RAPid SimPLE (RAPPLE) Targeted Radiation Treatment vs. Whole Brain Radiotherapy: A Retrospective Study of Matched Patients with Brain Metastases and Poor Prognosis

Abstract

Patients with brain metastases and poor prognosis are often treated with whole brain radiotherapy (WBRT) which can cause a variety of side effects. Our institution devised a new brain-sparing radiotherapy technique to treat multiple brain metastasis for patients whose poor prognosis does not warrant SRS. This study compares the oncologic outcomes of matched patients treated with RAPPLE and WBRT. RAPPLE uses single-isocenter, coplanar volumetric modulated arc therapy and a non-stereotactic head-shell with IntegraBite™. Brain metastasis were contoured in a single gross tumor volume and expanded by 3 mm to create a planning target volume, of which 99.5% was covered with 95-110% of 20 Gy in 5 fractions. Patients treated with a first course of RAPPLE from January 2017 to December 2021 were identified in an institutional database. Using age, cancer diagnosis, and treatment date, we identified a matched cohort of patients receiving a first course of WBRT with 20 Gy in 5 fractions. Overall survival (OS) was calculated using the Kaplan-Meier method, and intracranial progression was calculated using cumulative incidence with a competing risk of death. Log-rank, Cox regression and Fine-Gray analyses were used for comparisons. Paired t-tests were used to compare patient-reported fatigue measured using 5-level Likert scales before and 2-6 weeks after radiotherapy. The RAPPLE and WBRT cohorts each had 137 patients. The matched median age was 69 years. Primary diagnoses were lung cancer (72%) and other cancers (28%). The minimum, median, and maximum numbers of metastases treated with RAPPLE were 1, 3, and 18, respectively. The median Karnofsky Performance Score (KPS) was 70 in both cohorts. The median survival was 4.1 months for RAPPLE and 4.2 months for WBRT, and the 18-month OS was 11% for RAPPLE and 12% for WBRT (log-rank p = 0.8). On multivariable analysis, KPS, diagnosis, extracranial disease, and use of systemic therapy before and after RT were predictive of OS, but use of RAPPLE vs. WBRT was not (HR = 0.97, 95% CI: 0.75-1.25, p = 0.8). The 18-month cumulative incidence of intracranial progression was 0.49 for RAPPLE and 0.37 for WBRT (p = 0.04). After RAPPLE, 17% required more focal RT and 4% required salvage WBRT, while after WBRT, 3% required focal RT and 4% required repeat WBRT. After RAPPLE, mean patient-reported fatigue remained stable from baseline to first follow-up (2.18 vs. 2.27, p = 0.9), but, after WBRT, it worsened from baseline to first follow-up (1.95 vs. 2.63, p = 0.002). As expected, after RAPPLE, more targeted radiotherapy was required for intracranial progression, but there was no difference in OS between the RAPPLE and WBRT cohorts. Patients reported significantly worse fatigue after WBRT. Almost all patients (96%) treated with RAPPLE avoided WBRT.