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 (18)F-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 (18)F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.