Tumor Volume Analysis as a Predictive Marker for Prolonged Survival in Anaplastic Lymphoma Kinase-rearranged Advanced Non-Small Cell Lung Cancer Patients Treated With Crizotinib.

Purpose: Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early predictive marker for prolonged survival. Materials and Methods: Cases of 42 patients with ALK-rearranged advanced NSCLC (16 men, 26 women; median age: 55.7 y) treated with crizotinib as their first ALK-directed therapy were retrospectively studied. Tumor volume measurements of dominant lung lesions were performed on baseline computed tomography and follow-up computed tomography at 8 weeks of therapy. The relationships between the 8-week volume change (%) and overall survival (OS) were investigated. Results: The 8-week tumor volume change ranged from -99.3% to 117.5% (median: -57.7%). Using the 25th percentile of the 8-week volume change of -74%, 11 patients with >74% volume decrease at 8 weeks had a significantly longer OS compared with 31 patients with <= 74% decrease (median OS: 92.0 vs. 22.8 mo; P=0.0048). In multivariable analyses using Cox proportional hazards models, the 8-week volume decrease of >74% was significantly associated with longer OS (hazard ratio=0.14, 95% confidence interval: 0.03-0.59; Cox P=0.008) after adjusting for tumor stage (stage IV vs. recurrent NSCLC, hazard ratio=5.6, 95% confidence interval: 1.29-24.3; P=0.02). Conclusions: The 8-week tumor volume decrease of >74% is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib.