Data from Clinicogenomic and Histopathologic Analyses of Supermassive Intrahepatic Cholangiocarcinoma and the Role of Ablative Radiotherapy

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AbstractPurpose: Ablative radiotherapy (RT) improves clinical outcomes in patients with unresectable intrahepatic cholangiocarcinoma (ICC). Applicability to “supermassive” ICC remains uncertain given smaller tumor diameters in previous studies. We hypothesize that supermassive ICCs are not mutationally or histopathologically different from nonsupermassive ICCs and so would respond favorably to ablative RT. Experimental Design: This is a retrospective study of patients with supermassive ICC treated at the University of Texas MD Anderson Cancer Center (MDACC) and the National Cancer Database (NCDB). Patients treated at MDACC with unresectable ICC, ≥10 cm in diameter, treated with ablative RT or chemotherapy alone were included. Among NCDB patients, patients treated with chemotherapy alone were included. We analyzed overall survival (OS), tumor-related liver failure (TRLF), and treatment toxicity. We further analyzed mutational status and histopathology in supermassive and nonsupermassive ICC tumors. Results: We identified 63 patients treated at MDACC. Patients treated with RT showed improved OS compared with patients treated with chemotherapy alone (median OS: 28.7 vs. 11.9 months; adjusted HR = 0.4; P = 0.02). Patients treated with chemotherapy alone had a higher rate of TRLF compared with those who received RT (47.1% vs. 12.1%; P = 0.01). The RT cohort had improved OS compared with a frequency-matched NCDB chemotherapy-only cohort of supermassive ICC (37.6 vs. 8.9 months, P < 0.001). No major differences in mutational status or histopathology were noted between supermassive and nonsupermassive ICC tumors. Conclusions: Patients with supermassive ICC did not show a distinct mutational or histopathologic profile compared with those with nonsupermassive ICC and had promising outcomes with manageable toxicity when treated with ablative RT.

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