Cargando…

Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy

SIMPLE SUMMARY: Sidedness of primary tumor is a well-established prognostic marker and is predictive for anti-EGFR efficacy in RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. As molecular markers change rather continuously throughout the colon, we ask whether the exact primary tumor...

Descripción completa

Detalles Bibliográficos
Autores principales: Alig, Annabel H. S., Heinemann, Volker, Geissler, Michael, Fischer von Weikersthal, Ludwig, Decker, Thomas, Heinrich, Kathrin, Held, Swantje, Weiss, Lena, Fischer, Laura E., Moosmann, Nicolas, Stahler, Arndt, Jelas, Ivan, Kurreck, Annika, von Einem, Jobst C., Reinacher-Schick, Anke C., Tannapfel, Andrea, Giessen-Jung, Clemens, Stintzing, Sebastian, Modest, Dominik P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833757/
https://www.ncbi.nlm.nih.gov/pubmed/35158793
http://dx.doi.org/10.3390/cancers14030526
_version_ 1784649022930157568
author Alig, Annabel H. S.
Heinemann, Volker
Geissler, Michael
Fischer von Weikersthal, Ludwig
Decker, Thomas
Heinrich, Kathrin
Held, Swantje
Weiss, Lena
Fischer, Laura E.
Moosmann, Nicolas
Stahler, Arndt
Jelas, Ivan
Kurreck, Annika
von Einem, Jobst C.
Reinacher-Schick, Anke C.
Tannapfel, Andrea
Giessen-Jung, Clemens
Stintzing, Sebastian
Modest, Dominik P.
author_facet Alig, Annabel H. S.
Heinemann, Volker
Geissler, Michael
Fischer von Weikersthal, Ludwig
Decker, Thomas
Heinrich, Kathrin
Held, Swantje
Weiss, Lena
Fischer, Laura E.
Moosmann, Nicolas
Stahler, Arndt
Jelas, Ivan
Kurreck, Annika
von Einem, Jobst C.
Reinacher-Schick, Anke C.
Tannapfel, Andrea
Giessen-Jung, Clemens
Stintzing, Sebastian
Modest, Dominik P.
author_sort Alig, Annabel H. S.
collection PubMed
description SIMPLE SUMMARY: Sidedness of primary tumor is a well-established prognostic marker and is predictive for anti-EGFR efficacy in RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. As molecular markers change rather continuously throughout the colon, we ask whether the exact primary tumor location (PTL) is a better prognostic marker than sidedness and predictive for anti-EGFR efficacy in RAS/BRAF wild-type mCRC. We retrospectively analyzed five studies containing various therapy protocols concerning primary tumor location, dividing the colorectal frame into six segments. In our cohort, PTL has a prognostic impact on disease spread and overall survival. Only distal segments benefitted when receiving anti-EGFR containing therapy regarding overall survival. Intermediate segments were indifferent and caecal primaries had a detrimental effect receiving anti-EGFR based therapy. Being a retrospective analysis and challenging the standard of basing anti-EGFR treatment on sidedness in RAS/BRAF wild-type mCRC, future studies are necessary to confirm and further investigate our hypothesis-generating results. ABSTRACT: Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the relevance of primary tumor location (PTL) in RAS/BRAF wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan–Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver (p = 0.001), lung (p = 0.047), peritoneal (p < 0.001) and lymph nodes (p = 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in RAS/BRAF wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered.
format Online
Article
Text
id pubmed-8833757
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88337572022-02-12 Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy Alig, Annabel H. S. Heinemann, Volker Geissler, Michael Fischer von Weikersthal, Ludwig Decker, Thomas Heinrich, Kathrin Held, Swantje Weiss, Lena Fischer, Laura E. Moosmann, Nicolas Stahler, Arndt Jelas, Ivan Kurreck, Annika von Einem, Jobst C. Reinacher-Schick, Anke C. Tannapfel, Andrea Giessen-Jung, Clemens Stintzing, Sebastian Modest, Dominik P. Cancers (Basel) Article SIMPLE SUMMARY: Sidedness of primary tumor is a well-established prognostic marker and is predictive for anti-EGFR efficacy in RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. As molecular markers change rather continuously throughout the colon, we ask whether the exact primary tumor location (PTL) is a better prognostic marker than sidedness and predictive for anti-EGFR efficacy in RAS/BRAF wild-type mCRC. We retrospectively analyzed five studies containing various therapy protocols concerning primary tumor location, dividing the colorectal frame into six segments. In our cohort, PTL has a prognostic impact on disease spread and overall survival. Only distal segments benefitted when receiving anti-EGFR containing therapy regarding overall survival. Intermediate segments were indifferent and caecal primaries had a detrimental effect receiving anti-EGFR based therapy. Being a retrospective analysis and challenging the standard of basing anti-EGFR treatment on sidedness in RAS/BRAF wild-type mCRC, future studies are necessary to confirm and further investigate our hypothesis-generating results. ABSTRACT: Primary tumor sidedness (left vs. right) has prognostic and predictive impact on anti-EGFR agent efficacy and thus management of metastatic colorectal cancer (mCRC). This analysis evaluates the relevance of primary tumor location (PTL) in RAS/BRAF wild-type mCRC patients, when dividing the colorectal frame into six segments. This pooled analysis, performed on a single-patient basis of five randomized first-line therapy trials, evaluates the impact of exact PTL classification on baseline characteristics, prognosis and prediction of anti-EGFR antibody efficacy by chi-square and log-rank tests, the Kaplan–Meier method, Cox and logistic regressions. The PTL was significantly associated with metastatic spread: liver (p = 0.001), lung (p = 0.047), peritoneal (p < 0.001) and lymph nodes (p = 0.048). A multivariate analysis indicated an impact on anti-EGFR agent efficacy in terms of overall survival depending on the exact primary tumor location: from detrimental in caecal (HR 2.63), rather neutral effects in the ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99) and left flexure/descending colon (HR 0.91) to clear benefit in sigmoid (HR 0.71) and rectal (HR 0.58) primaries. Exact primary tumor location affects anti-EGFR antibody efficacy in a rather continuous than a dichotomous fashion in RAS/BRAF wild-type mCRC patients. This perspective might help to support clinical decisions when anti-EGFR antibodies are considered. MDPI 2022-01-21 /pmc/articles/PMC8833757/ /pubmed/35158793 http://dx.doi.org/10.3390/cancers14030526 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alig, Annabel H. S.
Heinemann, Volker
Geissler, Michael
Fischer von Weikersthal, Ludwig
Decker, Thomas
Heinrich, Kathrin
Held, Swantje
Weiss, Lena
Fischer, Laura E.
Moosmann, Nicolas
Stahler, Arndt
Jelas, Ivan
Kurreck, Annika
von Einem, Jobst C.
Reinacher-Schick, Anke C.
Tannapfel, Andrea
Giessen-Jung, Clemens
Stintzing, Sebastian
Modest, Dominik P.
Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title_full Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title_fullStr Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title_full_unstemmed Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title_short Exact Primary Tumor Location in mCRC: Prognostic Value and Predictive Impact on Anti-EGFR mAb Efficacy
title_sort exact primary tumor location in mcrc: prognostic value and predictive impact on anti-egfr mab efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833757/
https://www.ncbi.nlm.nih.gov/pubmed/35158793
http://dx.doi.org/10.3390/cancers14030526
work_keys_str_mv AT aligannabelhs exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT heinemannvolker exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT geisslermichael exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT fischervonweikersthalludwig exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT deckerthomas exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT heinrichkathrin exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT heldswantje exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT weisslena exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT fischerlaurae exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT moosmannnicolas exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT stahlerarndt exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT jelasivan exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT kurreckannika exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT voneinemjobstc exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT reinacherschickankec exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT tannapfelandrea exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT giessenjungclemens exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT stintzingsebastian exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy
AT modestdominikp exactprimarytumorlocationinmcrcprognosticvalueandpredictiveimpactonantiegfrmabefficacy