Comparison of NTCP Models Using Liver Function Obtained From Different Contrast Agent-Based DCE-MRI after SBRT in Hepatocellular Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> To develop improved NTCP models of liver function using pre-/during-treatment DCE-MRI for adaptation of radiation therapy (RT) in hepatocellular cancer (HCC) patients who receive SBRT. The liver function map based on Gadoxetate uptake rate (k1) is compared to portal venous perfusion for HCC NTCP models. <h3>Materials/Methods</h3> 194 HCC patients who received SBRT were evaluated. Subcohorts of patients (n = 23, each) with either portal venous perfusion or Gadoxetate uptake rate k1 liver function maps calculated from DCE MRI using respective Gd-DTPA or Gadoxetic-Acid were analyzed. In addition, patients with pre-RT Child-Pugh (C-P) score > 8 for the Gadoxetate map subgroup were excluded and the remaining patients (n = 18) analyzed to explore the effect of pre-RT liver condition to the models. Median prescription doses of 50 Gy were delivered in 3 fractions or 5 fractions (split course with a 1-month break). Physical doses were converted into EQD2 for analysis. A logistic dose-response model was used to estimate the fraction of liver functional loss (change of k1 between pre-/during-RT) as a function of subregional liver dose. NTCP was estimated using the cumulative functional reserve model for change in C-P scores (2-point change in the score). Model parameters were calculated using maximum-likelihood estimations. The logistic local dose-response model coupled with the cumulative functional reserve NTCP model were compared between k1 and perfusion portal venous liver function maps. <h3>Results</h3> In the logistic model, dose that causes 50% reduction of function is much lower for k1 map, D50 of 10.2 Gy (all C-P) /14.8 Gy (pre-RT C-P < = 8) compared to 23.5Gy for perfusion. This may be due to the difference in image biomarkers or the population heterogeneity. As noted, excluding the high pre-RT CP patients, the D50 increases from 10.2 Gy to 14.8 Gy, which may indicate that worse pre-RT liver condition patients will tend to lose more liver function at lower dose. k1 map results showed a steeper response curve for C-P change compared to perfusion results using the NTCP Functional reserve model, with of 2.09/1.52 for k1 and 1.08 for perfusion. The position corresponding to 50% complication probability rate (f₅₀) are similar for both. <h3>Conclusion</h3> Functional maps showed steeper and lower dose for 50% complication compared with previous perfusion results. Considering its superiority to perfusion maps in representing liver "function", this may indicate a lower limit for normal liver dose or better dose distribution to preserve more liver function. The preliminary findings will be validated in a larger and independent cohort.