Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non–small cell lung cancer
Authors: Ma Liang-Hua , Li Guang , Zhang Hong-Wei , Wang Zhi-Yu , Dang Jun , Zhang Shuo , Yao Lei , Zhang Xiao-Meng 
Published: November 2018

Object
This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non–small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT).

Methods
One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117 patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated.

Results
The MST for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier–estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p = 0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases).

Conclusions
The overall survival results in the present study were similar to those in other studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.