Optimal Treatment Strategy of Radiotherapy and Crizotinib for Patients with Brain Metastasis from ALK-Rearranged Non-Small-Cell Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy and anaplastic lymphoma kinase (ALK) inhibitors are treatment options for brain metastasis (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). This study aimed to find the optimal treatment strategy for patients with BM from ALK-rearranged NSCLC. <h3>Materials/Methods</h3> Between 2012 and 2017, consecutive patients with BM from ALK-rearranged NSCLC treated with crizotinib and radiotherapy in our institution were reviewed and enrolled into the study. Patients were treated with sequential radiotherapy and crizotinib (upfront radiotherapy or crizotinib followed by the other at intracranial progression), or concurrent radiotherapy and crizotinib. The cumulative incidence of intracranial progression free survival (iPFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. A two-sided p value ≤ 0.05 were considered statistically significant. <h3>Results</h3> Totally 41 patients were enrolled, including 24 (58.5%) with sequential treatment and 17 (41.5%) with concurrent treatment. The diagnosis-specific graded prognostic assessment (DS-GPA) score was 0-2 in 25 (60.1%) patients and > 2 in 16 (39.0%) patients, respectively. There were 13(31.7%), 17 (41.5%), and 11 (26.8%) patients treated with stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and WBRT with simultaneous in-field boost (SIB), respectively. The median iPFS and OS in all patients were 33.5 (95% CI 30.8-36.2) months and 63.9 (95% CI 46.0-81.9) months, respectively. There was no significant difference of iPFS or OS between the sequential treatment group and the concurrent treatment group. However, in DS-GPA scores of 0-2, the iPFS was longer in the sequential treatment group than concurrent treatment group (67.9 months vs.32.6 months, <i>P</i>=0.045), but the difference of OS was not significant between the two groups (38.9 months vs. 32.6 months, <i>P</i>=0.829). Moreover, the median iPFS of patients receiving SRS, WBRT alone, and WBRT with SIB was 33.5 months, 43.6 months, and 63.9 months (P=0.047). The corresponding median OS was not reached, 26.0 months, and 67.9 months, respectively (<i>P</i><0.001). <h3>Conclusion</h3> For patients with BM from ALK-rearranged NSCLC in our study, sequential crizotinib and brain radiotherapy for patients with DS-GPA score of 0-2 achieve better iPFS. In addition, WBRT with SIB achieves the best iPFS.