Prospective Study of Serial Imaging Comparing Fluorodeoxyglucose Positron Emission Tomography (PET) and Fluorothymidine PET During Radical Chemoradiation for Non-Small Cell Lung Cancer: Reduction of Detectable Proliferation Associated With Worse Survival

Abstract

Toinvestigate the associations between interim tumor responses on 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography (PET) and 18F-fluorothymidine (18F-FLT) PET and patient outcomes, especially progression-free survival (PFS) and overall survival (OS), in non-small cell lung cancer (NSCLC) patients. Patients with FDG-PET/computed tomography stage I-III NSCLC were prescribed concurrent chemotherapy and radiation therapy (60Gy in 30 fractions). Scans were acquired at baseline (FDG-PET/computed tomography [FDGBL] for radiation therapy planning and FLT-PET [FLTBL]), week 2 (FDGwk2 and FLTwk2), and week 4 (FDGwk4 and FLTwk4) of chemoradiation therapy. Tumor responses were categorized as complete or partial responses or stable or progressive disease (SD, PD) using European Organization for Research and Treatment of Cancer criteria. Associations between response, OS, and PFS were analyzed with univariate Cox regressions and plotted using Kaplan-Meier curves. Between 2009 and 2013, 60 patients were recruited. Thirty-seven (62%) were male, and the median age was 66years (range, 31-86years). Two-year OS and PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLTwk2 compared with complete response/partial response was associated with longer OS (hazard ratio [95% confidence interval] 2.01 [0.87-4.65], P=.082) and PFS (2.01 [0.92-4.36], P=.061). Weeks 2 and 4 FDG PET/CT were not significantly associated with survival. Study scans provided additional information to FDGBL in 21 patients (35%). Distant metastases detected in 3 patients on FLTBL and in 2 patients on FDG/FLTwk2 changed treatment intent from curative to palliative. Locoregional progression during radiation therapy was observed in 5 (8%) patients, prompting larger radiation therapy fields. Stable uptake of 18F-FLT at week 2 was paradoxically associated with longer OS and PFS. This suggests that suppression of tumor cell proliferation may protect against radiation-induced tumor cell killing. Baseline FLT, FLTwk2, and FDGwk2 detected rapid distant and locoregional progression in 10 patients (17%), prompting changes in management.