Hypofractionated Stereotactic Radiotherapy with or without Whole Brain Radiotherapy with Helical Tomotherapy for Multiple Brain Metastases – Long-Term Follow-Up Results of a Phase II Trial

Abstract

<h3>Purpose/Objective(s)</h3> Multiple brain metastases (BMs) remain a therapeutic challenge. Helical tomotherapy (HT) is a novel technique which has shown favorable dosimetric properties in previous studies. The aim of this single institutional phase II trial was to investigate the feasibility and safety of hypofractionated stereotactic radiotherapy (HFSRT) with or without simultaneous whole brain radiotherapy (WBRT) by HT in treating patients with multiple BMs. <h3>Materials/Methods</h3> Patients with at least 3 BMs were enrolled. The prescribed dose was 40 Gy in 20 fractions for WBRT and 60 Gy in 20 fractions for BMs simultaneously, or only focal HFSRT for the lesions with optimized doses based on tumor volumes and locations. After 2/3 course of radiation, patients received MRI scan, and gross tumor volume (GTV) was re-contoured if the volume of lesion was decreased. An adaptive second phase plan would be made to fulfill the rest of radiotherapy based on the new target. The primary endpoint was intracranial progression free survival (IPFS). The secondary endpoints were local control (LC), overall survival (OS), brain metastasis-specific survival (BMSS) and toxicities. <h3>Results</h3> Between September 2014 and June 2017, 69 patients (male: female=28:41) were enrolled and finally been analyzed. 63.8% of them were non-small cell lung cancer (NSCLC). The median number of lesions was 6 (3- 43) and the median total volume was 18.3 cc (0.4- 93.1 cc). The median follow-up time was 40.1 months. The 1-year LC, IPFS, OS and BMSS rates were 96.4%, 80.5%, 71.0% and 94.6%, respectively. The median survival time was 18.1 months (95% CI, 15.5- 20.7). After 2/3 course of radiation, 23 patients (33.3%) with 111 lesions were re-contoured due to volume decrease. The median GTV decrease rate was 39.7% (1.0%- 89.0%). Only 1 patient (1.4%) had Grade 3 hematological toxicity and the radiation necrosis rate was 2.9%. <h3>Conclusion</h3> Helical tomotherapy was well tolerated and could significantly extend IPFS compared with historical controls in multiple BMs. Large randomized clinical trials are warranted.