologies, Medicine and Pharmacy Faculties, University of Limoges, F-87025 Limoges Cedex, France; CNRS 3503 Department, Federative Research Institute, Genomic, Environment, Immunity, Health and Therapeutics, University of Limoges, F-87025 Limoges Cedex, France.

Previous studies have reported the association between brain-derived neurotrophic factor (BDNF) and tumor development in numerous cancers. However, the accurate implication of the two specific ligands of tropomyosin kinase B receptor, BDNF and neurotrophic factor 4 (NT4/5), has not been studied in colorectal cancer (CRC) patients. The present study investigated the significance of serum BDNF and the NT4/5 in association with the intake of psychoactive drugs in CRC patients. Soluble BDNF and NT4 in the serum were assessed by ELISA. Although no correlation of BDNF and NT4 with the CRC stage was identified, a positive correlation was found between NT4 and the intake of psychoactive drugs (P=0.0457). For BDNF, a correlation was found in particular with the intake of benzodiazepine (P=0.0221). As BDNF and NT4/5 are implicated in the response of psychoactive treatments applied to manage depression, which frequently occurs in cancer patients, they cannot be used as prognostic or diagnostic markers for CRC in these patients. However, high expression of BDNF and NT4 was significantly associated with better survival. Therefore, these NTs may be used as markers for monitoring depression or predicting survival in CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/br.2016.801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244794PMC
January 2017

Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

World J Gastroenterol 2013 Sep;19(35):5940-2

Jérémie Jacques, Fabrice Projetti, Romain Legros, Virginie Valgueblasse, Matthieu Sarabi, Paul Carrier, Fabien Fredon, Stéphane Bouvier, Véronique Loustaud-Ratti, Denis Sautereau, Service d'Hépato-gastro-entérologie, CHU Dupuytren, 87042 Limoges, France.

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v19.i35.5940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793152PMC
September 2013

Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors.

Cancer Res 2013 Jun 16;73(12):3499-510. Epub 2013 Apr 16.

Institut Gustave Roussy; Institut National de la Santé et de la Recherche Medicale (INSERM) U1015, France.

Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8(+) T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3(+) TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3(+) TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56(bright) (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-13-0371DOI Listing
June 2013

Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors.

Nat Med 2011 Jun 8;17(6):700-7. Epub 2011 May 8.

Institut Gustave Roussy (IGR), Villejuif, France.

The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms. In a retrospective analysis of 80 individuals with GIST, predominant expression of the immunosuppressive NKp30c isoform (over the immunostimulatory NKp30a and NKp30b isoforms) was associated with reduced survival of subjects, decreased NKp30-dependent tumor necrosis factor-α (TNF-α) and CD107a release, and defective interferon-γ (IFN-γ) and interleukin-12 (IL-12) secretion in the NK-DC cross-talk that could be restored by blocking of IL-10. Preferential NKp30c expression resulted partly from a single-nucleotide polymorphism at position 3790 in the 3' untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nm.2366DOI Listing
June 2011