Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Mark Lawler, Deborah Alsina, Richard A Adams, Annie S Anderson, Gina Brown, Nicola S Fearnhead, Stephen W Fenwick, Stephen P Halloran, Daniel Hochhauser, Mark A Hull, Viktor H Koelzer, Angus G K McNair, Kevin J Monahan, Inke Näthke, Christine Norton, Marco R Novelli, Robert J C Steele, Anne L Thomas, Lisa M Wilde, Richard H Wilson, Ian Tomlinson, Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative, Sam H Ahmedzai, Jervoise Andreyev, Nicholas Arbuthnot, Wendy Atkin, Simon Bach, Lindy Berkman, Nicola Bloor, Victor Boulter, David Brewster, Karen Brown, John Burn, Jean-Baptiste Cazier, Ian Chau, Jeremy Cheadle, Ann Cole, Vicky Coyle, David Cunningham, Mark Davies, Julian Downward, Malcom Dunlop, Callum Fraser, Marco Gerlinger, Adam Glaser, Vicky Goh, David González De Castro, Trevor Graham, John Griffith, Steve Halligan, Willie Hamilton, Julie Hepburn, Rachel Haynes, Joe Higgins, Georgina Hold, Georgy Holden, Richard Houlston, Gill Hubbard, Tariq Iqba, Alexandra E Irvine, Tim Iveson, Nick Jakowiw, Ian Jackson, Monica Jefford, Dan Longley, Ultan Mcdermott, Michael Machesney, Jane Maher, Julian Marchesi, Tim Maughan, Gary Middleton, Barbara Moss, Mark Moss, Peter Murchie, Peter O'sullivan, Clint Robertson, Matt Rutter, Leslie Samuel, Owen Sansom, John Saxton, Ed Seward, Ricky Sharma, Tracy Smith, Andrea Sottoriva, Will Steward, Phil Stocker, Gillian Sweetman, Christian Von Wagner, Ann Williams, Doug Winton, Mark Lawler, Deborah Alsina, Richard A Adams, Annie S Anderson, Gina Brown, Nicola S Fearnhead, Stephen W Fenwick, Stephen P Halloran, Daniel Hochhauser, Mark A Hull, Viktor H Koelzer, Angus G K McNair, Kevin J Monahan, Inke Näthke, Christine Norton, Marco R Novelli, Robert J C Steele, Anne L Thomas, Lisa M Wilde, Richard H Wilson, Ian Tomlinson, Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative, Sam H Ahmedzai, Jervoise Andreyev, Nicholas Arbuthnot, Wendy Atkin, Simon Bach, Lindy Berkman, Nicola Bloor, Victor Boulter, David Brewster, Karen Brown, John Burn, Jean-Baptiste Cazier, Ian Chau, Jeremy Cheadle, Ann Cole, Vicky Coyle, David Cunningham, Mark Davies, Julian Downward, Malcom Dunlop, Callum Fraser, Marco Gerlinger, Adam Glaser, Vicky Goh, David González De Castro, Trevor Graham, John Griffith, Steve Halligan, Willie Hamilton, Julie Hepburn, Rachel Haynes, Joe Higgins, Georgina Hold, Georgy Holden, Richard Houlston, Gill Hubbard, Tariq Iqba, Alexandra E Irvine, Tim Iveson, Nick Jakowiw, Ian Jackson, Monica Jefford, Dan Longley, Ultan Mcdermott, Michael Machesney, Jane Maher, Julian Marchesi, Tim Maughan, Gary Middleton, Barbara Moss, Mark Moss, Peter Murchie, Peter O'sullivan, Clint Robertson, Matt Rutter, Leslie Samuel, Owen Sansom, John Saxton, Ed Seward, Ricky Sharma, Tracy Smith, Andrea Sottoriva, Will Steward, Phil Stocker, Gillian Sweetman, Christian Von Wagner, Ann Williams, Doug Winton

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.

Keywords: colorectal cancer.

Conflict of interest statement

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.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative process.

References

    1. Arnold M, Sierra MS, Laversanne M, et al. . Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66:683–91. 10.1136/gutjnl-2015-310912
    1. Cancer Research UK. Bowel cancer statistics. (accessed 08 Sep 2017).
    1. The American Cancer Society. (accessed 08 Sep 2017).
    1. Mariotto AB, Yabroff KR, Shao Y, et al. . Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst 2011;103:117–28. 10.1093/jnci/djq495
    1. Luengo-Fernandez R, Leal J, Gray A, et al. . Economic burden of cancer across the European Union: a population-based cost analysis. Lancet Oncol 2013;14:1165–74. 10.1016/S1470-2045(13)70442-X
    1. National Cancer Institute. (accessed 08 Sep 2017).
    1. Cancer Research UK. How much we spend on research. (accessed 08 Sep 2017).
    1. Eccles SA, Aboagye EO, Ali S, et al. . Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Res 2013;15:R92 10.1186/bcr3493
    1. Lobert VH, Mouradov D, Heath JK. Focusing the spotlight on the zebrafish intestine to illuminate mechanisms of colorectal cancer. Adv Exp Med Biol 2016;916:411–37. 10.1007/978-3-319-30654-4_18
    1. Rasmussen LJ, Heinen CD, Royer-Pokora B, et al. . Pathological assessment of mismatch repair gene variants in Lynch syndrome: past, present, and future. Hum Mutat 2012;33:1617–25. 10.1002/humu.22168
    1. Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 2017;169:985–99. 10.1016/j.cell.2017.05.016
    1. Maccaroni E, Bracci R, Giampieri R, et al. . Prognostic impact of mismatch repair genes germline defects in colorectal cancer patients: are all mutations equal? Oncotarget 2015;6:38737–48. 10.18632/oncotarget.5395
    1. Guinney J, Dienstmann R, Wang X, et al. . The consensus molecular subtypes of colorectal cancer. Nat Med 2015;21:1350–6. 10.1038/nm.3967
    1. Isella C, Brundu F, Bellomo SE, et al. . Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer. Nat Commun 2017;8:15107 10.1038/ncomms15107
    1. Dunne PD, Alderdice M, O’Reilly PG, et al. . Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification. Nat Commun 2017;8:15657 10.1038/ncomms15657
    1. Isella C, Terrasi A, Bellomo SE, et al. . Stromal contribution to the colorectal cancer transcriptome. Nat Genet 2015;47:312–9. 10.1038/ng.3224
    1. Calon A, Lonardo E, Berenguer-Llergo A, et al. . Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 2015;47:320–9. 10.1038/ng.3225
    1. Dunne PD, McArt DG, Bradley CA, et al. . Challenging the cancer molecular stratification dogma: intratumoral heterogeneity undermines consensus molecular subtypes and potential diagnostic value in colorectal cancer. Clin Cancer Res 2016;22:4095–104. 10.1158/1078-0432.CCR-16-0032
    1. Naxerova K, Reiter JG, Brachtel E, et al. . Origins of lymphatic and distant metastases in human colorectal cancer. Science 2017;357:55–60. 10.1126/science.aai8515
    1. Villalba M, Evans SR, Vidal-Vanaclocha F, et al. . Role of TGF-β in metastatic colon cancer: it is finally time for targeted therapy. Cell Tissue Res 2017:29–39. 10.1007/s00441-017-2633-9
    1. Hong AW, Meng Z, Guan KL. The Hippo pathway in intestinal regeneration and disease. Nat Rev Gastroenterol Hepatol 2016;13:324–37. 10.1038/nrgastro.2016.59
    1. Xia T, Konno H, Ahn J, et al. . Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep 2016;14:282–97. 10.1016/j.celrep.2015.12.029
    1. Jackstadt R, Sansom OJ. Mouse models of intestinal cancer. J Pathol 2016;238:141–51. 10.1002/path.4645
    1. Su LK, Kinzler KW, Vogelstein B, et al. . Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992;256:1114.
    1. Bertotti A, Migliardi G, Galimi F, et al. . A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 2011;1:508–23. 10.1158/-11-0109
    1. Sato T, Vries RG, Snippert HJ, et al. . Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262–5. 10.1038/nature07935
    1. Omar Al-Hassi H, Ng O, Brookes M. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 2017. (Epub ahead of print: 04 May 2017). 10.1136/gutjnl-2017-314219
    1. Simonds NI, Ghazarian AA, Pimentel CB, et al. . Review of the gene-environment interaction literature in cancer: what do we know? Genet Epidemiol 2016;40:356–65. 10.1002/gepi.21967
    1. Peters U, Bien S, Zubair N, et al. . Genetic architecture of colorectal cancer. Gut 2015;64:1623–36. 10.1136/gutjnl-2013-306705
    1. Chubb D, Broderick P, Dobbins SE, et al. . Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. Nat Commun 2016;7:11883 10.1038/ncomms11883
    1. Vogtmann E, Goedert JJ. Epidemiologic studies of the human microbiome and cancer. Br J Cancer 2016;114:237–42. 10.1038/bjc.2015.465
    1. Torres Stone RA, Waring ME, Cutrona SL, et al. . The association of dietary quality with colorectal cancer among normal weight, overweight and obese men and women: a prospective longitudinal study in the USA. BMJ Open 2017;7:e015619 10.1136/bmjopen-2016-015619
    1. Aleksandrova K, Pischon T, Jenab M, et al. . Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study. BMC Med 2014;12:168 10.1186/s12916-014-0168-4
    1. van Duijnhoven FJ, Bueno-De-Mesquita HB, Calligaro M, et al. . Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition. Gut 2011;60:1094–102. 10.1136/gut.2010.225011
    1. González N, Prieto I, Del Puerto-Nevado L, et al. . 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget 2017;8:18456–85. 10.18632/oncotarget.14472
    1. Nan H, Hutter CM, Lin Y, et al. . Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA 2015;313:1133–42. 10.1001/jama.2015.1815
    1. Weinberg DS, Myers RE, Keenan E, et al. . Genetic and environmental risk assessment and colorectal cancer screening in an average-risk population: a randomized trial. Ann Intern Med 2014;161:537–45. 10.7326/M14-0765
    1. Cancer Prevention Program. Genetics and epidemiology of colorectal cancer consortium (GECCO). (accessed 08 Sep 2017).
    1. National Cancer Institute. Epidemiology and genomics research program. (accessed 08 Sep 2017).
    1. Zeng C, Matsuda K, Jia WH, et al. . Identification of susceptibility loci and genes for colorectal cancer risk. Gastroenterology 2016;150:1633–45. 10.1053/j.gastro.2016.02.076
    1. Hsu L, Jeon J, Brenner H, et al. . A model to determine colorectal cancer risk using common genetic susceptibility loci. Gastroenterology 2015;148:1330–9. 10.1053/j.gastro.2015.02.010
    1. Scarbrough PM, Weber RP, Iversen ES, et al. . A cross-cancer genetic association analysis of the DNA repair and DNA damage signaling pathways for lung, ovary, prostate, breast, and colorectal cancer. Cancer Epidemiol Biomarkers Prev 2016;25:193–200. 10.1158/1055-9965.EPI-15-0649
    1. Zhang B, Jia WH, Matsuda K, et al. . Large-scale genetic study in east asians identifies six new loci associated with colorectal cancer risk. Nat Genet 2014;46:533–42. 10.1038/ng.2985
    1. Wang H, Burnett T, Kono S, et al. . Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun 2014;5:4613 10.1038/ncomms5613
    1. Evans DG, Brentnall A, Byers H, et al. . The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study. J Med Genet 2017;54:111–3. 10.1136/jmedgenet-2016-104125
    1. Shi J, Park JH, Duan J, et al. . Winner’s curse correction and variable thresholding improve performance of polygenic risk modeling based on genome-wide association study summary-level data. PLoS Genet 2016;12:e1006493 10.1371/journal.pgen.1006493
    1. Kantor ED, Hutter CM, Minnier J, et al. . Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci. Cancer Epidemiol Biomarkers Prev 2014;23:1824–33. 10.1158/1055-9965.EPI-14-0062
    1. Figueiredo JC, Hsu L, Hutter CM, et al. . on behalf of CCFR; GECCO. Genome-wide diet-gene interaction analyses for risk of colorectal cancer. PLoS Genet 2014;10:e1004228.
    1. Park SY, Boushey CJ, Wilkens LR, et al. . High-quality diets associate with reduced risk of colorectal cancer: analyses of diet quality indexes in the multiethnic cohort. Gastroenterology 2017;153:386–94. 10.1053/j.gastro.2017.04.004
    1. Gong J, Hutter CM, Newcomb PA, et al. . Genome-wide interaction analyses between genetic variants and alcohol consumption and smoking for risk of colorectal cancer. PLoS Genet 2016;12:e1006296 10.1371/journal.pgen.1006296
    1. Monahan KJ, Alsina D, Bach S, et al. . Urgent improvements needed to diagnose and manage Lynch syndrome. BMJ 2017;356:j1388 10.1136/bmj.j1388
    1. Chamnan P, Simmons RK, Khaw KT, et al. . Estimating the population impact of screening strategies for identifying and treating people at high risk of cardiovascular disease: modelling study. BMJ 2010;340:c1693 10.1136/bmj.c1693
    1. Anderson AS, Caswell S, Macleod M, et al. . Awareness of lifestyle and colorectal cancer risk: findings from the BeWEL study. Biomed Res Int 2015;2015:1–5. 10.1155/2015/871613
    1. National Cancer Research Center. How was research funding from NCRI Partners spent in 2015? (accessed 08 Sep 2017).
    1. Movahedi M, Bishop DT, Macrae F, et al. . Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: a prospective investigation in the CAPP2 study. J Clin Oncol 2015;33:3591–7. 10.1200/JCO.2014.58.9952
    1. World Cancer Research Fund. How was research funding from NCRI Partners spent in 2015? (accessed 08 Sep 2017).
    1. Garrett WS. Cancer and the microbiota. Science 2015;348:80–6. 10.1126/science.aaa4972
    1. Arnold M, Leitzmann M, Freisling H, et al. . Obesity and cancer: An update of the global impact. Cancer Epidemiol 2016;41:8–15. 10.1016/j.canep.2016.01.003
    1. Ma Y, Yang Y, Wang F, et al. . Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One 2013;8:e53916 10.1371/journal.pone.0053916
    1. Lauby-Secretan B, Scoccianti C, Loomis D, et al. . Body fatness and cancer-viewpoint of the IARC working group. N Engl J Med 2016;375:794–8. 10.1056/NEJMsr1606602
    1. Wolin KY, Yan Y, Colditz GA, et al. . Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer 2009;100:611–6. 10.1038/sj.bjc.6604917
    1. Burn J, Gerdes AM, Macrae F, et al. . Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011;378:2081–7. 10.1016/S0140-6736(11)61049-0
    1. Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer 2016;16:173–86. 10.1038/nrc.2016.4
    1. Bibbins-Domingo K, U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 2016;164:836–45. 10.7326/M16-0577
    1. Cuzick J, Thorat MA, Bosetti C, et al. . Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2015;26:47–57. 10.1093/annonc/mdu225
    1. Smith SG, Foy R, McGowan J, et al. . General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey. Fam Cancer 2017:509–16. 10.1007/s10689-017-9986-9
    1. Patterson RE, Colditz GA, Hu FB, et al. . The 2011-2016 transdisciplinary research on energetics and cancer (TREC) initiative: rationale and design. Cancer Causes Control 2013;24:695–704. 10.1007/s10552-013-0150-z
    1. Bhatt AP, Redinbo MR, Bultman SJ. The role of the microbiome in cancer development and therapy. CA Cancer J Clin 2017;67:326–44. 10.3322/caac.21398
    1. Bultman SJ. The microbiome and its potential as a cancer preventive intervention. Semin Oncol 2016;43:97–106. 10.1053/j.seminoncol.2015.09.001
    1. Moug SJ, Bryce A, Mutrie N, et al. . Lifestyle interventions are feasible in patients with colorectal cancer with potential short-term health benefits: a systematic review. Int J Colorectal Dis 2017;32:765–75. 10.1007/s00384-017-2797-5
    1. Anderson AS, Mackison D, Boath C, et al. . Promoting changes in diet and physical activity in breast and colorectal cancer screening settings: an unexplored opportunity for endorsing healthy behaviors. Cancer Prev Res 2013;6:165–72. 10.1158/1940-6207.CAPR-12-0385
    1. Benson VS, Atkin WS, Green J, et al. . And international colorectal cancer screening network. toward standardizing and reporting colorectal cancer screening indicators on an international level: the international colorectal cancer screening network. Int J Cancer 2012;130:2961–73.
    1. Moss S, Mathews C, Day TJ, et al. . Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England. Gut 2017;66:1631–44. 10.1136/gutjnl-2015-310691
    1. Digby J, Fraser CG, Carey FA, et al. . Interval cancers using a quantitative faecal immunochemical test (FIT) for haemoglobin when colonoscopy capacity is limited. J Med Screen 2016;23:130–4. 10.1177/0969141315609634
    1. Atkin W, Wooldrage K, Parkin DM, et al. . Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK flexible sigmoidoscopy screening randomised controlled trial. Lancet 2017;389:1299–311. 10.1016/S0140-6736(17)30396-3
    1. Peacock O, Clayton S, Atkinson F, et al. . ’Be Clear on Cancer': the impact of the UK national bowel cancer awareness campaign. Colorectal Dis 2013;15:963–7. 10.1111/codi.12220
    1. Bethune R, Marshall MJ, Mitchell SJ, et al. . Did the ’be clear on bowel cancer' public awareness campaign pilot result in a higher rate of cancer detection? Postgrad Med J 2013;89:390–3. 10.1136/postgradmedj-2012-131014
    1. Mowat C, Digby J, Strachan JA, et al. . Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut 2016;65:1463–9. 10.1136/gutjnl-2015-309579
    1. NICE. Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care. (accessed 08 Sep 2017).
    1. Bretthauer M, Kaminski MF, Løberg M, et al. . Nordic-european initiative on colorectal cancer (NordICC) study group. population-based colonoscopy screening for colorectal cancer: a randomized clinical trial. JAMA Intern Med 2016;176:894–902.
    1. You JJ, Liu Y, Kirby J, et al. . Virtual colonoscopy, optical colonoscopy, or fecal occult blood testing for colorectal cancer screening: results of a pilot randomized controlled trial. Trials 2015;16:296 10.1186/s13063-015-0826-7
    1. Sali L, Mascalchi M, Falchini M, et al. . Reduced and full-preparation CT colonography, fecal immunochemical test, and colonoscopy for population screening of colorectal cancer: a randomized trial. J Natl Cancer Inst 2016;108:djv319 10.1093/jnci/djv319
    1. Hewitson P, Glasziou P, Watson E, et al. . Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol 2008;103:1541–9. 10.1111/j.1572-0241.2008.01875.x
    1. McDonald PJ, Strachan JA, Digby J, et al. . Faecal haemoglobin concentrations by gender and age: implications for population-based screening for colorectal cancer. Clin Chem Lab Med 2011;50:935–40. 10.1515/CCLM.2011.815
    1. Birks J, Bankhead C, Holt TA, et al. . Evaluation of a prediction model for colorectal cancer: retrospective analysis of 2.5 million patient records. Cancer Med 2017;6:2453–60. 10.1002/cam4.1183
    1. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. . Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014;370:1287–97. 10.1056/NEJMoa1311194
    1. Song L, Yu H, Jia J, et al. . A systematic review of the performance of the SEPT9 gene methylation assay in colorectal cancer screening, monitoring, diagnosis and prognosis. Cancer Biomark 2017;18:425–32. 10.3233/CBM-160321
    1. Sonoda H, Kohnoe S, Yamazato T, et al. . Colorectal cancer screening with odour material by canine scent detection. Gut 2011;60:814–9. 10.1136/gut.2010.218305
    1. Tan CR, Zhou L, El-Deiry WS. Circulating tumor cells versus circulating tumor DNA in colorectal cancer: pros and cons. Curr Colorectal Cancer Rep 2016;12:151–61. 10.1007/s11888-016-0320-y
    1. Yu J, Feng Q, Wong SH, et al. . Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 2017;66:70–8. 10.1136/gutjnl-2015-309800
    1. Muguruma N, Tanaka K, Teramae S, et al. . Colon capsule endoscopy: toward the future. Clin J Gastroenterol 2017;10:1–6. 10.1007/s12328-016-0710-3
    1. Tie J, Wang Y, Tomasetti C, et al. . Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 2016;8:346ra92 10.1126/scitranslmed.aaf6219
    1. Schøler LV, Reinert T, Ørntoft MW, et al. . Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer. Clin Cancer Res 2017;23:5437–45. 10.1158/1078-0432.CCR-17-0510
    1. Brierley JD, Gospodarowicz MK, Wittekind C, TNM classification of malignant tumours. 8th ed Oxford: Wiley-Blackwell, 2016.
    1. Edge SB. American Joint Committee on Cancer AJCC cancer staging manual. 7th ed New York: Springer, 2010.
    1. Lugli A, Kirsch R, Ajioka Y, et al. . Recommendations for reporting tumor budding in colorectal cancer based on the international tumor budding consensus conference (ITBCC) 2016. Mod Pathol 2017;30:1299–311. 10.1038/modpathol.2017.46
    1. Galon J, Mlecnik B, Bindea G, et al. . Towards the introduction of the ’Immunoscore' in the classification of malignant tumours. J Pathol 2014;232:199–209. 10.1002/path.4287
    1. Pathology and prognostic determinants of colorectal cancer. (accessed 08 Sep 2017).
    1. Amin MB, Greene FL, Edge SB, et al. . The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67:93–9. 10.3322/caac.21388
    1. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330–7. 10.1038/nature11252
    1. Paasinen-Sohns A, Koelzer VH, Frank A, et al. . Single-center experience with a targeted next generation sequencing assay for assessment of relevant somatic alterations in solid tumors. Neoplasia 2017;19:196–206. 10.1016/j.neo.2017.01.003
    1. De Roock W, De Vriendt V, Normanno N, et al. . KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol 2011;12:594–603. 10.1016/S1470-2045(10)70209-6
    1. Lee AM, Shi Q, Pavey E, et al. . DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147). J Natl Cancer Inst 2014;106:dju298 10.1093/jnci/dju298
    1. Yeh YS, Tsai HL, Huang CW, et al. . Prospective analysis of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab plus FOLFIRI as the first-line setting: study protocol for a randomized controlled trial. Trials 2016;17:17–46. 10.1186/s13063-016-1153-3
    1. Le DT, Uram JN, Wang H, et al. . PD-1 Blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509–20. 10.1056/NEJMoa1500596
    1. De Sousa E Melo F, Wang X, Jansen M, et al. . Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013;19:614–8. 10.1038/nm.3174
    1. Sadanandam A, Lyssiotis CA, Homicsko K, et al. . A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013;19:619–25. 10.1038/nm.3175
    1. Marisa L, de Reyniès A, Duval A, et al. . Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013;10:e1001453 10.1371/journal.pmed.1001453
    1. Li G, Bankhead P, Dunne PD, et al. . Embracing an integromic approach to tissue biomarker research in cancer: Perspectives and lessons learned. Brief Bioinform 2017;18:634–46. 10.1093/bib/bbw044
    1. Harpaz N, Polydorides AD. Colorectal dysplasia in chronic inflammatory bowel disease: pathology, clinical implications, and pathogenesis. Arch Pathol Lab Med 2010;134:876–95. 10.1043/1543-2165-134.6.876
    1. Coverlizza S, Risio M, Ferrari A, et al. . Colorectal adenomas containing invasive carcinoma. pathologic assessment of lymph node metastatic potential. Cancer 1989;64:1937–47. 10.1002/1097-0142(19891101)64:9<1937::AID-CNCR2820640929>;2-X
    1. Beaton C, Twine CP, Williams GL, et al. . Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Colorectal Dis 2013;15:788–97. 10.1111/codi.12129
    1. von Karsa L, Patnick J, Segnan N, et al. . European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication. Endoscopy 2013;45:51–9. 10.1055/s-0032-1325997
    1. Kannarkatt J, Joseph J, Kurniali PC, et al. . Adjuvant chemotherapy for stage II colon cancer: a clinical dilemma. J Oncol Pract 2017;13:233–41. 10.1200/JOP.2016.017210
    1. Gray R, Barnwell J, McConkey C, et al. . Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 2007;370:2020–9. 10.1016/S0140-6736(07)61866-2
    1. O’Connell MJ, Campbell ME, Goldberg RM, et al. . Survival following recurrence in stage II and III colon cancer: findings from the ACCENT data set. J Clin Oncol 2008;26:2336–41. 10.1200/JCO.2007.15.8261
    1. Kopetz S, Tabernero J, Rosenberg R, et al. . Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer patients more accurately than clinical factors. Oncologist 2015;20:127–33. 10.1634/theoncologist.2014-0325
    1. André T, Boni C, Mounedji-Boudiaf L, et al. . Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–51. 10.1056/NEJMoa032709
    1. Kobayashi H, Mochizuki H, Sugihara K, et al. . Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery 2007;141:67–75. 10.1016/j.surg.2006.07.020
    1. Stålhammar G, Fuentes Martinez N, Lippert M, et al. . Digital image analysis outperforms manual biomarker assessment in breast cancer. Mod Pathol 2016;29:318–29. 10.1038/modpathol.2016.34
    1. Life SciencesIndustrial Strategy. A report to the Government from the life sciences sector. (accessed 08 Sep 2017).
    1. Genomics Education Programme. Developing people for health and healthcare. (accessed 08 Sep 2017).
    1. Haspel RL, Rinder HM, Frank KM, et al. . The current state of resident training in genomic pathology: a comprehensive analysis using the resident in-service examination. Am J Clin Pathol 2014;142:445–51. 10.1309/AJCPH2A4XTXJUKDZ
    1. Kuhry E, Schwenk WF, Gaupset R, et al. . Long-term results of laparoscopic colorectal cancer resection. Cochrane Database Syst Rev 2008;2:CD003432 10.1002/14651858.CD003432.pub2
    1. Veldkamp R, Kuhry E, Hop WC, et al. . Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial. Lancet Oncol 2005;6:477–84. 10.1016/S1470-2045(05)70221-7
    1. Morris EJA, Finan PJ, Spencer K, et al. . Wide Variation in the Use of Radiotherapy in the Management of Surgically Treated Rectal Cancer Across the English National Health Service. Clin Oncol 2016;28:522–31. 10.1016/j.clon.2016.02.002
    1. Klinkhammer-Schalke M, Lindberg P, Koller M, et al. . Direct improvement of quality of life in colorectal cancer patients using a tailored pathway with quality of life diagnosis and therapy (DIQOL): study protocol for a randomised controlled trial. Trials 2015;16:460 10.1186/s13063-015-0972-y
    1. Department of Oncology. Roosevelt Drive Oxford. (accessed 08 Sep 2017).
    1. Shi Q, Sobrero AF, Shields AF, et al. . Prospective pooled analysis of six phase III trials investigating duration of adjuvant (adjuv) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with stage III colon cancer (CC): the IDEA (International Duration Evaluation of Adjuvant chemotherapy) collaboration. J Clin Oncol 2017;35(18_suppl):LBA1 10.1200/JCO.2017.35.18_suppl.LBA1
    1. Coyle C, Cafferty FH, Rowley S, et al. . ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemp Clin Trials 2016;51:56–64. 10.1016/j.cct.2016.10.004
    1. Courneya KS, Booth CM, Gill S, et al. . The colon health and life-long exercise change trial: a randomized trial of the national cancer institute of canada clinical trials group. Curr Oncol 2008;15:279–85.
    1. Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 2012;13:1152–60. 10.1016/S1470-2045(12)70348-0
    1. Richards T, Coulter A, Wicks P. Time to deliver patient centred care. BMJ 2015;350:h530 10.1136/bmj.h530
    1. Heald RJ, Beets G, Carvalho C. Report from a consensus meeting: response to chemoradiotherapy in rectal cancer - predictor of cure and a crucial new choice for the patient: on behalf of the Champalimaud 2014 Faculty for ’Rectal cancer: when NOT to operate'. Colorectal Dis 2014;16:334–7. 10.1111/codi.12627
    1. Renehan AG, Malcomson L, Emsley R, et al. . Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 2016;17:174–83. 10.1016/S1470-2045(15)00467-2
    1. Ackland GL, Iqbal S, Paredes LG, et al. . Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial. Lancet Respir Med 2015;3:33–41. 10.1016/S2213-2600(14)70205-X
    1. O’Connor ME, Kirwan CJ, Pearse RM, et al. . Incidence and associations of acute kidney injury after major abdominal surgery. Intensive Care Med 2016;42:521–30. 10.1007/s00134-015-4157-7
    1. Sievers CK, Kratz JD, Zurbriggen LD, et al. . The multidisciplinary management of colorectal cancer: present and future paradigms. Clin Colon Rectal Surg 2016;29:232–8. 10.1055/s-0036-1584292
    1. Albert MR, Atallah SB, deBeche-Adams TC, et al. . Transanal minimally invasive surgery (TAMIS) for local excision of benign neoplasms and early-stage rectal cancer: efficacy and outcomes in the first 50 patients. Dis Colon Rectum 2013;56:301–7. 10.1097/DCR.0b013e31827ca313
    1. Andratschke NH, Nieder C, Heppt F, et al. . Stereotactic radiation therapy for liver metastases: factors affecting local control and survival. Radiat Oncol 2015;10:69 10.1186/s13014-015-0369-9
    1. Palma S, Zwenger AO, Croce MV, et al. . From molecular biology to clinical trials: toward personalized colorectal cancer therapy. Clin Colorectal Cancer 2016;15:104–15. 10.1016/j.clcc.2015.11.001
    1. Moris D, Pawlik TM. Personalized treatment in patients with colorectal liver metastases. J Surg Res 2017;216:26–9. 10.1016/j.jss.2017.04.013
    1. Sharma RA, Plummer R, Stock JK, et al. . Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol 2016;13:627–42. 10.1038/nrclinonc.2016.79
    1. McCulloch P, Altman DG, Campbell WB, et al. . No surgical innovation without evaluation: the IDEAL recommendations. Lancet 2009;374:1105–12. 10.1016/S0140-6736(09)61116-8
    1. Cancer Research UK. Bowel cancer incidence statistics. (accessed 08 Sep 2017).
    1. National Cancer Institute. Drugs approved for colon and rectal cancer. (accessed 08 Sep 2017).
    1. Garon EB, Rizvi NA, Hui R, et al. . Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018–28. 10.1056/NEJMoa1501824
    1. Robert C, Thomas L, Bondarenko I, et al. . Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517–26. 10.1056/NEJMoa1104621
    1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. . Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23–34. 10.1056/NEJMoa1504030
    1. Overman MJ, McDermott R, Leach JL, et al. . Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 2017;18:1182–91. 10.1016/S1470-2045(17)30422-9
    1. Rentsch M, Schiergens T, Khandoga A, et al. . Surgery for colorectal cancer – trends, developments, and future perspectives. Visc Med 2016;32:184–91. 10.1159/000446490
    1. Mirnezami R, Moran BJ, Harvey K, et al. . Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases. World J Gastroenterol 2014;20:14018–32. 10.3748/wjg.v20.i38.14018
    1. Lee DJ, Sagar PM, Sadadcharam G, et al. . Advances in surgical management for locally recurrent rectal cancer: How far have we come? World J Gastroenterol 2017;23:4170–80. 10.3748/wjg.v23.i23.4170
    1. van Dam RM, Wong-Lun-Hing EM, van Breukelen GJ, et al. . Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS® programme (ORANGE II-trial): study protocol for a randomised controlled trial. Trials 2012;13:54 10.1186/1745-6215-13-54
    1. ISRCTN registry. LAVA: Liver resection surgery versus thermal ablation for colorectal liver metastases. (accessed 08 Sep 2017).
    1. U.S National Library of Medicine. Chemotherapy and Maximal Tumor Debulking of Multi-organ Colorectal Cancer Metastases (ORCHESTRA). (accessed 08 Sep 2017).
    1. Lawler M, Kaplan R, Wilson RH, et al. . Changing the paradigm—multistage multiarm randomized trials and stratified cancer medicine. Oncologist 2015;20:849–51. 10.1634/theoncologist.2015-0014
    1. Cho M, Carter J, Harari S, et al. . The interrelationships of the gut microbiome and inflammation in colorectal carcinogenesis. Clin Lab Med 2014;34:699–710. 10.1016/j.cll.2014.08.002
    1. Zeuner A, Todaro M, Stassi G, et al. . Colorectal cancer stem cells: from the crypt to the clinic. Cell Stem Cell 2014;15:692–705. 10.1016/j.stem.2014.11.012
    1. McGranahan N, Furness AJ, Rosenthal R, et al. . Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016;351:1463–9. 10.1126/science.aaf1490
    1. Le DT, Durham JN, Smith KN, et al. . Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409–13. 10.1126/science.aan6733
    1. Galon J, Costes A, Sanchez-Cabo F, et al. . Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313:1960–4. 10.1126/science.1129139
    1. Wang X, Yang Y, Huycke MM. Microbiome-driven carcinogenesis in colorectal cancer: models and mechanisms. Free Radic Biol Med 2017;105:3–15. 10.1016/j.freeradbiomed.2016.10.504
    1. Whistance RN, Conroy T, Chie W, et al. . European organisation for the research and treatment of cancer quality of life group. clinical and psychometric validation of the EORTC QLQ-CR29 questionnaire module to assess health-related quality of life in patients with colorectal cancer. Eur J Cancer 2009;45:3017–26.
    1. Cherny NI, Sullivan R, Dafni U, et al. . A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the european society for medical oncology magnitude of clinical benefit scale (ESMO-MCBS). Ann Oncol 2015;26:1547–73. 10.1093/annonc/mdv249
    1. Wong CK, Guo VY, Chen J, et al. . Methodological and reporting quality of comparative studies evaluating health-related quality of life of colorectal cancer patients and controls: a systematic review. Dis Colon Rectum 2016;59:1073–86. 10.1097/DCR.0000000000000618
    1. Quidde J, Hegewisch-Becker S, Graeven U, et al. . Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial. Ann Oncol 2016;27:2203–10. 10.1093/annonc/mdw425
    1. Bours MJ, van der Linden BW, Winkels RM, et al. . Candidate predictors of health-related quality of life of colorectal cancer survivors: a systematic review. Oncologist 2016;21:433–52. 10.1634/theoncologist.2015-0258
    1. Bryant CL, Lunniss PJ, Knowles CH, et al. . Anterior resection syndrome. Lancet Oncol 2012;13:e403–8. 10.1016/S1470-2045(12)70236-X
    1. Andreyev J. Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients. Lancet Oncol 2007;8:1007–17. 10.1016/S1470-2045(07)70341-8
    1. Battersby NJ, Juul T, Christensen P, et al. . Predicting the risk of bowel-related quality-of-life impairment after restorative resection for rectal cancer: a multicenter cross-sectional study. Dis Colon Rectum 2016;59:270–80. 10.1097/DCR.0000000000000552
    1. Scheer AS, Boushey RP, Liang S, et al. . The long-term gastrointestinal functional outcomes following curative anterior resection in adults with rectal cancer: a systematic review and meta-analysis. Dis Colon Rectum 2011;54:1589–97. 10.1097/DCR.0b013e3182214f11
    1. Birgisson H, Påhlman L, Gunnarsson U, et al. . Late adverse effects of radiation therapy for rectal cancer – a systematic overview. Acta Oncol 2007;46:504–16. 10.1080/02841860701348670
    1. Maris A, Devreese AM, D’Hoore A, et al. . Treatment options to improve anorectal function following rectal resection: a systematic review. Colorectal Dis 2013;15:e67–78. 10.1111/codi.12036
    1. Lin KY, Granger CL, Denehy L, et al. . Pelvic floor muscle training for bowel dysfunction following colorectal cancer surgery: a systematic review. Neurourol Urodyn 2015;34:703–12. 10.1002/nau.22654
    1. Visser WS, Te Riele WW, Boerma D, et al. . Pelvic floor rehabilitation to improve functional outcome after a low anterior resection: a systematic review. Ann Coloproctol 2014;30:109–14. 10.3393/ac.2014.30.3.109
    1. Glover M, Smerdon GR, Andreyev HJ, et al. . Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. Lancet Oncol 2016;17:224–33. 10.1016/S1470-2045(15)00461-1
    1. Andreyev HJ, Benton BE, Lalji A, et al. . Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial. Lancet 2013;382:2084–92. 10.1016/S0140-6736(13)61648-7
    1. Andreyev HJ, Muls AC, Norton C, et al. . Guidance: The practical management of the gastrointestinal symptoms of pelvic radiation disease. Frontline Gastroenterol 2015;6:53–72. 10.1136/flgastro-2014-100468
    1. Rodriguez JL, Hawkins NA, Berkowitz Z, et al. . Factors associated with health-related quality of life among colorectal cancer survivors. Am J Prev Med 2015;49:S518–S527. 10.1016/j.amepre.2015.08.007
    1. Demark-Wahnefried W, Rogers LQ, Alfano CM, et al. . Practical clinical interventions for diet, physical activity, and weight control in cancer survivors. CA Cancer J Clin 2015;65:167–89. 10.3322/caac.21265
    1. Wu W, Guo F, Ye J, et al. . Pre- and post-diagnosis physical activity is associated with survival benefits of colorectal cancer patients: a systematic review and meta-analysis. Oncotarget 2016;7:52095–103. 10.18632/oncotarget.10603
    1. Soares-Miranda L, Abreu S, Silva M, et al. . Cancer survivor study (CASUS) on colorectal patients: longitudinal study on physical activity, fitness, nutrition, and its influences on quality of life, disease recurrence, and survival. Rationale and design. Int J Colorectal Dis 2017;32:75–81. 10.1007/s00384-016-2671-x
    1. Alfano CM, Bluethmann SM, Tesauro G, et al. . NCI funding trends and priorities in physical activity and energy balance research among cancer survivors. J Natl Cancer Inst 2016;108 10.1093/jnci/djv285
    1. Blanch-Hartigan D, Forsythe LP, Alfano CM, et al. . Provision and discussion of survivorship care plans among cancer survivors: results of a nationally representative survey of oncologists and primary care physicians. J Clin Oncol 2014;32:1578–85. 10.1200/JCO.2013.51.7540
    1. Numico G, Pinto C, Gori S, et al. . Clinical and organizational issues in the management of surviving breast and colorectal cancer patients: attitudes and feelings of medical oncologists. PLoS One 2014;9:e101170 10.1371/journal.pone.0101170
    1. de Lorenzo F, Haylock P. Preface. Cancer 2013;119(Suppl 11):2089–93. 10.1002/cncr.28063
    1. Richards M, Corner J, Maher J. The National Cancer Survivorship Initiative: new and emerging evidence on the ongoing needs of cancer survivors. Br J Cancer 2011;105(Suppl 1):S1–4. 10.1038/bjc.2011.416
    1. Macmillan Cancer Support. Care after Cancer. (accessed 08 Sep 2017).
    1. El-Shami K, Oeffinger KC, Erb NL, et al. . American cancer society colorectal cancer survivorship care guidelines. CA Cancer J Clin 2015;65:427–55. 10.3322/caac.21286
    1. Global Alliance for Genomics and Health. Enabling genomic data sharing for the benefit of human health. (accessed 08 Sep 2017).
    1. Siu LL, Lawler M, Haussler D, et al. . Facilitating a culture of responsible and effective sharing of cancer genome data. Nat Med 2016;22:464–71. 10.1038/nm.4089
    1. Lawler M, Haussler D, Siu LL, et al. . Sharing clinical and genomic data on cancer – the need for global solutions. N Engl J Med 2017;376:2006–9. 10.1056/NEJMp1612254
    1. McArt DG, Blayney JK, Boyle DP, et al. . PICan: An integromics framework for dynamic cancer biomarker discovery. Mol Oncol 2015;9:1234–40. 10.1016/j.molonc.2015.02.002
    1. Tannock IF, Hickman JA. Limits to precision cancer medicine. N Engl J Med 2017;376:96–7. 10.1056/NEJMc1613563
    1. Power E, Simon A, Juszczyk D, et al. . Assessing awareness of colorectal cancer symptoms: measure development and results from a population survey in the UK. BMC Cancer 2011;11:366 10.1186/1471-2407-11-366
    1. Keighley MR, O’Morain C, Giacosa A, et al. . Public awareness of risk factors and screening for colorectal cancer in Europe. Eur J Cancer Prev 2004;13:257–62. 10.1097/01.cej.0000136575.01493.9b
    1. Gray SW, Armstrong K, Demichele A, et al. . Colon cancer patient information seeking and the adoption of targeted therapy for on-label and off-label indications. Cancer 2009;115:1424–34. 10.1002/cncr.24186
    1. Brown S, Greenfield D, Thompson J. Knowledge and awareness of long-term and late treatment consequences amongst colorectal cancer survivors: a qualitative study. Eur J Oncol Nurs 2016;20:191–8. 10.1016/j.ejon.2015.08.005
    1. Craig P, Dieppe P, Macintyre S, et al. . Developing and evaluating complex interventions: the new medical research council guidance. BMJ 2008;337:a1655 10.1136/bmj.a1655
    1. Moore GF, Audrey S, Barker M, et al. . Process evaluation of complex interventions: medical research council guidance. BMJ 2015;350:h1258 10.1136/bmj.h1258
    1. Cancer Research UK. Understanding gpattitudes to cancerpreventing drugs. (accessed 08 Sep 2017).
    1. Glaser AW, Fraser LK, Corner J, et al. . Patient-reported outcomes of cancer survivors in england 1-5 years after diagnosis: a cross-sectional survey. BMJ Open 2013;3:e002317 10.1136/bmjopen-2012-002317
    1. McNair AG, Whistance RN, Forsythe RO, et al. . Synthesis and summary of patient-reported outcome measures to inform the development of a core outcome set in colorectal cancer surgery. Colorectal Dis 2015;17:O217–229. 10.1111/codi.13021
    1. Lawler M, Le Chevalier T, et al. . European Cancer Concord (ECC). Lancet Oncol 2014;15:258–60.
    1. Kehl KL, Arora NK, Schrag D, et al. . Discussions about clinical trials among patients with newly diagnosed lung and colorectal cancer. J Natl Cancer Inst 2014;106 pii: dju216 10.1093/jnci/dju216
    1. Ciardiello F, Adams R, Tabernero J, et al. . Awareness, understanding, and adoption of precision medicine to deliver personalized treatment for patients with cancer: a multinational survey comparison of physicians and patients. Oncologist 2016;21:292–300. 10.1634/theoncologist.2015-0279

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