Optimal Management of Patients with Advanced or Metastatic Cholangiocarcinoma: An Evidence-Based Review

Ioffe, Dina; Phull, Pooja; Dotan, Efrat

doi:10.2147/cmar.s276104

Cited by 9 publications

(6 citation statements)

References 109 publications

(135 reference statements)

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“…The common patterns of destruction are osteolytic or mixed osteolytic and osteosclerotic lesions [ 19 ]. For patients with unresectable advanced disease, the median OS is less than one year and poor performance status (ECOG ≥ 2) is the strongest prognostic factor [ 20 ]. Yan et al [ 10 ] analyzed a total of 981 patients diagnosed with stage IV ICC.…”

Section: Discussionmentioning

confidence: 99%

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis

et al. 2023

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Background: Metastatic intrahepatic cholangiocarcinoma still has a dismal prognosis. The aim of our study was to investigate the prognostic role of bone metastases in patients affected by intrahepatic cholangiocarcinoma. Methods: A total of 186 metastatic intrahepatic cholangiocarcinoma patients were retrospectively reviewed. Clinicopathologic and survival data were collected and reviewed, in particular overall survival, progression-free survival after first-line treatment and time from end of first-line therapy to cancer death. Results: Around 11% of intrahepatic cholangiocarcinoma patients developed bone metastases. This subgroup of patients showed no differences in progression-free survival to first-line chemotherapy but had a shorter median overall survival of 4 months compared to the group with liver involvement only (p = 0.03). If treated, the outcome for ECOG PS 2 patients with bone metastases was worse in comparison to patients with liver involvement only with poor performance status (p = 0.003). The presence of bone metastases, poor performance status and no subsequent second-line treatment was associated with a worse outcome in multivariate analysis. Conclusions: Patients with intrahepatic carcinoma and bone metastases with poor ECOG performance status might be treated with best supportive care and not active chemotherapy treatment, the decisions which have to be shared with patients.

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Section: Discussionmentioning

confidence: 99%

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis

et al. 2023

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“…Most patients with CCA are ineligible for LR because they have locally advanced or metastatic disease at the time of presentation and undergo systemic treatment. [163] Sex has not been identified as a factor associated with the response of CCA to different treatment protocols and survival [164][165][166][167][168][169][170][171][172][173][174][175][176][177] except in one study conducted in Taiwan, in which male sex was an independent predictor of poor overall survival but not of tumor response in patients treated with gemcitabine/cisplatin. [178] The influence of sex on treatment response is rarely examined in clinical trials, and no sexbased recommendation for systemic therapy selection has been proposed.…”

Section: Systemic Treatmentsmentioning

confidence: 99%

Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review

et al. 2023

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Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sexrelated inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender

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“…Microsatellite instability (MSI-high) or mismatch repair de ciency (dMMR) is found in 2-3% of biliary tract cancers (Ioffe et al 2021). This alteration agnostic FDA-and EMA-approval of pembrolizumab, a monoclonal antibody, for dMMR tumors and tumors with high tumor mutational burden (TMB) (Le et al…”

Section: Introductionmentioning

confidence: 99%

Therapeutic yield of extensive molecular profiling in cholangiocarcinoma: a retrospective single center study.

Vancanneyt

Wilmsen

Luyten

et al. 2023

Preprint

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Introduction: Current available systemic therapies for advanced cholangiocarcinoma (CCA) are of limited effectiveness and prognosis is poor. Recently, introduction of next-generation sequencing (NGS) technologies led to a better understanding of the genetic pathophysiology and consequently, identification of molecular alterations for targeted treatment. Aim: To determine the proportion of actionable alterations using extensive molecular profiling in a routine diagnostic setting and to study the effect of targeted treatment on disease control. Methods: Results of extensive molecular testing by either FoundationOne NGS or an in-house developed 96 cancer gene panel were retrospectively collected from patients with locally advanced or metastatic CCA diagnosed between 01/12/2018 and 01/08/2021 in a single center. Gene variants were classified according to ESCAT and correlated with efficacy endpoints. Results: Of 125 patients included, 65 patients had an intrahepatic CCA (iCCA). FGFR2 fusions and IDH1/BAP1 mutations were more frequent in iCCA, while KRAS and SMAD4 mutations were predominant in extrahepatic CCA (eCCA). Targetable alterations (ESCAT tiers I-IV) were identified in 73,6% of patients. Overall survival was significantly better for higher tiers regardless of treatment. Thirteen patients (10.4%) received targeted treatment based on molecular profiling, with a median progression free survival (PFS) of 7,3 months. Conclusions: Extensive molecular characterization led to the identification of targetable and potentially targetable alterations in a significant proportion of patients with locally advanced or metastatic CCA. We confirmed the association between higher ESCAT tier and benefit of a targeted treatment. Molecular analysis should therefore be considered in all patients fit enough for systemic treatment.

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Optimal Management of Patients with Advanced or Metastatic Cholangiocarcinoma: An Evidence-Based Review

Cited by 9 publications

References 109 publications

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis

Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review

Therapeutic yield of extensive molecular profiling in cholangiocarcinoma: a retrospective single center study.

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