Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis

Abstract

Background: The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [90 Y]-resin microspheres and to explore possible clinical and imaging derived prognostic factors. Methods: FDG PET/CT was used to measure response of individual lesions to a measured absorbed dose, derived from post-treatment 90 Y PET imaging. Predicted dose was also derived from planning [ 99m Tc]-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 (D avg ), 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 clinicopathological variables were evaluated and compared to overall survival. Results: Sixty-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 D avg 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 D avg 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. Conclusions: Lesions 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.

Validation of post‐treatment PET‐based dosimetry software for hepatic radioembolization of Yttrium‐90 microspheres

“…Furthermore, post‐treatment imaging can provide precise information on the microsphere distribution. Emerging data show that it is common to have an inhomogeneous distribution of 90 Y microspheres within both individual lesions and across the entire liver parenchyma . This is contrary to the current assumptions of treatment planning, specifically in regards to activity prescription calculations for this procedure, which assume a uniform distribution of activity.…”

“…Radioembolization (RE) via Yttrium‐90 ( 90 Y) microspheres enables selective internal radiotherapy (SIRT) for hepatic malignancies. Guidelines exist for the careful planning of the RE procedure, specifically with the use of pretreatment angiograms and Technetium‐99m labeled macroaggregated albumin ( 99m Tc‐MAA) single photon emission computed tomography (SPECT) for calculating lung shunt fraction and predicting extrahepatic flow . However, these images are often imprecise simulators of actual microsphere distribution and poor predictors of individual lesion response in patients with metastatic disease, such as colorectal cancer .…”

“…This is contrary to the current assumptions of treatment planning, specifically in regards to activity prescription calculations for this procedure, which assume a uniform distribution of activity. This inhomogeneous distribution of 90 Y microspheres often results in mixed clinical outcomes in patients with multiple lesions . Extending post‐procedural imaging beyond quality control and toward quantitative dosimetry can offer significant clinical utility to users of 90 Y microspheres.…”

“…Extending post‐procedural imaging beyond quality control and toward quantitative dosimetry can offer significant clinical utility to users of 90 Y microspheres. Numerous studies using voxel‐based dosimetry have reported that dosimetric quantities, such as D avg and D 70 , derived from post‐radioembolization PET images can predict clinical outcomes on a lesion‐by‐lesion basis . Knowledge of a lesion's potential response or progression can help guide salvage therapy much sooner than what clinical workflows currently allow…”

“…Voxel S values are DPKs translated to cubic voxel geometries for application to cumulated activity in nuclear medicine images, and are generated by EGS4 Monte Carlo code . DPK and voxel S values have been used for 90 Y PET‐based dosimetry, but until recently have only been applied with in‐house developed code at each institution . Still, Willowson et al., Lea et al., and Fowler et al.…”