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Histological intratumoral heterogeneity in pretreatment esophageal cancer biopsies predicts survival benefit from neoadjuvant chemotherapy: results from the UK MRC OE02 trial

Davarzani, N; Hewitt, LC; Hale, MD; Melotte, V; Nankivell, M; Hutchins, GGA; Cunningham, D; ... Grabsch, H; + view all (2020) Histological intratumoral heterogeneity in pretreatment esophageal cancer biopsies predicts survival benefit from neoadjuvant chemotherapy: results from the UK MRC OE02 trial. Diseases of the Esophagus , 33 (8) , Article doaa058. 10.1093/dote/doaa058. Green open access

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Abstract

Despite the use of multimodal treatment, survival of esophageal cancer (EC) patients remains poor. One proposed explanation for the relatively poor response to cytotoxic chemotherapy is intratumor heterogeneity. The aim was to establish a statistical model to objectively measure intratumor heterogeneity of the proportion of tumor (IHPoT) and to use this newly developed method to measure IHPoT in the pretreatment biopsies from from EC patients recruited to the OE02 trial. A statistical mixed effect model (MEM) was established for estimating IHPoT based on variation in hematoxylin/eosin (HE) stained pretreatment biopsy pieces from the same individual in 218 OE02 trial patients (103 treated by chemotherapy and surgery (chemo+surgery); 115 patients treated by surgery alone). The relationship between IHPoT, prognosis, chemotherapy survival benefit, and clinicopathological variables was assessed. About 97 (44.5%) and 121 (55.5%) ECs showed high and low IHPoT, respectively. There was no significant difference in IHPoT between surgery (median [range], 0.1637 [0–3.17]) and chemo+surgery (median [range], 0.1692 [0–2.69]) patients (P = 0.43). Chemo+surgery patients with low IHPoT had a significantly longer survival than surgery patients (HR = 1.81, 95% CI: 1.20–2.75, P = 0.005). There was no survival difference between chemo+surgery and surgery patients with high IHPoT (HR = 1.15, 95% CI: 0.72–1.81, P = 0.566). This is the first study suggesting that IHPoT measured in the pretreatment biopsy can predict chemotherapy survival benefit in EC patients. IHPoT may represent a clinically useful biomarker for patient treatment stratification. Future studies should determine if pathologists can reliably estimate IHPoT.

Type: Article
Title: Histological intratumoral heterogeneity in pretreatment esophageal cancer biopsies predicts survival benefit from neoadjuvant chemotherapy: results from the UK MRC OE02 trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/dote/doaa058
Publisher version: https://doi.org/10.1093/dote/doaa058
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10125081
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