305 - Identification of Conserved Recovery Phenotypes in Liver Re-Irradiation: A Longitudinal Study Using 99m Tc-Sulfur Colloid SPECT/CT
Presenter(s)
Y. Kim1, S. Apisarnthanarax2, S. R. Bowen1, S. Cui1, J. Fu3, Y. He1, J. Takayesu2, P. Yeh1, M. J. Nyflot1, and C. Grassberger1; 1Department of Radiation Oncology, University of Washington/Fred Hutchinson Cancer Center, Seattle, WA, 2Department of Radiation Oncology, University of Washington, Seattle, WA, 3Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA
Purpose/Objective(s): We used longitudinal 99mTc-sulfur colloid (SC) SPECT/CT in patients undergoing liver re-irradiation (reRT) to characterize individual dose-dependent functional responses and investigated whether these response patterns, defined as functional phenotypes, are conserved across subsequent reRTs.
Materials/Methods: All patients treated with 5 fraction SBRT or 15-fraction proton therapy since 2013 were reviewed for reRT cases with pre-RT SPECT scans for longitudinal analysis. Doses were converted to EQD2 (a/ß=3). Fractional functional liver volume (fFLV), defined as percent of functional voxels within 10 Gy bins, was calculated using 40% of 99th-percentile uptake. Cohen’s D quantified the effect size of longitudinal changes within each bin, with a significance threshold of |d|>0.5. Patients were classified into two phenotypes based on longitudinal fFLV changes: recovered (compensatory regeneration back to or surpassing baseline fFLV in low-dose regions receiving <10 Gy EQD2), and non-recovered (significant, non-recovering functional loss down to low dose levels).
Results: Eleven patients with 27 RT courses and 39 SPECT scans were included with a median RT interval of 19 months (range: 3-45). All patients remained Child-Pugh (CP) A or non-cirrhotic. Following reRT, the median overall survival (OS) was 28 months without liver toxicity. Within the cohort, recovery was seen in irradiated liver that received up to an average 30 Gy EQD2 (10-40), but not above 50 Gy EQD2. Individual fFLV analysis identified 4 recovered vs 7 non-recovered cases. In the low-dose region, recovered cases showed an average 11.7% increase in fFLV, while non-recovered cases showed 6.8% decline. In the 5 patients that received a third course of RT, the initial functional phenotype was strictly conserved for reRT: non-recovery after the first course aligned with accelerated functional loss during subsequent reRTs, regardless of the time interval.
Conclusion: Liver functional response follows distinct, patient-specific phenotypes conserved across multiple reRT courses among patients with similar CP scores. This longitudinal study, including a third RT course subset, provides rare evidence of phenotype stability through repeated radiation. This image-based approach complements conventional biomarkers by identifying CP-stable patients who exhibit deteriorated functional reserves, distinguishing them from resilient patients who maintain recovery capacity even in re-irradiated regions.