Background: 
There is an unmet need for objective and radiotherapy modality specific metrics for mitigating radiation-induced liver disease (RILD) in primary liver cancer (PLC) patients with cirrhosis. We hypothesize that [99mTc]-sulfur colloid (SC) SPECT/CT can provide global and spatial metrics for improved RILD-risk stratification in patients treated with proton therapy (PT).

Methods:
We retrospectively reviewed 47 patients treated with PT with Child-Pugh (CP)-A (68%) or CP-B/C (32%) cirrhosis that underwent pretreatment SC SPECT/CT scans. SC SPECT imaging was mined for intensity threshold-based functional liver volumes (FLV), mean liver-spleen uptake ratio (L/Smean), and total liver function (TLF = FLV*L/Smean). Cox regression was performed for correlation to RILD-specific survival (RILD-SS) and overall survival (OS) and logistic regression for correlation to CP-score 2+ and/or grade 3+ liver enzymes (CP+2/LFTs).

Results:
Baseline CP-score (p=0.003) and functional liver parameters of FLV (p=0.023), L/Smean (p=0.003), and TLF (p=0.003) were significant univariate predictors of RILD-SS, but not CT-derived anatomic dosimetric metrics. Risk stratification using TLF > 0.65, representative of high global liver function, into low and high risk subgroups predicted for a 100% vs 17% 1-year RILD-SS (p<10E-6). Functional liver imaging metrics remained independently associated with RILD-SS when adjusting for CP-score. Global metrics of TLF (p=0.013) and L/Smean (p=0.040) were superior predictors of RILD-SS relative to CP-score (p>0.6). Whereas baseline CP-score was the only significant factor for CP+2/LFTs prediction (p=0.016), functional liver metrics retained significance when evaluating for OS.

Conclusions:
Baseline functional imaging liver metrics improved hepatotoxicity risk prediction in PLC patients treated with PT.

Functional liver imaging for hepatotoxicity risk prediction in primary liver cancer patients with cirrhosis treated with proton therapy