In Silico Validation of MCID Platform for Monte Carlo-Based Voxel Dosimetry Applied to 90Y-Radioembolization of Liver Malignancies

The aim was the validation of a platform for internal dosimetry, named MCID, based on patient-specific images and direct Monte Carlo (MC) simulations, for radioembolization of liver tumors with 90Y-labeled microspheres. CT of real patients were used to create voxelized phantoms with different density and activity maps. SPECT acquisitions were simulated by the SIMIND MC code. Input macros for the GATE/Geant4 code were generated by MCID, loading coregistered morphological and functional images and performing image segmentation. The dosimetric results obtained from the direct MC simulations and from conventional MIRD approach at both organ and voxel level, in condition of homogeneous tissues, were compared, obtaining differences of about 0.3% and within 3%, respectively, whereas differences increased (up to 14%) introducing tissue heterogeneities in phantoms. Mean absorbed dose for spherical regions of different sizes (10 mm ≤ r ≤ 30 mm) from MC code and from OLINDA/EXM were also compared obtaining differences varying in the range 7–69%, which decreased to 2–9% after correcting for partial volume effects (PVEs) from imaging, confirming that differences were mostly due to PVEs, even though a still high difference for the smallest sphere suggested possible source description mismatching. This study validated the MCID platform, which allows the fast implementation of a patient-specific GATE simulation, avoiding complex and time-consuming manual coding. It also points out the relevance of personalized dosimetry, accounting for inhomogeneities, in order to avoid absorbed dose misestimations.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

Background Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. Methods Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. Results Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. Conclusions Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

EFFICACY OF 90Y-RADIOEMBOLIZATION IN METASTATIC COLORECTAL CANCER DEPENDING ON THE PRIMARY TUMOR SIDE

Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side. We performed a retrospective analysis of n=73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival. Prior to RE all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n=22/73 (30.1%) patients the primary tumor side was in the right colon, in n=51/73 (69.9%) patients in the left colon. Hepatic tumor burden was ≤25% in n=36/73 (49.3%) patients and >25% in n=37/73 (50.7%) patients. At 3 months, n=21 (33.8%) patients showed treatment response [n=2 (3.2%) complete response, n=19 (30.6%) partial response], n=13 (21.0%) stable disease, and n=28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p=0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher compared with >25% (13.9 vs. 4.3 months, p<0.001). The median overall survival was 6.1 months. The median survival after RE in hepatic-metastatic CRC depends on the primary tumor side and the pre-procedural hepatic tumor burden.