Value of Functional Liver Imaging in Heavily Pre-Treated Hepatocellular Carcinoma Patients

Abstract

There is an ongoing need for mitigating radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC), particularly in cirrhotic and heavily pre-treated patients with multiple prior liver-directed therapies (LDTs). We hypothesize that global and spatial functional dosimetry parameters obtained from [99mTc]-sulfur colloid (SC) SPECT/CT imaging could be of significant value in heavily pre-treated HCC patients. We retrospectively reviewed 47 HCC patients treated with low (0-2) vs. high (3+) number of prior LDTs, excluding radiofrequency ablation, who underwent SC SPECT/CT imaging for radiotherapy (RT) planning. From this cohort, we performed a case-matched analysis that controlled for baseline Child-Pugh (CP) class and RT modality. Global functional metrics, including the FLV30 (ratio of the functional liver volume at 30% maximum SC intensity divided by the anatomic liver-GTV volume), and anatomic dosimetry (liver-GTV) were extracted as previously published. Prior LDT subgroup comparisons were performed with Fisher Exact and Chi-square tests for categorical variables, as well as Mann-Whitney tests for continuous variables. We identified 24 case-matched HCC patients with either low LDTs (n=12) or high LDTs (n=12). Median age was 69 (49-89) with baseline CP-A (87.5%), and CP-B (12.5%). The median follow-up was 602 days (11-1102). RT modality was either SBRT (n=12) or hypofractionated proton RT (n=12). Median number of prior LDTs were 0 (0-2) in the low LDT group and 3.5 (3-8) in the high LDT group. The groups had no difference in underlying tumor or anatomic liver volumes (p>0.356). FLV30 ratio was lower in high LDT (73% of liver-GTV) vs. low LDT (83% of liver-GTV) patients (p=0.050), suggesting larger discrepancies between CT-defined anatomic liver volumes and FLVs in heavily pre-treated patients. The high LDT group had increased SC SPECT heterogeneity as measured by the coefficient of variation (0.46 vs 0.38, p=0.038). Figure 1 illustrates the spatial heterogeneity seen on SC SPECT/CT scans in patients with high LDTs compared to those with low LDTs. Analysis of the entire cohort (n=47) revealed that CP-A patients had a trend towards being more heavily pre-treated compared to C-B/C (p=0.074). SC SPECT/CT functional liver imaging captures compromised regions of liver function not apparent on CT imaging and may be particularly useful for RT planning in HCC patients who have received multiple catheter-based therapies.