Optimizing Yttrium-90 Radioembolization Dosimetry for Hepatocellular Carcinoma: A Korean Perspective

Abstract

Yttrium-90 transarterial radioembolization (TARE) has emerged as a valuable treatment option for hepatocellular carcinoma (HCC) and is being increasingly incorporated into clinical guidelines. Recent advancements in dosimetry, including personalized dosimetry and multi-compartment modeling, have significantly improved tumor response and clinical outcomes. Although high tumor-absorbed doses are associated with better oncologic control, careful dose adjustment is essential for minimizing toxicity to normal liver tissue and lungs. This review explores the key aspects of TARE dosimetry, including single- and multi-compartment modeling, differences between resin and glass microspheres, dose-response relationships, and strategies to mitigate hepatotoxicity and radiation pneumonitis. Various clinical applications of TARE have been discussed, ranging from curative-intent radiation segmentectomy and lobectomy to palliative treatment of diffuse and macrovascular invasion-associated HCCs. In South Korea, where cadaveric liver transplantation is limited, a multidisciplinary approach is particularly important for optimizing treatment strategies and preserving liver function for potential future interventions. As dosimetry continues to evolve, further research is required to refine dose optimization protocols and validate their clinical impact in different patient populations, including those in South Korea.

Keywords: Dosimetry; Hepatocelluar carcinoma; Radioembolization; Yttrium-90.

Fig. 1. Annual TARE cases in South Korea. Since December 2020, with the partial coverage of TARE by the National Health Insurance, both the number of cases and hospitals offering TARE have rapidly increased. TARE = transarterial radioembolization

Fig. 2. Dosimetry in an 89-year-old female with a 6.0-cm solitary hepatocellular carcinoma. A: In single-compartment dosimetry, the perfused liver dose (yellow area) in the right posterior segments is 150 Gy. B: In multi-compartment dosimetry, the absorbed dose in the right posterior segments is divided into a tumor dose (red area) of 419.6 Gy and non-tumor liver dose (green area) of 92.1 Gy.

Fig. 3. Comparison of the radiation dose required to achieve a 400-Gy tumor dose between single- and multi-compartment dosimetry in various clinical settings. A: In lobar treatment for a 3-cm solitary tumor, the required radiation dose differs significantly between the two dosimetry models (8.48 GBq vs. 1.17 GBq). B: For a larger tumor, the discrepancy in the radiation dose is reduced (8.48 GBq vs. 5.51 GBq). C: When the TNR is low, the discrepancy in the radiation dose is also reduced (8.48 GBq vs. 4.30 GBq). D: When a small treatment volume is targeted through selective infusion of microspheres (radiation subsegmentectomy), the required radiation doses are significantly reduced in both dosimetry models (0.44 GBq vs. 0.16 GBq). TNR = tumor-to-normal ratio, TARE = transarterial radioembolization, LSF = lung shunt fraction

Fig. 4. Specific activity of glass and resin microspheres. Glass microspheres have an activity of 4000 Bq/microsphere on the calibration day, which decays over 12 days to 180 Bq/microsphere. The specific activity of 4-day pre-calibrated resin microspheres overlaps with this range. Y-90 = Yttrium-90

Fig. 5. Radiation segmentectomy in an 86-year-old female with a 4.0-cm solitary hepatocellular carcinoma. A: Contrast-enhanced CT shows a hypervascular tumor (arrow) in S8. B: Radiation segmentectomy was performed with 1.22 GBq glass microspheres through A8 without a planning angiography and an macroaggregated albumin scan for lung shunt fraction evaluation. C: A post-treatment PET image overlaid on the pre-treatment CT shows hot uptake at the tumor (arrow) and confirms a perfused liver dose of 550.7 Gy and tumor dose of 936.1 Gy. D: A 38-month follow-up CT shows complete response with dystrophic calcification of the tumor (arrow).

Fig. 6. Surgical resection after TARE in a 62-year-old male with a 7.5-cm solitary hepatocellular carcinoma. A: Contrast-enhanced CT shows a hypervascular tumor (arrow) in S8/4. B: During planning angiography for TARE, tumor supply by A4 (arrowhead on right-side image) is identified; therefore, selective TACE was performed through A4. TARE was then performed with 3.5 GBq resin microspheres through the RAHA (RAHA on left-side image) after temporary embolization of multiple A5 branches (arrows) using quick-soluble gelatin sponge particles to preserve normal liver tissue in S5. C: A 6-month follow-up CT shows tumor shrinkage but residual enhancement (arrow) with Lipiodol uptake, likely supplied by A4. Left lobe hypertrophy is also observed (increase in the distance between the middle hepatic vein and the left lateral tip from 11.5 cm to 14.0 cm), allowing right hemihepatectomy. D: A CT scan 1 month after the surgery shows no residual tumor or intrahepatic recurrence in the left lobe. TARE = transarterial radioembolization, TACE = transarterial chemoembolization, RAHA = right anterior hepatic artery

Fig. 7. Sequential radiation major hepatectomy in an 82-year-old male with large hepatocellular carcinoma. A: Liver MRI shows a 10.6-cm hypervascular tumor (arrows) mainly in the right anterior segments, with several tiny satellites in S5 (not shown). B: After the infusion of quick-soluble gelatin sponge particles through A6 (white arrows) to preserve normal liver tissue and through A4 (arrowhead) to redistribute intratumoral perfusion to the tumor from the RHA, TARE was performed with 3-GBq resin microspheres through the RHA. A post-treatment PET scan confirms a perfused liver dose of 166.0 Gy and tumor dose of 352.3 Gy, and shows a non-uptake area on the medial side of the tumor (black arrow). C: Four months later, sequential TARE was performed with selective infusion of 3.56-GBq glass microspheres through A4, A7, and the RAHA. PET scan confirms a perfused liver dose of 310.0 Gy and a tumor dose of 532.6 Gy. D: A CT scan 10 months after the second TARE shows complete response with dystrophic calcification of the tumor (arrows). RHA = right hepatic artery, TARE = transarterial radioembolization, RAHA = right anterior hepatic artery

Fig. 8. Combination of TARE and TACE in a 73-year-old male with multifocal hepatocellular carcinoma widely spread in both lobes. A: Liver MRI shows an 8.0-cm hypervascular mass (arrows) in the right lobe, with multiple small enhancing nodules in both lobes (arrowheads). B: A total of 5.5-GBq glass microspheres were infused through A7 and the RAHA for the dominant tumor. A post-treatment PET scan confirms a perfused liver dose of 314.0 Gy and tumor dose of 541.5 Gy. C: Two months later, angiography of the right and left hepatic arteries shows a significant reduction in enhancement of the TARE-treated tumor (arrows). Additional palliative TACE was performed for multiple residual small enhancing nodules in both lobes. D: A CT scan taken 4 months after TARE shows reduced enhancement of the dominant tumor (arrows), with multiple lipiodol-laden lesions (arrowheads) in both lobes. Despite consecutive TARE and TACE treatments, liver function was preserved, enabling safe conversion to systemic treatment. TARE = transarterial radioembolization, TACE = transarterial chemoembolization, RAHA = right anterior hepatic artery

Fig. 9. Combined treatment of TARE and TACE in a 67-year-old male with multifocal hepatocellular carcinoma. A: Liver MRI shows multiple large hypervascular masses (arrows) in the right lobe, with a single 4.5-cm tumor (arrowheads) in the left lobe. B: Planning angiography for TARE was performed, during which selective TACE for the tumor (arrowheads) in S2 was also conducted through A2. For TARE, 7.1-GBq glass microspheres were used, with lobar infusion through the RHA and selective infusion through A1, A7, and the RIPA. C: Follow-up CT shows a significant reduction in tumor size and enhancement, with residual enhancing solid components (arrows) remaining. D: Additional TACE was performed. Angiography shows a notable decrease in enhancement of the TARE-treated tumors in the right lobe. E: Follow-up CT confirms lipiodol deposition (arrows) in the previously suspected viable portion. F: Multiple additional TACE sessions were performed (not shown). At 74 months, MRI showed atrophy of the right posterior segments (circle) but no residual enhancing tumor in the liver. TARE = transarterial radioembolization, TACE = transarterial chemoembolization, RHA = right hepatic artery, RIPA = right inferior phrenic artery

Fig. 10. Surgical resection after ablative TARE in a 50-year-old male with infiltrative HCC and portal vein invasion. A: Liver MRI shows an infiltrative HCC mainly in S3, with portal vein invasion extending to the left main portal vein (arrows). B: Angiography showing tumor staining (arrows). A total of 5.34-GBq glass microspheres were infused through the LHA and A4b (middle hepatic artery) after infusion of quick-soluble gelatin sponge particles through A2 (arrowhead) to preserve the normal liver tissue. C: A post-treatment PET image overlaid on the pre-treatment MRI shows hot uptake in the tumor and portal vein tumor thrombi (arrows), confirming a perfused liver dose of 373.5 Gy in the left lobe and tumor dose of 573.9 Gy. D: A 4-month follow-up MRI shows radiological complete response of the tumor (arrows). Consequently, left hemihepatectomy was performed. E: Pathologic analysis confirms near-total necrosis (0.1 × 0.1 cm viable portion). F: A 12-month follow-up CT after the surgery shows no intrahepatic tumor recurrence. TARE = transarterial radioembolization, HCC = hepatocellular carcinoma, LHA = left hepatic artery