Systemic Therapy for Combined Hepatocellular-Cholangiocarcinoma: A Single-Institution Experience

Abstract

Background: Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. Patients and Methods: We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. Results: A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment-57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (P=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; P=.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Conclusions: Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.

Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma

“…This was partially because the pattern of tumor markers and the imaging ndings of cHCC-CCA recurrence resemble those of HCC. Due to the small number of the cHCC-CCA cases, the optimal treatment for cHCC-CCA recurrence remains unclear [18][19][20]. However, to our knowledge, this report is the rst to describe the characteristics of cHCC-CCA recurrence in detail [12,21].…”

Treatment of Combined Hepatocellular and Cholangiocarcinoma

“…To date, the report of Trikalinos et al is the most extensive study in the literature. This study included a total of 123 HCC-CC patients [75]. Among these patients, 68 had metastatic disease and were treated with systemic therapy: 16 patients received gemcitabine alone or in combination with 5-fluoropyrimidine (GEM+5-FU); 41 patients received gemcitabine plus a platinum drug (cisplatin or oxaliplatin); 7 patients received sorafenib monotherapy, and four patients were treated with other drugs.…”

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

“…Non-surgical treatment options in patients with localized disease include ablation procedures, transarterial (chemo)embolization (TA(C)E), hepatic arterial infusional chemotherapy, radioembolization, and systemic therapy (68,71). The data for benefit of loco-regional therapies in cHCC-ICC is limited to small retrospective studies but there are recognizable partial response rates which may allow subsequent surgical resection and potentially survival benefit (4,68,76,77).…”

“…The comparative data on systemic therapy in cHCC-ICC is sparse, but tends to favor the efficacy of chemotherapy over sorafenib (77,92,93). In small retrospective studies (n = 41, 28 and 17), cytotoxic regimens seem to achieve a reasonable response rate and modest mOS benefit (77,92,93).…”

“…The comparative data on systemic therapy in cHCC-ICC is sparse, but tends to favor the efficacy of chemotherapy over sorafenib (77,92,93). In small retrospective studies (n = 41, 28 and 17), cytotoxic regimens seem to achieve a reasonable response rate and modest mOS benefit (77,92,93). In the largest of these cohorts, there were no recorded objective responses for sorafenib monotherapy (n = 5 evaluable), the median progression free survival (mPFS) was 4.8 m (n = 7) and mOS was 9.6 m (n = 7), whereas for gemcitabine-cisplatin doublet chemotherapy, the partial response rate was 24% (9/37 evaluable), mPFS was 8.0 m (n = 41), and mOS was 11.5 m (n = 41) (77).…”