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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
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 |