Abstract

In the era of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT) for brain metastases is now increasingly reserved for cases of diffuse intracranial disease or as salvage. The purpose of this study was to describe WBRT practice patterns at a tertiary cancer center with a high-volume radiosurgical practice, with the hypothesis that patients treated with WBRT at our institution have limited survival as measured by 30-day mortality after treatment. Retrospective chart review was performed for 257 patients treated with WBRT for brain metastases between May 2011 to December 2018. Univariate and multivariate binary logistic regression analyses were performed to identify factors associated with WBRT within 30 days of death. Median age at WBRT was 61 years (IQR 52-69). Patients had non-small cell lung cancer (39%), breast cancer (26%), small cell lung cancer (9%), and melanoma (7%). At the time of WBRT, 63% of patients had uncontrolled extracranial metastatic disease, and 29% had imaging evidence of leptomeningeal disease. 32% of patients had focal treatment for brain metastases prior to WBRT; of this subset, 17% had surgery alone, 48% had SRS alone, and 35% had both prior surgery and SRS. The most common dose-fractionation schedules prescribed for WBRT were 30 Gy in 10 fractions (80%) and 20 Gy in 5 fractions (12%). 11% of patients were unable to complete the prescribed course of radiation. After WBRT, the 6-month actuarial rate of intracranial progression-free survival was 85%. 55% of those who progressed received additional salvage radiation. Median time from the diagnosis of brain metastasis to death was 8.5 months (IQR 2.7-20.7), and median survival from WBRT to death was 4.0 months (IQR 1.4-13.0). 19% of patients died within 30 days of WBRT. Patients with KPS <70 (44%) had median survival of 2.1 months after WBRT, compared with 8.1 months in those with KPS ≥70 (56%) (p<0.0001). On univariate analysis, factors predicting for death within 30 days of WBRT included age >70 (p = 0.048), KPS <70 (p = 0.0003), uncontrolled disease at the primary site (p = 0.027), and uncontrolled extracranial metastatic disease (p = 0.01). On multivariate analysis, age >70 (HR 2.30, 95% CI 1.02-5.19, p = 0.045), KPS <70 (HR 2.75, 95% CI 1.31-5.78, p = 0.008), and uncontrolled extracranial metastatic disease (HR 6.28, 95% CI 1.40-28.16, p = 0.016) remained significant predictors for death within 30 days of WBRT. This study illustrates the poor prognosis of patients requiring WBRT at a tertiary cancer center, with a 30-day mortality rate of 19%. In shared decision-making discussions with patients, clinicians must balance the toxicity or futility of treatment with the potential expected benefits, especially in older patients with poor functional status and uncontrolled extracranial disease.

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