Abstract
BackgroundThe aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [90Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors.MethodsFDG PET/CT was used to measure response of individual lesions to a measured absorbed dose, derived from post-treatment 90Y PET imaging. Predicted dose was also derived from planning [99mTc]-MAA SPECT data. Peak standardised uptake value and total lesion glycolysis (TLG) were explored as response measures, and compared to dose metrics including average dose (Davg), biologically effective dose, minimum dose to 70% of lesion volume and volume receiving at least 50 Gy. Prognostic factors examined included baseline TLG, RAS mutation status, FDG heterogeneity and dose heterogeneity. In an exploratory analysis, response and clinico-pathological variables were evaluated and compared to overall survival.ResultsSixty-three lesions were analysed from 22 patients. Poor agreement was seen between predicted and measured dose values. TLG was a superior measure of response, and all dose metrics were significant prognostic factors, with a Davg of ~50 Gy derived as the critical threshold for a significant response (>50% reduction in TLG). No significant correlation was found between baseline TLG or RAS mutation status and response. Measured dose heterogeneity was a significant prognostic factor and when combined with Davg had a positive predictive value for response >80%. In the exploratory analysis for prognostic factors of survival, low hepatic tumour burden and mean reduction in TLG >65% were independently associated with improved overall survival.ConclusionsLesions receiving an average dose greater than 50 Gy are likely to have a significant response. For lesions receiving less than 50 Gy, dose heterogeneity is a significant prognostic factor. Lesions receiving an average dose less than 20 Gy are unlikely to respond. A reduction in TLG may be associated with improved overall survival.
Highlights
The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [90Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors
After adjusting for extrahepatic disease and Rat sarcoma (RAS) mutation status, we found strong evidence of an independent effect of hepatic tumour burden on risk of mortality (HR 1.08, 95% confidence interval (CI) 1.03–1.12, p = 0.0009)
Absorbed dose derived from 90Y Positron emission tomography (PET) imaging posttherapy is a good predictor of response, and lesions receiving an average dose greater than 50 Gy are likely to have a significant response to treatment
Summary
The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [90Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors. Radioembolisation with yttrium-90 (90Y)-labelled resin microspheres (SIR-Spheres, Sirtex Medical Ltd, Sydney, Australia) is a palliative treatment for metastatic colorectal cancer (mCRC) in the liver. There is evidence in the literature that mutant RAS cell lines (socalled as they were initially identified in “rat sarcoma” cells) are more radio-resistant compared to wild type RAS [14, 15]; a difference that has recently been shown to affect overall survival following radioembolisation [16, 17], suggesting a more detailed approach to accurate dose–response profiling is needed
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