Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases

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In a multi-institutional cohort study reported in JAMA Oncology, Eitz et al found that hypofractionated stereotactic radiotherapy (HSRT) to the resection cavity in patients with brain metastases appears to be associated with an “excellent risk-benefit profile.”

As stated by the investigators, “For brain metastases, the combination of neurosurgical resection and postoperative HSRT is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking.”

Study Details

The international cohort study involved data from 558 patients with resected brain metastases (total of 581 resection cavities) who received postoperative HSRT between December 2003 and October 2019 at six participating centers. Patients with prior cranial radiotherapy (including whole-brain radiotherapy) and those with early termination of treatment were excluded. Patients received a median total dose of 30 Gy (range = 18–35 Gy) and a dose per fraction of 6 Gy (range = 5–10.7 Gy).

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Key Points

Median follow-up was 12.3 months (interquartile range = 5.0­–25.3 months) for all patients and 19.7 months (interquartile range = 8.6–37.9 months) for surviving patients.

Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years. Median overall survival was 21.2 months.

Local control rates were 84% at 1 year, 75% at 2 years, and 71% at 3 years.

Freedom from distant intracranial failure rates were 54% at 1 year, 42% at 2 years, and 35% at 3 years. Freedom from distant progression rates were 63% at 1 year, 45% at 2 years, and 39% at 3 years.

Radiation necrosis developed in 8.6% of patients (median time to occurrence = 13.1 months) and leptomeningeal disease developed in 13.1% (median time to occurrence = 5.8 months).

Neurologic toxic events of grade ≥ 3 occurred in 2.8% of patients at less than 6 months and in 4.1% at longer than 6 months after treatment.

On multivariate analysis, significant prognostic factors for overall survival were Karnofsky Performance Status score of ≥ 80% (hazard ratio [HR] = 0.61, P < .001), 22 to 33 days between resection and radiotherapy (HR = 1.50, P = .02), and a controlled primary tumor (HR = 0.69, P = .007).

Significant prognostic factors for local control were a single brain metastasis (HR = 0.57, P = .03) and a controlled primary tumor (HR = 0.59, P = .02).  

The investigators concluded, “To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic [therapies] and immunotherapies.”

Kerstin A. Eitz, PhD, of the Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, is the corresponding author for the JAMA Oncology article.

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