Risultati per: Melanoma cutaneo

This cohort study assesses incidence of primary invasive cutaneous malignant melanoma and mortality trends in Sweden, focusing on the population younger than the mean age of melanoma onset.

Current smokers are more likely to die from their melanoma than never-smokers, while former-smokers appear to have similar risks to never-smokers. Smokers have higher risks of sentinel node-positivity and of complications from node surgery. Study limitations included reliance on self-reporting of smoking status. In only seven studies did patients receive modern systemic therapies, limiting the ability to assess their relative efficacy in smokers and non-smokers.

In Reply We appreciate the thoughtful response by Akama-Garren and Hartman regarding ways of reducing fear of cancer recurrence (FCR) among patients with localized melanoma. They proposed 2 potential solutions: (1) psychological support (which we also proposed) and (2) changing terminology to recategorize melanoma in situ as melanocytic lesions with low risk of progression. In this reply, we discuss both proposals.

To the Editor Mahama et al administered a qualitative survey to assess the fear of cancer recurrence for 51 survivors of localized cutaneous melanoma. The authors found that despite good prognoses, approximately 75% of survivors had fear of cancer recurrence that was negatively associated with their psychological well-being, which, as noted by the authors, aligned with prior studies among patients with melanoma. Surprisingly, Mahama et al observed similar levels of clinical fear of cancer recurrence in patients with stage 0 and stage I to IIA localized cutaneous melanoma despite the fact that patients with stage 0 have a prognosis approaching 100% 5-year melanoma-specific survival. A systematic review of 46 studies found that 82% of survivors of thyroid cancer scored 13 or higher on the Fear of Cancer Recurrence Inventory (FCRI), suggesting that patients with melanoma and thyroid cancer share high levels of cancer worry despite relatively high survival rates compared with other cancers.

Con nivolumab più ipilimumab. Dieci anni fa il tasso di sopravvivenza era al 25% dopo un anno

Dal sistema immunitaria, per contrastare metastasi e recidive

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

Grazie alla combinazione con una molecola.

Grazie alla combinazione con una molecola.

Caressa e Bergomi, in ogni campo fondamentale gioco di squadra

Heritability is a factor that has been demonstrated to be strongly associated with the diagnosis of cutaneous melanoma, and there are several inherited gene variants that have been identified as melanoma risk alleles. Previous studies have mainly focused on invasive melanoma or on melanoma irrespective of invasiveness. In this issue of JAMA Dermatology, Ingold et al present their investigation on the influence of germline genetic variation on the risk of developing in situ vs invasive melanoma. The study by Ingold et al is a notable attempt to unravel a complicated biology as melanoma in situ traditionally is considered as a precursor to invasive melanomas, and the idea that these lesions in a sense represent different class of tumors with different etiology is unproven. The authors conducted this study using 5 different datasets of populations with European ancestry (from the UK, Finland, and Australia), with more than 10 000 and more than 3000 patients in total with invasive and in situ melanomas, respectively, together with more than 500 000 controls. The study is a meta-analysis of the different cohorts, assessing associations between common single-nucleotide variant (SNV) genotypes, comparing (1) invasive melanoma with controls, (2) in situ melanoma with controls, and (3) invasive melanoma with in situ melanoma (case-case analysis). Further, 3 separate bioinformatics approaches were applied: (1) genome-wide association study (GWAS) to identify significant chromosomal risk loci, (2) polygenic risk score (PRS) analyses based on 64 497 SNVs to identify joint score combining identified variants that had a P value threshold less than .10 in the case-case GWAS meta-analysis, and (3) SNV-based heritability, which is a method to assess how much of the variation in a trait can be explained by the cumulative effect of SNVs.

This genome-wide association study meta-analysis evaluates whether differences in risk of in situ melanoma and invasive melanoma are heritable.

Objective
This study evaluates the safety/efficacy of sabatolimab plus spartalizumab in patients with melanoma or non-small cell lung cancer (NSCLC).

Design, setting and participants
This is a phase 1–1b/2, open-label, multinational, multicentre study of patients with advanced/metastatic melanoma or NSCLC with ≥1 measurable lesion.

Interventions
Patients were given sabatolimab 800 mg every 4 weeks plus spartalizumab 400 mg every 4 weeks until unacceptable toxicity, disease progression and/or treatment discontinuation.

Outcome measures
The phase 2 primary outcome measure was overall response rate and secondary objectives included evaluation of the safety, tolerability, efficacy and pharmacokinetics of sabatolimab in combination with spartalizumab.

Results
33 patients (melanoma n=16, NSCLC n=17) received sabatolimab plus spartalizumab. 31 (94%) experienced ≥1 adverse event (AE); 15 (46%) experienced grade 3/4 events. The most frequent grade ≥3 AEs for NSCLC were anaemia, dyspnoea and pneumonia (each n=2, 12%); for patients with melanoma, the most frequent grade ≥3 AEs were physical health deterioration, hypokalaemia, hypophosphataemia, pathological fracture and tumour invasion (each n=1; 6%). One (3%) patient discontinued treatment due to AE. Stable disease was seen in three patients with melanoma (19%) and six patients with NSCLC (35%). Median progression-free survival was 1.8 (90% CI 1.7 to 1.9) and 1.7 (90% CI 1.1 to 3.4) months for patients with melanoma and NSCLC, respectively. Patients with stable disease had higher expression levels of CD8, LAG3, programmed death-ligand 1 and anti-T-cell immunoglobulin and mucin-domain containing-3 at baseline. The pharmacokinetics profile of sabatolimab was consistent with the phase 1 study.

Conclusions
Sabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types.

Trial registration number
NCT02608268.