F-fluorothymidine (FLT)-PET and diffusion-weighted MRI for early response evaluation in patients with small cell lung cancer: a pilot study.

Background: Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy.

Aim: We evaluated F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI.

Methods: Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUV, FLT-SUV, and ADC; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUV, FLT-SUV, and ADC were also analyzed for ability to predict final treatment response.

Results: Twelve patients with SCLC completed FLT-PET/MRI 1-9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUV was 2.0-22.7 in T-sites and 5.5-17.3 in N-sites. FLT-SUV was 0.6-11.5 in T-sites and 1.2-2.4 in N-sites. ADC was 0.76-1.74 × 10 mm/s in T-sites and 0.88-2.09 × 10 mm/s in N-sites. FLT-SUV correlated with FDG-SUV, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUV was not correlated with ADC, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUV was significantly lower in responding lesions than non-responding lesions (mean FLT-SUV in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUV in N-sites: 1.6 vs. 2.2; p = 0.013).

Conclusions: FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation.

Trial Registration: Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.