Publications by authors named "Pauline Rochefort"

6 Publications

  • Page 1 of 1

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

Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β.

PLoS Pathog 2018 08 8;14(8):e1007158. Epub 2018 Aug 8.

Centre International de recherche en Infectiologie, CIRI, Inserm, U1111, Lyon, France.

Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses and to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a powerful cytokine produced when viral motifs are sensed by innate receptors that are members of the inflammasome family. Whether oncoviruses such as HPV16 can activate the inflammasome pathway remains unknown. Here, we show that infection of human keratinocytes with HPV16 induced the secretion of IL-1β. Yet, upon expression of the viral early genes, IL-1β transcription was blocked. We went on to show that expression of the viral oncoprotein E6 in human keratinocytes inhibited IRF6 transcription which we revealed regulated IL-1β promoter activity. Preventing E6 expression using siRNA, or using E6 mutants that prevented degradation of p53, showed that p53 regulated IRF6 transcription. HPV16 abrogation of p53 binding to the IRF6 promoter was shown by ChIP in tissues from patients with cervical cancer. Thus E6 inhibition of IRF6 is an escape strategy used by HPV16 to block the production IL-1β. Our findings reveal a struggle between oncoviral persistence and host immunity; which is centered on IL-1β regulation.
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http://dx.doi.org/10.1371/journal.ppat.1007158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124776PMC
August 2018

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

A Retrospective Multicentric Study of Ewing Sarcoma Family of Tumors in Patients Older Than 50: Management and Outcome.

Sci Rep 2017 12 20;7(1):17917. Epub 2017 Dec 20.

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

Ewing's sarcoma family of tumors (EFTs) is a group of rare and aggressive tumors. Data on EFTs in patients (pts) ≥ 50 years are limited and these pts are often not eligible for clinical trials. Some, but not all, studies have reported inferior outcome for older pts with EFTs. We conducted an IRB-approved retrospective analysis among centers of the French Sarcoma Group on pts diagnosed with EFTs at age ≥50 between 2000 and 2012. Clinical features, treatment modality and outcomes were analyzed. Seventy-seven pts were identified, including 36 females (46.8%) and the median age at diagnosis was 56 years (range: 50-86). The primary tumor was located in soft tissue in 59 pts (76.6%). Fifty-six pts (72.7%) had localized disease, among them 49 (87.5%) received chemotherapy in addition to local therapy. Their estimated 3-yr OS and event-free survival (EFS) rates were respectively 73.3% and 62.2%. Recurrence occurred in 43 pts. The estimated 3-yr OS rate was 37% in pts with metastatic disease at presentation. EFTs in pts ≥50 years are more likely to originate from soft tissue and their outcomes appear to be worse than that of younger pts treated with modern protocols.
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http://dx.doi.org/10.1038/s41598-017-17733-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738347PMC
December 2017

Soluble VE-cadherin in metastatic breast cancer: an independent prognostic factor for both progression-free survival and overall survival.

Br J Cancer 2017 01 5;116(3):356-361. Epub 2017 Jan 5.

Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon F-69373, France.

Background: Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC.

Methods: Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study. Serum concentrations of VE-cadherin were measured at inclusion for 141 patients and 6 weeks after the beginning of chemotherapy, using a sandwich enzyme immunoassay.

Results: The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free (PFS) and overall survival (OS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level was an independent adverse prognostic variable for PFS (median PFS 9.7 (IC95: 8; 11.9) vs 5.8 (IC95: 4.1; 8) months P=0.0008) and OS (median OS 34 (IC95: 26.6; 47.1) vs 14.8 (IC95: 9.3; 21.4) months P=0.0007). Moreover, VE-cadherin decrease during chemotherapy was also associated with good prognosis.

Conclusions: Serum VE-cadherin levels correlate to poorer survival in patients with hormone-refractory MBC. As sVE-cadherin reflects tumour angiogenesis, this could have therapeutic implications for antiangiogenic treatment.
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http://dx.doi.org/10.1038/bjc.2016.427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294483PMC
January 2017

[ESMO ECCO 2015: The highlights of immunotherapy and targeted therapies].

Bull Cancer 2016 Jun 24;103(6):594-603. Epub 2016 May 24.

AERIO, 149, avenue du Maine, 75014 Paris, France; DITEP, Gustave-Roussy, 94805 Villejuif, France. Electronic address:

The ESMO/ECC congress (European Society for Medical Oncology/European Cancer Congress) took place in Vienna, Austria, September 25-29. The main topic of the conference was immunotherapies especially in advanced kidney cancer with nivolumab in phase III and in metastatic lung cancer with atezolizumab in phase II. Targeted therapies were also highlighted with cabozantinib proposed in advanced renal cancer or everolimus in differenciated neuroendocrine tumors grade 1 or 2. Furthermore the current challenges remain unchanged: improving patients' care through better selection and finding biomarkers using simple samples (blood or urine). Also early phases and personalized medicine found their place in the different presentations and were highlighted largely bringing new approaches in the treatment of metastatic patients.
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http://dx.doi.org/10.1016/j.bulcan.2016.04.001DOI Listing
June 2016