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Guidelines for treating brain metastases do not reflect current practice
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Radiation oncologists appear to lack consensus on whether stereotactic radiosurgery or whole-brain radiotherapy is the optimal treatment strategy for patients with more than three brain metastases, according to a study published in Cancer.
Further, stereotactic radiosurgery is used more frequently to treat brain metastases than is recommended in consensus guidelines.
“In this rapidly developing landscape of treatment options, it may be daunting for clinicians to choose an optimal management strategy for patients,” Percy Lee, MD, associate professor and vice chair of education in the department of radiation oncology at David Geffen School of Medicine at UCLA, told HemOnc Today. “We learned that radiation oncologists are not abiding by the guidelines that recommend whole-brain radiation therapy for patients with greater than three brain metastases. This is not necessarily wrong, but it does bring up an important issue over whether guidelines should be modified given the lack of data in this area.”
Brain metastases occur in an estimated 20% to 40% of patients with cancer and present a common challenge for oncologists. The National Comprehensive Cancer Network recommends stereotactic radiosurgery (SRS) for patients with three to four brain metastases. Whole-brain radiotherapy (WBRT) is usually recommended for patients with advanced disease and more than three to four metastases, but carries significant side effects, such as declines in cognitive function.
Lee and colleagues characterized practice patterns among practitioners to identify areas of controversy. Researchers emailed surveys to more than 5,000 radiation oncologists, asking them to describe treatment options for patients with varying numbers and degrees of metastases. Radiation oncologists provided their “cutoff number” they used when choosing between SRS or WBRT for lesions smaller than 3 cm.
In total, 711 (71% men) responded for a response rate of 12.5%, which Lee deemed “relatively low,” but not unexpected.
Twenty-six percent of the respondents had been practicing for more than 10 years, and 36% had been practicing for more than 20 years. Respondents resided in North or South America (81%), Europe (8%), Asia (8%), Oceania (3%) and Africa (< 1%). Seventeen percent specialized in central nervous system lesions, 41% had academic practices and 74% said they followed radiosurgery guidelines.
CNS specialists were more likely to treat patients with brain metastases with SRS.
However, there was a significant difference in the optimal number of lesions to treat with SRS or WBRT. More high-volume CNS specialists were willing to use SRS on patients with as many as eight lesions. Conversely, low-volume CNS specialists used SRS with a cutoff of 5.5 lesions, and non-CNS specialists had a cutoff of 5.1 lesions (P < .001).
The cutoff to use SRS was higher among United States–based providers than international providers (5.5 vs. 4.7). Providers with access to Gamma Knife or CyberKnife reported higher cutoff numbers than providers with access to linear accelerator-based SRS (6.6 vs. 4.8).
A majority of respondents (56%) identified patients with four to six brain metastases as being the most challenging to treat.
When delivering WBRT to patients with Karnofsky performance status higher than 70, most respondents (66%) used 30 Gy in 10 fractions; 26% of respondents used 37.5 Gy in 15 fractions. Another 11% of respondents elected to use hippocampal-sparing WBRT for these patients, which has demonstrated improved neurocognitive outcomes. However, the use of hippocampal-sparing WBRT dropped significantly for patients with poor Karnofsky performance status (5% for 9 lesions, 3% for 15 lesions).
“Given the blood–brain barrier, WBRT and SRS are the two best modalities to control brain metastases,” Lee said. “There are strategies to see if specific targeted therapies could have better penetration in the CNS, and if adding modifying drugs, such as memantine, to WBRT can reduce neurocognitive side effects of WBRT. Also, there is a strategy to spare the hippocampus with whole-brain radiation, as that region is thought to be the target and cause of toxicity with WBRT.”
Lee and colleagues noted an important limitation of the study was that they did not address epidermal growth factor receptor and tyrosine kinase inhibitors therapy.
“These agents effectively penetrate the blood–brain barrier and are reported to have response rates of up to 88% in prospective studies evaluating their upfront use in patients with brain metastases from adenocarcinoma,” Lee and colleagues wrote.
More prospective data are needed to determine long-term success of SRS in patients with more than three brain metastases, Lee said. – by Chuck Gormley
For more information:
Percy Lee, MD, can be reached at Department of Radiation Oncology, David Geffen School of Medicine, 200 UCLA Medical Plaza, B265, Los Angeles, CA 90095; email: percylee@mednet.ucla.edu.
Disclosure: Researchers report no relevant financial disclosures.
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