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 ¹⁸F-FDG and 3′-deoxy-3′-¹⁸F-fluorothymidine (¹⁸F-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. ¹⁸F-FDG PET and ¹⁸F-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 [SUV₅₀], 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 [SUV₇₀], 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 ¹⁸F-FDG PET and ¹⁸F-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, SUV₅₀, SUV_A50, and SUV_A41. Patients with a metabolic response measured by SUV_max and SUV_3Dpeak on late ¹⁸F-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 ¹⁸F-FLT or in late ¹⁸F-FDG. Conclusion: Early ¹⁸F-FDG PET and ¹⁸F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV_max, SUV₅₀, SUV_A50, and SUV_A41 measured with ¹⁸F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early ¹⁸F-FLT PET and late ¹⁸F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non–small cell lung cancer treated with erlotinib.