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Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.

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Publication Date
2016-11
ICR Author
Cunningham, David
Author
Hale, MD
Nankivell, M
Hutchins, GG
Stenning, SP
Langley, RE
Mueller, W
West, NP
Wright, AI
Treanor, D
Hewitt, LC
Allum, WH
Cunningham, D
Hayden, JD
Grabsch, HI
Type
Journal Article
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Abstract
<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial 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.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.
URL
https://repository.icr.ac.uk/handle/internal/360
Collections
  • Clinical Studies
Licenseref URL
https://creativecommons.org/licenses/by/4.0
Version of record
10.18632/oncotarget.12723
Subject
Humans
Esophageal Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Biopsy
Prognosis
Combined Modality Therapy
Survival Analysis
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Clinical Trials as Topic
Neoplasm Grading
Research team
Medicine (RMH Smith Cunningham)
Language
eng
Date accepted
2016-10-01
License start date
2016-11
Citation
Oncotarget, 2016, 7 (47), pp. 77565 - 77575

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