3501 - Laboratory and Dosimetric Predictors for Short Term Survival and Toxicity for HCC Patients Treated with SBRT

Purpose/Objective(s):

Identify prognostic laboratory values with measurement timepoints, dosimetric features, and thresholds for predicting short term survival (= 1 or 3 years) or worsening liver function for patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT).

Materials/Methods:

Records for a large, single-institution cohort of 527 treatment courses for 410 patients treated with SBRT in 3 or 5 fractions were analyzed. We assessed association of lab values at baseline, and at 3-month intervals post-treatment up to 12 mo, dosimetric and other factors with toxicity and overall survival (OS). Dosimetric factors included DVH curves in physical and biologically equivalent (EQD2Gy) doses. Analysis combining uni-variate statistical profiling with bootstrap resampling and multivariate Cox proportional hazards and AI modeling with extreme gradient boosting (XGBoost) and logistic regression (GLM) were used to evaluate strongest predictors. Median, 25%, and 75% quantiles, AUC, diagnostic odds ratio (DOR), sensitivity (SN), specificity (SP) and p values for Wilcox rank sum (WRS) and Kolmogorov–Smirnov (KS) were reported. Toxicity was scored as an increase in ALBI = 0.5; this is approximately equal to a Child Pugh score worsening of 2.

Results: At baseline, ALBI (DOR = 3.5) and ammonia values = 51.0 [47.0,53.0] (DOR = 2.65 [2.17,3.31]) were predictive of shorter OS. GTV volume = 16.27 [10.28,23.2] (DOR = 2.09 [1.86,2.36]), Liver-GTV: CV12EQD2Gy[%] = 73.22 [72.52,77.21] (DOR = 2.4 [2.2,2.80], and Liver-GTV:Mean[Gy] = 7.85 [6.28,8.55] (DOR = 2.2 [1.95,2.48]) were associated with both shorter survival and increase in ALBI. In patients surviving = 3 years, ALBI at 12 months post-treatment = -2.17 [-2.27, -1.97] (DOR = 9.54 [8.38,11.13]), total bilirubin = 1.6 [1.4,2.0] (DOR = 6.17 [5.25,7.12]), AST= 46.0 [45.0,46.0] (DOR = 5.25 [4.63,6.11]) , AFP = 87.0 [35.0,165.0](DOR = 5.5 [4.05,7.28]), neutrophile lymphocyte ratio NLR = 4.86 [4.67,5.0] (DOR= 4.88 [4.28,5.59]), INR = 1.2 [1.2,1.3] (DOR = 4.34 [3.79,4.98]) and Alkaline phosphatase = 130.0 [127.0,131.0] were the strongest predictors of shorter OS and toxicity.

Conclusion: This study substantiates the role of baseline and post-treatment ALBI, bilirubin, and INR in predicting toxicity in HCC patients undergoing SBRT, highlighting lower threshold values than previously recognized. It suggests that elevated ammonia is predictive of poor OS following SBRT, warranting investigation into the mechanisms involved. Identifying patients at high risk of toxicity and poor OS based on clinical and dosimetric factors is crucial for optimizing treatment planning. Findings could be used to direct earlier management of liver dysfunction and the development of additional liver sparing radiation techniques for those patients most at risk. Standardized Big Data and analysis streamlined evidence generation and explainability.