Volumetric tumor volume doubling time in lung cancer: a systematic review and meta-analysis

Background: Tumor growth patterns have important implications in screening intervals, treatment decisions, and prognosis. Our study aimed to characterize lung cancer volume doubling time (VDT) and identify correlations of tumor growth patterns. Method: We performed a systematic literature review of Medline, EMBASE, and Web of Science databases starting from 2004 until April 2022. We identified studies reporting volumetric measured VDT of pathologically confirmed primary lung cancer without intervention, and abstracted data to calculate pooled VDT and find correlations of growth patterns (rapid defined as VDT ≤ 400 days, indolent as VDT > 400 days, non-growth or shrinkage). Meta-analysis was performed for pooled mean VDT in overall lung cancer and its histological subtypes. Pooled mean VDT was calculated using a random-effects model. Results: We have identified 26 studies, including 2275 patients with primary lung cancer (mean age range 55 to 72 years, 61.6% men). For overall lung cancer, median VDT ranged from 139 to 357 days and pooled mean VDT was 213 days (95% CI 171 to 256 days, I2=90.0%). In subgroup analyses, pooled mean VDT of adenocarcinoma (solid and subsolid), squamous cell, small cell, and other lung cancer were 241, 731, 136, 71, and 183 days, respectively. Rapid growth accounted for 64.8% of overall lung cancer and 23.7% of adenocarcinoma. The most consistent correlations of rapid tumor growth included nodule solidity, non-adenocarcinoma histology subtype, and invasiveness in adenocarcinoma. Conclusion: Median VDT in overall lung cancer is always ≤ 400 days with around two-thirds being rapid; solidity and histological subtypes demonstrate the most consistent correlations.