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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449455/ https://www.ncbi.nlm.nih.gov/pubmed/34537078 http://dx.doi.org/10.1186/s13014-021-01903-5 |
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author | Wolfe, Adam R. Chablani, Priyanka Siedow, Michael R. Miller, Eric D. Walston, Steve Kendra, Kari L. Wuthrick, Evan Williams, Terence M. |
author_facet | Wolfe, Adam R. Chablani, Priyanka Siedow, Michael R. Miller, Eric D. Walston, Steve Kendra, Kari L. Wuthrick, Evan Williams, Terence M. |
author_sort | Wolfe, Adam R. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8449455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84494552021-09-20 BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma Wolfe, Adam R. Chablani, Priyanka Siedow, Michael R. Miller, Eric D. Walston, Steve Kendra, Kari L. Wuthrick, Evan Williams, Terence M. Radiat Oncol Research 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. BioMed Central 2021-09-18 /pmc/articles/PMC8449455/ /pubmed/34537078 http://dx.doi.org/10.1186/s13014-021-01903-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wolfe, Adam R. Chablani, Priyanka Siedow, Michael R. Miller, Eric D. Walston, Steve Kendra, Kari L. Wuthrick, Evan Williams, Terence M. BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title | BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title_full | BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title_fullStr | BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title_full_unstemmed | BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title_short | BRAF mutation correlates with worse local–regional control following radiation therapy in patients with stage III melanoma |
title_sort | braf mutation correlates with worse local–regional control following radiation therapy in patients with stage iii melanoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449455/ https://www.ncbi.nlm.nih.gov/pubmed/34537078 http://dx.doi.org/10.1186/s13014-021-01903-5 |
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