Assessment of Healthy Tissue Metabolism to Predict Outcomes in Oncologic [18F]FDG PET/CT

Abstract

Background: The use of 2-[18F]Fluoro-2-deoxy-d-glucose ([18F]FDG) in positron emission tomography/computed tomography (PET/CT) imaging is not specific to oncologic applications but reflects various pathologic processes with high metabolic activity. Thus, evaluating healthy tissue metabolism (HTM) based on [18F]FDG in cancer patients receiving cytotoxic anti-cancer treatment may provide prognostic information which could potentially assist in identifying patients at high risk of developing treatment-related adverse events (AEs) and those who may have poor outcome. However, unlike cancer imaging HTM assessment with [18F]FDG is lacking standardization in the research setting. Purpose: The main aim of this thesis was to review the applications of [18F]FDG PET/CT in the assessment of anti-cancer treatment-related AEs and to assess methods used in the literature to measure HTM. Further, to evaluate the repeatability and interobserver variation of HTM in lung cancer patients. Finally, HTM based on [18F]FDG uptake was assessed as an imaging biomarker to predicts AEs and outcomes in Hodgkin lymphoma (HL) patients. Methods: A comprehensive literature search was conducted in PubMed, Embase and Web of Science databases for published data on [18F]FDG uptake in different HT for assessment of AEs in cancer patients. Different common and modified methods of assessment were applied to measure [18F]FDG uptake in liver, spleen and other HT. Retrospective test-retest repeatability and interobserver analyses of HTM were also performed on 22 patients with non-small cell lung cancer who underwent [18F]FDG PET/CT of the thorax 2 days apart without intervening treatment (from a prospective study) to measure the maximum, mean and peak standardised uptake values (SUVmax, SUVmean and SUVpeak). Moreover, [18F]FDG uptake in 200 patients with advanced HL from the RATHL trial was retrospectively measured in bone marrow (BM), mediastinal blood pool (MBP), liver and spleen at baseline (PET0) and after 2 cycles of chemotherapy (PET2). Results: Out of the reviewed studies, (n = 80, 94%) reported an association between [18F]FDG uptake in HT and treatment-related AEs. Quantitative assessment using SUVmean was mainly applied in those studies to assess changes in HTM at multiple timepoint. Further evaluation of the liver, spleen and other HT showed that using SUVmean reduces bias across different methods. Further, applying fixed volume of interest (VOI) was comparable to more sophisticated approaches. In comparison to other PET metrics, SUVmean also showed better repeatability as expressed with the within-subject coefficient of variation (wCV) of 20% and high interobserver agreement of ≤10% in HT in the thorax; however, left ventricle uptake was highly variable in a test-retest analysis. In HL, HT uptake changed significantly during treatment. BM uptake at PET0 was associated with baseline haematological parameters, higher risk of neutropenia at cycles 1-2 and failure of early response. Non-responding patients with high BM uptake at PET2 had inferior progression-free survival (PFS). Conclusion: Most of the studies reviewed from the literature reported an association between HTM and treatment-related AEs among different cancer types and treatment modalities. SUVmean was mainly used in those studies to correlate changes in HTM with treatment-related AEs which was shown to be more stable than SUVmax and SUVpeak. [18F]FDG uptake in uninvolved BM has a prognostic value in HL.