Abstract
BackgroundIn 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.MethodsThis 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).ResultsFifty-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.ConclusionsStage 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.
Highlights
In patients with melanoma, a common site of metastasis is the regional lymph node (LN) basin, and patients with clinically positive regional LNs often undergo therapeutic lymph node dissection (LND) to reduce the riskWolfe et al Radiat Oncol (2021) 16:181 criteria are based on the phase III ANZMTG 01.02/ TROG 02.01 trial which randomized patients with clinically or pathologically positive LNs who had undergone lymphadenectomy to adjuvant radiation or observation and the trial results showed improved nodal relapse-free survival in the adjuvant radiation therapy (RT) arm compared to the observation group [3].The BRAF gene encodes a protein kinase (MAPK) that regulates cellular growth and proliferation in tumor cells [4]
In this retrospective single institutional study, we found stage III melanoma patients treated with LND and adjuvant RT whose tumor exhibited a BRAF mutation had significantly worse local–regional control compared to patients with BRAF negative tumors
In this study, we found an increased rate of local–regional recurrence after adjuvant RT in patients whose tumors are BRAF+ compared to BRAF
Summary
A common site of metastasis is the regional lymph node (LN) basin, and patients with clinically positive regional LNs often undergo therapeutic lymph node dissection (LND) to reduce the riskWolfe et al Radiat Oncol (2021) 16:181 criteria are based on the phase III ANZMTG 01.02/ TROG 02.01 trial which randomized patients with clinically or pathologically positive LNs who had undergone lymphadenectomy to adjuvant radiation or observation and the trial results showed improved nodal relapse-free survival in the adjuvant RT arm compared to the observation group [3].The BRAF gene encodes a protein kinase (MAPK) that regulates cellular growth and proliferation in tumor cells [4]. The most common mutation in the BRAF gene found in melanoma patients is the substitution of a glutamic acid for a valine at the amino acid 600 position (V600E). Stage III melanoma patients with BRAF mutations may receive adjuvant treatment with either the combination BRAF and MEK inhibitors, dabrafenib and trametinib or immunotherapy [6, 7]. We aimed to investigate the outcomes of adjuvant RT on local and regional LN control along with other clinical outcomes in patients with BRAF+ and BRAF− melanoma. 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. This study sought to compare the clinical outcomes after RT between patients with BRAF+ and BRAF− melanoma
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