An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care.

Targeting HER2 in metastatic gastroesophageal adenocarcinomas: What is new?

Gastric and esophageal adenocarcinomas represent a biologically heterogeneous disease. The identification, in early eighties, of human epidermal growth factor receptor 2 (HER2) overexpression, being present in 12 to 20% of the cases, marked a major milestone in the efforts of unraveling the molecular complexity of this disease. This led to the development of anti-HER2-therapies, trastuzumab being the first to demonstrate, in combination with cisplatin and 5FU/capecitabine chemotherapy, an improvement in response rate and survival in the first-line setting of patients with metastatic, HER2-positive gastroesophageal adenocarcinomas. Afterwards, during a decade, several studies have tried new strategies either to block HER2 pathway differently or to combine different anti-HER2, without efficacy. Everything changed with studies demonstrating additive effect between anti-HER2 and immune checkpoint inhibitors and leading to phase III clinical trials combining anti-HER2 and anti-PD-L1/PD1 therapies. Pembrolizumab, a PD-1 inhibitor, was recently granted by FDA an accelerated approval, in patients with HER2-positive gastro-oesophageal adenocarcinomas, in combination with trastuzumab and platinum-based chemotherapy following meaningful improvement in overall response rate over standard treatment. Progression-free and overall-survival results are still awaited to change our first-line standard treatment. Furthermore, new HER2 inhibitors have been developed, blocking HER2-mediated pathway signaling via different mechanisms from pan-HER inhibition to anti-HER2 antibody drug conjugates with promising results in pretreated patients. Trastuzumab-deruxtecan has in particular showed interesting results in pretreated patients. We present here a review of the recent data and perspectives in HER2-positive metastatic gastroesophageal adenocarcinomas.

A Promising Biomarker and Therapeutic Target in Patients with Advanced PDAC: The Stromal Protein ßig-h3.

With an overall survival rate of 2-9% at 5 years, pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the industrialized world and is predicted to become the second by 2030. Owing to often late diagnosis and rare actionable molecular alterations, PDAC has not yet benefited from the recent therapeutic advances that immune checkpoint inhibitors (ICI) have provided in other cancer types, except in specific subgroups of patients presenting with tumors with high mutational burden (TMB) or microsatellite instability (MSI). The tumor microenvironment (TME) plays a substantial role in therapeutic resistance by facilitating immune evasion. An extracellular stromal protein, ßig-h3/TGFßi, is involved in the pathogenesis of PDAC by hampering T cell activation and promoting stiffness of the TME. The study BIGHPANC included 41 patients with metastatic PDAC, and analyzed ßig-h3 levels in serum and tumor samples to assess the ßig-h3 prognostic value. ßig-h3 serum levels are significantly associated with overall survival (HR 2.05, 95%CI 1.07-3.93; p = 0.0301). Our results suggest that ßig-h3 serum levels may be considered a prognostic biomarker in patients with metastatic PDAC.

Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France.

Current evidence suggests that 30-50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (n = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (n = 7 and n = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits.

Hyperprogressive Disease After Combined Anti-PD-L1 and Anti-CTLA-4 Immunotherapy for MSI-H/dMMR Gastric Cancer: A Case Report.

Immune checkpoint inhibitors (ICI) have been developed in gastric adenocarcinomas and approved in first-line metastatic setting (in combination with chemotherapy) as well as in pretreated patients. Microsatellite instability-high (MSI-H) tumors are predicted to derive high benefit from ICI but data in gastric locations are limited. Here, we describe the case of a 68-year old patient with stage IV MSI-H gastric adenocarcinoma, referred to our center to receive immunotherapy after failure of standard of care (surgery with perioperative platin-based chemotherapy and paclitaxel plus ramucirumab at disease progression). The patient received one injection of durvalumab and tremelimumab and was hospitalized eighteen days after because of occlusive syndrome. The CT scan showed hyperprogression of the lymph nodes and hepatic lesions, compressing the gastric stump. He died few days later. Molecular analyses did not explain this outcome. To our knowledge, this is one of the first reported cases of hyperprogressive disease after combined ICI for a patient with MSI-H tumor. We review the potential causes and discuss the emerging literature regarding predictive factors of hyperprogression in the particular subset of MSI-H patients. If some data were available in retrospective studies, validation of strong predictive factors is needed to avoid such dramatic evolutions.

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

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] ref: yes = 0.26), neutrophil-to-lymphocyte ratio (NLR; OR ref >5 = 0.31), and peritoneal carcinomatosis (OR ref: yes = 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.

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

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.