Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma
Treatment planning systems (TPSs) have been used in external-beam radiation therapy to characterize three-dimensional dosimetry at the voxel level and to calculate radiation distribution. TPSs can be used during radioembolization (RE) of hepatocellular carcinoma (HCC) to assess the heterogeneity of distribution of 90Y in the liver with the hopes of identifying predictive factors related to tumor control and toxicity. In the current study, 45 90Y resin microsphere REs were performed on patients with Barcelona Clinic Liver Cancer stage B /C HCC and area under the dose-volume histograms (AUDVH) were calculated from post-therapy PET/CT scans to determine the volume of liver tumor targeting. The volume of the total liver (Virradiated liver), tumor (Vtumor), and nontumoral liver (Vnontumoral irradiated) treated was extracted from the TPS. Tumor control was assessed through routine follow-up multiphasic CT scans and progression-free survival (PFS), overall survival (OS), and toxicity were recorded.
Of the 42 included treatments, complete targeting of the tumor was achieved in 60% (n=25) of patients and the 6-month tumor control rate was 40.5% (n=17). Both univariate and multivariate analysis showed that complete tumor targeting and AUDVHtumor were significantly associated with tumor control with a dose threshold to predict tumor control of 61 Gy. The OS and PFS was significantly shorter in patients with incomplete tumor targeting (median OS = 4.5 months, mean PFS = 2.7 months) when compared to patients with complete tumor targeting (median OS = 19.2 month, median PFS = 7.9 months) (P < 0.001 and P < 0.001 respectively). Radioembolization-induced liver disease (REILD) occurred in 5 patients (11.9% of treatments), in which a mean dose of 78.9 Gy was delivered to the nontumoral liver. AUDVHtumor and tumor targeting using 3D voxel-based tumor dose provides a representative reflection of the dose received by the tumor and appears to be correlated with tumor control and responsiveness.
Figure 1. Example of TPS post-processing to obtain 3D voxel-based dosimetry and corresponding DVHs. (a) Baseline CT scan with manual segmentation of tumor (red), portal vein invasion (purple), and liver (yellow). We subtracted necrosis owing to previous ablation (blue). (b) 90Y PET/CT imaging. (c) Screenshot of 3D voxel-based dosimetry with isodose curves on TPS (complete tumor targeting). (d) DVHs for tumor (red), portal vein invasion (purple), nontumoral irradiated liver (orange), and whole liver (yellow).
Figure 4. Kaplan-Meier estimates. (a) PFS in patients with complete vs incomplete tumor targeting (P < .001). (b) OS in patients with complete vs incomplete tumor targeting (P ¼ .001). (c) PFS in patients depending on tumor targeting and a 61-Gy cutoff for AUDVH tumor (P < .001).
Through the utilization of a 3D voxel-based TPS, the authors concluded that tumor targeting and dose delivered to the tumor are predictive of tumor control. This planning system accounts for the heterogenous deposition of 90Y microspheres within the liver, whereas the partition model used for activity calculations fails to account for varied compartmental uptake. While the proposed TPS adds to the body of literature that supports complete tumor targeting, there is still disagreement regarding the threshold dose required for tumor control. Individual patient characteristics will likely need to be incorporated into the prognostic tools used for predicting dose response. Further, while complete tumor targeting is an admirable goal, factors including difficult selective catheterization, extrahepatic blood supply, and the presence of contralateral lobar disease limit the ability to achieve complete tumor targeting. However, research regarding predictive factors related to HCC responsiveness to RE is critical to improve the PFS and OS of patients.
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Allimant C, Kafrouni M, Delicque J, Ilonca D, Cassinotto C, Assenat E, et al. Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma. J Vasc Interv Radiol. 2018 Sep 11;
Jacob Bundy, MD, MPH
Department of Surgery
University of Michigan Health System