Role of molecular genetics in the clinical management of cholangiocarcinoma

Normanno, Nicola; Martinelli, Erika; Melisi, Davide; Pinto, Carmine; Rimassa, Lorenza; Santini, Daniele; Scarpa, Aldo

doi:10.1016/j.esmoop.2022.100505

Cited by 23 publications

(14 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, BTCs can be classified in intrahepatic, extrahepatic (hilar and distal) cholangiocarcinoma, and gallbladder cancer (GBC). These anatomical subtypes, moreover, have been further molecularly and genomically characterized demonstrating significant differences in mutations in IDH1/2 , FGFR2 , PIK3CA , ERRB2 , KRAS and BRAF genes 92 , 93 . Several studies have tried to shed light on the complexity of the tumor microenvironment (TME) of BTCs.…”

Section: Pd-l1 In Biliary Tract Carcinomamentioning

confidence: 99%

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

et al. 2022

View full text Add to dashboard Cite

Summary Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma). In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.

show abstract

Section: Pd-l1 In Biliary Tract Carcinomamentioning

confidence: 99%

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

et al. 2022

View full text Add to dashboard Cite

show abstract

“…With these new developments, progress continues to be made toward effective systemic therapies for advanced BTC. However, there remain some issues to be resolved, such as the amount of time it takes for the results of genomic testing to be obtained, the lack of methods to obtain a sufficient sample volume in unresectable cases, the lack of effective therapeutic agents for genetic alterations and the cost of genomic testing (19,(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of second‑line chemotherapy after gemcitabine and cisplatin plus S‑1 treatment for patients with advanced biliary tract cancer in the KHBO1401‑3A study

et al. 2023

View full text Add to dashboard Cite

Since the completion of the KHBO1401 study, which evaluated the efficacy of the combination of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S-1 (GCS), GCS has become a standard chemotherapy for patients with advanced biliary tract cancer (BTC). However, there are currently no data revealing second-line therapy options after GCS. The present study aimed to evaluate the survival outcomes of patients receiving second-line chemotherapy for advanced BTC, refractory or intolerant to GCS, using data from the KHBO1401 study. Patients who received a second-line treatment after GCS chemotherapy between July 2014 and February 2016 were retrospectively studied. Overall survival (OS) was calculated from the day of GCS treatment failure or the first day of second-line chemotherapy to the final follow-up date or until death from any cause. Among 83 patients refractory or intolerant to GCS chemotherapy, 51 (61%) received second-line chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S-1 (GS) (n=4) and S-1 (n=18). The 6-and 12-month OS rates were 66.7 and 44.4%, respectively, following second-line chemotherapy, and 6.3 and 3.1%, respectively, in the best supportive care group (P<0.0001). In addition, the 12-and 24-month OS rates were 59.3 and 36.2%, respectively, in the multidrug chemotherapy group, and 26.9 and 9.0%, respectively, in the single-agent chemotherapy group (P= 0.0191). These results suggested that second-line combination chemotherapy is a viable treatment option for patients with advanced BTC that is refractory or intolerant to first-line GCS therapy.

show abstract

“…In fact, the ESMO Precision Medicine Working Group has recommended that clinical research centers adopt multigene sequencing to screen patients who are eligible for clinical trials and to accelerate drug development, as well as prospectively collect data that may provide additional information on the use of this methodology in the future ( 17 ). For cholangiocarcinomas in particular, molecular techniques can evaluate the possibility to target actionable genomic alterations with approved agents such as include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions ( 18 ). Ivosidenib, for example, has been associated with a favorable benefit for OS vs placebo in patients whose tumor harbors aberrations in IDH1 ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy

et al. 2023

View full text Add to dashboard Cite

Cholangiocarcinoma is a rare group of tumors that involve the hepatic biliary tree. Prognosis for patients with cholangiocarcinoma remains dismal. Herein, we present survival trends over a long time period spanning almost 20 years in patients with advanced cholangiocarcinoma receiving systemic chemotherapy. We retrospectively analyzed a large multicenter dataset of cholangiocarcinoma outpatients evaluated in 14 centers within the Cholangiocarcinoma Italian Group Onlus (Gruppo Italiano Colangiocarcinoma Onlus, G.I.C.O.) between 2000 and 2017 (first-line), and 2002 and 2017 (second-line). Three time periods were considered: 2000-2009, 2010-2013, and 2014-2017. A total of 922 patients (51.19% male) with cholangiocarcinoma undergoing first-line therapy were evaluated. The median durations of follow-up for progression-free survival (PFS) and overall survival (OS) were 37 and 57 months, respectively. PFS at 12 months in the three periods of starting first-line therapy was similar, ranging from 11.71% to 15.25%. OS at 12 months progressively improved (38.30%, 44.61% and 49.52%, respectively), although the differences were not statistically significant after adjusting for age, disease status, and primary tumor site. A total of 410 patients (48.5% male) underwent second-line chemotherapy. The median durations of follow-up for PFS and OS were 47.6 and 41.90 months, respectively. An OS of 24.3%, 32.3%, and 33.1% was observed in 2002-2009, 2010-2013, and 2014-2017, respectively. Despite incremental benefits across years, our clinical experience confirms that modest overall advances have been achieved with first- and second-line chemotherapy in advanced cholangiocarcinoma. Efforts should focus on the identification of patients who derive the greatest benefit from treatment.

show abstract

Role of molecular genetics in the clinical management of cholangiocarcinoma

Cited by 23 publications

References 84 publications

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

Clinical outcomes of second‑line chemotherapy after gemcitabine and cisplatin plus S‑1 treatment for patients with advanced biliary tract cancer in the KHBO1401‑3A study

Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy

Contact Info

Product

Resources

About