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Original research
Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study
  1. Raoul C Reulen1,
  2. Kwok F Wong2,
  3. Chloe J Bright2,
  4. David L Winter1,
  5. Daniela Alessi3,
  6. Rodrigue M Allodji4,
  7. Francesca Bagnasco5,
  8. Edit Bárdi6,7,
  9. Andrea Bautz8,
  10. Julianne Byrne9,
  11. Elizabeth AM Feijen10,
  12. Miranda M Fidler-Benaoudia11,
  13. Ibrahim Diallo12,
  14. Stanislaw Garwicz13,
  15. Desiree Grabow14,
  16. Thorgerdur Gudmundsdottir8,15,
  17. Joyeeta Guha16,
  18. Nadia Haddy12,
  19. Stine Høgsholt8,17,
  20. Moncilo Jankovic18,
  21. Peter Kaatsch19,
  22. Melanie Kaiser19,
  23. Rahel Kuonen20,
  24. Helena Linge13,
  25. Hilde Øfstaas21,
  26. Cecile M Ronckers10,22,
  27. Eva-Maria Hau20,23,
  28. Roderick Skinner24,
  29. Flora E van Leeuwen25,
  30. Jop C Teepen10,
  31. Cristina Veres12,
  32. Wael Zrafi12,
  33. Ghazi Debiche12,
  34. Damien Llanas12,
  35. Monica Terenziani26,
  36. Giao Vu-Bezin12,
  37. Finn Wesenberg27,
  38. Thomas Wiebe13,
  39. Carlotta Sacerdote3,
  40. Zsuzsanna Jakab28,
  41. Riccardo Haupt29,
  42. Päivi M Lähteenmäki30,
  43. Lorna Zadravec Zaletel31,
  44. Claudia E Kuehni20,23,
  45. Jeanette F Winther8,32,
  46. Florent de Vathaire12,
  47. Leontien C Kremer10,22,
  48. Lars Hjorth13,
  49. Michael M Hawkins1
  1. 1Centre for Childhood Cancer Survivor Studies, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
  2. 2National Cancer Registration and Analysis Service, Public Health England, London, UK
  3. 3Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and AOU Città della Salute e della Scienza di Torino, Italy, Childhood cancer registry of piedmont, Turin, Italy
  4. 4Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France
  5. 5Epidemiology and Biostatistics Unit, Instituto Giannina Gaslini, Genova, Italy
  6. 62nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
  7. 7Kepler Universitätsklinikum, Linz, Austria
  8. 8Childhood Cancer Research Group, Danish Cancer Society Research Center, Copenhagen, Denmark
  9. 9Boyne Research Institute, Drogheda, Ireland
  10. 10Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
  11. 11Epidemiology and Prevention Research, Departments of Oncology and Community Health Sciences, Calgary, Alberta, Canada
  12. 12Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France, Villejuif, France
  13. 13Department of Clinical Sciences, Skåne University Hospital, Lund University, Pediatrics, Lund, Skåne, Sweden
  14. 14German Childhood Cancer Registry, University Medical Centre Mainz, Mainz, Germany
  15. 15Children’s Hospital, Landspitali University Hospital, Reykjavik, Iceland
  16. 16Public Health England and NHS England & Improvement, Birmingham, UK
  17. 17Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
  18. 18Pediatric Clinic, University of Milan-Bicocca, Hospital San Gerardo, Monza, Lombardia, Italy
  19. 19German Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
  20. 20Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, BE, Switzerland
  21. 21Norwegian National Advisory Unit on solid tumors in children, Oslo, Norway
  22. 22Department of pediatric Oncology, Emma Children’s Hospital & Academic Medical Center, Amsterdam, The Netherlands
  23. 23Department of Paediatrics, University Children's Hospital of Bern, University of Bern, Bern, BE, Switzerland
  24. 24Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Newcastle University Centre for Cancer, Newcastle Upon Tyne, UK
  25. 25Department of Epidemiology, Division of Psychosocial Research & Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  26. 26Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, Italy
  27. 27Norwegian Cancer Registry and Dept. of Pediatric Medicine, Oslo University Hospital and Institute of Clinical Medicine, Faculty of medicine, University of Oslo, Oslo, Norway
  28. 28Hungarian Childhood Cancer Registry, Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary
  29. 29Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
  30. 30Department of Pediatrics and Adolescent Medicine, Turku University and Turku University Hospital, Turku, Finland
  31. 31Division of Radiotherapy, Institute of Oncology, Ljubljana, Slovenia
  32. 32Department of Clinical Medicine, Faculty of Health, Aarhus University and University Hospital, Aarhus, Denmark
  1. Correspondence to Professor Michael M Hawkins, Centre for Childhood Cancer Survivor Studies, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK; m.m.hawkins{at}bham.ac.uk

Abstract

Background Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.

Methods The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.

Results 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN—comparable to the risk among members of the general population with at least two first-degree relatives affected.

Conclusions Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

  • CANCER EPIDEMIOLOGY
  • COLORECTAL CANCER SCREENING
  • COLORECTAL CANCER
  • GASTROINTESTINAL CANCER
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Footnotes

  • Deceased Deceased 27th November 2018, to whom this work is dedicated.

  • Contributors RCR, MH, EB, JB, SG, DG, PK, MT, FW, TW, CS, ZJ, RH, PL, LZZ, CK, JFW, FdV, LK, LH: study design and concept. RCR, KW, DW, MH: statistical analyses. RCR, MH: drafting of manuscript. RCR, KW, CB, DW, DA, RS, FB, EB, AB, JB, EAMF, MMF-B, ID, SG, DG, TG, JG, NH, SH, MJ, PK, MK, RK, HL, HØ, CR, E-MH, RS, FEvL, JT CV, ZW, GD, DI, MT, GV-B, FW, TW, CS, ZJ, RH, PL, LZZ, CK, JFW, FdV, LK, LH, MH: Interpretation of data and critically revising of manuscript. All authors read and approved the final version of the manuscript.

  • Funding The PanCareSurFup consortium and related work was supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 257 505. Additional financial support was received from: The Fondation Force de recherche sur le cancer de l'enfant (FORCE), The Italian Association for Cancer Research and the Compagnia San Paolo; The Fondo Chiara Rama ONLUS; The Swedish Childhood Cancer Fund; the French Association for Cancer Research (ARC); The French National Agency For Research (ANR) (Hope-Epi project); the French National Cancer Institute (INCA); Pfizer Foundation for Children and Adolescent Health; Slovenian Research Agency; the Swiss Paediatric Oncology Group; The Swiss Cancer League (KLS-3412-02-2014, KLS-3886-02-2016); The Swiss Cancer Research foundation (KFS-02783-02-2011, KFS-4157-02-2017); The Swiss National Science Foundation (PDFMP3_141775), The Dutch Cancer Society, The Norwegian Childhood Cancer Foundation, and Children with Cancer UK (grant no: 20457).

  • Competing interests HL and TW are shareholders in, and have signed an intellectual property agreement with the company Concidera Health. The company develops clinical decision support tools for childhood cancer survivorship.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was not obtained specifically for this study as it involved pooling of non-identifiable data. Ethical approval was obtained within the country of origin of each contributing subcohort separately.

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

  • Data availability statement Data are available on reasonable request. The data are not publicly available due to them containing semi-identifiable information that could compromise research participant privacy. Nonetheless, additional summary tables of count data or person-years are available from the corresponding author on request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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