Tumor differentiation, location, and first-line chemotherapy responses are more predictive of progression-free survival (PFS) rate than gene mutations for patients with unresectable cholangiocarcinoma (CC), according to the results of a retrospective study published online in Alternative Therapies in Health and Medicine.

Gene mutations also did not significantly influence treatment response, the authors said. One favorable prognostic factor for improved treatment response to immunotherapy was high microsatellite instability (MSI-H).

Investigators enrolled 201 patients who were treated for CC at a single center in China between May 2014 and December 2018. Using version 1.1 of the Response Evaluation Criteria in Solid Tumors, the investigators assessed the therapeutic efficacy of gemcitabine-based treatments in 109 patients and fluorouracil-based treatments in 40 patients.

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According to the data analysis, the median follow-up time, PFS, and overall survival (OS) were 12.1, 7, and 17 months, respectively. PFS was longest in those with extrahepatic bile duct CC and shortest in those with intrahepatic CC, which indicated that tumor location may impact survival rate. Additionally, patients with low tumor differentiation had poorer survival rates.

For the 152 patients with complete data on treatment efficacy, 44% showed no response to therapy. Gemcitabine-based treatments demonstrated a 72% disease control rate and an overall response rate of 23%, whereas fluorouracil-based treatments demonstrated a 60% disease control rate and an overall response rate of 5%.

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Gemcitabine chemotherapy was the first-line treatment, while fluorouracil chemotherapy was the second-line treatment. Other second-line treatments included the FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen, paclitaxel, anti-programmed death 1 (PD-1) antibodies, and tyrosine kinase inhibitors. Third-line treatments included tyrosine kinase inhibitors and anti-PD-1 antibodies.

The researchers then performed Next-Generation Sequencing to determine gene mutations using DNA extracted from tumor tissue samples from 59 patients. In this patient population, mutations occurred predominantly in the TP53, PI3KCA, RAS, ERBB2, and IDH genes. The researchers analyzed the effects of these genomic variations on protein function and disease progression and did not find any statistically significant association between specific gene mutations and PFS or OS.

Lastly, the investigators performed a microsatellite instability assay on all tumor tissue samples which were sequenced. They labeled tumors with instability in at least 2 of 5 microsatellites as having MSI-H status. They then analyzed the relationship between MSI-H status and treatment response.

Despite the study’s limitations, the authors attested that the findings from this investigation “provided useful, real-world data on treatment modalities and their efficacy in patients with advanced cholangiocarcinoma.”


Zeng T, Tao C, Yang G, Chen X, Yuan Z. Prognosis of advanced cholangiocarcinoma in the palliative care setting: a series of 201 cases. Altern Ther Health Med. Published online October 15, 2021.