Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real-world study.
cholangiocarcinoma
genetics
prognostic factors
real-word study
tumor heterogeneity
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
revised:
14
12
2023
received:
06
11
2023
accepted:
16
12
2023
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
8
3
2024
Statut:
ppublish
Résumé
Cholangiocarcinoma (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. This 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. Enrolled 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. Advanced 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.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Cholangiocarcinoma (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.
METHODS
METHODS
This 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.
RESULTS
RESULTS
Enrolled 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.
CONCLUSIONS
CONCLUSIONS
Advanced 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e6892Subventions
Organisme : Ministero della Salute
ID : Ricerca corrente 2022 L4/8
Informations de copyright
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: epidemiology and risk factors. Liver Int. 2019;39(Suppl 1):19-31. doi:10.1111/liv.14095
Blechacz B. Cholangiocarcinoma: current knowledge and new developments. Gut Liver. 2017;11:13-26. doi:10.5009/gnl15568
Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397:428-444. doi:10.1016/S0140-6736(21)00153-7
Valle J, Wasan H, Palmer DH, et al. ABC-02 trial investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273-1281. doi:10.1056/NEJMoa0908721
Oh DY, He AR, Qin S, et al. For the TOPAZ-1 investigators. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1:1. doi:10.1056/EVIDoa2200015
Lamarca A, Palmer DH, Wasan HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22:690-701. doi:10.1016/S1470-2045(21)00027-9
Ying J, Chen J. Combination versus mono-therapy as salvage treatment for advanced biliary tract cancer: a comprehensive meta-analysis of published data. Crit Rev Oncol Hematol. 2019;139:134-142. doi:10.1016/j.critrevonc.2019.01.001
Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25:2328-2338. doi:10.1093/annonc/mdu162
Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36:276-282. doi:10.1200/JCO.2017.75.5009
Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671-684. doi:10.1016/S1470-2045(20)30109-1
Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:796-807. doi:10.1016/S1470-2045(20)30157-1
Manne A, Woods E, Tsung A, Mittra A. Biliary tract cancers: treatment updates and future directions in the era of precision medicine and Immuno-oncology. Front Oncol. 2021;11:768009. doi:10.3389/fonc.2021.768009
Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:127-140. doi:10.1016/j.annonc.2022.10.506
Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247. doi:10.1016/j.ejca.2008.10.026
Capuozzo M, Santorsola M, Landi L, et al. Evolution of treatment in advanced cholangiocarcinoma: old and new towards precision oncology. Int J Mol Sci. 2022;23:15124. doi:10.3390/ijms232315124
Seung SJ, Saherawala H, Syed I, Shephard C, Clouthier DL, Chen E. Real-world treatment patterns and survival outcomes for treated biliary tract cancer patients using administrative databases in Ontario. J Gastrointest Oncol. 2023;14:1806-1816. doi:10.21037/jgo-23-155
Maeda O, Ebata T, Shimokata T, et al. Chemotherapy for biliary tract cancer: real-world experience in a single institute. Nagoya J Med Sci. 2020;82:725-733. doi:10.18999/nagjms.82.4.725
Koshiol J, Yu B, Kabadi SM, Baria K, Shroff RT. Epidemiologic patterns of biliary tract cancer in the United States: 2001-2015. BMC Cancer. 2022;22:1178. doi:10.1186/s12885-022-10286-z
Kim BJ, Hyung J, Yoo C, et al. Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients. Cancer Chemother Pharmacol. 2017;80:209-215. doi:10.1007/s00280-017-3353-2
Izquierdo-Sanchez L, Lamarca A, La Casta A, et al. Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA registry. J Hepatol. 2022;76:1109-1121. doi:10.1016/j.jhep.2021.12.010
Sirica AE, Gores GJ, Groopman JD, et al. Intrahepatic cholangiocarcinoma: continuing challenges and translational advances. Hepatology. 2019;69:1803-1815. doi:10.1002/hep.30289
Javle M, Lee S, Azad NS, et al. Temporal changes in cholangiocarcinoma incidence and mortality in the United States from 2001 to 2017. Oncologist. 2022;27:874-883. doi:10.1093/oncolo/oyac150
Lleo A, Colapietro F, Maisonneuve P, et al. Risk stratification of cholangiocarcinoma patients presenting with jaundice: a retrospective analysis from a tertiary referral center. Cancers (Basel). 2021;13:2070. doi:10.3390/cancers13092070
Ottaiano A, Circelli L, Santorsola M, et al. Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions. Mol Oncol. 2022;16:319-332. doi:10.1002/1878-0261.13122
Christou N, Bergen ES, Canton C, et al. Impact of diabetes and metformin use on recurrence and outcome in stage II-III colon cancer patients-a pooled analysis of three adjuvant trials. Eur J Cancer. 2022;166:100-111. doi:10.1016/j.ejca.2022.02.005
Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO precision medicine working group. Ann Oncol. 2020 Nov;31(11):1491-1505. doi:10.1016/j.annonc.2020.07.014