Cargando…

Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC‐06 trial reported the superiority of FOLFOX vs clinical observation as a second‐line treatment. Still, the s...

Descripción completa

Detalles Bibliográficos
Autores principales: Tovoli, Francesco, Garajová, Ingrid, Gelsomino, Fabio, Iavarone, Massimo, Federico, Piera, Salati, Massimiliano, Corianò, Matilde, Caputo, Francesco, De Lorenzo, Stefania, Granito, Alessandro, Renzulli, Matteo, Daniele, Bruno, Piscaglia, Fabio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300150/
https://www.ncbi.nlm.nih.gov/pubmed/34826193
http://dx.doi.org/10.1111/liv.15117
_version_ 1784751145517842432
author Tovoli, Francesco
Garajová, Ingrid
Gelsomino, Fabio
Iavarone, Massimo
Federico, Piera
Salati, Massimiliano
Corianò, Matilde
Caputo, Francesco
De Lorenzo, Stefania
Granito, Alessandro
Renzulli, Matteo
Daniele, Bruno
Piscaglia, Fabio
author_facet Tovoli, Francesco
Garajová, Ingrid
Gelsomino, Fabio
Iavarone, Massimo
Federico, Piera
Salati, Massimiliano
Corianò, Matilde
Caputo, Francesco
De Lorenzo, Stefania
Granito, Alessandro
Renzulli, Matteo
Daniele, Bruno
Piscaglia, Fabio
author_sort Tovoli, Francesco
collection PubMed
description BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC‐06 trial reported the superiority of FOLFOX vs clinical observation as a second‐line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post‐progression survival (PPS), similar to hepatocellular carcinoma. METHODS: Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). RESULTS: We included 206 patients from 5 centres. The median OS was 14.1 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509‐0.961], performance status >2.445 [1.788‐3.344], permanent first‐line discontinuation 16.072 [5.102‐50.633], registration of ascites 2.226 [1.448‐3.420] or bilirubin >3 mg/dl 3.004 [1.935‐4.664] during the follow‐up, and disease progression 2.523 [1.261‐5.050]. The appearance of NEH independently predicted OS 2.18 [1.55‐3.06] in patients with radiological progression. Amongst 138 patients eligible for second‐line treatment, PPS was 16.8 and 5.9 months in cases without and with NEH, respectively (P = .001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333‐2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3 mg/dl and ascites. CONCLUSIONS: PPS of iCCA is influenced by progression pattern, with important implications for second‐line trial design and analysis.
format Online
Article
Text
id pubmed-9300150
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-93001502022-07-21 Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials Tovoli, Francesco Garajová, Ingrid Gelsomino, Fabio Iavarone, Massimo Federico, Piera Salati, Massimiliano Corianò, Matilde Caputo, Francesco De Lorenzo, Stefania Granito, Alessandro Renzulli, Matteo Daniele, Bruno Piscaglia, Fabio Liver Int Liver Cancer BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC‐06 trial reported the superiority of FOLFOX vs clinical observation as a second‐line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post‐progression survival (PPS), similar to hepatocellular carcinoma. METHODS: Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). RESULTS: We included 206 patients from 5 centres. The median OS was 14.1 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509‐0.961], performance status >2.445 [1.788‐3.344], permanent first‐line discontinuation 16.072 [5.102‐50.633], registration of ascites 2.226 [1.448‐3.420] or bilirubin >3 mg/dl 3.004 [1.935‐4.664] during the follow‐up, and disease progression 2.523 [1.261‐5.050]. The appearance of NEH independently predicted OS 2.18 [1.55‐3.06] in patients with radiological progression. Amongst 138 patients eligible for second‐line treatment, PPS was 16.8 and 5.9 months in cases without and with NEH, respectively (P = .001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333‐2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3 mg/dl and ascites. CONCLUSIONS: PPS of iCCA is influenced by progression pattern, with important implications for second‐line trial design and analysis. John Wiley and Sons Inc. 2021-12-10 2022-02 /pmc/articles/PMC9300150/ /pubmed/34826193 http://dx.doi.org/10.1111/liv.15117 Text en © 2021 The Authors. Liver International published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Liver Cancer
Tovoli, Francesco
Garajová, Ingrid
Gelsomino, Fabio
Iavarone, Massimo
Federico, Piera
Salati, Massimiliano
Corianò, Matilde
Caputo, Francesco
De Lorenzo, Stefania
Granito, Alessandro
Renzulli, Matteo
Daniele, Bruno
Piscaglia, Fabio
Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title_full Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title_fullStr Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title_full_unstemmed Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title_short Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second‐line clinical trials
title_sort pattern of progression of intrahepatic cholangiocarcinoma: implications for second‐line clinical trials
topic Liver Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300150/
https://www.ncbi.nlm.nih.gov/pubmed/34826193
http://dx.doi.org/10.1111/liv.15117
work_keys_str_mv AT tovolifrancesco patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT garajovaingrid patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT gelsominofabio patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT iavaronemassimo patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT federicopiera patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT salatimassimiliano patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT corianomatilde patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT caputofrancesco patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT delorenzostefania patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT granitoalessandro patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT renzullimatteo patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT danielebruno patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials
AT piscagliafabio patternofprogressionofintrahepaticcholangiocarcinomaimplicationsforsecondlineclinicaltrials