Prognostic and Predictive Significance of Primary Tumor Localization and HER2 Expression in the Treatment of Patients with KRAS Wild-Type Metastatic Colorectal Cancer: Single-Centre Experience from Serbia
The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients...
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| Published in | Journal of personalized medicine Vol. 14; no. 8; p. 879 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Switzerland
MDPI AG
20.08.2024
MDPI |
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| Online Access | Get full text |
| ISSN | 2075-4426 2075-4426 |
| DOI | 10.3390/jpm14080879 |
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| Abstract | The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. |
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| AbstractList | The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, = 0.005) and progression-free survival (PFS) (6 vs. 3 months, < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma ( < 0.001), RCC location ( = 0.022), perineural invasion ( = 0.034), and tumors at the resection margin ( = 0.001) as independent predictors of OS, while mucinous adenocarcinoma ( = 0.001) and RCC location ( = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results ( < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma ( p < 0.001), RCC location ( p = 0.022), perineural invasion ( p = 0.034), and tumors at the resection margin ( p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma ( p = 0.001) and RCC location ( p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results ( p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival.The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. |
| Author | Radić, Jelena Kolarov-Bjelobrk, Ivana Vidović, Vladimir Kožik, Bojana Nikolić, Ivan Vasiljević, Tijana Djurić, Aleksandar |
| AuthorAffiliation | 3 Department of Pathology and Laboratory Diagnostic, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia 4 Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia 2 Department of Medical Oncology, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia; aleksandardjuric555@gmail.com (A.D.); vladimir_vidovic@hotmail.com (V.V.) 1 Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; jelena.radic@mf.uns.ac.rs (J.R.); ivan.nikolic@mf.uns.ac.rs (I.N.); ivana.kolarov-bjelobrk@mf.uns.ac.rs (I.K.-B.); tijana.vasiljevic@mf.uns.ac.rs (T.V.) |
| AuthorAffiliation_xml | – name: 2 Department of Medical Oncology, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia; aleksandardjuric555@gmail.com (A.D.); vladimir_vidovic@hotmail.com (V.V.) – name: 4 Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia – name: 3 Department of Pathology and Laboratory Diagnostic, Oncology Institute of Vojvodina, 21204 Sremska Kamenica, Serbia – name: 1 Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; jelena.radic@mf.uns.ac.rs (J.R.); ivan.nikolic@mf.uns.ac.rs (I.N.); ivana.kolarov-bjelobrk@mf.uns.ac.rs (I.K.-B.); tijana.vasiljevic@mf.uns.ac.rs (T.V.) |
| Author_xml | – sequence: 1 givenname: Jelena orcidid: 0000-0001-9721-7414 surname: Radić fullname: Radić, Jelena – sequence: 2 givenname: Ivan orcidid: 0000-0003-3023-6703 surname: Nikolić fullname: Nikolić, Ivan – sequence: 3 givenname: Ivana orcidid: 0000-0003-1239-4994 surname: Kolarov-Bjelobrk fullname: Kolarov-Bjelobrk, Ivana – sequence: 4 givenname: Tijana orcidid: 0000-0003-2721-006X surname: Vasiljević fullname: Vasiljević, Tijana – sequence: 5 givenname: Aleksandar orcidid: 0000-0003-0897-4128 surname: Djurić fullname: Djurić, Aleksandar – sequence: 6 givenname: Vladimir surname: Vidović fullname: Vidović, Vladimir – sequence: 7 givenname: Bojana orcidid: 0000-0002-2983-4151 surname: Kožik fullname: Kožik, Bojana |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39202071$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1016/j.ctrv.2010.07.008 10.1631/jzus.B0820273 10.1007/s00384-006-0192-8 10.1093/annonc/mdu275 10.1200/JCO.2008.17.6453 10.1200/JCO.2011.36.4414 10.1016/j.ctarc.2022.100632 10.1093/annonc/mdx119 10.47852/bonviewMEDIN32021546 10.1093/oxfordjournals.jmicro.a023433 10.14740/gr1062w 10.1186/s12879-014-0733-7 10.6004/jnccn.2017.0002 10.1590/0102-672020190001e1479 10.1200/PO.18.00226 10.1007/s11605-019-04308-8 10.1016/j.clcc.2020.02.007 10.2147/IJN.S287732 10.1093/jnci/dju427 10.1016/S1470-2045(18)30904-5 10.35772/ghm.2020.01096 10.1053/j.seminoncol.2017.06.003 10.1634/theoncologist.2018-0117 10.1038/ajg.2013.249 10.1245/s10434-019-08100-5 10.1038/bjc.2014.483 10.1016/j.ejso.2014.11.001 10.1093/annonc/mdx175 10.1136/gutjnl-2020-321534 10.1155/2014/852748 10.3390/jcm13102810 10.1200/JCO.2017.75.3780 10.1016/j.annonc.2020.01.011 10.1016/S1470-2045(16)00150-9 10.1016/j.clcc.2020.11.002 10.1093/annonc/mdy100 10.1186/s13000-015-0380-3 10.1007/978-3-319-95228-4 10.1093/jnci/djx253 10.20944/preprints202406.0515.v1 10.3390/cancers13112647 10.1016/j.annonc.2022.07.1942 10.1001/jamaoncol.2016.3797 10.1158/1078-0432.CCR-14-0332 10.1155/2021/2131787 10.3389/fmicb.2015.00020 10.1038/nm.3870 |
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| Keywords | anti-EGFR therapy metastatic colorectal cancer HER2 expression KRAS status primary tumor localization |
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| SubjectTerms | Adenocarcinoma Cancer therapies Colon cancer Colorectal cancer Colorectal carcinoma Epidermal growth factor Epidermal growth factor receptors ErbB-2 protein Immunotherapy K-Ras protein Localization Medical prognosis Metastases Metastasis Multivariate analysis Mutation Oncology Patients Survival Tumors |
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| Title | Prognostic and Predictive Significance of Primary Tumor Localization and HER2 Expression in the Treatment of Patients with KRAS Wild-Type Metastatic Colorectal Cancer: Single-Centre Experience from Serbia |
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