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Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy

SIMPLE SUMMARY: Those with a history of colorectal cancer benefit from aspirin following completion of treatment, however, it is believed that this benefit is restricted to patients who have tumors with certain mutations. It is not known whether taking aspirin during active treatment helps patients...

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Autores principales: Farrugia, Mark K., Long, Mark D., Mattson, David M., Flaherty, Leayn T., Dong, Bowen, Cortes Gomez, Eduardo, Wei, Lei, Witkiewicz, Agnieszka K., Yao, Song, Kalinski, Pawel, Singh, Anurag K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826684/
https://www.ncbi.nlm.nih.gov/pubmed/33430037
http://dx.doi.org/10.3390/cancers13020205
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author Farrugia, Mark K.
Long, Mark D.
Mattson, David M.
Flaherty, Leayn T.
Dong, Bowen
Cortes Gomez, Eduardo
Wei, Lei
Witkiewicz, Agnieszka K.
Yao, Song
Kalinski, Pawel
Singh, Anurag K.
author_facet Farrugia, Mark K.
Long, Mark D.
Mattson, David M.
Flaherty, Leayn T.
Dong, Bowen
Cortes Gomez, Eduardo
Wei, Lei
Witkiewicz, Agnieszka K.
Yao, Song
Kalinski, Pawel
Singh, Anurag K.
author_sort Farrugia, Mark K.
collection PubMed
description SIMPLE SUMMARY: Those with a history of colorectal cancer benefit from aspirin following completion of treatment, however, it is believed that this benefit is restricted to patients who have tumors with certain mutations. It is not known whether taking aspirin during active treatment helps patients or whether it depends on tumor genetics in this setting. We investigated 147 patients who underwent chemoradiation for rectal cancer at our institution, including 42 who were taking aspirin at the time of chemoradiation. Concurrent aspirin use was associated with significantly improved tumor control and survival. Genetic analysis of the tumor did not indicate that these benefits were restricted to certain molecular conditions. Interestingly, aspirin was associated with more advantageous immune response in tumor specimens. Based on these findings, the addition of aspirin to chemoradiation should be considered for rectal cancer patients, independent of molecular conditions. ABSTRACT: Background: The benefit of aspirin in rectal cancer during chemoradiation therapy (CRT) and the factors affecting its efficacy are not well characterized. We compared the outcomes of rectal patients undergoing neoadjuvant CRT based on aspirin use. Methods: Patients undergoing CRT for rectal cancer from 2010 to 2018 were evaluated. Aspirin use was determined by medication list prior to treatment. RNA sequencing and subsequent gene set enrichment analysis was performed on surgically resected specimens. Results: 147 patients underwent neoadjuvant CRT with a median follow-up of 38.2 months. Forty-two patients were taking aspirin prior to CRT. Aspirin users had significantly less local and distant progression, and improved progression-free and overall survival. On RNA-sequencing, neither PI3KCA nor KRAS mutational status were associated with the benefit of aspirin use or tumor downstaging. PTGS2/COX2 expression trended lower in aspirin users, but not with tumor response. Aspirin use was associated with increases of M1 macrophages, plasma cells, CD8+ T cells, and reduction of M2 macrophages in the resected tumor. Conclusions: Concurrent aspirin use during neoadjuvant CRT was associated with improved local and distant tumor control leading to significantly improved survival. Neither mutations in KRAS or PI3CKA, nor the levels of COX-2 expression at the time of resection of the residual tumor were predictive of these aspirin benefits.
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spelling pubmed-78266842021-01-25 Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy Farrugia, Mark K. Long, Mark D. Mattson, David M. Flaherty, Leayn T. Dong, Bowen Cortes Gomez, Eduardo Wei, Lei Witkiewicz, Agnieszka K. Yao, Song Kalinski, Pawel Singh, Anurag K. Cancers (Basel) Article SIMPLE SUMMARY: Those with a history of colorectal cancer benefit from aspirin following completion of treatment, however, it is believed that this benefit is restricted to patients who have tumors with certain mutations. It is not known whether taking aspirin during active treatment helps patients or whether it depends on tumor genetics in this setting. We investigated 147 patients who underwent chemoradiation for rectal cancer at our institution, including 42 who were taking aspirin at the time of chemoradiation. Concurrent aspirin use was associated with significantly improved tumor control and survival. Genetic analysis of the tumor did not indicate that these benefits were restricted to certain molecular conditions. Interestingly, aspirin was associated with more advantageous immune response in tumor specimens. Based on these findings, the addition of aspirin to chemoradiation should be considered for rectal cancer patients, independent of molecular conditions. ABSTRACT: Background: The benefit of aspirin in rectal cancer during chemoradiation therapy (CRT) and the factors affecting its efficacy are not well characterized. We compared the outcomes of rectal patients undergoing neoadjuvant CRT based on aspirin use. Methods: Patients undergoing CRT for rectal cancer from 2010 to 2018 were evaluated. Aspirin use was determined by medication list prior to treatment. RNA sequencing and subsequent gene set enrichment analysis was performed on surgically resected specimens. Results: 147 patients underwent neoadjuvant CRT with a median follow-up of 38.2 months. Forty-two patients were taking aspirin prior to CRT. Aspirin users had significantly less local and distant progression, and improved progression-free and overall survival. On RNA-sequencing, neither PI3KCA nor KRAS mutational status were associated with the benefit of aspirin use or tumor downstaging. PTGS2/COX2 expression trended lower in aspirin users, but not with tumor response. Aspirin use was associated with increases of M1 macrophages, plasma cells, CD8+ T cells, and reduction of M2 macrophages in the resected tumor. Conclusions: Concurrent aspirin use during neoadjuvant CRT was associated with improved local and distant tumor control leading to significantly improved survival. Neither mutations in KRAS or PI3CKA, nor the levels of COX-2 expression at the time of resection of the residual tumor were predictive of these aspirin benefits. MDPI 2021-01-08 /pmc/articles/PMC7826684/ /pubmed/33430037 http://dx.doi.org/10.3390/cancers13020205 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Farrugia, Mark K.
Long, Mark D.
Mattson, David M.
Flaherty, Leayn T.
Dong, Bowen
Cortes Gomez, Eduardo
Wei, Lei
Witkiewicz, Agnieszka K.
Yao, Song
Kalinski, Pawel
Singh, Anurag K.
Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title_full Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title_fullStr Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title_full_unstemmed Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title_short Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy
title_sort concurrent aspirin use is associated with improved outcome in rectal cancer patients who undergo chemoradiation therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826684/
https://www.ncbi.nlm.nih.gov/pubmed/33430037
http://dx.doi.org/10.3390/cancers13020205
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