Hale, MD, Nankivell, M, Hutchins, GG et al. (11 more authors) (2016) Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma –results from the UK MRC OE02 trial. Oncotarget, 7 (47). pp. 77565-77575. ISSN 1949-2553
Abstract
Background Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. Patients and methods PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. Results PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0·006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1·94 (1·39-2·71), unlike those with lower or higher PoT (PoT<40%, N=39, HR:1·25 (0·66-2·35); PoT>70% (N=28, HR:0·65 (0·36-1·18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0·0402. Conclusion This is the first study to identify in a representative subgroup of patients from a large randomized phase III trial in OeC patients that the proportion of tumour in the pre- chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification. Key message Proportion of tumour is a novel biomarker which can be measured in the pre- treatment diagnostic biopsy and which may enable the identification of chemotherapy responders and non-responders among patients with oesophageal carcinoma. Proportion of tumour could easily become part of the routine reporting of oesophageal cancer biopsies and may aid in managing patients with borderline resectable cancer.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, The Author(s). This article is licensed under a Creative Commons Attribution 3.0 License. |
Keywords: | oesophageal cancer; proportion of tumour; neoadjuvant chemotherapy; biomarker; tumour stroma |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK C26441/A8944 Yorkshire Cancer Research L386 |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Oct 2016 10:46 |
Last Modified: | 05 Oct 2017 16:22 |
Published Version: | http://dx.doi.org/10.18632/oncotarget.12723 |
Status: | Published |
Publisher: | Impact Journals |
Identification Number: | 10.18632/oncotarget.12723 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:105702 |