LINAC-Based Stereotactic Irradiation For Patients With Up To Ten Brain Metastases

Abstract

The Japanese Leksell Gamma Knife (JLGK) 0901 study showed the noninferiority of stereotactic radiosurgery for patients with 5 to 10 brain metastases (BMs) and for those with 2 to 4 BMs in terms of overall survival and safety. However, it is not clear whether this result can be generalized to LINAC-based stereotactic irradiation (STI). The purpose of this retrospective study is to evaluate clinical outcomes of patients with 1 to 10 BMs treated by LINAC-based STI at our institution. We retrospectively reviewed 186 consecutive patients with 1 to 10 BMs treated with LINAC-based STI without prior whole-brain radiation therapy (WBRT) between July 2016 and June 2018. These patients were classified into three groups according to the number of BMs: group A, one BM (n = 85); group B, 2 to 4 BMs (n = 70); and group C, 5 to 10 BMs (n = 31). Overall survival, local control of treated tumor, appearance of new lesion, and the incidence of radiation necrosis (RN) were analyzed in each group. Median age of patients of group A, B, and C was 68 (range: 23-88), 71 (range: 19-88), and 68 (range: 21-82), respectively. Median planning target volume in group A, B, and C was 5.2 cc (range: 0.2-79.0 cc), 7.5 cc (range: 0.6-73.3 cc), and 9.2 cc (range: 2.4-37.6 cc), respectively. Median follow-up period was 270 days (range: 3-1111 days). Median overall survival after STI was significantly longer in group A than in group B (20.0 months [95% CI, 10.3–27.9] vs 7.4 months [5.0–11.3]; hazard ratio (HR) 0.59 [95% CI, 0.40–0.88]; P = 0.01) and group C (5.0 months [4.0–8.9]; HR 0.42 [95% CI, 0.26–0.70]; P<0.01). However, median overall survival for the two groups of B and C did not differ (HR 0.73 [95% CI, 0.46–1.19]; P = 0.21). Grade 1-3 RN occurred in 42 out of 165 patients in whom follow-up MRI was available and the proportion of patients who experienced grade 1-3 RN did not differ between the groups (24 patients in group A, 15 patients in group B, and 3 patients in group C). There was no incidence of grade 4 or 5 RN. The local control rate at treated tumor did not differ between the groups. Although the rate of new lesion appearance at 1 year after STI was significantly lower in group A (34.2%) than in group B (53.7%; HR 0.53 [95% CI, 0.31–0.89]; P = 0.01) and group C (67.9%; HR 0.30 [95% CI, 0.15–0.59]; P<0.01), the rate of new lesion appearance did not differ between group B and C ([95% CI, 0.30–1.08]; P = 0.08). Overall survival, local control of treated tumor, appearance of new lesion, and the incidence of RN after LINAC-based STI were not significantly different between patients with 5 to 10 BMs and those with 2 to 4 BMs. LINAC-based STI without WBRT seems to be a feasible treatment strategy for patients with 5 to 10 BMs as well as for those with 2 to 4 BMs.