Prevalence of Sarcopenia and Impact on Survival in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours.

Sarcopenia in patients with cancer is associated with adverse outcomes such as shorter survival. However, there exists little evidence regarding the prevalence of sarcopenia in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Patients with a histologically confirmed newly diagnosed metastatic GEP-NET between 2006 and 2018, CT scan, and anthropometric data at diagnosis were included in this study. CT scans were analysed for the presence of sarcopenia and correlated with overall survival (OS). In total, 183 patients, 87 male (48%), with a median age of 62 years (IQR 52-68 years), were included. In 44 patients (24%), there was a pancreas NET, and in 136 patients, there was a small bowel NET (74%). Sarcopenia was present in 128 patients (69%) and unrelated to BMI (median 25.1). There were significant survival differences between patients with pancreatic and small bowel NETs at 86 vs. 141 months, respectively (p = 0.04). For patients with pancreatic NETs, the presence of sarcopenia was independently associated with shorter OS (HR 3.79 95% CI 1.1-13.03, p-value 0.035). A high prevalence of sarcopenia at the time of diagnosis of a metastatic GEP-NET was seen and associated with worse OS in patients with pancreatic NETs. Further research should focus on how to reverse sarcopenia and its impact on OS and/or quality of life.

The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline.

The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

Somatic mosaicism by a de novo MLH1 mutation as a cause of Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is caused by germline mismatch repair (MMR) gene mutations. De novo MMR gene mutations are rare, and somatic mosaicism in LS is thought to be infrequent. We describe the first case of somatic mosaicism by a de novo MLH1 mutation for a patient diagnosed with a rectosigmoid adenocarcinoma at age 31. METHODS: Twelve years after initial colorectal cancer diagnosis, tumor tissue of the patient was tested with sensitive next generation sequencing (NGS) analysis for the presence of somatic MMR mutations. RESULTS: In tumor tissue, an inactivating MLH1 mutation (c.518_519del; p.(Tyr173Trpfs*18)) was detected, which was also present at low level in the blood of the patient. In both parents, as well as the patient's sisters, the mutation was not present. CONCLUSION: We show that low-level mosaicism can be detected by using high-coverage targeted NGS panels on constitutional and/or tumor DNA. This report illustrates that by using sensitive sequencing techniques, more cases of genetic diseases driven by mosaic mutations may be identified, with important clinical consequences for patients and family members.

Do Men and Women Need to Be Screened Differently with Fecal Immunochemical Testing? A Cost-Effectiveness Analysis.

Background: Several studies suggest that test characteristics for the fecal immunochemical test (FIT) differ by gender, triggering a debate on whether men and women should be screened differently. We used the microsimulation model MISCAN-Colon to evaluate whether screening stratified by gender is cost-effective.Methods: We estimated gender-specific FIT characteristics based on first-round positivity and detection rates observed in a FIT screening pilot (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and costs of 480 gender-specific FIT screening strategies and compared them with uniform screening.Results: Biennial FIT screening from ages 50 to 75 was less effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY) gained, respectively] at higher costs (€42,161 vs. -€5,471, respectively). However, the incremental QALYs gained and costs of annual screening compared with biennial screening were more similar for both genders (8.7 QALYs gained and €26,394 for women vs. 6.7 QALYs gained and €20,863 for men). Considering all evaluated screening strategies, optimal gender-based screening yielded at most 7% more QALYs gained than optimal uniform screening and even resulted in equal costs and QALYs gained from a willingness-to-pay threshold of €1,300.Conclusions: FIT screening is less effective in women, but the incremental cost-effectiveness is similar in men and women. Consequently, screening stratified by gender is not more cost-effective than uniform FIT screening.Impact: Our conclusions support the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev; 26(8); 1328-36. ©2017 AACR.