Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer

Roseweir, A. K. et al. (2020) Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer. Journal of Pathology: Clinical Research, 6(4), pp. 283-296. (doi: 10.1002/cjp2.171) (PMID:32401426) (PMCID:PMC7578335)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James and Park, Mr James and Horgan, Professor Paul and McMillan, Professor Donald and Harkin, Mrs Andrea and Roseweir, Dr Antonia and Roxburgh, Professor Campbell and Edwards, Professor Joanne and Powell, Dr Arfon and Graham, Dr Janet and Sansom, Professor Owen
• Authors: Roseweir, A. K., Park, J. H., ten Hoorn, S., Powell, A. G.M.T., Aherne, S., Roxburgh, C. S.D., McMillan, D. C., Horgan, P. G., Ryan, E., Sheahan, K., Vermeulen, L., Paul, J., Harkin, A., Graham, J., Sansom, O., Church, D. N., Tomlinson, I., Saunders, M., Iveson, T. J., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Pathology: Clinical Research
• Publisher: Wiley
• ISSN: 2056-4538
• ISSN (Online): 2056-4538
• Published Online: 13 May 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journal of Pathology: Clinical Research 6(4): 283-296
• Publisher Policy: Reproduced under a Creative Commons license