Personalized Dosimetry with Intensification Using ⁹⁰Y-Loaded Glass Microsphere Radioembolization Induces Prolonged Overall Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis

Abstract

The objective of this study was to evaluate the response rate and survival of hepatocellular carcinoma portal vein thrombosis (PVT) patients treated with 90 Y-loaded glass microspheres using a personalized dosimetry and intensification concept. Methods: The microspheres were administered to 41 hepatocellular carcinoma PVT patients (main 5 12; lobar/segmental 5 29). 99m Tc-macroaggregated albumin SPECT/CT quantitative analysis was used to calculate the tumor dose (TD), healthy injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 mo using the criteria of the European Association for the Study of the Liver, with CT follow-up lasting until disease progression or death. Survival was assessed using the Kaplan-Meier method. Results: The mean injected activity was 3.1 ± 1.5 GBq, and mean ILD was 143 ± 49 Gy. When a TD threshold of 205 Gy was applied, 99m Tc-macroaggregated albumin SPECT/CT achieved a 100% sensitivity and 90% overall accuracy (0 false-negatives; 4 false-positives) in response prediction. On the basis of TD and HILD values, 37% of patients received an intensification of the treatment (increased injected activity with the aim of achieving a TD $ 205 Gy and HILD , 120 Gy, applying an ILD . 150 Gy). This intensification resulted in a high response rate (85%) without increased liver toxicity of grade 3 or higher (6% vs. 12% in the patients who did not receive treatment intensification; not statistically significant). For the total 41 patients, median overall survival (OS) was 18 mo (95% confidence interval, 11-25 mo). For patients with a TD of less than 205 Gy, median OS was 4.3 mo (3.7-5 mo), versus 18.2 mo (8.5-28.7 mo) for those with a TD of 205 Gy or more (P 5 0.005). Median OS was 20.9 mo for patients with a TD of 205 Gy or more and good PVT targeting (n 5 36). OS was 12 mo (3 mo to N) for patients with main PVT, versus 21.5 mo (12-28.7 mo) for those with segmental or lobar PVT (not statistically significant). For the 5 patients with complete portal vein revascularization who underwent lobar hepatectomy, median OS was not reached yet exceeded 24.5 mo and was significantly higher than that of other patients (P 5 0.0493). Conclusion: Using a 99m Tc-macroaggregated albumin SPECT/CT personalized dosimetry and intensification concept with 90 Y-loaded glass microspheres induced prolonged OS for PVT patients as compared with the standard of care (sorafenib), without increasing liver toxicity. Prospective randomized studies are therefore warranted.

90Y Hepatic Radioembolization: An Update on Current Practice and Recent Developments

“…However, radioembolization has a low embolic effect, and most of the arterial tree remains patent after treatment (6,7). Radioembolization in the setting of PVT is therefore safe and can sometimes lead to complete portal vein revascularization, even in main PVT (8). In contrast to transarterial chemoembolization (TACE), PVT is not considered a contraindication.…”

“…In contrast to transarterial chemoembolization (TACE), PVT is not considered a contraindication. Radioembolization is an emerging indication in early-advanced hepatocellular carcinoma (HCC) (Barcelona Clinical Liver Cancer [BCLC] C, liver-dominant, Eastern Cooperative Oncology Group [ECOG] 1-2, PVT) (8). On the basis of current evidence, application of radioembolization in patients with a ChildPugh score higher than B7 and main PVT should be weighed carefully, because of the limited potential survival benefit after radioembolization (4.5-5 mo in Child-Pugh B patients and 2.5 mo in Child-Pugh C patients vs. 2.7-4.0 mo in untreated patients) (9)(10)(11)(12).…”

Intraarterial Hepatic SPECT/CT Imaging Using 99mTc-Macroaggregated Albumin in Preparation for Radioembolization

“…In these patients, PET/CT demonstrated that microspheres distributed within the PVT (24). Overall survival of these patients improved using the boosted personalized dose method described by Garin et al in which the tumor dose of 205 Gy was achieved through increasing the lobar dose to a 150-Gy maximum (25). From our study, the perfused volume would include both the right and the left lobar volumes for 62.5% of the patients with HCC and PVT.…”

Radioembolization with 90Y-loaded microspheres: high clinical impact of treatment simulation with MAA-based dosimetry

“…Secondly, a more personalized oncological approach is believed to potentially yield superior clinical results. This last point certainly appears to be true when using MAA SPECT/CT dosimetry and intensification for PVT patients, with an OS rate reaching 20 months for good candidates [15]. Lastly, the availability of this predictive factor of response and survival prior to therapy initiation is a clear advantage for radioembolization, as this is not the case with other therapeutic approaches used for liver cancer, such as chemotherapy, targeted therapies or chemoembolization.…”

“…This point is of particular significance for three main reasons. First of all, given that MAA dosimetry is available prior to therapy initiation, it can lead to a fully personalized approach with a better selection of responders, improved identification of patients at risk of liver failure, and can even be used for treatment intensification, as recently suggested [11,15]. Secondly, a more personalized oncological approach is believed to potentially yield superior clinical results.…”