Data from Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection

Abstract

<div>AbstractPurpose:<p>Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions.</p>Experimental Design:<p>Patients with liver-limited IHC with or without LNM treated with resection (<i>N</i> = 237), hepatic arterial infusion chemotherapy (HAIC; <i>N</i> = 196), or systemic chemotherapy alone (SYS; <i>N</i> = 140) at our institution between 2000 and 2018 were included. Genomic sequencing was analyzed to determine whether genetic alterations could stratify outcomes for patients with LNM.</p>Results:<p>For node-negative patients, resection was associated with the longest median overall survival [OS, 59.9 months; 95% confidence interval (CI), 47.2–74.31], followed by HAIC (24.9 months; 95% CI, 20.3–29.6), and SYS (13.7 months; 95% CI, 8.9–15.9; <i>P</i> < 0.001). There was no difference in survival for node-positive patients treated with resection (median OS, 19.7 months; 95% CI, 12.1–27.2) or HAIC (18.1 months; 95% CI, 14.1–26.6; <i>P</i> = 0.560); however, survival in both groups was greater than SYS (11.2 months; 95% CI, 14.1–26.6; <i>P</i> = 0.024). Node-positive patients with at least one high-risk genetic alteration (<i>TP53</i> mutation, <i>KRAS</i> mutation, <i>CDKN2A/B</i> deletion) had worse survival compared to wild-type patients (median OS, 12.1 months; 95% CI, 5.7–21.5; <i>P</i> = 0.002), regardless of treatment. Conversely, there was no difference in survival for node-positive patients with <i>IDH1/2</i> mutations compared to wild-type patients.</p>Conclusions:<p>There was no difference in OS for patients with node-positive IHC treated by resection versus HAIC, and both treatments had better survival than SYS alone. The presence of high-risk genetic alterations provides valuable prognostic information that may help guide treatment.</p></div>