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ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation

Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing...

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Autores principales: Huang, Ming-Yii, Lee, Hsin-Hua, Huang, Ching-Wen, Huang, Chun-Ming, Ma, Cheng-Jen, Yin, Tzu-Chieh, Tsai, Hsiang-Lin, Chai, Chee-Yin, Chen, Yi-Ting, Wang, Jaw-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491057/
https://www.ncbi.nlm.nih.gov/pubmed/32963618
http://dx.doi.org/10.3892/ol.2020.12075
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author Huang, Ming-Yii
Lee, Hsin-Hua
Huang, Ching-Wen
Huang, Chun-Ming
Ma, Cheng-Jen
Yin, Tzu-Chieh
Tsai, Hsiang-Lin
Chai, Chee-Yin
Chen, Yi-Ting
Wang, Jaw-Yuan
author_facet Huang, Ming-Yii
Lee, Hsin-Hua
Huang, Ching-Wen
Huang, Chun-Ming
Ma, Cheng-Jen
Yin, Tzu-Chieh
Tsai, Hsiang-Lin
Chai, Chee-Yin
Chen, Yi-Ting
Wang, Jaw-Yuan
author_sort Huang, Ming-Yii
collection PubMed
description Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing the therapeutic sequence administered to patients with cT4b CRC to improve clinical outcomes is crucial. In the present study, patients with unresectable cT4b and nodal stage N1-2 CRC were investigated at a single institution. A total of 20 consecutive patients were treated with pre-operative concurrent chemoradiation by using 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) since February 2015 and were regularly followed up until March 2020. Due to their poor response to concurrent chemoradiation (CCRT) with FOLFOX, the chemotherapy regimen was changed to irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as the second-line neoadjuvant treatment. Genetic alterations, such as microsatellite instability (MSI), were documented, and the expression levels of excision repair cross-complementing group 1 (ERCC1) and ERCC2 were examined. Of the 20 patients, the tumors of 14 patients (70%) became resectable after FOLFIRI administration. The median duration between the last date of radiotherapy and surgery was 32.7 weeks (range, 10.1–59.3 weeks). Of note, 4 of the 14 patients with resectable tumors (28.6%) achieved a pathologic complete response. The median overall survival and progression-free survival were 27.5 months (range, 12–39 months) and 27.5 months (range, 8–39 months), respectively. The cancerous specimens of all of the patients (100%) exhibited ERCC2 overexpression and 18 specimens (90%) had ERCC1 overexpression. Only one tumor (5%) exhibited high MSI. The present study indicated that ERCC overexpression associated with the poor response of FOLFOX-based CCRT and FOLFIRI after FOLFOX-based CCRT failure may have a potential role in conversion to resectable tumors by neoadjuvant treatment in cT4b CRC. However, a further prospective study with more patients is required to improve the precision of the conclusions.
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spelling pubmed-74910572020-09-21 ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation Huang, Ming-Yii Lee, Hsin-Hua Huang, Ching-Wen Huang, Chun-Ming Ma, Cheng-Jen Yin, Tzu-Chieh Tsai, Hsiang-Lin Chai, Chee-Yin Chen, Yi-Ting Wang, Jaw-Yuan Oncol Lett Articles Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing the therapeutic sequence administered to patients with cT4b CRC to improve clinical outcomes is crucial. In the present study, patients with unresectable cT4b and nodal stage N1-2 CRC were investigated at a single institution. A total of 20 consecutive patients were treated with pre-operative concurrent chemoradiation by using 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) since February 2015 and were regularly followed up until March 2020. Due to their poor response to concurrent chemoradiation (CCRT) with FOLFOX, the chemotherapy regimen was changed to irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as the second-line neoadjuvant treatment. Genetic alterations, such as microsatellite instability (MSI), were documented, and the expression levels of excision repair cross-complementing group 1 (ERCC1) and ERCC2 were examined. Of the 20 patients, the tumors of 14 patients (70%) became resectable after FOLFIRI administration. The median duration between the last date of radiotherapy and surgery was 32.7 weeks (range, 10.1–59.3 weeks). Of note, 4 of the 14 patients with resectable tumors (28.6%) achieved a pathologic complete response. The median overall survival and progression-free survival were 27.5 months (range, 12–39 months) and 27.5 months (range, 8–39 months), respectively. The cancerous specimens of all of the patients (100%) exhibited ERCC2 overexpression and 18 specimens (90%) had ERCC1 overexpression. Only one tumor (5%) exhibited high MSI. The present study indicated that ERCC overexpression associated with the poor response of FOLFOX-based CCRT and FOLFIRI after FOLFOX-based CCRT failure may have a potential role in conversion to resectable tumors by neoadjuvant treatment in cT4b CRC. However, a further prospective study with more patients is required to improve the precision of the conclusions. D.A. Spandidos 2020-11 2020-09-08 /pmc/articles/PMC7491057/ /pubmed/32963618 http://dx.doi.org/10.3892/ol.2020.12075 Text en Copyright: © Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Huang, Ming-Yii
Lee, Hsin-Hua
Huang, Ching-Wen
Huang, Chun-Ming
Ma, Cheng-Jen
Yin, Tzu-Chieh
Tsai, Hsiang-Lin
Chai, Chee-Yin
Chen, Yi-Ting
Wang, Jaw-Yuan
ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title_full ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title_fullStr ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title_full_unstemmed ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title_short ERCC overexpression associated with a poor response of cT4b colorectal cancer with FOLFOX-based neoadjuvant concurrent chemoradiation
title_sort ercc overexpression associated with a poor response of ct4b colorectal cancer with folfox-based neoadjuvant concurrent chemoradiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491057/
https://www.ncbi.nlm.nih.gov/pubmed/32963618
http://dx.doi.org/10.3892/ol.2020.12075
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