Explore the vast range of titles available.

Preclinical studies have suggested that metformin has anti-tumour effects, likely due to blockage of mammalian target of rapamycin pathway through adenosine monophosphate-activated protein kinase and decreased insulin levels. A retrospective study showed that metformin added to everolimus to treat type 2 diabetes mellitus offered longer progression-free survival (PFS) in patients with pancreatic neuroendocrine tumours (NET). To evaluate the efficacy and safety of metformin monotherapy in patients with advanced/metastatic well-differentiated NET (WD-NET) of gastroenteropancreatic (GEP) or pulmonary origin. Single-arm phase II trial of metformin 850 mg PO twice daily until progression or intolerance for patients with progressive metastatic well-differentiated GEP or pulmonary NET. The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were response rate, PFS, toxicity and variations in glycaemic profiles (glycaemia, glycated haemoglobin and peptide C and insulin) at baseline, at 30 and 90 days. From 2014 to 2019, 28 patients were enrolled: median age was 50 years; 84% had non-functional NET, 86% were of GEP origin and 62% had G2 NET. At the time of last follow-up, 26 patients had progression, with 13 (46%) presenting DCR at 6 months and a median PFS of 6.3 months (95% confidence interval: 3.2-9.3). There was no objective response, but one patient with refractory carcinoid syndrome had complete symptom relief, lasting for more than 5 years. Variations in glycaemic profiles were not associated with DCR at 6 months. Diarrhoea was the most common adverse event, being grade 3 or 4 in 10% of the cases. Metformin monotherapy offers modest anti-tumour activity in well-differentiated GEP or lung NET.

[This corrects the article on p. 1 in vol. 16.].[This corrects the article on p. 1 in vol. 16.].

Background: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p< 0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIV- pts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS.