Postoperative hypofractionated stereotactic radiotherapy effective for brain metastases
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Local hypofractionated stereotactic radiotherapy to the resection cavity demonstrated a favorable risk-benefit profile among patients with brain metastases, according to results of an international, multicenter cohort study.
The local control observed in this study appeared favorable compared with previously published data on stereotactic radiosurgery, suggesting hypofractionated stereotactic radiotherapy should be considered in this setting, according to researchers.
“For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking,” Kerstin A. Eitz, PhD, researcher in the department of radiation oncology at Klinikum rechts der Isar Technical University Munich, in Germany, and colleagues wrote.
For this reason, investigators assessed prognostic factors and outcomes among 558 patients (mean age, 61 years; 53.9% women) with 581 resected cavities who underwent hypofractionated stereotactic radiotherapy between Dec. 1, 2003, and Oct. 31, 2019. The median total dose of radiation was 30 Gy (range, 18-35) at a dose per fraction of 6 Gy (range, 5-10.7).
Exclusion criteria included receipt of prior cranial radiotherapy or early termination of treatment.
OS, local control, and analysis of prognostic factors associated with OS and local control served as primary endpoints. Secondary endpoints included distant intracranial failure, distant progression and incidence of neurologic toxicity.
Median follow-up was 12.3 months (interquartile range [IQR], 5-25.3) for all patients and 19.7 months (IQR, 8.6-37.9) for surviving patients.
Median OS was 21.2 months (95% CI, 18.1-24.2), with more than half (57%) of patient deaths occurring at the time of data analysis. One-year OS was 65%, followed by 46% at 2 years and 33% at 3 years.
Ninety-four percent of patients achieved local control at 5 months, which decreased to 84% at 1 year, 75% at 2 years and 71% at 3 years (median not reached). Local recurrence occurred in 16.5% of patients, with a probability of local failure of 3% at 3 months, 5% at 5 months, 9% at 8 months, 11% at 10 months, 13% at 1 year, 17% at 2 years and 19% at 3 years.
Median time to distant intracranial failure was 14.7 months (95% CI, 10.8-18.5) and median time to distant progression was 19.6 months (95% CI, 16.2-23).
Results of multivariate analysis showed prognostic factors associated with improved OS included a Karnofsky performance status score of 80% or greater (HR = 0.61; 95% CI, 0.46-0.82) and a controlled primary tumor (HR = 0.69; 95% CI, 0.52-0.9). Factors associated with local control included having a single brain metastasis (HR = 0.57; 95% CI, 0.35-0.93) and a controlled primary tumor (HR = 0.59; 95% CI, 0.39-0.92).
Leptomeningeal disease occurred among 13.1% of patients and 8.6% experienced radiation necrosis. Grade 3 or higher neurologic toxic events occurred among 2.8% of patients within 6 months of treatment and among 4.1% of patients more than 6 months after treatment.
“Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies,” Eitz and colleagues wrote.
Although this study provides important generalizable data on hypofractionated stereotactic radiotherapy, more prospective data are needed regarding local control and radionecrosis after ensuring uniform treatment margins, dose normalization and prescription isodose lines, according to an accompanying editorial by Debra Nana Yeboa, MD, assistant professor in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, and Iris C. Gibbs, MD, FACR, FASTRO, professor of radiation oncology at Stanford University Medical Center.
“Although the study ... on multivariable analysis did not identify a correlation of outcomes with volume or histologic subtype, these findings highlight the need to address whether hypofractionation schedules may be better suited for particular histologic subtypes or target volume sizes,” they wrote. “In addition to addressing the question on the role of stereotactic radiosurgery vs. hypofractionated stereotactic radiotherapy in the prospective setting, the risk of leptomeningeal disease in cavity treatment requires further analysis with preoperative stereotactic radiosurgery randomized clinical trials.”
References:
- Eitz KA, et al. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.4630.
- Yeboa DN and Gibbs IC. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.4400.
Perspective
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Stephanie E. Weiss, MD, FASTRO
Although single-fraction stereotactic radiosurgery offers excellent control of brain metastases, studies suggest that it’s less robust and is associated with higher rates of radionecrosis and leptomeningeal spread when offered as adjuvant therapy after resection. Small series suggest better local control and toxicity when a small margin is added to the surgical cavity target and is delivered with a more moderate dose per day over three to five fractions.
This multicenter cohort study is the largest to investigate outcomes after hypofractionated stereotactic radiotherapy and found better and more durable local control, less toxicity and a lower incidence of leptomeningeal disease than conventional postoperative stereotactic radiosurgery. Although this study is not a randomized controlled trial comparing the two techniques head-to-head, it does offer guidance and reassurance to physicians trying to make best clinical decisions for their patients who require adjuvant radiation after resection of brain metastases.
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