The role of whole brain radiation therapy in the management of melanoma brain metastases.


BACKGROUND: Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as "radioresistant," the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). METHODS: We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). CONCLUSIONS: Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials.





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Publication Info

Dyer, Michael A, Nils D Arvold, Yu-Hui Chen, Nancy E Pinnell, Timur Mitin, Eudocia Q Lee, F Stephen Hodi, Nageatte Ibrahim, et al. (2014). The role of whole brain radiation therapy in the management of melanoma brain metastases. Radiat Oncol, 9. p. 143. 10.1186/1748-717X-9-143 Retrieved from

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Scott Richard Floyd

Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology

Diseases of the brain carry particular morbidity and mortality, given the fundamental function of the brain for human life and quality of life. Disease of the brain are also particularly difficult to study, given the complexity of the brain. Model systems that capture this complexity, but still allow for experiments to test therapies and mechanisms of disease are badly needed.  We have developed an experimental model system that uses slices made from rat and mouse brains to create a test platform to research new treatments for brain diseases such as stroke, Alzheimer's disease, Huntington's disease and brain tumors. This model system reduces the number of experimental animals used, and streamlines experiments so that final testing in laboratory animals is more efficient. We use this brainslice system and limited numbers of experimental animals to test drugs and genetic pathways to treat stroke, Alzheimer's disease, Huntington's disease and brain tumors. As many brain tumors are treated with radiation therapy, we have a particular interest in the cellular response to DNA damage caused by radiation. DNA damage signaling and repair are fundamental processes necessary for cells to maintain genomic integrity. Problems with these processes can lead to cancer. As many cancer cells have altered DNA damage and repair pathways, we can apply DNA damage as cancer therapy. Our knowledge of how normal and neoplastic cells handle DNA damage is still incomplete. A deeper understanding can lead to improved cancer treatment, and to better protection from the harmful effects of DNA damaging agents like radiation. To this end, we plan experiments that test the effects of radiation on normal animal tissues and animal models of cancer, as well as molecular pathways in brain diseases such as Alzheimer’s, Huntington’s and stroke.

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