An Imaging Feature From Pre-Therapy Computed Tomography (CT) Scans Correlates With Pathological and the Clinical Outcomes in Patients (Pts) With Intrahepatic Cholangiocarcinoma (iCCA)

Abstract

Intrahepatic cholangiocarcinoma (iCCA) remains a highly lethal disease. Biomarkers are needed to identify pts who may benefit from specific therapeutic strategies. Here, we hypothesized that imaging features derived from pre-therapy CT are associated with histopathological and clinical outcomes.Retrospectively, we identified 60 pts with localized iCCA (24 M, 36 F, median age 65 [range 26-84]), who received upfront resection as a discovery cohort (D1) and 87 pts with locally advanced iCCA (49 M, 38 F, median age 64 [range 30-88]) who received chemo and radiation therapy as a validation cohort (D2). Using the pre-therapy CT, we contoured the tumors in the arterial phase and used a voxel-based method to quantify the tumors enhancing volume (normalized to liver parenchyma), and called this quantification: volumetric enhancement (VE). Using the training cohort only, we performed receiver operating characteristic (ROC) analysis to evaluate the classification ability of VE in differentiating long vs short (36 months) overall survival (OS), and to obtain an optimal cut-off for validation in D2. Corresponding slides from resection specimens of 38 pts from D1 were stained with H&E and digitally analyzed to quantify the tumor infiltration percentage. We used Pearson correlation coefficient, likelihood ratio, Kaplan-Meier and Cox-proportional hazard for statistical analyses.As a continuous variable, higher VE values were associated with better OS in D1 (RR = 0.97, 95% CI [0.95-0.99], P = 0.0007) and D2 (RR = 0.96, 95% CI [0.95-0.98], P < 0.0001). On multivariate analyses, VE as a continuous variable was an independent prognostic factor for OS accounting for traditional covariates in D1 (RR = 0.97, 95% CI [0.95-0.99], P = 0.002) and D2 (RR = 0.96, 95% CI [0.94-0.98], P < 0.0001). Using D1, VE demonstrated high accuracy in classifying pts with short vs. long term survival (Area under the curve (AUC) = 0.77), with an optimal threshold of 32.2% to dichotomize the VE into low versus high. Kaplan-Meier analysis showed that pts with high VE tumors had better median OS (145 vs 34 months, P = 0.002 and 46 vs 22 months, P < 0.0001), and distant metastasis free survival DMFS (107 vs 11 months, P < 0.0001 and 29 vs 13 months, P < 0.0001) compared to those with low VE tumors in D1 and D2 respectively. Pts with low VE tumors were more likely to have a higher nodal positivity rate compared to those with high VE tumors in D1 (P = 0.002). Tumors with high VE values had higher histopathological tumor infiltration percentage compared to those with lower VE values (⍴ = 0.72, P < 0.0001).A CT-based measure of volumetric enhancement was associated with clinical and biological differences in resectable and unresectable iCCA, which may help personalize use of chemotherapy, radiation, and surgery in this disease.