title: Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors: Matthew D
authors: MD
authors: Hale
authors: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors: Matthew
authors: M
authors: Nankivell
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.|Department of Histopathology, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Gordon G
authors: GG
authors: Hutchins
authors: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors: Sally P
authors: SP
authors: Stenning
authors: Medical Research Council Clinical Trials Unit at University College London, London, UK.
authors: Ruth E
authors: RE
authors: Langley
authors: Gemeinschaftspraxis Pathologie, Starnberg, Germany.
authors: Wolfram
authors: W
authors: Mueller
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.|Department of Histopathology, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Nicholas P
authors: NP
authors: West
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors: Alexander I
authors: AI
authors: Wright
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.|Department of Histopathology, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Darren
authors: D
authors: Treanor
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.|Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
authors: Lindsay C
authors: LC
authors: Hewitt
authors: The Royal Marsden Hospital NHS Foundation Trust, London and Surrey, UK.
authors: William H
authors: WH
authors: Allum
authors: The Royal Marsden Hospital NHS Foundation Trust, London and Surrey, UK.
authors: David
authors: D
authors: Cunningham
authors: Department of Upper Gastrointestinal Surgery, St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors: Jeremy D
authors: JD
authors: Hayden
authors: Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.|Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.
authors: Heike I
authors: HI
authors: Grabsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016019:Survival Analysis
keywords: biomarker; neoadjuvant chemotherapy; oesophageal cancer; proportion of tumour; tumour stroma