PI: Prof.dr. Leontien Kremer, pediatrician
Survivorship research
Even many years after treatment, childhood cancer survivors are at high risk of developing long-term health effects resulting from their previous cancer treatment. Our group is focusing on quantification of the role of cancer treatment and other important risk factors as they impact health and quality of life, the development, validation and implementation of prediction models and potential (eHealth) interventions. Nationally our group collaborates with the LATER outpatient clinic, LATER central data office, and survivors. In the Netherlands, we have identified more than 12,000 5-year survivors treated for childhood cancer between 1963 and 2014. More than 6,000 of them participated in the multidisciplinary national Dutch Childhood Cancer Survivor Study 1 (DCCSS1), which included data about childhood cancer diagnosis and treatment, health, lifestyle, and psychosocial functioning from questionnaires, and data on health outcomes from linkage to health registries. So far, 2,400 survivors participated in the DCCSS2 study and visited the LATER outpatient clinic for additional medical data and blood sample collection. The national LATER research is unique in the world. Current research topics that we address are late mortality, burden of disease, subsequent tumors, cardiovascular toxicity, fertility, lifestyle, aging, frailty, fatigue, psychosocial health, radiation epidemiology, health care burden and evaluation of care. We participate as a partner in the European PanCareSurFup project, with our focus on cardiac disease after treatment for childhood cancer and guideline development, including models of care and transition. In European PanCareLIFE we participate as a partner with our focus on guideline development for fertility and fertility preservation. In addition, Leontien Kremer is leading the European PanCareFollowUp study on the implementation of survivorship care in four countries and the development of an eHealth lifestyle intervention. Moreover, we perform collaborative studies with the Childhood Cancer Survivor Study, United States.

Systematic reviews, guidelines and outcomes of care
Systematic reviews are of great importance in the current era of evidence-based medicine. They provide transparent and reproducible insight into the available scientific evidence for a specific question and the possible lack thereof. It thereby provides a starting point for new clinical research in pediatric oncology. Systematic reviews also form the basis for clinical practice guidelines, which are essential for the translation of scientific evidence into daily clinical practice. The editorial base of Cochrane Childhood Cancer, based in the Princess Máxima Center, is responsible for the (inter)national support, the editorial process and the publication in the Cochrane Library (an internet journal IF 7.755) of Cochrane systematic reviews on childhood cancer. Furthermore, our group provides the evidence-based methodology for developing guidelines within pediatric oncology. We produce international harmonized guidelines for the long-term follow-up care for childhood cancer survivors and fertility preservation for children with cancer, and national and international supportive care guidelines. Moreover, we focus on developing outcome indicators to measure the quality of care. Leontien Kremer is the founder and co-chair of the IGHG, together with Melissa Hudson from the St. Jude Children’s Research Hospital, Memphis, United States.
More information
Job opportunities in our research department
Links
www.childhoodcancer.cochrane.org
Media and news
Verbeteringen in LATER-kennis hebben meteen effect op de zorg
29 oktober 2020 promotie Ardine Reedijk
2020
Feijen EAM, van Dalen EC, van der Pal HJH, Reulen RC, Winter DL, Keuhni CE, Morsellino V, Alessi D, Allodji RS, Byrne J, Bardi E, Jakab Z, Grabow D, Garwicz S, Haddy N, Jankovic M, Kaatsch P, Levitt GA, Ronckers CM, Schindera C, Skinner R, Zalatel L, Hjorth L, Tissing WJE, De Vathaire F, Hawkins MM, Kremer LCM; PanCareSurFup consortium. (2020) Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study. Heart. PMID: 32826285.
Leerink, J. M., Feijen, E. L. A. M., van der Pal, H. J. H., Kok, W. E. M., Mavinkurve-Groothuis, A. M. C., Kapusta, L., . . . Group, L. S. (2020). Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study. American heart journal. PMID: 31733449
Leerink JM, Baat ECd, Feijen EAM, Bellersen L, Dalen ECv, Grotenhuis HB, Kapusta L, Kok WEM, Loonen J, Pal HJHvd, Pluijm SMF, Teske AJ, Mavinkurve-Groothuis AMC, Merkx R and Kremer LCM. (2020) Cardiac Disease in Childhood Cancer Survivors. JACC: CardioOncology. 2020;2:363-378. PMID
Mulder RL, van Kalsbeek RJ, Hudson MM, Skinner R, Kremer LCM. The Critical Role of Clinical Practice Guidelines and Indicators in High-Quality Survivorship After Childhood Cancer. Pediatr Clin North Am. PMID: 33131535.
Mulder RL, Hudson MM, Bhatia S, Landier W, Levitt G, Constine LS, Wallace WH,van Leeuwen FE, Ronckers CM, Henderson TO, Moskowitz CS, Friedman DN, Ng AK, Jenkinson HC, Demoor-Goldschmidt C, Skinner R, Kremer LCM, Oeffinger KC. (2020) Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group. J Clin Oncol. PMID: 33078972
Reedijk AMJ, Zijtregtop EAM, Coebergh JWW, Meyer-Wentrup FAG, Hebeda KM, Zwaan CM, Janssens GOR, Pieters R, Plattel WJ, Dinmohamed AG, Zijlstra JM, Kremer LCM, Lugtenburg PJ, Beishuizen A, Karim-Kos HE. (2020) Improved survival for adolescents and young adults with Hodgkin lymphoma and continued high survival for children in the Netherlands: a population-based study during 1990-2015. Br J Haematol. PMID: 32030738
Skoetz N, Goldkuhle M, van Dalen EC, Akl EA, Trivella M, Mustafa RA, Nowak A,
Dahm P, Schünemann H, Bender R; GRADE Working Group (2020). GRADE guidelines 27: how tocalculate absolute effects for time-to-event outcomes in summary of findings tables and Evidence Profiles. J Clin Epidemiol. PMID: 31711910.
Streefkerk N, Fioole LCE, Beijer JGM, Feijen ELAM, Teepen JC, Winther JF, Ronckers CM, Loonen JJ, van Dulmen-den Broeder E, Skinner R, Hudson MM, Tissing WJE, Korevaar JC, Mulder RL, Kremer LCM. Large variation in assessment and outcome definitions to describe the burden of long-term morbidity in childhood cancer survivors: A systematic review. Pediatr Blood Cancer. PMID: 32881287.
Streefkerk N, Tissing WJE, Korevaar JC, van Dulmen-den Broeder E, Bresters D, van der Heiden-van der Loo M, van de Heuvel-Eibrink MM, Van Leeuwen FE, Loonen J, van der Pal HHJ, Ronckers CM, Versluys AB, de Vries ACH, Feijen EAM, Kremer LCM; Dutch LATER Study Group. (2020) A detailed insight in the high risks of hospitalizations in long-term childhood cancer survivors-A Dutch LATER linkage study. PLoS One. PMID: 32427994
Tas, M. L., Reedijk, A. M. J., Karim-Kos, H. E., Kremer, L. C. M., van de Ven, C. P., Dierselhuis, M. P., . . . van Noesel, M. M. (2020). Neuroblastoma between 1990 and 2014 in the Netherlands: Increased incidence and improved survival of high-risk neuroblastoma. European journal of cancer (Oxford, England : 1990). PMID: 31726247
Van As JW, van den Berg H, van Dalen EC. (2020) Different infusion durations for preventing platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev. 2020 Jan 21;1(1):CD010885. doi: 10.1002/14651858.CD010885.pub5.
Verbruggen LC, Wang Y, Armenian SH, Ehrhardt MJ, van der Pal HJH, van Dalen EC, van As JW, Bardi E, Baust K, Berger C, Castagnola E, Devine KA, Gebauer J, Marchak JG, Glaser AW, Groll AH, Haeusler GM, den Hartogh J, Haupt R, Hjorth L, Kato M, Kepák T, Koopman MMWR, Langer T, Maeda M, Michel G, Muraca M, Nathan PC, van den Oever SR, Pavasovic V, Sato S, Schulte F, Sung L, Tissing W, Uyttebroeck A, Mulder RL, Kuehni C, Skinner R, Hudson MM, Kremer LCM. Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer: A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Pediatr Blood Cancer. 2020 Dec;67(12):e28702. PMID: 32969160
Verbruggen LC, Hudson MM, Bowers DC, Ronckers CM, Armstrong GT, Skinner R, Hoving EW, Janssens GO, van der Pal HJH, Kremer LCM, Mulder RL. (2020) Variations in screening and management practices for subsequent asymptomatic meningiomas in childhood, adolescent and young adult cancer survivors. J Neurooncol. PMID: 32088813.
2019
Allodji, R. S., Hawkins, M. M., Bright, C. J., Fidler-Benaoudia, M. M., Winter, D. L., Alessi, D., . . . Reulen, R. C. (2019). Risk of subsequent primary leukaemias among 69,460 five-year survivors of childhood cancer diagnosed from 1940 to 2008 in Europe: A cohort study within PanCareSurFup. European journal of cancer (Oxford, England : 1990). PMID: 31260818
Brennan-Jones CG, McMahen C, Van Dalen EC (2019). Cochrane corner: platinum-induced hearing loss after treatment for childhood cancer. Int J Audiol. PMID: 30545270
Clemens, E., Broer, L., Langer, T., Uitterlinden, A. G., de Vries, A. C. H., van Grotel, M., . . . PanCare, L. c. (2019). Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study. The pharmacogenomics journal. PMID: 31666714
Clemens, E., Meijer, A. J., Broer, L., Langer, T., van der Kooi, A.-L. L., Uitterlinden, A. G., . . . van den Heuvel-Eibrink, M. M. (2019). Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study. JMIR research protocols. PMID: 30888333
Clemens, E., van den Heuvel-Eibrink, M. M., Mulder, R. L., Kremer, L. C. M., Hudson, M. M., Skinner, R., . . . International Guideline Harmonization Group ototoxicity, g. (2019). Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium. The Lancet. Oncology. PMID: 30614474
Constine, L. S., Ronckers, C. M., Hua, C. H., Olch, A., Kremer, L. C. M., Jackson, A., & Bentzen, S. M. (2019). Pediatric Normal Tissue Effects in the Clinic (PENTEC): An International Collaboration to Analyse Normal Tissue Radiation Dose-Volume Response Relationships for Paediatric Cancer Patients. Clinical oncology (Royal College of Radiologists (Great Britain)). PMID: 30670336
Dreesens, D., Kremer, L., & van der Weijden, T. (2019). The Dutch chaos case: A scoping review of knowledge and decision support tools available to clinicians in the Netherlands. Health policy (Amsterdam, Netherlands). PMID: 31722782
Dreesens, D., Stiggelbout, A., Agoritsas, T., Elwyn, G., Flottorp, S., Grimshaw, J., . . . van der Weijden, T. (2019). A conceptual framework for patient-directed knowledge tools to support patient-centred care: Results from an evidence-informed consensus meeting. Patient education and counseling. PMID: 31118137
Dreesens, D., Veul, L., Westermann, J., Wijnands, N., Kremer, L., van der Weijden, T., & Verhagen, E. (2019). The clinical practice guideline palliative care for children and other strategies to enhance shared decision-making in pediatric palliative care; pediatricians' critical reflections. BMC pediatrics. PMID: 31783822
Feijen, E. A. M., Leisenring, W. M., Stratton, K. L., Ness, K. K., van der Pal, H. J. H., van Dalen, E. C., . . . Chow, E. J. (2019). Derivation of Anthracycline and Anthraquinone Equivalence Ratios to Doxorubicin for Late-Onset Cardiotoxicity. JAMA oncology. PMID: 30703192
Feijen, E. A. M. L., Font-Gonzalez, A., Van der Pal, H. J. H., Kok, W. E. M., Geskus, R. B., Ronckers, C. M., . . . Group, D. L. S. (2019). Risk and Temporal Changes of Heart Failure Among 5-Year Childhood Cancer Survivors: a DCOG-LATER Study. Journal of the American Heart Association. PMID: 30595059
Kok, J. L., Teepen, J. C., van der Pal, H. J., van Leeuwen, F. E., Tissing, W. J. E., Neggers, S. J. C. M. M., . . . Group, D.-L. S. (2019). Incidence of and Risk Factors for Histologically Confirmed Solid Benign Tumors Among Long-term Survivors of Childhood Cancer. JAMA oncology. PMID: 30920605
Kok, J. L., Teepen, J. C., van Leeuwen, F. E., Tissing, W. J. E., Neggers, S. J. C. M. M., van der Pal, H. J., . . . Ronckers, C. M. (2019). Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age. Neuro-oncology. PMID: 30099534
Kooijmans EC, Bökenkamp A, Tjahjadi NS, Tettero JM, van Dulmen-den Broeder E, van der Pal HJ, Veening MA (2019). Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev. PMID: 30855726
Leerink, J. M., Verkleij, S. J., Feijen, E. A. M., Mavinkurve-Groothuis, A. M. C., Pourier, M. S., Ylänen, K., . . . Kok, W. E. M. (2019). Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review. Heart (British Cardiac Society). PMID: 30158136
Loeffen, E. A. H., Knops, R. R. G., Boerhof, J., Feijen, E. A. M. L., Merks, J. H. M., Reedijk, A. M. J., . . . Tissing, W. J. E. (2019). Treatment-related mortality in children with cancer: Prevalence and risk factors. European journal of cancer (Oxford, England : 1990). PMID: 31569066
Loeffen, E. A. H., Kremer, L. C. M., van de Wetering, M. D., Mulder, R. L., Font-Gonzalez, A., Dupuis, L. L., . . . Pain in Children with Cancer Guideline Development, P. (2019). Reducing pain in children with cancer: Methodology for the development of a clinical practice guideline. Pediatric blood & cancer. PMID: 30848078
Michel, G., Mulder, R. L., van der Pal, H. J. H., Skinner, R., Bárdi, E., Brown, M. C., . . . Levitt, G. (2019). Evidence-based recommendations for the organization of long-term follow-up care for childhood and adolescent cancer survivors: a report from the PanCareSurFup Guidelines Working Group. Journal of cancer survivorship : research and practice. PMID: 31396878
Mulder RL, Bresters D, Van den Hof M, Koot BG, Castellino SM, Loke YKK, Post PN, Postma A, Szőnyi LP, Levitt GA, Bardi E, Skinner R, van Dalen EC (2019). Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database Syst Rev. PMID: 30985922
Peinemann F, van Dalen EC, Enk H, Tytgat GA (2019). Anti-GD2 antibody-containing immunotherapy postconsolidation therapy for people with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation. Cochrane Database Syst Rev. PMID: 31016728
Reedijk, A. M. J., Klein, K., Coebergh, J. W. W., Kremer, L. C., Dinmohamed, A. G., de Haas, V., . . . Karim-Kos, H. E. (2019). Improved survival for children and young adolescents with acute myeloid leukemia: a Dutch study on incidence, survival and mortality. Leukemia. PMID: 30568171
Skoetz N, Goldkuhle M, Weigl A, Dwan K, Labonté V, Dahm P, Meerpohl JJ, Djulbegovic B, van Dalen EC. Methodological review showed correct absolute effect size estimates for time-to-event outcomes in less than one-third of cancer-related systematic reviews. J Clin Epidemiol. 2019 Apr;108:1-9.
Streefkerk, N., Heins, M. J., Teepen, J. C., Feijen, E. A. M., Bresters, D., van Dulmen-den Broeder, E., . . . Group, D.-L. S. (2019). The involvement of primary care physicians in care for childhood cancer survivors. Pediatric blood & cancer. PMID: 31033160
Teepen, J. C., Kok, J. L., Kremer, L. C., Tissing, W. J. E., van den Heuvel-Eibrink, M. M., Loonen, J. J., . . . Group, D.-L. S. (2019). Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study. Journal of the National Cancer Institute. PMID: 30802904
Teepen, J. C., Kremer, L. C., van der Heiden-van der Loo, M., Tissing, W. J., van der Pal, H. J., van den Heuvel-Eibrink, M. M., . . . Group, D.-L. S. (2019). Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort. Cancer causes & control : CCC. PMID: 31300947
Teepen, J. C., Ronckers, C. M., & Kremer, L. C. M. (2019). Colorectal Cancer Screening in Childhood Cancer Survivors. Journal of the National Cancer Institute. PMID: 30980664
Ten Berg, S., Loeffen, E. A. H., van de Wetering, M. D., Martens, D. H. J., van Ede, C. M., Kremer, L. C. M., & Tissing, W. J. E. (2019). Development of pediatric oncology supportive care indicators: Evaluation of febrile neutropenia care in the north of the Netherlands. Pediatric blood & cancer. PMID: 30318786
Vaarwerk, B., Schoot, R. A., Maurice-Stam, H., Slater, O., Hartley, B., Saeed, P., . . . Merks, J. H. M. (2019). Psychosocial well-being of long-term survivors of pediatric head-neck rhabdomyosarcoma. Pediatric blood & cancer. PMID: 30318743
Van As JW, van den Berg H, van Dalen EC. Medical interventions for the prevention of platinum-induced hearing loss in children withcancer. CochraneDatabase Syst Rev. PMID: 31063591
Van de Loo, L. E. X. M., van den Berg, M. H., Overbeek, A., van Dijk, M., Damen, L., Lambalk, C. B., . . . Group, D. L.-V. S. (2019). Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors. Fertility and sterility. PMID: 30691634