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

Purpose: To investigate 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.

Methods and materials: Patients with FDG-PET/computed tomography stage I-III NSCLC were prescribed concurrent chemotherapy and radiation therapy (60 Gy in 30 fractions). Scans were acquired at baseline (FDG-PET/computed tomography [FDG_BL] for radiation therapy planning and FLT-PET [FLT_BL]), week 2 (FDG_wk2 and FLT_wk2), and week 4 (FDG_wk4 and FLT_wk4) 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.

Results: Between 2009 and 2013, 60 patients were recruited. Thirty-seven (62%) were male, and the median age was 66 years (range, 31-86 years). Two-year OS and PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLT_wk2 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 FDG_BL in 21 patients (35%). Distant metastases detected in 3 patients on FLT_BL and in 2 patients on FDG/FLT_wk2 changed treatment intent from curative to palliative. Locoregional progression during radiation therapy was observed in 5 (8%) patients, prompting larger radiation therapy fields.

Conclusions: 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, FLT_wk2, and FDG_wk2 detected rapid distant and locoregional progression in 10 patients (17%), prompting changes in management.