Volume Doubling Times of Lung Adenocarcinomas: Correlation with Predominant Histologic Subtypes and Prognosis

Background The volume doubling time (VDT) is a key parameter in the differentiation of aggressive tumors from slow-growing tumors. How different histologic subtypes of primary lung adenocarcinomas vary in their VDT and the prognostic value of this measurement is unknown. Purpose To investigate differences in VDT between the predominant histologic subtypes of primary lung adenocarcinomas and to assess the correlation between VDT and prognosis. Materials and Methods This retrospective study included patients who underwent at least two serial CT examinations before undergoing operation between July 2010 and December 2018. Three-dimensional tumor segmentation was performed on two CT images and VDTs were calculated. VDTs were compared between predominant histologic subtypes and lesion types by using Kruskal-Wallis tests. Disease-free survival (DFS) was obtained in patients undergoing surgical procedures before July 2017. Univariable and multivariable Cox proportional hazards regression analyses were performed to determine predictors of DFS. Results Among 268 patients (mean age, 64 years ± 8 [standard deviation]; 143 men), there were 30 lepidic, 87 acinar, 109 papillary, and 42 solid or micropapillary predominant subtypes. The median VDT was 529 days (interquartile range, 278–872 days) for lung adenocarcinomas. VDTs differed across subtypes (P < .001) and were shortest in solid or micropapillary subtypes (229 days; interquartile range, 77–530 days). Solid lesions (VDT, 248 days) had shorter VDTs than subsolid lesions (part-solid lesions, 665 days; nonsolid lesions, 648 days) (P < .001). In the 148 patients (mean age, 64 years ± 8; 89 men) included in the survival analysis, 35 patients had disease recurrence and 17 patients died. VDT (<400 days) was an independent risk factor for poor DFS (hazard ratio, 2.6; P = .01) and higher TNM stage. Adding VDT to TNM stage improved model performance (C-index, 0.69 for TNM stage vs 0.77 for combined VDT class and TNM stage; P = .002). Conclusion Volume doubling times varied significantly according to the predominant histologic subtypes of lung adenocarcinoma and had additional prognostic value for disease-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ko in this issue.