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Comparison of the Clinical Features, Treatment Patterns, and Tumor Mutations of Patients with Intrahepatic and Extrahepatic CCA

2020 Year in Review: Cholangiocarcinoma — December 19, 2020

Retrospective chart review data indicate that intrahepatic CCA and extrahepatic CCA exhibit disparate clinical features and molecular profile, and divergent treatment patterns.

To inform treatment decision, better insights on the clinical and molecular features distinguishing patients with intrahepatic CCA and extrahepatic CCA are warranted. Results of a retrospective chart review that compared the clinicopathologic and molecular characteristics of intrahepatic CCA and extrahepatic CCA as well as treatment patterns were reported at the ASCO 2020 Gastrointestinal Cancers Symposium and summarized here.

A retrospective chart review was performed at 8 institutions on patients with histologically confirmed intrahepatic CCA or extrahepatic CCA diagnosed after June 2009. Information relating to demographics, risk factors, treatments, pathology, and OS was collected. Molecular profiling of tumor tissue was also performed.

A total of 737 patients with CCA were enrolled. Of these, 538 (73%) had a diagnosis of intrahepatic CCA and 199 (27%) had extrahepatic CCA. Compared with the extrahepatic CCA cohort, patients in the intrahepatic CCA cohort were significantly more likely to be female (52% vs 42%; P = .013), present with lymph node metastasis (35% vs 22%; P = .0004), have solid organ metastasis primarily to the liver (85% vs 58%; P <.0001) or lung (37% vs 14%; P = .0011), have tumors ≥5 cm at resection (47.5% vs 5%; P <.0001), and have a larger tumor size (5.5 cm vs 2.5 cm; P <.0001). In terms of treatment pattern, patients in the intrahepatic CCA cohort more often received liver-directed therapy (45% vs 26%; P = .0004), targeted therapy (17% vs 4%; P = .0002), and were more often enrolled in a clinical trial (23% vs 11%; P = .004). In comparison with the intrahepatic CCA cohort, patients in the extrahepatic CCA cohort were more likely to be male (58% vs 48%; P = .013), have peritoneal metastasis (35% vs 25%; P = .0343), undergone surgery (55% vs 30%; P <.0001), and receive adjuvant chemoradiation (80% vs 29%; P <.0001).

Mutation profiling was performed in 381 (52%) patients. Of these, 301 patients had intrahepatic CCA and 80 had extrahepatic CCA. The findings of the molecular analysis indicated that patients with intrahepatic CCA were significantly more likely to have IDH1 mutations (P <.0001) and FGFR2 fusions (P = .0004), whereas patients with extrahepatic CCA were more likely to have KRAS mutations (P = .0004), APC mutations (P = .0027), SMAD4 mutations (P = .0051), and TP53 mutations (P = .043).

These data indicate that patients with intrahepatic CCA and extrahepatic CCA show differences in their clinical features and molecular profiling, leading to disparate treatment patterns.

Source: Pappas L, et al. J Clin Oncol. 2020;38(4_suppl). Abstract 580.

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