Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology

Capuozzo, Maurizio; Santorsola, Mariachiara; Landi, Loris; Granata, Vincenza; Perri, Francesco; Celotto, Venere; Gualillo, Oreste; Nasti, Guglielmo; Ottaiano, Alessandro

doi:10.3390/ijms232315124

Cited by 10 publications

(10 citation statements)

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“…The three most frequent alterations involved the ARID1A, tp53, and CDKN2A genes (Supplementary File 3). The incidence of the most common genetic alterations, compared to what is described in the scientific literature, 15 is reported in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real‐world study

Ottaiano,

Santorsola,

Diana

et al. 2024

Cancer Medicine

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Background and AimsCholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real‐world data for enhanced understanding and patient care.MethodsThis multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan–Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first‐line chemotherapy) and OS. Genetic profiling was conducted selectively.ResultsEnrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first‐line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one‐third received no systemic treatment. After a median 14‐month follow‐up, 81 CCA‐related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first‐line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14–0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04–3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes.ConclusionsAdvanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.

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Section: Resultsmentioning

confidence: 99%

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real‐world study

Ottaiano,

Santorsola,

Diana

et al. 2024

Cancer Medicine

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“…AXIN1 has a mutation frequency of 1–2% in patients with CCA, according to data from CBioPortal and COSMIC ( Table 1 ). A frequency of mutations in this gene of 15% of cases has also been reported [ 49 ]. Hypermutation and unique mutational signatures have been described in iCCA samples from young printing press workers exposed to haloalkanes (n = 4).…”

Section: Molecular Alterations In the Wnt/β-catenin Pathway In Ccamentioning

confidence: 99%

Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity

Lozano

Sanchon-Sanchez

Morente-Carrasco

et al. 2023

Cells

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The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role. Alteration of β-catenin expression and subcellular localization has been associated with worse outcomes in some CCA subtypes. This heterogeneity, which also affects cellular and in vivo models commonly used to study CCA biology and anticancer drug development, must be taken into account for CCA investigation to more accurately extrapolate basic laboratory research to the clinical situation. A better understanding of the altered Wnt/β-catenin pathway in relationship with the heterogeneous forms of CCA is mandatory for developing novel diagnostic tools and therapeutic strategies for patients suffering from this lethal disease.

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“…Cholangiocarcinoma (CCA) is the liver’s second most common primary malignancy [ 1 , 2 ]. Due to the increasing incidence of CCA, several studies have focused on improving the diagnosis, prognosis, and treatment of patients [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Update on the Applications of Radiomics in Diagnosis, Staging, and Recurrence of Intrahepatic Cholangiocarcinoma

et al. 2023

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Background: This paper offers an assessment of radiomics tools in the evaluation of intrahepatic cholangiocarcinoma. Methods: The PubMed database was searched for papers published in the English language no earlier than October 2022. Results: We found 236 studies, and 37 satisfied our research criteria. Several studies addressed multidisciplinary topics, especially diagnosis, prognosis, response to therapy, and prediction of staging (TNM) or pathomorphological patterns. In this review, we have covered diagnostic tools developed through machine learning, deep learning, and neural network for the recurrence and prediction of biological characteristics. The majority of the studies were retrospective. Conclusions: It is possible to conclude that many performing models have been developed to make differential diagnosis easier for radiologists to predict recurrence and genomic patterns. However, all the studies were retrospective, lacking further external validation in prospective and multicentric cohorts. Furthermore, the radiomics models and the expression of results should be standardized and automatized to be applicable in clinical practice.

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Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology

Cited by 10 publications

References 85 publications

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real‐world study

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real‐world study

Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity

Update on the Applications of Radiomics in Diagnosis, Staging, and Recurrence of Intrahepatic Cholangiocarcinoma

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