# The relationship between yttrium-90 glass microspheres specific activity, particle density and treatment outcomes in HCC and mCRC

## TL;DR

This study found no significant difference in treatment outcomes for liver cancer patients based on when they received yttrium-90 microspheres, but noted more side effects with later treatments.

## Contribution

The study is the first to combine data from two large trials to analyze the timing of yttrium-90 microsphere treatment effects on cancer outcomes.

## Key findings

- No significant difference in overall response rates or survival was found between early and later treatment weeks.
- Week 2 treatment showed a trend toward higher rates of specific adverse events compared to week 1.
- Dosimetry data supported the lack of efficacy differences between treatment weeks.

## Abstract

To investigate relationships between treatment week, relative to Ytrrium-90 (90Y) glass microsphere calibration (i.e., specific activity and particle density), and outcomes for hepatocellular carcinoma (HCC) or colorectal cancer liver metastasis (mCRC).

Multinational, multicenter study TARGET (retrospective; n = 209 HCC patients) was combined with EPOCH (phase III trial; n = 428 mCRC patients). Efficacy included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), hepatic PFS, and tumour marker response rates. Safety included clinical and laboratory toxicity. Retrospective multicompartment dosimetry, tumour and normal tissue absorbed dose were available for TARGET; single compartment dosimetry was available for EPOCH.

No efficacy relationship was found relative to treatment week for TARGET or EPOCH. mRECIST ORR in TARGET for weeks 1 and 2 were 74/125 (59.2%) and 55/84 (65.5%), and by RECIST 1.1 in EPOCH were 54/142 (38.0%) and 15/43 (34.9%), respectively (p > 0.05). Median OS for TARGET weeks 1 and 2 were 21.4 and 20.3 months (p = 0.07), and in EPOCH were 14.9 and 16.4 months, respectively (p = 0.37). No difference in the TARGET primary endpoint of hyperbilirubinemia was noted for weeks 1 and 2, odds ratio 0.64, p = 0.59. TARGET ≥ grade 3 device-related adverse events (AEs) for weeks 1 (16.8%) and 2 (26.2%) were not significantly different (p = 0.11). EPOCH rates of ≥ grade 3 asthenia for weeks 1 (9.2%) and 2 (23.3%) were statistically different (p = 0.01).

No efficacy treatment benefit for week 2 versus week 1 was observed in TARGET or EPOCH, but week 2 treatment trended towards a higher rate and severity of specific AEs.

The online version contains supplementary material available at 10.1007/s00259-025-07334-8.