Quantitative analysis of response to treatment with erlotinib in advanced non-small cell lung cancer using 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET

Abstract

The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in patients with advanced non-small cell lung cancer.

Methods: Data were used from a prospective trial involving patients with untreated stage IV non-small cell lung cancer. (18)F-FDG PET and (18)F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV(max)], 2-dimensional peak SUV [SUV(2Dpeak)], 3-dimensional [3D] peak SUV [SUV(3Dpeak)], 3D isocontour at 50% of the maximum pixel value [SUV(50)], 3D isocontour at 50% adapted for background [SUV(A50)], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV(A41)], 3D isocontour at 70% of the maximum pixel value [SUV(70)], 3D isocontour at 70% adapted for background [SUV(A70)], and relative SUV threshold level [SUV(RTL)]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and a log-rank test.

Results: Patients with a metabolic response on early (18)F-FDG PET and (18)F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV(max), SUV(50), SUV(A50), and SUV(A41.) Patients with a metabolic response measured by SUV(max) and SUV(3Dpeak) on late (18)F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan-Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early (18)F-FLT or in late (18)F-FDG.

Conclusion: Early (18)F-FDG PET and (18)F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV(max), SUV(50), SUV(A50), and SUV(A41) measured with (18)F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early (18)F-FLT PET and late (18)F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non-small cell lung cancer treated with erlotinib.