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Postoperative stereotactic radiosurgery may represent new standard of care for brain metastases
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Postoperative stereotactic radiosurgery conferred equivalent OS as whole-brain radiation therapy but improved preservation of cognitive functioning and quality of life in patients with resected metastatic brain disease, according to phase 3 trial results presented at the ASTRO Annual Meeting.
“Whole-brain radiation therapy is typically given to patients after they have resection of brain metastases, as it significantly improves local control in the surgical bed,” Paul D. Brown, MD, professor of radiation oncology at Mayo Clinic in Rochester, Minnesota, said during a press conference. “However, whole-brain radiation therapy offers no survival benefit, and is associated with significant toxicities, such as complete hair loss that can become permanent, significant fatigue, and redness of skin. In addition, there are concerns regarding the long-term cognitive impact of whole-brain radiation therapy.”
Stereotactic radiosurgery delivered to the surgical bed has emerged as a potential alternative to whole-brain radiation therapy after open resection. However, no prior trial directly compared standard-of-care whole-brain irradiation to radiosurgery.
Brown and colleagues randomly assigned 194 patients (median age, 61 years) to whole-brain radiation therapy or stereotactic radiosurgery. Study criteria included a single resected metastasis, with up to three unresected metastases, and a cavity diameter measuring less than 5 cm.
Cognitive deterioration–free survival and OS served as co-primary endpoints. Secondary endpoints included local control, time to intracranial failure and quality of life.
At baseline, the most common primary tumor site was lung (59%), and more than two-thirds of patients (77%) had a single metastasis.
Median follow-up was 15.6 months (range, 0-48.5).
Researchers observed no significantly difference in OS based on treatment group. Median OS was 11.5 months in the stereotactic radiosurgery arm and 11.8 months in the whole-brain radiation therapy arm.
However, cognitive deterioration occurred more frequently in patients assigned whole-brain radiation therapy (85.7% vs. 53.8%; P = .0006). Patients assigned whole-brain radiation therapy also experienced significantly shorter cognitive deterioration–free survival (median, 2.8 months vs. 3.2 months; P < .0001).
The whole-brain radiation therapy arm experienced greater cognitive deterioration at 6 months in the domains of immediate recall (47.9% vs. 17.3%; P < .0001), delayed recall (62.5% vs. 27.5%; P < .0001) and processing speed (37.5% vs. 17.3%; P = .03).
Long-term surgical bed control favored whole-brain radiation therapy at 6 months (90% vs. 78.6%) and 12 months (74% vs. 54.7%; P < .0001).
Stereotactic radiosurgery conferred better quality-of-life outcomes after 3 months, including smaller reductions in overall quality of life (mean change from baseline, –1.5 vs. –7; P = .03) and physical well-being (–6.4 vs. –20.2; P = .002).
Quality-of-life outcomes continued to favor stereotactic radiosurgery at 6 months, including brain-specific concerns (2.9 vs. –4.4; P = .045) and physical well-being (–3.2 vs. –15.1; P = .016).
“Since whole-brain radiation therapy takes between 2 weeks and 3 weeks, this is a significant portion of time [for patients] to be at a medical center, instead of being at home with their families,” Brown said. “It also causes delays in systemic therapy, such as immunotherapies, targeted therapies and more standard chemotherapies. Radiosurgery has the advantage that it is administered in a 1-day session.”
Stereotactic radiosurgery should become a standard of care in this patient population, Brown said.
“[Stereotactic radiosurgery] achieves equivalent survival to whole-brain radiation therapy with much better preservation of cognitive function, better quality of life, and less toxicity,” Brown said. – by Cameron Kelsall
Reference:
Brown PD, et al. Abstract LBA-1. Presented at: ASTRO Annual Meeting; Sept. 25-28, 2016; Boston.
Disclosure: Brown reports no relevant financial disclosures.
Perspective
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Samuel Chao, MD
The study conducted by Brown and colleagues looked specifically at patients who underwent resection of brain metastases, followed by whole-brain irradiation or radiosurgery. Radiosurgery to the surgical cavity had been done at a number of institutions prior to this study, and results often showed that we could achieve excellent local control with this modality alone.
When Paul D. Brown, MD, presented the findings of the study at this year’s ASTRO Annual Meeting, I was surprised that the local control rate associated with radiosurgery was not as strong as what we have seen in prior studies. This likely speaks to the fact that this is a national, multi-institutional study, and every institution may have different methodologies, even with the researchers striving hard to control for exactly that. There might be differences, for example, in the patients being placed on study, which speaks to institutional preferences of which patients should receive whole-brain irradiation vs. radiosurgery.
Whether we should offer radiosurgery to the resection cavity for all patients with brain metastases has been an ongoing question in the radiation oncology community. It is certainly easier to apply whole-brain radiation therapy, but many doctors have been concerned with the toxicities and deficits associated with the treatment, which Brown and colleagues confirm in their study.
This study shows that radiosurgery to the resection cavity is feasible and safe, and confirmed that it conferred lower cognitive function loss. However, we must acknowledge that the rates of lower control were not as good as we would have anticipated.
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