18F-FDG PET-defined therapy response to predict acute hematologic toxicity for anal cancer patients treated with chemoradiation.

Abstract

775 Background: Hematologic toxicities (HT) induced during chemoradiotherapy (CRT) for anal cancer can lead to increased infection rates, bleeding, asthenia, and unplanned breaks compromising treatment efficacy. We hypothesize that HT in anal cancer patients treated with CRT correlate with change in active bone marrow (ABM) characterized by pre- and post-CRT 18F-FDG PET/CT (PET). Methods: Twenty-eight locally advanced anal cancer patients treated with definitive CRT from 2011-2016 were identified. PET scans were obtained 0-2 weeks pre- and 6-8 weeks post-CRT. HT was evaluated by weekly white blood cell count, absolute neutrophil count (ANC), hemoglobin (Hg) and platelet nadirs. Total bone marrow (TBM) was defined on CT images, and segmented into three subregions: lumbosacral (LS), left and right iliac pelvis. PET images were normalized to bone outside of the TBM uptakes. ABM was characterized in all PET images as the volume having standard uptake value SUV > 40% of SUVmax in the TBM. Image variables (global, subregional SUVmean, SUVmax, ABMs) of pre- and post-CRT and their differential changes were evaluated as predictors of HT. Locoregional radiomics features were calculated using a 3D kernel-based approach. HT prediction was modeled by logistic regression with the Lasso algorithm with 10-fold cross-validation. HT endpoints were defined as change between baseline blood nadir and the lowest nadir values during and up to 2 weeks after CRT. Results: The lasso regression identified 5 predictors of HT (pre-SUVmax, post-LS-ABM, LS-ABM change, homogeneity texture change, and variance). Ratios of LS-ABMs to TBM were reduced from 18.9% (pre-CRT) to 16.3% (post-CRT). This reduction of LS-ABM significantly correlated with acute HT measured by ANC (p < 0.001) and Hg (p < 0.001) nadirs. Conclusions: PET-derived active BM changes between pre- and post-CRT significantly associated with HT in anal cancer patients undergoing definitive CRT. LS-ABM is a robust surrogate for evaluation of HT and can be used to develop BM-sparing radiotherapy for reduction of potential HT.