RESUMEN
Objective To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy ( FSRT ) combined with temozolomide ( TMZ ) for large brain metastases ( BMs ) in a prospective phaseⅡclinical 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.