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RADIOTHERAPY AND RADIOSURGERY EVIDENCE IN BRAIN METASTASES
Whole-Brain Radiotherapy and Stereotactic Radiosurgery in
Brain Metastases: What Is the Evidence?
Minesh P. Mehta, MD, and Manmeet S. Ahluwalia, MD
OVERVIEW
The overall local treatment paradigm of brain metastases, which includes whole-brain radiotherapy (WBRT) and stereotactic radiosurgery
(SRS), continues to evolve. Local therapies play an important role in the management of brain metastases. The choice of local
therapy depends on factors that involve the patient (performance status, expected survival, and age), the prior treatment history, and
the tumor (type and subtype, number, size, location of metastases, and extracranial disease status). Multidisciplinary collaboration is
required to facilitate an individualized plan to improve the outcome of disease in patients with this life-limiting complication. There has
been concern about the neurocognitive effects of WBRT. A number of approaches that mitigate cognitive dysfunction, such as
pharmacologic intervention (memantine) or a hippocampal-sparing strategy, have been studied in a prospective manner with WBRT.
Although there has been an increase in the use of SRS in the management of brain metastases in recent years, WBRT retains an
important therapeutic role.
One of the fırst descriptions of WBRT is from Chao et al, 1
who demonstrated a high rate of short-duration palliation.
Several subsequent large trials established a signifıcant
palliative role for this modality. Borgelt et al 2 demonstrated
equivalency between various dose-fractionation schema by
reviewing the Radiation Therapy Oncology Group (RTOG)
trial outcomes; currently, 30 Gy in 10 fractions and 37.5 Gy in
15 fractions are considered standard doses for WBRT. 2 For
almost 5 decades, WBRT has remained the primary modality
for the treatment of the vast majority of patients with brain
metastases, but, starting in the 1990s, several new treatment
refınements have led to the redefınition of its role.
THE PARAMOUNTCY OF LOCAL CONTROL CHANGES
THE PARADIGM
After the 1990 study by Patchell, which established a survival
benefıt from resection of a single metastatic lesion to the
brain beyond that of WBRT alone, the next logical question
was whether or not WBRT is necessary after resection at all.
In 1998, in a randomized study, the addition of WBRT after
complete tumor resection decreased intracranial failure from
70% to 18% (p 0.001) and decreased local recurrence from
46% to 10% (p 0.001). 3 Although there was improved survival
with the use of WBRT, this was not signifıcant, which is
an observation worth noting, with the caveat that this study
was not powered to assess a survival benefıt. Three major directional
thrusts emerged as a consequence of this work:
First, in several quarters, WBRT became a routine and accepted
standard of care after resection to dramatically and
convincingly lower intracranial relapse; second, SRS became
widespread as a modality for the local control of at-fırst limited
number of brain metastatic lesions but more recently of
multiple lesions; third, the role of WBRT in terms of enhancing
local control came under intense scrutiny because of concerns
regarding its potential for neurotoxicity and a
perceived lack of a survival benefıt. The bidirectional evolutionary
ramifıcations of the latter trend were to better understand
the mechanisms underlying some of these
neurotoxicities and efforts to modulate these through the
conduct of innovative clinical trials, as well as to become
more selective regarding the application of WBRT primarily
for patients who had multiple (with a flexible defınition of
this concept) brain metastases. This selection often has been
in the context of a combined approach with systemic therapeutics,
a direction that recently has experienced an upsurge
because of the emergence of blood-brain barrier–penetrating
agents, primarily in malignancies with driver mutations.
THE EMERGENCE OF RADIOSURGERY AS AN
EFFECTIVE LOCAL CONTROL THERAPY
SRS now has become the most widely used focal treatment
modality for patients who have brain metastasis. The effıcacy
From the Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD; Burkhardt Brain Tumor Neuro-Oncology Center, Neurological Institute, Cleveland Clinic,
Cleveland, OH.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: Minesh M. Mehta, MBChB, FASTRO, Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene St., GGK19, Baltimore, MD 21201;
email: mmehta@umm.edu.
© 2015 by American Society of Clinical Oncology.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
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