Hypofractionated stereotactic radiotherapy for brain metastases in lung cancer patients: Dose‒response effect and toxicity

Background: Lung cancer is the main cause of brain metastases, and approximately 40% of lung cancer patients are found to have brain metastasis during the course of the disease. For patients with limited brain metastases, hypofractionated stereotactic radiotherapy (HSRT) has been proven feasible. However, the optimal dose schedule of HSRT remains inconclusive. We aimed to investigate the dose response and toxicity in patients treated with HSRT. Methods: A retrospective analysis was performed of lung cancer patients treated with 5-fraction HSRT for 1–10 brain metastases at Hangzhou Cancer Hospital from January 1, 2019, to January 1, 2021. All patients were followed up with MRI every 3 months after HSRT. The 1-year intracranial local control rate (iLC) was estimated using the Kaplan‒Meier method. The adverse radiation effects (AREs) were evaluated according to the criteria of the CTCAE 5.0. Results: Forty patients with 70 brain metastases were reviewed. The median prescription dose was 30 (range, 25–40) Gy. The median maximum diameter of brain metastases was 1.3 (range, 0.6-4.0) cm. The 1-year iLC was 75.6% for patients treated with ≤ 30 Gy vs. 88.8% for patients treated with > 30 Gy ( P  = 0.09). For patients treated with HSRT combined with targeted therapy, immunotherapy and chemotherapy, the 1-year iLC was 88.9%, 100%, and 45.0%, respectively. No significant associations were observed between maximum diameter, tumour location, pathological type, or number of brain metastases. The rate of all-grade AREs was 32.5%. All AREs were grade 1–2 except for 2 patients with a total dose of 40 Gy who experienced grade 3 headache. Conclusions: Increasing the prescription dose of HSRT for brain metastases is expected to improve local control, but the occurrence of side effects should also be carefully considered. Systemic therapy can impact the iLC rate, and individualized treatment regimens need to be developed.