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Recent advances in clinical practice
Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer
  1. Mark Lawler1,
  2. Deborah Alsina2,
  3. Richard A Adams3,
  4. Annie S Anderson4,
  5. Gina Brown5,
  6. Nicola S Fearnhead6,
  7. Stephen W Fenwick7,
  8. Stephen P Halloran8,
  9. Daniel Hochhauser9,
  10. Mark A Hull10,
  11. Viktor H Koelzer11,
  12. Angus G K McNair12,
  13. Kevin J Monahan13,
  14. Inke Näthke14,
  15. Christine Norton15,
  16. Marco R Novelli16,
  17. Robert J C Steele4,
  18. Anne L Thomas17,
  19. Lisa M Wilde2,18,
  20. Richard H Wilson1,
  21. Ian Tomlinson19
  22. on behalf of the Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative
    1. 1 Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
    2. 2 Bowel Cancer UK, London, UK
    3. 3 School of Medicine, Cardiff University, Cardiff, UK
    4. 4 Research into Cancer Prevention and Screening, University of Dundee, Dundee, UK
    5. 5 Department of Radiology, Royal Marsden Hospital, Sutton, UK
    6. 6 Department of Colorectal Surgery, Addenbrooke’s Hospital, Cambridge, UK
    7. 7 Hepatobiliary Surgery Unit, Aintree University Hospital, Liverpool, UK
    8. 8 Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
    9. 9 Department of Oncology, University College London Cancer Institute, London, UK
    10. 10 Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
    11. 11 Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK
    12. 12 Centre for Surgical Research, University of Bristol, Bristol, UK
    13. 13 Family History of Bowel Cancer Clinic, Imperial College London, London, UK
    14. 14 School of Life Sciences, University of Dundee, Dundee, UK
    15. 15 Florence Nightingale Faculty of Nursing and Midwifery, King’s College London, London, UK
    16. 16 Research Department of Pathology, University College London Medical School, London, UK
    17. 17 Leicester Cancer Research Centre, University of Leicester, Leicester, UK
    18. 18 Atticus Consultants Ltd, Croydon, UK
    19. 19 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
    1. Correspondence to Professor Mark Lawler, Centre for Cancer Research and Cell Biology Queen’s University Belfast, University Road, Belfast BT7 1NN, UK; mark.lawler{at}qub.ac.uk

    Abstract

    Objective Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.

    Design RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants.

    Results Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders.

    Conclusion Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.

    • colorectal cancer

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

    https://doi.org/10.1136/gutjnl-2017-315333

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      Footnotes

      • Contributors Conception and design of study: ML, DA, LMW, RHW, IT. Acquisition of data through questionnaires, attending meetings and drafting of initial reports: ML, DA, RAA, ASA, GB, NSF, SWF, SPH, DH, MAH, AGKM, KJM, IN, CN, MRN, RJCS, ALT, LMW, RHW, IT, SHA, JA, NA, WA, SB, LB, NB, VB, DB, KB, JB, JBC, IC, JC, AC, VC, DC, MD, JD, MD, CF, MG, AG, VG, DGdC, TG, JG, SH, WH, JH, RH, JH, GH, GH, RH, GH, TI, SI, TI, NJ, IJ, MJ, DL, UM, MM, JM, JM, TM, GM, BM, MM, PM, POS, CR, MR; LS, OS, JS, ES, RS, TS, AS, WS, PS, GS, CVW, AW, DW. Drafting of the manuscript: ML, DA, RAA, ASA, GB, NSF, SWF, SPH, DH, MAH, VHK, AGKM, KJM, IN, CN, MN, RJCS, ALT, LW, RHW, IT. Revising the manuscript critically for important intellectual content: ML, DA, RAA, ASA, GB, NSF, SWF, SPH, DH, MAH, VHK, AGKM, KJM, IN, CN, MN, RJCS, ALT, LW, RHW, IT. Approval of the version of the manuscript to be published: ML, DA, RAA, ASA, GB, NSF, SWF, SPH, DH, MAH, VHK, AGKM, KJM, IN, CN, MN, RJCS, ALT, LW, RHW, IT.

      • Funding The study was funded by Bowel Cancer UK, the Norman Foster Foundation and the Tom Simms Memorial Fund at Queen’s University Belfast.

      • Competing interests ML reports support from Pfizer, outside the submitted work; DA reports grants from the Norman Foster Foundation, grants from the Tom Simms Memorial Fund at Queen’s University Belfast, during the conduct of the study; Dr Andreyev reports other from Entrinsic Health Solutions, Inc and personal fees from Macmillan Cancer Support, outside the submitted work; Professor Atkin reports grants from Cancer Research UK, outside the submitted work; Mr Bach reports personal fees from Ethicon Inc, outside the submitted work; Professor Burn has a patent A novel panel of short coding repeats suitable for high-throughput detection of microsatellite instability pending to Newcastle University; Dr Chau reports grants from Eli-Lily, Janssen-Cilag, Sanofi Oncology, Merck-Serono, and Novartis, personal fees from Taiho, Pfizer, Amgen, Eli-Lily, outside the submitted work; Professor Cheadle has a patent MUTYH gene variants licensed to Myriad Genetics and receives royalties; Professor Cunningham reports grants from Amgen, AstraZeneca, Bayer, Celgene, Medimmune, Merck Serono, Merrimack, and Sanofi, outside the submitted work; Professor Fraser reports personal fees from Immunostics Inc, Ocean, NJ, USA, Kyowa, Tokyo, Japan, and support for travel from Alpha Labs Ltd, Eastleigh, Hants, UK, during the conduct of the study; DH reports MRC CASE Award with Merck Serono for project unrelated to this submission and research support from Merck Serono for project unrelated to this submission; MH reports other from consultancy for Thetis Pharma, outside the submitted work; CN reports personal fees from Takeda and Ferring, outside the submitted work; Dr Sharma reports grants, personal fees and other from Sirtex, grants, personal fees and other from BTG, during the conduct of the study; AT reports personal fees from BMS Advisory Board, Roche Speaker Panel, Amgen Advisory Board, and Servier Advisory Board, outside the submitted work; LMW reports personal fees from Atticus Consultants Ltd, during the conduct of the study; RW reports personal fees from BMS Advisory Board, Clovis Oncology Advisory Board, Halozyme Advisory Board, Amgen Advisory Board, Servier Advisory Board, and Sirtex Independent Data Monitoring and Safety Committee, all outside the submitted work. RA, Professor Ahmedzai, ASA, Mr Arbuthnot, Mrs Berkman, Miss Bloor, Mr Boulter, Mrs Cole, Dr Brewster, GB, Professor Cazier, Dr Coyle, Mr Davies, Professor Downward, Professor Dunlop, NSF, SF, Dr Gerlinger, Dr Glaser, Professor Goh, Professor González De Castro, Dr Graham, Mr Griffith, Professor Halligan, SPH, Professor Hamilton, Mrs Hepburn, Dr Hold, Mr Holden, Professor Houlston, Dr Hubbard, Dr Iqbal, Dr Irvine, Dr Iveson, Mr Jackson, Mr Jakowiw, Mrs Jefford, Professor Longley, Dr McDermott, AGKM, Mr Machesney, Professor Maher, Professor Marchesi, Professor Maughan, Professor Middleton, Mr Moss, Mrs Moss, KJM, Dr Murchie, IN, MRN, Mr O’Sullivan, Mr Robertson, Professor Rutter, Dr Sansom, Dr Samuel, Professor Saxton, Dr Seward, Mrs Smith, Dr Sottoriva, RS, Professor Steward, Mr Stocker, Mrs Sweetman, IT, Dr Von Wagner and Professor Williams have nothing to disclose.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Collaborators Working Group members (* denotes Bowel Cancer UK Medical Advisory Board member, + denotes Bowel Cancer UK Scientific Advisory Board member, and β denotes former or current Bowel Cancer UK Trustee): Professor Emeritus Sam H Ahmedzai, Dr Jervoise Andreyev*, Professor Wendy Atkin*, Mr Simon Bach, Dr David Brewster, Professor Karen Brown, Professor Sir John Burn*+, Professor Jean-Baptiste Cazier, Dr Ian Chau, Professor Jeremy Cheadle, Dr Vicky Coyle, Professor David Cunningham, Professor Julian Downward, Professor Malcom Dunlop, Professor Callum Fraser, Dr Marco Gerlinger, Dr Adam Glaser, Professor Vicky Goh, Professor David González de Castro, Professor Trevor Graham, Mr John Griffith, Professor Steve Halligan, Professor Willie Hamilton*, Mrs Rachel Haynes, Dr Georgina Hold, Professor Richard Houlston, Dr Gill Hubbard, Dr Tariq Iqba, Mrs Sandra Irvine, Dr Tim Iveson*, Professor Dan Longley, Dr Ultan McDermott, Mr Michael Machesney*, Professor Jane Maher, Professor Julian Marchesi, Professor Tim Maughan, Professor Gary Middleton, Mrs Barbara Moss, Mr Mark Moss, Dr Peter Murchie, Professor Matt Rutter, Dr Leslie Samuel, Professor Owen Sansom, Professor John Saxton, Dr Ed Seward, Dr Ricky Sharma, Dr Andrea Sottoriva, Professor Will Steward, Dr Christian Von Wagner, Professor Ann Williams, and Professor Doug Winton. BCUK-RG Evaluation Day participants: Mr Nicholas Arbuthnot, Mrs Lindy Berkman, Miss Nicola Bloor, Mr Victor Boulter, Mrs Ann Cole, Mr Mark Davies, Mrs Julie Hepburn, Mr Joe Higginsβ, Mr Georgy Holden, Dr Alexandra E Irvine, Mr Nick Jakowiw, Mr Ian Jackson, Mrs Monica Jefford, Mrs Barbara Moss, Mr Mark Moss, Mr Peter O’Sullivan, Mr Clint Robertson, Mrs Tracy Smith, Mr Phil Stocker, and Mrs Gillian Sweetman.