A prospective study of serial imaging comparing FDG-PET and FLT PET during radical chemo-radiation for Non-Small Cell Lung Cancer: reduction of detectable proliferation associated with worse survival

Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sarah Everitt, David Ball, Rodney J. Hicks, Jason Callahan, Nikki Plumridge, Jenny Trinh, Alan Herschtal, Tomas Kron, Michael Mac Manus
PurposeMonitoring tumor cell metabolism and tumor proliferation with FDG PET and FLT PET, respectively, during chemo-radiation therapy (CRT) may enable adaptive radiotherapy and provide prognostic information. We acquired serial 18F-FDG and 18F-FLT-PET/CT, during radical CRT and correlated tumor response with progression free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients.Methods and materialsPatients with FDG-PET/CT stage I-III NSCLC were prescribed concurrent chemotherapy and RT (60 Gy in 30 fractions). Scans were acquired at baseline [FDG-PET/CT (FDGBL) for RT planning and FLT-PET (FLTBL)], week two (FDGwk2 and FLTwk2) and week four (FDGwk4 and FLTwk4) of CRT. Tumour responses were categorised as complete or partial responses (CR, PR), stable or progressive disease (SD, PD) using EORTC criteria. Associations between response, OS and PFS were analysed with univariate Cox regressions and plotted using Kaplan-Meier curves.ResultsBetween 2009-2013, 60 patients were recruited. 37 (62%) were males and median age was 66 years (range 31-86). Two-year OS and PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLTwk2 compared with CR/PR was associated with longer OS HR [95% CI], 2.01 [0.87, 4.65] p=0.082 and PFS 2.01 [0.92, 4.36] p=0.061. Weeks 2 and 4 FDG PET/CT were not significantly associated with survival. Study scans provided additional information to FDGBL in 21 (35%) patients. Distant metastases detected in three patients on FLTBL and in two patients on FDG/FLTwk2 changed treatment intent from curative to palliative. Loco-regional progression during RT was observed in five (8%) patients, prompting larger RT fields.ConclusionsStable uptake of 18F-FLT at week two was paradoxically associated with longer OS and PFS. This suggests that suppression of tumor cell proliferation may protect against radiation induced tumour cell killing. Baseline FLT, FLTwk2 and FDGwk2 detected rapid distant and loco-regional progression in 10 (17%) patients prompting changes in management.

Teaser

Sixty Non-Small Cell Lung Cancer (NSCLC) patients, prescribed curative intent chemo-radiation therapy, were prospectively studied. ¹⁸F-FDG and ¹⁸F-FLT-PET/CT scans were acquired at baseline, week two and week four to monitor tumor cell metabolism and proliferation, respectively. Stable uptake of ¹⁸F-FLT at week two was associated with superior overall survival compared to patients whose tumors demonstrated reduced or absent ¹⁸F-FLT uptake. This suggests that suppression of tumor cell proliferation may weaken the tumoricidal effect of chemoradiation.


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