Efficacy of hypofractionated stereotactic radiotherapy combined with temozolomide for large brain metastases: a prospective clinical study

Objective: To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy (FSRT) combined with temozolomide (TMZ) for large brain metastases (BMs) in a prospective phase n clinical trial. Methods: From 2010 to 2015, a total of 33 patients were enrolled as subjects. The median Karnofsky Performance Status scores before and after treatment were 70 and 80, respectively. The major primary tumor was non-small cell lung cancer (57.6%). The brain metastasis had a diameter of > 3 cm or a volume of > 6 cm³. The radiation dose was 52 Gy in 13 fractions or 52.2 Gy in 15 fractions. Patients received TMZ at a dose of 75 mg/m² per day concurrently. The radiotherapy was followed by 6 cycles of adjuvant treatment with TMZ (150 mg/m², days 1-5, 28 days per cycle). Patients were reexamined by magnetic resonance imaging (MRI) during the treatment. The radiation field would be shrunk if the gross target volume (GTV) was reduced by > 20%. The treatment outcomes were evaluated by MRI at 2-3 months after treatment. Results: The total numbers of tumors and GTVs were 95 and 38, respectively. Twenty-four (63%) out of the 38 GTVs had a volume larger than 10 cm³ and the median GTV was 15.3 cm³ (5.7-142.8 cm³). Twenty-two (67%) out of the 33 patients achieved field shrinking during the treatment, and the median reduction rate of GTV was 44%(21%-88%). The median total dose was 59.5 Gy, and 100% and 21.2% of patients completed the concurrent and adjuvant treatment with TMZ, respectively. In all patients, the overall response rate was 97.0%; the 1-year local control, intracranial progression-free survival, and overall survival rates were 97%, 70%, and 62%, respectively; the median survival time was 15.3 months. The main adverse reactions were grade 1-2 nausea and vomiting. One patient got grade 3 liver function impairment. Conclusions: FSRT combined with TMZ is a safe and effective approach for treating large BMs. More than 50% of patients can achieve field shrinking to shorten treatment duration and reduce toxicity. Clinical Trial Registry ClinicalTrials.gov, registration number: NCT02654106. (authors)