Abstract

BackgroundSmall 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.AimWe evaluated 18F-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.MethodsPatients 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-SUVpeak, FLT-SUVpeak, and ADCmedian; 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-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response.ResultsTwelve 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-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013).ConclusionsFLT-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 registrationClinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

Highlights

  • Functional imaging, such as positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-Magnetic resonance imaging (MRI)), are important tools to gain non-invasive information about tumor biology and tumor heterogeneity. 18F-fluorodeoxy-glucose (FDG)PET/CT has established its role in staging of small cell lung cancer (SCLC) (Ruben and Ball 2012) and causes stage migration in up to 40% of the patients influencing the choice of treatment and outcome

  • Patient data FLT-PET/MRI was conducted in 12 patients, but in one patient, DW-MRI of thorax failed

  • We showed that persistent proliferation measured by FLT-PET 1–9 days after start of chemotherapy is a potential predictor of non-response to treatment, whereas the value of DW-MRI early after treatment start was unconvincing as apparent diffusion coefficient (ADC) was not associated with final response

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Summary

Introduction

Functional imaging, such as positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI), are important tools to gain non-invasive information about tumor biology and tumor heterogeneity. 18F-fluorodeoxy-glucose (FDG)PET/CT has established its role in staging of small cell lung cancer (SCLC) (Ruben and Ball 2012) and causes stage migration in up to 40% of the patients influencing the choice of treatment and outcome (van Loon et al 2011). FDG-PET has shown prognostic value in SCLC (Langer et al 2014; Lee et al 2014; Park et al 2014; Aktan et al 2017; Kim et al 2018; Mirili et al 2019; Fu et al 2018; Chang et al 2019), but the potential of FDG-PET for early response evaluation remains unclear (Yamamoto et al 2009; Fischer et al 2006). SCLC is an aggressive cancer with more than two-thirds of the patients presenting in stage IV (Dayen et al 2017). Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Aim: We evaluated 18F-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

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