BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma

Background In patients with stage III melanoma, the use of adjuvant radiation therapy (RT) after lymph node dissection (LND) may be currently considered in selected high-risk patients to improve tumor control. Melanomas harbor BRAF mutations (BRAF+) in 40–50% of cases, the majority of which are on the V600E residue. This study sought to compare the clinical outcomes after RT between patients with BRAF+ and BRAF− melanoma. Methods This was a retrospective review of 105 Stage III melanoma patients treated at our institution with LND followed by adjuvant RT from 2006 to 2019. BRAF mutational status was determined on the primary skin or nodal tissue samples from all patients. We compared characteristics of the BRAF+ and BRAF− groups using Fisher’s exact test and Wilcoxon rank sum test and performed univariate and multivariate analysis using Kaplan–Meier estimates, log-rank tests, and Cox proportional hazards modeling with the clinical outcomes of local–regional lymph node control, distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). Results Fifty-three (50%) patients harbored a BRAF mutation (92%, pV600E). BRAF+ patients were younger and had primary tumors more commonly found in the trunk vs head and neck compared to BRAF- patients (p < 0.05). The 5 year local–regional control in the BRAF + patients was 60% compared to 81% in the BRAF- patients (HR 4.5, 95% CI 1.3–15.5, p = 0.02). There were no significant differences in 5-year DMFS, RFS, and OS rates between the two BRAF patient groups. The presence of 4 or more positive LNs remained a significant prognostic factor for local–regional lymph node control, RFS, and OS in multivariate analysis. Conclusions Stage III melanoma patients with BRAF mutation treated with adjuvant RT had > 4 times increased risk of local recurrence or regional lymph node recurrence. These results could be useful for adjuvant RT consideration in lymph node positive melanoma patients and supports other data that BRAF mutation confers radiation resistance.

Adjuvant immunotherapy recommendations for stage III melanoma: physician and nurse interviews

Background Adjuvant immunotherapy is revolutionising care for patients with resected stage III and IV melanoma. However, immunotherapy may be associated with toxicity, making treatment decisions complicated. This study aimed to identify factors physicians and nurses considered regarding adjuvant immunotherapy for melanoma. Methods In-depth interviews were conducted with physicians (medical oncologists, surgeons and dermatologists) and nurses managing patients with resected stage III melanoma at three Australian tertiary melanoma centres between July 2019 and March 2020. Factors considered regarding adjuvant immunotherapy were explored. Recruitment continued until data saturation and thematic analysis was undertaken. Results Twenty-five physicians and nurses, aged 28–68 years, 60% females, including eleven (44%) medical oncologists, eight (32%) surgeons, five (20%) nurses, and one (4%) dermatologist were interviewed. Over half the sample managed five or more new resected stage III patients per month who could be eligible for adjuvant immunotherapy. Three themes about adjuvant immunotherapy recommendations emerged: [1] clinical and patient factors, [2] treatment information provision, and [3] individual physician/nurse factors. Melanoma sub-stage and an individual patient’s therapy risk/benefit profile were primary considerations. Secondary factors included uncertainty about adjuvant immunotherapy’s effectiveness and their views about treatment burden patients might consider acceptable. Conclusions Patients’ disease sub-stage and their treatment risk versus benefit drove the melanoma health care professionals’ adjuvant immunotherapy endorsement. Findings clarify clinician preferences and values, aiding clinical communication with patients and facilitating clinical decision-making about management options for resected stage III melanoma.