A Dutch phase III randomized multicenter trial: whole brain radiotherapy versus stereotactic radiotherapy for 4–10 brain metastases

Abstract

Background The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods Patients with 4 to 10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at three months post-treatment. Results The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 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 by 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23). The actuarial one-year survival rates were 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (p=0.22). Conclusion In patients with 4 to 10 BM, SRS alone resulted in one-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial

“…Therefore, only 29 out of a planned 230 patients were randomized into groups, of whom 20 patients were included in this QoL analysis. Due to this small study population, no major significant differences could be determined between the two treatment groups' survival and a possible outlier, which we did not found, could possible influence our data (18). In radiation oncology, clinical-trial failure is common.…”

“…Both of these patients had experienced epileptic seizures prior to SRT treatment, and their seizures were controlled with medication. Toxicity among the study participants mainly consisted of hair loss and fatigue among the WBRT group (18). We observed a significant difference in hair loss at 3 months post-treatment between the two study groups, with poorer results for the patients who had been treated with WBRT (P=0.014).…”

“…The trial's materials and methods were reported in a recently published paper that discussed other endpoints than QoL, such as survival and prognostic factors (18). We will briefly outline these materials and methods here.…”

“…Our NCT02353000 randomized controlled study compared WBRT to SRT to determine whether SRT is a better palliative treatment than WBRT vis-à-vis QoL outcomes for patients with 4 to 10 low-volume BM and a favorable prognosis. The study's primary endpoints were published previously (18). Its secondary endpoints, which focus on QoL and involve the use of multiple methods, are presented in the current paper.…”

Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions

“…Recently, the first phase III randomized controlled trial (Dutch Trial) investigating WBRT versus SRS for patients with 4–10 BM suggested that SRS is a valid palliative treatment option for patients with polymetastatic disease for the reduced incidence of toxicity and for the preservation of QoL. Anyway, the trial was closed prematurely, mainly as a result of patients’ and doctors’ preference for SRS, and no definitive results were produced on the non-inferiority of SRS in term of OS and brain failure-free survival ( 106 ).…”