Case-control study of fractionated stereotactic radiotherapy combined with temozolomide for large brain metastases

Abstract

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases. Methods Between 2009 and 2017, 84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT, n=42) and RT group (FSRT alone, n=42). The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions. Patients were reexamined by magnetic resonance imaging (MRI) during treatment. The radiation field would be shrunk if the gross target volume (GTV) was reduced. The clinical efficacy was evaluated at postoperative 2 to 3 months. The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS), progression-free survival (PFS), overall survival (OS), brain metastasis-specific survival (BMSS) and adverse events. The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis. Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment, 75% of the lesions in the CRT group were reduced compared with 34% in the RT group (P=0.000). The local control (LC) rate in the CRT and RT groups was 100% and 98%.The median follow-up time was 16.1 months (range, 2.1-105.7 months). In the CRT group, the LRFS (P=0.040), IPFS (P=0.022), PFS (P=0.045), OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group, respectively. In the CRT group, the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33%, significantly higher compared with 26% in the RT group (P=0.006). No grade IV-V adverse events occurred in both groups. Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases. Key words: Neoplasm, brain metastasis/Fractionated stereotactic radiotherapy; Neoplasm, brain metastasis/chemotherapy; Temozolomide; Treatment outcome