Circulating tumour DNA and melanoma survival: A systematic literature review and meta-analysis.

We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85-3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26-3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75-6.63) and OS (SHR 3.91, 95 %CI 1.97-7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Between-estimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advanced-stage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics.

Liver toxicity in the era of immune checkpoint inhibitors: A practical approach.

Immune checkpoint inhibitors have revolutionized the cancer treatment with an approved efficacy in different solid tumors and hematologic malignancies. These agents are increasing the indication in cancer treatment, but can be associated with serious immune-related adverse effects (IRAEs). Dermatologic and gastrointestinal toxicities are the most common IRAE followed by endocrinopathies with a different time of occurrence. Rarely cases of gastrointestinal toxicities are observed almost 2 years after initiation of the therapy. In this review we focus on liver toxicity related to these immunotherapeutic agents for which the largest amount of safety data is available. The management of drug-induced liver toxicity is very complicated and in same cases may take a long period of time to be resolved. A prompt recognition of liver IRAEs and an appropriate management of this event, requiring close collaboration with other specialist figures, could improve its treatment with evident implication on the efficacy of the therapy.