Rodrigue S Allodji1, Mike M Hawkins2, Chloe J Bright2, Miranda M Fidler-Benaoudia3, David L Winter2, Daniela Alessi4, Brice Fresneau5, Neige Journy6, Vera Morsellino7, Edit Bárdi8, Andrea Bautz9, Julianne Byrne10, Elizabeth Lieke Am Feijen11, Jop C Teepen11, Giao Vu-Bezin6, Carole Rubino6, Stanislaw Garwicz12, Desiree Grabow13, Thorgerdur Gudmundsdottir14, Joyeeta Guha2, Eva-Maria Hau15, Momcilo Jankovic16, Peter Kaatsch13, Melanie Kaiser13, Helena Linge12, Monica Muraca7, Damien Llanas6, Cristina Veres6, Hilde Øfstaas17, Ibrahima Diallo6, Imene Mansouri6, Cecile M Ronckers11, Roderick Skinner18, Monica Terenziani19, Finn Wesenberg20, Thomas Wiebe12, Carlotta Sacerdote4, Zsuzsanna Jakab21, Riccardo Haupt7, Päivi Lähteenmäki22, Lorna Zadravec Zaletel23, Claudia E Kuehni15, Jeanette F Winther24, Gisela Michel25, Leontien C M Kremer11, Lars Hjorth12, Nadia Haddy26, Florent de Vathaire6, Raoul C Reulen2. 1. Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, Robert Aitken Building, University of Birmingham, Birmingham, UK; Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France; Polytechnic School of Abomey-Calavi (EPAC), University of Abomey-Calavi, 01 P.O. Box 2009, Cotonou, Benin. Electronic address: rodrigue.allodji@gustaveroussy.fr. 2. Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, Robert Aitken Building, University of Birmingham, Birmingham, UK. 3. Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, Robert Aitken Building, University of Birmingham, Birmingham, UK; Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta, Canada. 4. Childhood 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. 5. Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France; Department of Pediatric Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 6. Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France. 7. Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. 8. St Anna Kinderspital Wien, Austria; Department of Paediatrics and Adolescent Medicine, Kepler University Hospital, Linz, Austria. 9. Danish Cancer Society Research Center, Childhood Cancer Research Group, Copenhagen, Denmark. 10. Boyne Research Institute, Drogheda, Ireland. 11. Department of Pediatric Oncology, Amsterdam UMC, Emma Children's Hospital, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. 12. Lund University, Skane University Hospital, Department of Clinical Sciences, Paediatrics, Lund, Sweden. 13. German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Mainz, Germany. 14. Department of Paediatrics and Adolescent Medicine, Kepler University Hospital, Linz, Austria; Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 15. Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Switzerland; Department of Paediatrics, University Children's Hospital of Bern, University of Bern, Switzerland. 16. Foundation MBBM, Hemato-Oncology Center, University of Milano-Bicocca, Via Cadore 38, 20900 Monza, MB, Italy. 17. Norwegian National Advisory Unit on Solid Tumors in Children, Norway. 18. Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, And Northern Institute of Cancer Research, Newcastle University, Newcastle Upon Tyne, UK. 19. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 20. Norwegian Cancer Registry and Dept. of Pediatric Medicine, Oslo University Hospital and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway. 21. Hungarian Childhood Cancer Registry, 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. 22. Turku University and Turku University Hospital, Department of Pediatric and Adolescent Medicine, Turku, Finland. 23. Institute of Oncology, Ljubljana, Slovenia. 24. Danish Cancer Society Research Center, Childhood Cancer Research Group, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. 25. Department of Health Sciences and Health Policy, University of Lucerne, Frohburgstrasse 3, PO Box 4466, 6002, Lucerne, Switzerland. 26. Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, Robert Aitken Building, University of Birmingham, Birmingham, UK; Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, University Paris Saclay, Gustave Roussy, Villejuif, France.
Abstract
BACKGROUND: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. METHODS: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. RESULTS: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. CONCLUSIONS: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.
BACKGROUND: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. METHODS: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. RESULTS: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. CONCLUSIONS: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.
Authors: Rodrigue S Allodji; Margaret A Tucker; Michael M Hawkins; Marie-Cécile Le Deley; Cristina Veres; Rita Weathers; Rebecca Howell; Dave Winter; Nadia Haddy; Carole Rubino; Ibrahima Diallo; Mark P Little; Lindsay M Morton; Florent de Vathaire Journal: Int J Cancer Date: 2020-11-09 Impact factor: 7.316