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Demonstration of differential radiosensitivity based upon mutation profile in metastatic melanoma treated with

Charles E Rutter1, Kimberly L Johung1, Xiaopan Yao2

  • 1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA.

Journal of Radiosurgery and SBRT
|January 4, 2018
PubMed
Abstract

Insights

N-RAS mutations improve local control for melanoma brain metastases treated with stereotactic radiosurgery (SRS). Wild-type and B-RAF/c-KIT mutated tumors show higher recurrence rates, guiding personalized radiotherapy.

Area of Science:

  • Neuro-oncology
  • Radiation Oncology
  • Medical Genetics

Background:

  • Metastatic melanoma frequently affects the brain, necessitating effective radiotherapy.
  • Melanoma brain metastases exhibit heterogeneous radiosensitivity, requiring identification of predictive subsets.
  • Stereotactic radiosurgery (SRS) is a key treatment, but outcomes vary.

Purpose of the Study:

  • To investigate the association between specific gene mutations (B-RAF, N-RAS, c-KIT) and local tumor control after SRS for melanoma brain metastases.
  • To identify patient subsets with differential radiosensitivity to optimize radiotherapy strategies.

Main Methods:

  • Analysis of a prospective SRS database for patients with metastatic melanoma.
  • Genetic testing of tumors for B-RAF, N-RAS, and c-KIT alterations.
  • Review of post-SRS imaging to assess tumor recurrence and statistical modeling (Cox proportional hazards) to determine failure rates.

Main Results:

  • 102 patients and 1,028 brain metastases were analyzed.
  • N-RAS mutated tumors showed significantly lower local recurrence rates post-SRS compared to wild-type (HR 0.17, p=0.017).
  • B-RAF and c-KIT mutations were not significantly associated with local recurrence rates; N-RAS benefit persisted in multivariate analysis (HR 0.18, p=0.029).

Conclusions:

  • N-RAS mutation status is a significant predictor of improved local control following SRS for melanoma brain metastases.
  • Wild-type and B-RAF/c-KIT mutated tumors are associated with higher rates of local recurrence.
  • These findings suggest potential for integrating genetic markers into treatment decisions for melanoma brain metastases.
Keywords:
BRAFNRASmelanomaradiosensitivityradiosurgery

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