Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer
Abstract Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cjp2.171 |
| _version_ | 1818212129159774208 |
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| author | Antonia K Roseweir James H Park Sanne ten Hoorn Arfon GMT Powell Susan Aherne Campbell SD Roxburgh Donald C McMillan Paul G Horgan Elizabeth Ryan Kieran Sheahan Louis Vermeulen James Paul Andrea Harkin Janet Graham Owen Sansom David N Church Ian Tomlinson Mark Saunders Tim J Iveson Joanne Edwards |
| author_facet | Antonia K Roseweir James H Park Sanne ten Hoorn Arfon GMT Powell Susan Aherne Campbell SD Roxburgh Donald C McMillan Paul G Horgan Elizabeth Ryan Kieran Sheahan Louis Vermeulen James Paul Andrea Harkin Janet Graham Owen Sansom David N Church Ian Tomlinson Mark Saunders Tim J Iveson Joanne Edwards |
| author_sort | Antonia K Roseweir |
| collection | DOAJ |
| description | Abstract Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I–III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease‐free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II–III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893‐patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146‐patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (pinteraction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy. |
| first_indexed | 2024-12-12T05:43:29Z |
| format | Article |
| id | doaj.art-86ccccce88334b4890153382c13043e0 |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-12-12T05:43:29Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-86ccccce88334b4890153382c13043e02022-12-22T00:35:51ZengWileyThe Journal of Pathology: Clinical Research2056-45382020-10-016428329610.1002/cjp2.171Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancerAntonia K Roseweir0James H Park1Sanne ten Hoorn2Arfon GMT Powell3Susan Aherne4Campbell SD Roxburgh5Donald C McMillan6Paul G Horgan7Elizabeth Ryan8Kieran Sheahan9Louis Vermeulen10James Paul11Andrea Harkin12Janet Graham13Owen Sansom14David N Church15Ian Tomlinson16Mark Saunders17Tim J Iveson18Joanne Edwards19School of Medicine University of Glasgow Glasgow UKSchool of Medicine University of Glasgow Glasgow UKLaboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Amsterdam UMC University of Amsterdam, Cancer Center Amsterdam, Oncode Institute Amsterdam The NetherlandsDivision of Cancer and Genetics Cardiff University Cardiff UKSchool of Medicine University College Dublin and Centre for Colorectal Disease, St Vincent's University Hospital Dublin IrelandSchool of Medicine University of Glasgow Glasgow UKSchool of Medicine University of Glasgow Glasgow UKSchool of Medicine University of Glasgow Glasgow UKSchool of Medicine University College Dublin and Centre for Colorectal Disease, St Vincent's University Hospital Dublin IrelandSchool of Medicine University College Dublin and Centre for Colorectal Disease, St Vincent's University Hospital Dublin IrelandLaboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Amsterdam UMC University of Amsterdam, Cancer Center Amsterdam, Oncode Institute Amsterdam The NetherlandsCRUK Clinical Trials Unit The Beatson West of Scotland Cancer Centre, Gartnavel Hospital Glasgow UKCRUK Clinical Trials Unit The Beatson West of Scotland Cancer Centre, Gartnavel Hospital Glasgow UKCRUK Clinical Trials Unit The Beatson West of Scotland Cancer Centre, Gartnavel Hospital Glasgow UKInstitute of Cancer Sciences University of Glasgow Glasgow UKWellcome Centre for Human Genetics University of Oxford Oxford UKEdinburgh Cancer Research Centre, IGMM University of Edinburgh Edinburgh UKThe Christie NHS Foundation Trust Manchester UKSouthampton University Hospital NHS Foundation Trust Southampton UKInstitute of Cancer Sciences University of Glasgow Glasgow UKAbstract Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I–III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease‐free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II–III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893‐patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146‐patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (pinteraction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy.https://doi.org/10.1002/cjp2.171colorectal cancersubtypinghistopathologyadjuvant treatmentrecurrenceprecision medicine |
| spellingShingle | Antonia K Roseweir James H Park Sanne ten Hoorn Arfon GMT Powell Susan Aherne Campbell SD Roxburgh Donald C McMillan Paul G Horgan Elizabeth Ryan Kieran Sheahan Louis Vermeulen James Paul Andrea Harkin Janet Graham Owen Sansom David N Church Ian Tomlinson Mark Saunders Tim J Iveson Joanne Edwards Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer The Journal of Pathology: Clinical Research colorectal cancer subtyping histopathology adjuvant treatment recurrence precision medicine |
| title | Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer |
| title_full | Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer |
| title_fullStr | Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer |
| title_full_unstemmed | Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer |
| title_short | Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer |
| title_sort | histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage iii colorectal cancer |
| topic | colorectal cancer subtyping histopathology adjuvant treatment recurrence precision medicine |
| url | https://doi.org/10.1002/cjp2.171 |
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