ASTRO 2016: Stereotactic Radiosurgery Decreases Rate of Postoperative Local Recurrence for Brain Metastases
Stereotactic radiosurgery (SRS) for cancer patients who receive the treatment for brain metastases decreases the likelihood of local recurrence, but shows no positive difference in terms of overall survival or distant brain metastases rates when compared to observation alone following surgical resection of brain metastases, according to research presented by Mahajan et al at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO).
Brain metastases occur in a large number of patients with common cancers and are more prevalent than many primary tumors, including primary brain tumors, lymphoma, and colon cancer. Rates of brain metastasis have risen in recent years, as well. When cancer spreads to the brain, surgical resection can be employed to confirm the diagnosis, remove the lesion(s), or to reduce pressure in the brain. After resection, whole-brain radiation therapy (WBRT) to the surgical cavity limits the growth of new lesions in the brain, yet radiation to healthy brain tissue can lead to cognitive decline and other toxicities. With SRS, oncologists deliver a single fraction of precise, high-dose radiation, while preserving surrounding brain tissue.
“Over the past several years, with advances in technology, radiation to only the surgical bed of the resected lesion has become of interest,” said Anita Mahajan, MD, Professor of Radiation Oncology at MD Anderson Cancer Center and lead author of the study. “While oncology teams see the potential of radiosurgery, its novelty means that we have limited prospective evidence of its efficacy.”
Study Background
Study participants included 132 patients (128 eventually analyzed) with 1–3 metastatic brain tumors who wished to avoid or delay WBRT following complete surgical resection of at least one brain metastasis. The median patient age was 59, and there were no relevant demographic differences between the treatment groups. Patients were randomly assigned to one of two arms, either SRS to the surgical cavity (or cavities for patients with more than one lesion removed) (n = 63) or observation alone (n = 65). Patients were stratified by number of brain metastases (1 vs 2–3), primary cancer type (melanoma vs other histology) and pre-operative tumor size (less than vs greater than three centimeters). Researchers assigned radiation dose for the SRS surgical cavity group (12, 14 or 16 Gy) based on cavity volume at time of radiosurgery.
Failure of local control, the primary endpoint of the study, was assessed through follow-up magnetic resonance imaging (MRI) by the study neuroradiologist to determine whether local tumors recurred in the area treated with SRS. Researchers also examined the rates of OS, development of distant brain metastases, time to WBRT, and complications following SRS. Hazard ratios (HR) and corresponding confidence intervals (CI) were computed to compare treatment arms. The median follow-up time was 13 months, with a range of 0.3 to 71 months.
Findings
Radiosurgery to the surgical bed significantly reduced local recurrence of the resected tumor. At 6 months following treatment, local control rates were 83% for the SRS surgical cavity group and 57% for the observation group. At 12 months follow-up, the local control rates were 72% for the SRS surgical cavity group, compared to 45% for the observation group (HR = 0.46; P = .01).
Although SRS improved local control, there were no differences between treatment arms for regional recurrence, overall survival, or time to WBRT. At 12 months after treatment, 58% of the SRS surgical cavity patients had developed distant brain metastases, compared to 67% in the observation group, though the difference was statistically nonsignificant (HR = 0.79; P = .29). Median overall survival was 17 months for both groups (HR = 1.22; P = .37). WBRT was given to 24 of the 64 patients in the SRS surgical cavity group within an average time frame of 16.1 months, compared to 30 of 67 patients in the observation group within an average time frame of 15.2 months (HR = 0.8; P = .42). No significant complications were noted in the SRS surgical cavity patients.
In terms of nontreatment factors, only tumor size impacted local control, as determined by multivariate Cox regression analysis. A presurgery tumor size of greater than 3 cm was associated with worse local control, but local recurrence was not significantly affected by the number of brain metastases or the patients’ histology or graded prognosis assessments.
“Our research shows that radiosurgery in this patient cohort does reduce the incidence of local recurrence, although the findings for overall brain control, overall survival, and time until whole brain radiation therapy limit our ability to conclude an obvious clinical benefit,” said Dr. Mahajan. “In addition, it appears that smaller tumors may not need postoperative radiosurgery after resection, since the local failure rate for tumors smaller than 2.5 centimeters was very low.”
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