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The role of whole brain radiation therapy in the management of melanoma brain metastases.
Abstract
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.
Type
Journal articleSubject
AdultAged
Aged, 80 and over
Brain Neoplasms
Cranial Irradiation
Disease Management
Female
Follow-Up Studies
Humans
Male
Melanoma
Middle Aged
Neoplasm Staging
Prognosis
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Intensity-Modulated
Retrospective Studies
Skin Neoplasms
Survival Rate
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https://hdl.handle.net/10161/15936Published Version (Please cite this version)
10.1186/1748-717X-9-143Publication Info
Dyer, Michael A; Arvold, Nils D; Chen, Yu-Hui; Pinnell, Nancy E; Mitin, Timur; Lee,
Eudocia Q; ... Alexander, Brian M (2014). The role of whole brain radiation therapy in the management of melanoma brain metastases.
Radiat Oncol, 9. pp. 143. 10.1186/1748-717X-9-143. Retrieved from https://hdl.handle.net/10161/15936.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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

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