Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial

Abstract

Purpose In recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC, and to recommend imaging biomarkers appropriate for routine clinical applications. Methods Patients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included. Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast-oriented thresholding and local-background partial-volume-effect-correction algorithms. For each patient, the following indices were measured: metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial-volume-corrected TLG (pvcTLG) and pvcSUVmean for the whole-body, primary tumor and regional lymph nodes. The association between each index and patient outcome was assessed using Cox proportional hazards regression. Optimal cut-off points were estimated using recursive binary partitioning in a conditional inference framework and used in Kaplan-Meier curves with log-rank testing. The discriminatory ability of each index was examined using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC(t)). Results 196 patients were included. Pretreatment whole-body and primary tumor MTV, TLG and pvcTLG were independently prognostic of OS. Optimal cut-off points were 175.0, 270.9, and 35.5 cm3 for whole-body TLG, pvcTLG, and MTV, and were 168.2, 239.8, and 17.4 cm3 for primary tumor TLG, pvcTLG, and MTV, respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were uniformly higher than that of SUV measures over all time points. Primary tumor and whole-body parameters demonstrated similar patterns of separation for those patients above versus below the optimal cut-off points in Kaplan-Meier curves, and in time-dependent ROC analysis. Conclusion We demonstrated that pretreatment whole-body and primary tumor volumetric FDG-PET/CT parameters, including MTV, TLG, and pvcTLG, are strongly prognostic for OS in patients with locally advanced NSCLC, and have similar discriminatory ability. Therefore, we believe that, after validation in future trials, the derived optimal cut-off points for primary tumor volumetric FDG-PET/CT parameters, or their more refined versions, could be incorporated into routine clinical practice, and may provide more accurate prognostication and staging based on tumor metabolic features.

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

“…Indeed, in patients managed for stage IV NSCLC, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) appeared significant on overall survival and were more effective than maximal and mean standardized uptake value (SUVmax and SUVmean). Other authors 10 confirmed the value of PET/CT volume parameters in patients managed for non-operable stage IIb/III NSCLC.…”

Prognostic value of baseline metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography/computed tomography in melanoma patients treated with ipilimumab therapy

“…The prognostic value of wMTVs on baseline PET/CT in patients treated with chemotherapy or radiotherapy has been extensively studied for various malignancies, including lymphoma [18], breast cancer [19], non-small cell lung cancer [20], and head and neck cancer [21]. Most studies have indicated that high wMTV or wTLG are strongly correlated with poor outcome.…”

Prognostic significance of semi-quantitative FDG-PET parameters in stage I non-small cell lung cancer treated with carbon-ion radiotherapy

“…We also evaluated the histological differences of MTV in risk stratification for survival outcome. MTV-based risk stratification has already been reported in locally advanced NSCLC, by Salavati et al [15], but histology was not considered. Although a previous report of differences in glucose metabolism in AC and SCC exists [12], little attention has been paid for incorporating the differences between histology in prognostic studies [8][9][10][11].…”