Intratumoural immune signature to identify patients with primary colorectal cancer who do not require follow-up after resection: an observational study

Accepted/In Press date: 1 June 2020

Published date: 1 January 2021

Additional Information: Funding Information: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 2. See the NIHR Journals Library website for further project information. Funding Information: The initial intention was to manually count cells using a standard microscope. Although this proved possible, rapidly became clear that the time required for the project was not feasible. Our calculation was that counting 17 TMAs for two antibodies only would take around 480 hours or 80 6-hour days. Consideration was given to using a ‘citizen science’-type programme,19 but there were no resources to organise such a complex system. In 2015, it became clear that automated analysis was coming to the fore, and in 2016 a Digital Pathology Accelerator award to Belfast and Southampton enabled appropriate hardware and software to be installed. Attempts were made to scan the TMAs on a Zeiss Axio Scan.Z120 (ZEISS, Oberkochen, Germany) whole-slide scanner at resolution equivalent to ×20 magnification. Initial image analysis was carried out using QuPath (developed at the University of Edinburgh; originally created at the Centre for Cancer Research & Cell Biology at Queen’s University Belfast as part of research projects funded by Invest Northern Ireland and Cancer Research UK).21 Unfortunately, neither the hardware nor the software functioned correctly. Funding Information: The original FACS proposal did not include funding to obtain tissue from the primary tumours of the patients in the study but the ethics permissions and patient consent allowed for this. The present grant funding enabled the collection of tissue blocks from the centres. This work was undertaken by the Southampton Clinical Trials Unit and tissue stored in the Human Tissue Authority-registered Southampton Tissue Bank until used. Funding Information: part of research projects funded by Invest Northern Ireland and Cancer Research UK). Various technical issues were encountered, including misregistration of the tissue microarray cores by the software (requiring manual relocation, which was a prolonged exercise). Some preliminary data were obtained on 287 patients prior to the scientist running the scanner relocating. These results represent only part of the cohort and, as such, are unsuitable for publication. However, they give an indication that a signal is present which warrants pursuing the project further. Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 11/136/83. The contractual start date was in January 2013. The draft report began editorial review in July 2019 and was accepted for publication in June 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Publisher Copyright: © Queen’s Printer and Controller of HMSO 2021.

Keywords: BIOMARKERS, HUMAN, CELL COUNT, COLORECTAL NEOPLASMS, COLORECTAL SURGERY, RECURRENCE, STAINING AND LABELLING, T LYMPHOCYTES, TISSUE MICROARRAY, TUMOUR INFILTRATING T LYMPHOCYTES

Local EPrints ID: 446476

URI: http://eprints.soton.ac.uk/id/eprint/446476

DOI: doi:10.3310/hta25020

ISSN: 1366-5278

PURE UUID: 5abc0c04-8853-48ff-a3c3-90cf94ae59fe

ORCID for John N Primrose: orcid.org/0000-0002-2069-7605

Date deposited: 11 Feb 2021 17:30

Last modified: 17 Mar 2024 02:40