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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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 |
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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 |
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