Whole Brain Radiotherapy vs. Stereotactic Radiotherapy for 4-10 Brain Metastases: A Prematurely Closed Dutch Phase III Randomized Multicenter Trial

Abstract

Background: Since publication of the QUARTZ trial, the clinical value of whole brain radiotherapy (WBRT) for brain metastases is a matter of debate due to significant side effects. In order to avoid these side effects and to improve local tumor control, stereotactic radiosurgery (SRS) is an attractive treatment option. We have initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS alone than after WBRT in patients with newly diagnosed multiple brain metastases. Methods: Patients with 4 up to 10 brain metastases (BM) were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). Primary endpoint was difference in quality of life (QOL) at three months after radiotherapy compared to baseline (EQ5D5L EUROQOL score). Findings: The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized between July 2016 and May 2018, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions per patient was 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3 ). QOL at three months decreased in the SRS group with 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23).The actuarial one year survival was 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one year brain salvage free survival was 50% (SRS) and 78% (WBRT) (p=0.22). Interpretation: In patients with 4 up to 10 BM, SRS alone resulted in one-year survival in 57% of patients while maintaining quality of life. Due to premature closure of the trial, no statistical significant differences could be determined between SRS alone and WBRT in the investigated endpoints. Trial Registration: NCT02353000 Funding Statement: Varian Medical Systems, the Dutch technology Foundation STW, and Kankeronderzoekfonds Limburg. Declaration of Interests: No competing interests to declare. Ethics Approval Statement: All patients willing to participate gave written informed consent. The study protocol was approved by the medical ethical committee of the Maastricht University Medical Center, The Netherlands.