Faculty, Staff and Student Publications

Language

English

Publication Date

1-22-2026

Journal

JHEP Reports

DOI

10.1016/j.jhepr.2026.101743

PMID

41825097

Abstract

Background & aims: This phase I trial evaluated the safety of hypofractionated liver reirradiation (reRT) with preferential sparing of functional liver identified by technetium-99m sulfur colloid single-photon emission computed tomography (Tc-99m SC SPECT; hereafter SPECT) for patients previously treated with external beam radiotherapy or transarterial radioembolization.

Methods: A 3+3 design evaluated the safety of two escalating SPECT-based functional liver volumetric dose constraints. Dose-limiting toxicities (DLTs), liver segment volumes, and MRI functional liver imaging score, relative liver enhancement, and elastography were assessed.

Results: Thirteen patients were enrolled from 2018 to 2021. Median reRT gross tumor volume was 61 cm3 (range 1-677 cm3). Median non-tumor CT and SPECT liver volumes spared from ≥24 Gy were 1,076 cm3 (range 712-1,649 cm3) and 740 cm3 (range 533-1,001 cm3), respectively. The first three patients in dose level 0 (sparing ≥400 cm3 functional liver from ≥24 Gy) and the next three patients in dose level +1 (sparing ≥300 cm3 functional liver from ≥24 Gy) experienced no DLTs. Of the next seven patients treated using dose level +1 constraints, one developed acute (≤8 weeks) grade 3 ascites, and one developed late grade 3 ascites, both possibly attributable to reRT. None developed radiation-induced liver disease. At 6-8 weeks follow-up, hypertrophy was observed in untreated liver segments from six patients. Atrophy was observed in treated liver segments from five patients. Quantitative MRI changes were associated with DLTs. One-year cumulative incidence of in-field progression was 23% (95% CI, 6-47). One-year overall survival was 62% (95% CI, 40-95).

Conclusions: SPECT may facilitate safe reRT for liver tumors.

Impact and implications: Although ablative liver-directed radiotherapy confers excellent local control rates for patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases, recurrence in the previously uninvolved liver occurs in 50-70% of cases, and retreatment is often challenging given the risk of radiation-induced liver disease. We conducted a phase I trial investigating hypofractionated liver reRT after previous external beam radiotherapy or transarterial radioembolization, which was safely facilitated with the aid of SPECT functional liver imaging, to preferentially identify and spare functional liver. Compensatory liver hypertrophy was observed, and dynamic quantitative MRI biomarkers were associated with functional liver changes. Thus, the incorporation of advanced functional imaging techniques could help expand retreatment options for patients with limited remaining hepatic reserve.

Keywords

Liver cancers, Phase I trial, Quantitative imaging biomarkers, Reirradiation, SPECT

Comments

Clinical trials registration: the study is registered at ClinicalTrials.gov (NCT02626312).

Published Open-Access

yes

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