Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer

Purpose We evaluated the value of variable F-18-FDG PET/CT parameters for the prediction of disease progression after concurrent chemoradiotherapy (CCRT) in patients with inoperable stage III non-small-cell lung cancer (NSCLC). Methods One hundred sixteen pretreatment FDG PET/CT scans of inoperable stage III NSCLC were retrospectively reviewed (stage IIIA: 51; stage IIIB: 65). The volume of interest was automatically drawn for each primary lung tumor, and PET parameters were assessed as follows: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) using the boundaries presenting SUV intensity exceeding 3.0, and the area under the curve of the cumulative SUV-volume histograms (AUC-CSH), which is known to reflect the tumor heterogeneity. Progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared with each PET and clinical parameters by univariate and multivariate survival analysis. Results In the ROC analysis, the optimal cutoff values of SUVmax, MTV (cm(3)), and AUC-CSH for prediction of PFS were determined as 21.5, 27.7, and 4,800, respectively. In univariate analysis, PFS was statistically significantly reduced in those with AUC-CSH<4,800 (p =0.004). In multivariate analysis, AUC-CSH and SUVmax were statistically significant independent prognostic factors (HR 3.35, 95 % CI 1.79-6.28, p <0.001; HR 0.25, 95% CI 0.09-0.70, p =0.008, respectively). Multivariate analysis showed that AUC-CSH was the most significant independent prognostic factor for LRFS and DMFS (HR 3.27, 95 % CI 1.54-6.94, p =0.002; HR 2.79, 95 % CI 1.42-5.50, p =0.003). Conclusions Intratumoral metabolic heterogeneity of primary lung tumor in F-18-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.