Context.—Malignant melanoma is an aggressive tumor that produces exosomes, which contain microRNAs (miRNAs) that could be of utility in following tumoral cell dysregulation. MicroR-125b is a miRNA whose down-regulation seems to be implicated in melanoma progression. Objective.—To analyze miR-125b levels in serum, and in exosomes obtained from serum, from patients with advanced melanoma. Design.—Serum samples were obtained from 21 patients with advanced melanoma, from 16 disease-free patients with melanoma, and from 19 healthy volunteers. Exosomes were isolated from serum by precipitation, and miR-16 and miR-125b levels were quantified by real-time polymerase chain reaction. Results.—MicroR-16, but not miR-125b, was detected in all samples, and miR-16 levels were significantly higher in serum than they were in exosomes. MicroR-16 expression levels did not differ significantly between the 2 groups (patients with melanoma and healthy donors). There was a significant relationship between miR-125b and miR-16 levels in exosomes. Additionally, miR-125b levels in exosomes were significantly lower in patients with melanoma compared with disease-free patients with melanoma and healthy controls. Conclusions.—Exosomes can provide a suitable material to measure circulating miRNA in melanoma, and miR-16 can be used as an endogenous normalizer. Lower levels of miR-125b in exosomes obtained from serum are associated with advanced melanoma disease, probably reflecting the tumoral cell dysregulation.

Background: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second-or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third-or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%,.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. Conclusions: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

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Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56–0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.

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