High impact of macroaggregated albumin-based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with 90 Y-loaded glass microsphere radioembolization

Abstract

Background & aims: Efficacy of radioembolization is derived from radioinduced damage, whereas tumour dosimetry is not considered as yet in prospective clinical trials.

Objectives: This study evaluates the impact of tumour dose (TD), based on ^99m Tc macroaggregated albumin (MAA) quantification, on response and overall survival (OS).

Materials and methods: We consecutively included 85 patients with hepatocellular carcinoma treated with ⁹⁰ Y-loaded glass microspheres. TD was calculated using a quantitative analysis of the MAA SPECT/CT. Responses were assessed after 3 months using the European Association for the Study of the Liver criteria. OS was assessed using Kaplan-Meier tests.

Results: Response rate was 80.3% on lesion-based analysis (n=132), and 77.5% on patient-based analysis. The response rate was only 9.1% for patients with TD <205 Gy against 89.7% for those with TD ≥205 Gy (P<10^-7 ). Non-portal vein thrombosis (PVT) patients exhibited a median OS of 11.75 m (95% CI: 3-30.7 m) for TD <205 Gy, and 25 m (95% CI: 15-34.7 m) for TD ≥205 Gy (P=.0391). PVT patients exhibited a 4.35 m median OS (95% CI: 2-8 m) for TD<205 Gy, and 15.7 m (95% CI: 9.5-25.5 m) for TD ≥205 Gy, (P=.0004), with HR of 6.99. PVT patients exhibited a median OS of 3.6 m (95% CI: 2-8 m) when PVT MAA targeting was poor or with TD <205 Gy (poor candidate), vs 17.5 m (95% CI: 11-26.5 m) for the others identified as good candidates (P<.0001), with HR of 12.85.

Conclusion: This study confirms the highly predictive value of MAA-based TD evaluation for response and OS. TD evaluation and PVT MAA targeting should be further evaluated in ongoing trials, whereas personalized dosimetry should be implemented in new trial designs.

Keywords: overall survival; predictive dosimetry; radioembolization; response.

Figure 1

Portal vein thrombosis (PVT) macroaggregated albumin (MAA) targeting evaluation. Example of good targeting (PVT uptake higher than the liver) of a main branch PVT (CT scan, white arrow: A) with high MAA uptake on the SPECT CT (B). Example of poor targeting (PVT uptake lower or equal than the liver) of a main branch PVT (CT scan, white arrow: C) with no MAA uptake on the SPECT CT (D)

Figure 2

Tumour dose distribution regarding EASL response status. (A) Lesion‐based analysis. (B) Patient‐based analysis

Figure 3

Kaplan‐Meier estimates of OS. (A) OS for the overall population accordingly to tumour dose (TD) (85 patients). (B) OS for patients without portal vein thrombosis (PVT) accordingly to TD (54 patients i.e. 63.5%). (C) OS for PVT patients accordingly to TD (31 patients, i.e. 36.5%). (D) OS for PVT patients accordingly to the good or poor candidate to RE status