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1. Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study

Author

Heymer, Emma J., Hawkins, Michael M., Winter, David L., Teepen, Jop C., Sunguc, Ceren, Ronckers, Cécile M., Allodji, Rodrigue S., Alessi, Daniela, Sugden, Elaine, Belle, Fabiën N., Bagnasco, Francesca, Byrne, Julianne, Bárdi, Edit, Garwicz, Stanislaw, Grabow, Desiree, Jankovic, Momcilo, Kaatsch, Peter, Kaiser, Melanie, Michel, Gisela, Schindera, Christina, Haddy, Nadia, Journy, Neige, Česen Mazić, Maja, Skinner, Roderick, Kok, Judith L., Gunnes, Maria W., Wiebe, Thomas, Sacerdote, Carlotta, Maule, Milena M., Terenziani, Monica, Jakab, Zsuzsanna, Winther, Jeanette F., Lähteenmäki, Päivi M., Zadravec Zaletel, Lorna, Haupt, Riccardo, Kuehni, Claudia E., Kremer, Leontien C., de Vathaire, Florent, Hjorth, Lars, and Reulen, Raoul C.

Published
2024
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2. Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors: A DCCSS LATER Study

Author

Merkx, Remy, Leerink, Jan M., Feijen, E. (Lieke) A.M., de Baat, Esmée C., Bellersen, Louise, Bresters, Dorine, van Dalen, Elvira C., van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, van den Heuvel-Eibrink, Marry M., Kok, Judith L., Louwerens, Marloes, Maas, Angela H.E.M., Neggers, Sebastian J.C.M.M., Ronckers, Cécile M., Teepen, Jop C., Teske, Arco J., Tissing, Wim J.E., de Vries, Andrica C.H., Weijers, Gert, de Korte, Chris L., Loonen, Jacqueline, Mavinkurve-Groothuis, Annelies M.C., van der Pal, Helena J.H., Kremer, Leontien C.M., Kok, Wouter E.M., and Kapusta, Livia

Published
2023
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3. Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors: A Dutch LATER study

Author

Louwerens, Marloes, de Vries, Andrica, Jaspers, Monique, Hollema, Nynke, den Hartogh, Jaap, Schouten-van Meeteren, Netteke, Verbruggen, Lisanne C., Kok, Judith L., Teepen, Jop C., Janssens, Geert O., de Boer, Charlotte M., Stalpers, Lukas J.A., Vernooij, Meike W., van Dulmen-den Broeder, Eline, Loonen, Jacqueline J., van den Heuvel-Eibrink, Marry M., Tissing, Wim J.E., van der Heiden-van der Loo, Margriet, Versluys, Anne Birgitta, Neggers, Sebastian J.C.M.M., van Leeuwen, Flora E., Hoving, Eelco W., Wesseling, Pieter, Kremer, Leontine C.M., Ronckers, Cécile M., and van der Pal, Helena J.H.

Published
2021
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5. Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors

Author

de Baat, Esmée C, primary, Merkx, Remy, additional, Leerink, Jan M, additional, Boerhout, Coen, additional, van der Pal, Heleen J H, additional, van Dalen, Elvira C, additional, Loonen, Jacqueline, additional, Bresters, Dorine, additional, van Dulmen-den Broeder, Eline, additional, van der Heiden-van der Loo, Margriet, additional, van den Heuvel, Marry M, additional, Kok, Judith L, additional, Louwerens, Marloes, additional, Neggers, Sebastian J C M M, additional, Ronckers, Cecline M, additional, Teepen, Jop C, additional, Tissing, Wim J E, additional, de Vries, Andrica C, additional, Kapusta, Livia, additional, Kremer, Leontien C M, additional, Mavinkurve-Groothuis, Annelies M C, additional, Kok, Wouter E M, additional, and Feijen, Elizabeth A M, additional

Published
2024
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6. Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors

Author

De Baat, Esmée C., Merkx, Remy, Leerink, Jan M., Boerhout, Coen, Van Der Pal, Heleen J.H., Van Dalen, Elvira C., Loonen, Jacqueline, Bresters, Dorine, Van Dulmen-Den Broeder, Eline, Van Der Heiden-Van Der Loo, Margriet, Van Den Heuvel, Marry M., Kok, Judith L., Louwerens, Marloes, Neggers, Sebastian J.C.M.M., Ronckers, Cecline M., Teepen, Jop C., Tissing, Wim J.E., De Vries, Andrica C., Kapusta, Livia, Kremer, Leontien C.M., Mavinkurve-Groothuis, Annelies M.C., Kok, Wouter E.M., Feijen, Elizabeth A.M., De Baat, Esmée C., Merkx, Remy, Leerink, Jan M., Boerhout, Coen, Van Der Pal, Heleen J.H., Van Dalen, Elvira C., Loonen, Jacqueline, Bresters, Dorine, Van Dulmen-Den Broeder, Eline, Van Der Heiden-Van Der Loo, Margriet, Van Den Heuvel, Marry M., Kok, Judith L., Louwerens, Marloes, Neggers, Sebastian J.C.M.M., Ronckers, Cecline M., Teepen, Jop C., Tissing, Wim J.E., De Vries, Andrica C., Kapusta, Livia, Kremer, Leontien C.M., Mavinkurve-Groothuis, Annelies M.C., Kok, Wouter E.M., and Feijen, Elizabeth A.M.

Abstract

Background: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors. Methods: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories. Among 880 survivors who received anthracycline, mitoxantrone or heart radiotherapy, logistic regression models using least absolute shrinkage and selection operator identified ECG abnormalities associated with three abnormal LVEF categories (<52% in male/<54% in female, <50% and <45%). We assessed the overall contribution of these ECG abnormalities to clinical regression models predicting abnormal LVEF, assuming an absence of systolic dysfunction with a <1% threshold probability. Results: 16% of survivors (52% female, mean age 34.7 years) and 14% of siblings had major ECG abnormalities. ECG abnormalities increased with decreasing LVEF. Integrating selected ECG data into the baseline model significantly improved prediction of sex-specific abnormal LVEF (c-statistic 0.66 vs 0.71), LVEF <50% (0.66 vs 0.76) and LVEF <45% (0.80 vs 0.86). While no survivor met the preset probability threshold in the first two models, the third model used five ECG variables to predict LVEF <45% and was applicable for ruling out (sensitivity 93%, specificity 56%, negative predictive value 99.6%). Calibration and internal validation tests performed well. Conclusion: A clinical prediction model with ECG data (left bundle branch block, left atrial enlargement, left heart axis, Cornell's criteria for left ventricular hypertrophy and heart rate) may aid in ruling out LVEF <45%.

Published
2024

7. Adverse late health outcomes among children treated with 3D radiotherapy techniques:Study design of the Dutch pediatric 3D-RT study

Author

Beijer, Josien G.M., Kok, Judith L., Janssens, Geert O., Streefkerk, Nina, de Vries, Andrica C.H., Slagter, Cleo, Maduro, John H., Kroon, Petra S., Grootenhuis, Martha A., van Dulmen-den Broeder, Eline, Loonen, Jacqueline J., Wendling, Markus, Tissing, Wim J.E., van der Pal, Helena J., Louwerens, Marloes, Bel, Arjan, den Hartogh, Jaap, van der Heiden-van der Loo, Margriet, Kremer, Leontien C.M., Teepen, Jop C., Ronckers, Cécile M., Beijer, Josien G.M., Kok, Judith L., Janssens, Geert O., Streefkerk, Nina, de Vries, Andrica C.H., Slagter, Cleo, Maduro, John H., Kroon, Petra S., Grootenhuis, Martha A., van Dulmen-den Broeder, Eline, Loonen, Jacqueline J., Wendling, Markus, Tissing, Wim J.E., van der Pal, Helena J., Louwerens, Marloes, Bel, Arjan, den Hartogh, Jaap, van der Heiden-van der Loo, Margriet, Kremer, Leontien C.M., Teepen, Jop C., and Ronckers, Cécile M.

Abstract

Background: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. Aims: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. Methods and Results: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000–2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9–14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. Conclusion: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.

Published
2023

8. Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors:A DCCSS LATER Study

Author

Merkx, Remy, Leerink, Jan M., Feijen, E. (Lieke) A.M., de Baat, Esmée C., Bellersen, Louise, Bresters, Dorine, van Dalen, Elvira C., van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, van den Heuvel-Eibrink, Marry M., Kok, Judith L., Louwerens, Marloes, Maas, Angela H.E.M., Neggers, Sebastian J.C.M.M., Ronckers, Cécile M., Teepen, Jop C., Teske, Arco J., Tissing, Wim J.E., de Vries, Andrica C.H., Weijers, Gert, de Korte, Chris L., Loonen, Jacqueline, Mavinkurve-Groothuis, Annelies M.C., van der Pal, Helena J.H., Kremer, Leontien C.M., Kok, Wouter E.M., Kapusta, Livia, Merkx, Remy, Leerink, Jan M., Feijen, E. (Lieke) A.M., de Baat, Esmée C., Bellersen, Louise, Bresters, Dorine, van Dalen, Elvira C., van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, van den Heuvel-Eibrink, Marry M., Kok, Judith L., Louwerens, Marloes, Maas, Angela H.E.M., Neggers, Sebastian J.C.M.M., Ronckers, Cécile M., Teepen, Jop C., Teske, Arco J., Tissing, Wim J.E., de Vries, Andrica C.H., Weijers, Gert, de Korte, Chris L., Loonen, Jacqueline, Mavinkurve-Groothuis, Annelies M.C., van der Pal, Helena J.H., Kremer, Leontien C.M., Kok, Wouter E.M., and Kapusta, Livia

Abstract

Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity. Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors. Methods: This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings. Of CCS, n = 1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RTheart]) and n = 143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression. Results: CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as <52% in men, <54% in women) occurred most commonly in CCS treated with anthracyclines and RTheart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RTheart, either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunction grade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RTheart dose. Abnormal GLS was associated with female sex, RTheart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors. Conclusions: Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-term CCS. Their diagnostic value may differ according to cardiotoxic expos

Published
2023

9. Questionnaire- and linkage-based outcomes in Dutch childhood cancer survivors:Methodology of the DCCSS LATER study part 1

Author

Teepen, Jop C., Kok, Judith L., Feijen, Elizabeth A.M., Loonen, Jacqueline J., van den Heuvel-Eibrink, Marry M., van der Pal, Helena J., Tissing, Wim J.E., Bresters, Dorine, Versluys, Birgitta, Grootenhuis, Martha A., Louwerens, Marloes, Neggers, Sebastian J.C.M.M., van Santen, Hanneke M., de Vries, Andrica, Janssens, Geert O., den Hartogh, Jaap G., van Leeuwen, Flora E., Hollema, Nynke, Streefkerk, Nina, Kilsdonk, Ellen, van der Heiden-van der Loo, Margriet, van Dulmen-den Broeder, Eline, Ronckers, Cécile M., Kremer, Leontien C.M., Teepen, Jop C., Kok, Judith L., Feijen, Elizabeth A.M., Loonen, Jacqueline J., van den Heuvel-Eibrink, Marry M., van der Pal, Helena J., Tissing, Wim J.E., Bresters, Dorine, Versluys, Birgitta, Grootenhuis, Martha A., Louwerens, Marloes, Neggers, Sebastian J.C.M.M., van Santen, Hanneke M., de Vries, Andrica, Janssens, Geert O., den Hartogh, Jaap G., van Leeuwen, Flora E., Hollema, Nynke, Streefkerk, Nina, Kilsdonk, Ellen, van der Heiden-van der Loo, Margriet, van Dulmen-den Broeder, Eline, Ronckers, Cécile M., and Kremer, Leontien C.M.

Abstract

Background: Childhood cancer survivors are at risk for developing long-term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well-established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963–2001) part 1; questionnaire and linkage studies. Methods: The LATER cohort includes 5-year childhood cancer survivors, diagnosed in the period 1963–2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries. Results: In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations. Conclusion: Research with data of the LATER cohort will provide new insights into risks of and risk factors for long-term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long-term adverse health outcomes. The data collected will be a solid baseline foundation for future follow-up studies.

Published
2023

10. Adverse late health outcomes among children treated with 3D radiotherapy techniques: Study design of the Dutch pediatric 3D-RT study

Author

MS Radiotherapie, Cancer, PMC Medisch specialisten, Klinische Fysica RT, Child Health, Zorg en O&O, Beijer, Josien G.M., Kok, Judith L., Janssens, Geert O., Streefkerk, Nina, de Vries, Andrica C.H., Slagter, Cleo, Maduro, John H., Kroon, Petra S., Grootenhuis, Martha A., van Dulmen-den Broeder, Eline, Loonen, Jacqueline J., Wendling, Markus, Tissing, Wim J.E., van der Pal, Helena J., Louwerens, Marloes, Bel, Arjan, den Hartogh, Jaap, van der Heiden-van der Loo, Margriet, Kremer, Leontien C.M., Teepen, Jop C., Ronckers, Cécile M., MS Radiotherapie, Cancer, PMC Medisch specialisten, Klinische Fysica RT, Child Health, Zorg en O&O, Beijer, Josien G.M., Kok, Judith L., Janssens, Geert O., Streefkerk, Nina, de Vries, Andrica C.H., Slagter, Cleo, Maduro, John H., Kroon, Petra S., Grootenhuis, Martha A., van Dulmen-den Broeder, Eline, Loonen, Jacqueline J., Wendling, Markus, Tissing, Wim J.E., van der Pal, Helena J., Louwerens, Marloes, Bel, Arjan, den Hartogh, Jaap, van der Heiden-van der Loo, Margriet, Kremer, Leontien C.M., Teepen, Jop C., and Ronckers, Cécile M.

Published
2023

11. Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors: A PanCareSurFup Study.

Author

Heymer, Emma J., Jóźwiak, Katarzyna, Kremer, Leontien C., Winter, David L., de Vathaire, Florent, Sunguc, Ceren, Sugden, Elaine, Kok, Judith L., van der Pal, Helena J.H., Hjorth, Lars, Jakab, Zsuzsanna, Maule, Milena M., Haupt, Riccardo, Bagnasco, Francesca, Terenziani, Monica, Diallo, Ibrahima, Gunnes, Maria W., Sommer, Grit, Zadravec Zaletel, Lorna, and Kuehni, Claudia E.

Published
2024
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12. Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study

Author

Reulen, Raoul C., primary, Winter, David L., additional, Diallo, Ibrahim, additional, Veres, Cristina, additional, Llanas, Damien, additional, Allodji, Rodrigue S., additional, Bagnasco, Francesca, additional, Bárdi, Edit, additional, Feijen, Elizabeth A.M., additional, Alessi, Daniela, additional, Fidler-Benaoudia, Miranda M., additional, Høgsholt, Stine, additional, Teepen, Jop C., additional, Linge, Helena, additional, Haddy, Nadia, additional, Byrne, Julianne, additional, Debiche, Ghazi, additional, Grabow, Desiree, additional, Gudmundsdottir, Thorgerdur, additional, Fauchery, Romain, additional, Zrafi, Wael, additional, Michel, Gisela, additional, Øfstaas, Hilde, additional, Kaatsch, Peter, additional, Vu-Bezin, Giao, additional, Jenkinson, Helen, additional, Kaiser, Melanie, additional, Skinner, Roderick, additional, Cole, Trevor, additional, Waespe, Nicolas, additional, Sommer, Grit, additional, Nordenfelt, Susanne, additional, Jankovic, Momcilo, additional, Lähteenmäki Taalas, Tuomas, additional, Maule, Milena M., additional, van der Pal, Helena J.H., additional, Ronckers, Cécile M., additional, van Leeuwen, Flora E., additional, Kok, Judith L., additional, Terenziani, Monica, additional, Winther Gunnes, Maria, additional, Wiebe, Thomas, additional, Sacerdote, Carlotta, additional, Jakab, Zsuzsanna, additional, Haupt, Riccardo, additional, Lähteenmäki, Päivi M., additional, Zadravec Zaletel, Lorna, additional, Kuehni, Claudia E., additional, Falck Winther, Jeanette, additional, Kremer, Leontien C.M., additional, Hjorth, Lars, additional, de Vathaire, Florent, additional, and Hawkins, Michael M., additional

Published
2023
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13. Adverse late health outcomes among children treated with 3D radiotherapy techniques: Study design of the Dutch pediatric 3D‐RT study

Author

Beijer, Josien G. M., primary, Kok, Judith L., additional, Janssens, Geert O., additional, Streefkerk, Nina, additional, de Vries, Andrica C. H., additional, Slagter, Cleo, additional, Maduro, John H., additional, Kroon, Petra S., additional, Grootenhuis, Martha A., additional, van Dulmen‐den Broeder, Eline, additional, Loonen, Jacqueline J., additional, Wendling, Markus, additional, Tissing, Wim J. E., additional, van der Pal, Helena J., additional, Louwerens, Marloes, additional, Bel, Arjan, additional, den Hartogh, Jaap, additional, van der Heiden‐van der Loo, Margriet, additional, Kremer, Leontien C. M., additional, Teepen, Jop C., additional, and Ronckers, Cécile M., additional

Published
2023
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14. Prevalence and Risk Factors for Hyposalivation and Xerostomia in Childhood Cancer Survivors Following Different Treatment Modalities—A Dutch Childhood Cancer Survivor Study Late Effects 2 Clinical Study (DCCSS LATER 2)

Author

Stolze, Juliette, primary, Teepen, Jop C., additional, Raber-Durlacher, Judith E., additional, Loonen, Jacqueline J., additional, Kok, Judith L., additional, Tissing, Wim J. E., additional, de Vries, Andrica C. H., additional, Neggers, Sebastian J. C. M. M., additional, van Dulmen-den Broeder, Eline, additional, van den Heuvel-Eibrink, Marry M., additional, van der Pal, Helena J. H., additional, Versluys, A. Birgitta, additional, van der Heiden-van der Loo, Margriet, additional, Louwerens, Marloes, additional, Kremer, Leontien C. M., additional, Brand, Henk S., additional, and Bresters, Dorine, additional

Published
2022
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15. Prevalence and Risk Factors for Hyposalivation and Xerostomia in Childhood Cancer Survivors Following Different Treatment Modalities-A Dutch Childhood Cancer Survivor Study Late Effects 2 Clinical Study (DCCSS LATER 2)

Author

Stolze, Juliette, Teepen, J.C., Raber-Durlacher, Judith E., Loonen, J.J., Kok, Judith L., Tissing, W.J.E., Brand, Henk S., Bresters, Dorine, Stolze, Juliette, Teepen, J.C., Raber-Durlacher, Judith E., Loonen, J.J., Kok, Judith L., Tissing, W.J.E., Brand, Henk S., and Bresters, Dorine

Abstract

Contains fulltext : 253198.pdf (Publisher’s version ) (Open Access)

Published
2022

16. Questionnaire‐ and linkage‐based outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER study part 1.

Author

Teepen, Jop C., Kok, Judith L., Feijen, Elizabeth A. M., Loonen, Jacqueline J., van den Heuvel‐Eibrink, Marry M., van der Pal, Helena J., Tissing, Wim J. E., Bresters, Dorine, Versluys, Birgitta, Grootenhuis, Martha A., Louwerens, Marloes, Neggers, Sebastian J. C. M. M., van Santen, Hanneke M., de Vries, Andrica, Janssens, Geert O., den Hartogh, Jaap G., van Leeuwen, Flora E., Hollema, Nynke, Streefkerk, Nina, and Kilsdonk, Ellen

Subjects
*CHILDHOOD cancer, *CANCER survivors, *MEDICAL registries, *MEDICAL care use, *PEDIATRIC oncology, *CANCER fatigue
Abstract

Background: Childhood cancer survivors are at risk for developing long‐term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well‐established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963–2001) part 1; questionnaire and linkage studies. Methods: The LATER cohort includes 5‐year childhood cancer survivors, diagnosed in the period 1963–2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries. Results: In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations. Conclusion: Research with data of the LATER cohort will provide new insights into risks of and risk factors for long‐term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long‐term adverse health outcomes. The data collected will be a solid baseline foundation for future follow‐up studies. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch Hodgkin Late Effects and LATER Cohorts

Author

Moskowitz, Chaya S., primary, Ronckers, Cécile M., additional, Chou, Joanne F., additional, Smith, Susan A., additional, Friedman, Danielle Novetsky, additional, Barnea, Dana, additional, Kok, Judith L., additional, de Vries, Simone, additional, Wolden, Suzanne L., additional, Henderson, Tara O., additional, van der Pal, Helena J. H., additional, Kremer, Leontien C. M., additional, Neglia, Joseph P., additional, Turcotte, Lucie M., additional, Howell, Rebecca M., additional, Arnold, Michael A., additional, Schaapveld, Michael, additional, Aleman, Berthe, additional, Janus, Cecile, additional, Versluys, Birgitta, additional, Leisenring, Wendy, additional, Sklar, Charles A., additional, Begg, Colin B., additional, Pike, Malcolm C., additional, Armstrong, Gregory T., additional, Robison, Leslie L., additional, van Leeuwen, Flora E., additional, and Oeffinger, Kevin C., additional

Published
2021
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18. Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors: A Dutch LATER study

Author

Verbruggen, Lisanne C., primary, Kok, Judith L., additional, Teepen, Jop C., additional, Janssens, Geert O., additional, de Boer, Charlotte M., additional, Stalpers, Lukas J.A., additional, Vernooij, Meike W., additional, van Dulmen-den Broeder, Eline, additional, Loonen, Jacqueline J., additional, van den Heuvel-Eibrink, Marry M., additional, Tissing, Wim J.E., additional, van der Heiden-van der Loo, Margriet, additional, Versluys, Anne Birgitta, additional, Neggers, Sebastian J.C.M.M., additional, van Leeuwen, Flora E., additional, Hoving, Eelco W., additional, Wesseling, Pieter, additional, Kremer, Leontine C.M., additional, Ronckers, Cécile M., additional, van der Pal, Helena J.H., additional, Louwerens, Marloes, additional, de Vries, Andrica, additional, Jaspers, Monique, additional, Hollema, Nynke, additional, den Hartogh, Jaap, additional, and Schouten-van Meeteren, Netteke, additional

Published
2021
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19. Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors: A Dutch LATER study

Author

Verbruggen, Lisanne C., Kok, Judith L., Teepen, J.C., Janssens, Geert O., Boer, Charlotte M. de, Stalpers, Lukas J. A., Loonen, J.J., Ronckers, C.M., Pal, Helena J.H. van der, Verbruggen, Lisanne C., Kok, Judith L., Teepen, J.C., Janssens, Geert O., Boer, Charlotte M. de, Stalpers, Lukas J. A., Loonen, J.J., Ronckers, C.M., and Pal, Helena J.H. van der

Abstract

Contains fulltext : 233881.pdf (Publisher’s version ) (Closed access)

Published
2021

20. Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort : Contributions of radiation dose, exposed cranial volume, and age

Author

Kok, Judith L, Teepen, Jop C, van Leeuwen, Flora E, Tissing, Wim J E, Neggers, Sebastian J C M M, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, Birgitta, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, Aleman, Berthe M P, Daniels, Laurien A, Haasbeek, Cornelis J A, Hoeben, Bianca, Janssens, Geert O, Maduro, John H, Oldenburger, Foppe, van Rij, Caroline, Tersteeg, Robbert J H A, Hauptmann, Michael, Kremer, Leontien C M, Ronckers, Cécile M, and DCOG-LATER Study Group

Subjects
Cancer Research, Oncology, childhood cancer survivors, Clinical Neurology, cranial radiotherapy, radiation volume, radiation dose, meningioma
Abstract

Background. Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy. Methods. The Dutch Cancer Oncology Group-Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling. Results. Among 5843 CCSs (median follow-up: 23.3 y, range: 5.0-52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.01-0.15), while increased risks were observed for CrRT doses of 20-39 Gy (HR = 1.66, 95% CI: 0.83-3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30-6.08). CCSs whose cancers were diagnosed before age 5 versus 10-17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39-4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86-3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03-unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%-15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62-7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT. Conclusion. After CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians.

Published
2019

22. Colorectal Adenomas and Cancers After Childhood Cancer Treatment : A DCOG-LATER Record Linkage Study

Author

Teepen, J C, Kok, Judith L, van Leeuwen, Flora E, Tissing, Wim J E, Dolsma, Wil V, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, A B, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van den Berg, Marleen H, van der Heiden-van der Loo, Margriet, Hauptmann, Michael, Jongmans, M C, Overbeek, L I, van de Vijver, M J, Kremer, L C M, Ronckers, C M, Aleman, B M P, van den Berg, M H, Caron, H N, Daniels, L A, Dolsma, W, van Dulmen-den Broeder, E, Grootenhuis, M A, Haasbeek, C J, den Hartogh, J G, Hauptmann, M, van der Heiden-van der Loo, M, Hollema, N, Janssens, G O, Jaspers, M W M, Kok, J L, van Leeuwen, F E, Loonen, J, Maduro, J H, Neggers, S J C M M, Oldenburger, F, van der Pal, H J, Postma, A, Tersteeg, R J, Zsíros, J, and DCOG-LATER Study Group

Abstract

Background: Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk. Methods: The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n = 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided. Results: Among 5843 five-year survivors (median follow-up = 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval [CI] = 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI = 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference = .07) and vs 1.0% (95% CI = 0.3% to 2.6%) among siblings (6 cases) (Pdifference = .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] = 2.12, 95% CI = 1.24 to 3.60), total body irradiation (TBI; HR = 10.55, 95% CI = 5.20 to 21.42), cisplatin (HR = 2.13; 95% CI = 0.74 to 6.07 for

Published
2018

24. Incidence of and Risk Factors for Histologically Confirmed Solid Benign Tumors Among Long-term Survivors of Childhood Cancer

Author

Kok, Judith L., Teepen, J.C., Pal, Helena J. van der, Leeuwen, F.E. van, Tissing, W.J., Neggers, Sebastian J. C. M. M., Loonen, J.J., Hoeben, B.A.W., Jongmans, M.C.J., Kremer, L.C., Ronckers, C., Rij, C.M. van, Tersteeg, R.J.H.A., Kok, Judith L., Teepen, J.C., Pal, Helena J. van der, Leeuwen, F.E. van, Tissing, W.J., Neggers, Sebastian J. C. M. M., Loonen, J.J., Hoeben, B.A.W., Jongmans, M.C.J., Kremer, L.C., Ronckers, C., Rij, C.M. van, and Tersteeg, R.J.H.A.

Abstract

Contains fulltext : 204007.pdf (Publisher’s version ) (Closed access)

Published
2019

25. Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age

Author

Kok, Judith L., Teepen, J.C., Leeuwen, F.E. van, Tissing, W.J., Neggers, Sebastian J. C. M. M., Pal, Helena J. van der, Loonen, J.J., Hoeben, B.A.W., Kremer, L.C., Ronckers, C.M., Kok, Judith L., Teepen, J.C., Leeuwen, F.E. van, Tissing, W.J., Neggers, Sebastian J. C. M. M., Pal, Helena J. van der, Loonen, J.J., Hoeben, B.A.W., Kremer, L.C., and Ronckers, C.M.

Abstract

Contains fulltext : 202450.pdf (publisher's version ) (Closed access)

Published
2019

26. Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study

Author

Teepen, J.C., Kok, Judith L., Kremer, Leontien C., Tissing, W.J., Heuvel-Eibrink, M.M. van den, Loonen, J.J., Neggers, Sebastian J. C. M. M., Schaapveld, M., Teepen, J.C., Kok, Judith L., Kremer, Leontien C., Tissing, W.J., Heuvel-Eibrink, M.M. van den, Loonen, J.J., Neggers, Sebastian J. C. M. M., and Schaapveld, M.

Abstract

Contains fulltext : 209672.pdf (Publisher’s version ) (Closed access)

Published
2019

27. Long-Term Risk of Skin Cancer among Childhood Cancer Survivors : A DCOG-LATER Cohort Study

Author

Teepen, Jop C., Kok, Judith L., Kremer, Leontien C., Tissing, Wim J.E., Van Den Heuvel-Eibrink, Marry M., Loonen, Jacqueline J., Bresters, Dorine, Van Der Pal, Helena J., Versluys, Birgitta, Van Dulmen-Den Broeder, Eline, Nijsten, Tamar, Hauptmann, Michael, Hollema, Nynke, Dolsma, Wil V., Van Leeuwen, Flora E., Ronckers, Cécile M., Teepen, Jop C., Kok, Judith L., Kremer, Leontien C., Tissing, Wim J.E., Van Den Heuvel-Eibrink, Marry M., Loonen, Jacqueline J., Bresters, Dorine, Van Der Pal, Helena J., Versluys, Birgitta, Van Dulmen-Den Broeder, Eline, Nijsten, Tamar, Hauptmann, Michael, Hollema, Nynke, Dolsma, Wil V., Van Leeuwen, Flora E., and Ronckers, Cécile M.

Published
2019

28. Incidence of and Risk Factors for Histologically Confirmed Solid Benign Tumors among Long-term Survivors of Childhood Cancer

Author

PMC Medisch specialisten, SCT patientenzorg, Child Health, Speerpunt, Zorg en O&O, Endocrinologie patientenzorg, MS Radiotherapie, Cancer, Genetica Klinische Genetica, Klinische Fysica RT, Kok, Judith L., Teepen, Jop C., Van Der Pal, Helena J., Van Leeuwen, Flora E., Tissing, Wim J.E., Neggers, Sebastian J.C.M.M., Loonen, Jacqueline J., Louwerens, Marloes, Versluys, Birgitta, Van Den Heuvel-Eibrink, Marry M., Van Dulmen-Den Broeder, Eline, Jaspers, Monique M.W., Van Santen, Hanneke M., Van Der Heiden-Van Der Loo, Margriet, Janssens, Geert O., Maduro, John H., Bruggink, Annette H., Jongmans, Marjolijn C., Kremer, Leontien C.M., Ronckers, Cécile M., PMC Medisch specialisten, SCT patientenzorg, Child Health, Speerpunt, Zorg en O&O, Endocrinologie patientenzorg, MS Radiotherapie, Cancer, Genetica Klinische Genetica, Klinische Fysica RT, Kok, Judith L., Teepen, Jop C., Van Der Pal, Helena J., Van Leeuwen, Flora E., Tissing, Wim J.E., Neggers, Sebastian J.C.M.M., Loonen, Jacqueline J., Louwerens, Marloes, Versluys, Birgitta, Van Den Heuvel-Eibrink, Marry M., Van Dulmen-Den Broeder, Eline, Jaspers, Monique M.W., Van Santen, Hanneke M., Van Der Heiden-Van Der Loo, Margriet, Janssens, Geert O., Maduro, John H., Bruggink, Annette H., Jongmans, Marjolijn C., Kremer, Leontien C.M., and Ronckers, Cécile M.

Published
2019

29. Long-Term Risk of Skin Cancer among Childhood Cancer Survivors: A DCOG-LATER Cohort Study

Author

PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, Klinische Fysica RT, Teepen, Jop C., Kok, Judith L., Kremer, Leontien C., Tissing, Wim J.E., Van Den Heuvel-Eibrink, Marry M., Loonen, Jacqueline J., Bresters, Dorine, Van Der Pal, Helena J., Versluys, Birgitta, Van Dulmen-Den Broeder, Eline, Nijsten, Tamar, Hauptmann, Michael, Hollema, Nynke, Dolsma, Wil V., Van Leeuwen, Flora E., Ronckers, Cécile M., PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, Klinische Fysica RT, Teepen, Jop C., Kok, Judith L., Kremer, Leontien C., Tissing, Wim J.E., Van Den Heuvel-Eibrink, Marry M., Loonen, Jacqueline J., Bresters, Dorine, Van Der Pal, Helena J., Versluys, Birgitta, Van Dulmen-Den Broeder, Eline, Nijsten, Tamar, Hauptmann, Michael, Hollema, Nynke, Dolsma, Wil V., Van Leeuwen, Flora E., and Ronckers, Cécile M.

Published
2019

30. Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: Contributions of radiation dose, exposed cranial volume, and age

Author

PMC Medisch specialisten, SCT patientenzorg, Child Health, Zorg en O&O, MS Radiotherapie, Cancer, Klinische Fysica RT, Kok, Judith L, Teepen, Jop C, van Leeuwen, Flora E, Tissing, Wim J E, Neggers, Sebastian J C M M, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, Birgitta, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, Aleman, Berthe M P, Daniels, Laurien A, Haasbeek, Cornelis J A, Hoeben, Bianca, Janssens, Geert O, Maduro, John H, Oldenburger, Foppe, van Rij, Caroline, Tersteeg, Robbert J H A, Hauptmann, Michael, Kremer, Leontien C M, Ronckers, Cécile M, DCOG-LATER Study Group, PMC Medisch specialisten, SCT patientenzorg, Child Health, Zorg en O&O, MS Radiotherapie, Cancer, Klinische Fysica RT, Kok, Judith L, Teepen, Jop C, van Leeuwen, Flora E, Tissing, Wim J E, Neggers, Sebastian J C M M, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, Birgitta, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van der Heiden-van der Loo, Margriet, Aleman, Berthe M P, Daniels, Laurien A, Haasbeek, Cornelis J A, Hoeben, Bianca, Janssens, Geert O, Maduro, John H, Oldenburger, Foppe, van Rij, Caroline, Tersteeg, Robbert J H A, Hauptmann, Michael, Kremer, Leontien C M, Ronckers, Cécile M, and DCOG-LATER Study Group

Published
2019

31. Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study

Author

Genetica Klinische Genetica, PMC Medisch specialisten, SCT patientenzorg, Child Health, Zorg en O&O, Klinische Fysica RT, Speerpunt, MS Neonatologie, Fysica Radiotherapie Research, Onderzoeksgroep 7, Brain, ZL Cerebrovasculaire Ziekten Medisch, MS Radiotherapie, Cancer, Teepen, J C, Kok, Judith L, van Leeuwen, Flora E, Tissing, Wim J E, Dolsma, Wil V, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, A B, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van den Berg, Marleen H, van der Heiden-van der Loo, Margriet, Hauptmann, Michael, Jongmans, M C, Overbeek, L I, van de Vijver, M J, Kremer, L C M, Ronckers, C M, Aleman, B M P, van den Berg, M H, Caron, H N, Daniels, L A, Dolsma, W, van Dulmen-den Broeder, E, Grootenhuis, M A, Haasbeek, C J, den Hartogh, J G, Hauptmann, M, van der Heiden-van der Loo, M, Hollema, N, Janssens, G O, Jaspers, M W M, Kok, J L, van Leeuwen, F E, Loonen, J, Maduro, J H, Neggers, S J C M M, Oldenburger, F, van der Pal, H J, Postma, A, Tersteeg, R J, Zsíros, J, DCOG-LATER Study Group, Genetica Klinische Genetica, PMC Medisch specialisten, SCT patientenzorg, Child Health, Zorg en O&O, Klinische Fysica RT, Speerpunt, MS Neonatologie, Fysica Radiotherapie Research, Onderzoeksgroep 7, Brain, ZL Cerebrovasculaire Ziekten Medisch, MS Radiotherapie, Cancer, Teepen, J C, Kok, Judith L, van Leeuwen, Flora E, Tissing, Wim J E, Dolsma, Wil V, van der Pal, Helena J, Loonen, Jacqueline J, Bresters, Dorine, Versluys, A B, van den Heuvel-Eibrink, Marry M, van Dulmen-den Broeder, Eline, van den Berg, Marleen H, van der Heiden-van der Loo, Margriet, Hauptmann, Michael, Jongmans, M C, Overbeek, L I, van de Vijver, M J, Kremer, L C M, Ronckers, C M, Aleman, B M P, van den Berg, M H, Caron, H N, Daniels, L A, Dolsma, W, van Dulmen-den Broeder, E, Grootenhuis, M A, Haasbeek, C J, den Hartogh, J G, Hauptmann, M, van der Heiden-van der Loo, M, Hollema, N, Janssens, G O, Jaspers, M W M, Kok, J L, van Leeuwen, F E, Loonen, J, Maduro, J H, Neggers, S J C M M, Oldenburger, F, van der Pal, H J, Postma, A, Tersteeg, R J, Zsíros, J, and DCOG-LATER Study Group

Published
2018

32. Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.

Author

Teepen, Jop C, Kok, Judith L, Kremer, Leontien C, Tissing, Wim J E, Heuvel-Eibrink, Marry M van den, Loonen, Jacqueline J, Bresters, Dorine, Pal, Helena J van der, Versluys, Birgitta, Broeder, Eline van Dulmen-den, Nijsten, Tamar, Hauptmann, Michael, Hollema, Nynke, Dolsma, Wil V, Leeuwen, Flora E van, Ronckers, Cécile M, Group, DCOG-LATER Study, van den Heuvel-Eibrink, Marry M, van der Pal, Helena J, and van Dulmen-den Broeder, Eline

Subjects
*CHILDHOOD cancer, *SKIN cancer, *BASAL cell carcinoma, *CANCER patients, *CANCER risk factors, *CANCER radiotherapy complications, *ANTINEOPLASTIC agents
Abstract

Background: Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.Methods: The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.Results: Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).Conclusion: CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers. [ABSTRACT FROM AUTHOR]

Published
2019
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33. Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study.

Author

Teepen, Jop C., Kok, Judith L., van Leeuwen, Flora E., Tissing, Wim J. E., Dolsma, Wil V., van der Pal, Helena J., Loonen, Jacqueline J., Bresters, Dorine, Versluys, Birgitta, den Heuvel-Eibrink, Marry M. van, van Dulmen-den Broeder, Eline, den Berg, Marleen H. van, van der Heiden-van der Loo, Margriet, Hauptmann, Michael, Jongmans, Marjolijn C., Overbeek, Lucy I., de Vijver, Marc J. van, Kremer, Leontien C. M., Ronckers, Cécile M., and van den Heuvel-Eibrink, Marry M

Subjects
*COLON cancer treatment, *CHILDHOOD cancer, *TUMORS in children, *CANCER chemotherapy, *COHORT analysis
Abstract

Background: Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk.Methods: The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n = 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided.Results: Among 5843 five-year survivors (median follow-up = 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval [CI] = 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI = 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference = .07) and vs 1.0% (95% CI = 0.3% to 2.6%) among siblings (6 cases) (Pdifference = .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] = 2.12, 95% CI = 1.24 to 3.60), total body irradiation (TBI; HR = 10.55, 95% CI = 5.20 to 21.42), cisplatin (HR = 2.13; 95% CI = 0.74 to 6.07 for <480 mg/m²; HR = 3.85, 95% CI = 1.45 to 10.26 for ≥480 mg/m²; Ptrend = .62), a hepatoblastoma diagnosis (HR = 27.12, 95% CI = 8.80 to 83.58), and family history of early-onset CRC (HR = 20.46, 95% CI = 8.10 to 51.70). Procarbazine was statistically significantly associated among survivors without AP-RT/TBI (HR = 2.71, 95% CI = 1.28 to 5.74). Thirteen CRCs occurred.Conclusion: We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors. Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposis-associated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of CRC screening among high-risk childhood cancer survivors warrants consideration. [ABSTRACT FROM AUTHOR]

Published
2018
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34. Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort.

Author

Verbruggen LC, Kok JL, Kremer LCM, Janssens GO, Nederkoorn PJ, Penson A, Versluijs AB, de Vries ACH, Reedijk AMJ, Bresters D, Hoving EW, van Dulmen-den Broeder E, Loonen JJ, de Bont J, Wilbers J, Louwerens M, van der Heiden-van der Loo M, van den Heuvel-Eibrink MM, Pluijm SMF, Neggers SJCMM, Tissing WJE, Roos YBWEM, Ronckers CM, Teepen JC, and van der Pal HJH

Abstract

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed 50 Gy was associated with 6-fold increased risk, compared to upper body radiotherapy not involving the cranium (hazard ratio = 6.3, 95%CI: 3.3-12.1). In a subgroup with available data on lifestyle and comorbidities, hypertension (odds ratio[OR] = 6.2, 95%CI: 1.6-23.8) and obesity (BMI≥30 vs. <30 = 2.95, 95%CI: 1.1-8.0) significantly increased CVE risk. During CVE episode, 17 (16%) had a life-threatening situation, and two (2%) others died. In 28%, a second CVE developed during follow-up. At end of follow-up, 29% were deceased, and 40% of those alive were unable to carry out normal activities/active work. Childhood cancer survivors treated with higher doses of cranial radiotherapy are at highest risk for developing CVEs. CVEs occur at a young age and cause a high morbidity. Studies to investigate risk-reducing secondary preventive interventions are warranted., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2024
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35. Incidence of and Risk Factors for Histologically Confirmed Solid Benign Tumors Among Long-term Survivors of Childhood Cancer.

Author

Kok JL, Teepen JC, van der Pal HJ, van Leeuwen FE, Tissing WJE, Neggers SJCMM, Loonen JJ, Louwerens M, Versluys B, van den Heuvel-Eibrink MM, van Dulmen-den Broeder E, Jaspers MMW, van Santen HM, van der Heiden-van der Loo M, Janssens GO, Maduro JH, Bruggink AH, Jongmans MC, Kremer LCM, and Ronckers CM

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Cohort Studies, Female, Humans, Incidence, Male, Middle Aged, Neoplasms etiology, Neoplasms pathology, Netherlands epidemiology, Radiotherapy adverse effects, Registries, Risk Factors, Young Adult, Cancer Survivors statistics & numerical data, Neoplasms epidemiology
Abstract

Importance: Survivors of childhood cancer (CCSs) face risk of developing subsequent tumors. Solid benign tumors may be cancer precursors; benign tumors and cancers may share etiologic factors. However, comprehensive data on the risk for solid benign tumors are lacking., Objective: To quantify the incidence of and treatment-related risk factors for histologically confirmed solid nonskin benign tumors among CCSs., Design, Setting, and Participants: This record linkage study involves the Dutch Childhood Oncology Group-Long-Term Effects After Childhood Cancer (DCOG-LATER) cohort of 6165 individuals diagnosed with childhood cancer at younger than 18 years from January 1, 1963, through December 31, 2001, in 7 Dutch pediatric centers and who survived at least 5 years after the diagnosis. Study groups eligible for record linkage from 1990 onward included 5843 CCSs (94.8%) and 883 siblings. Benign tumors were identified from the population-based Dutch histopathology and cytopathology registry (PALGA). Follow-up was completed on May 1, 2015. Data were analyzed from January 1, 1990, through May 1, 2015., Main Outcomes and Measures: Cumulative incidence of any subsequent benign tumor for cohort strata and multivariable Cox proportional hazards regression models (hazard ratios [HRs]) were used to evaluate potential risk factors for 8 major benign tumor subtypes., Results: Of the 5843 eligible CCSs (55.9% male), 542 (9.3%) developed a histologically confirmed subsequent benign tumor after a median follow-up of 22.7 years (range, 5.0-52.2 years). Among women, abdominopelvic radiotherapy inferred dose-dependent increased risks for uterine leiomyoma (n = 43) for doses of less than 20 Gy (HR, 1.9; 95% CI, 0.5-7.0), 20 to less than 30 Gy (HR, 3.4; 95% CI, 1.1-10.4), and at least 30 Gy (HR, 5.4; 95% CI, 2.4-12.4) compared with no abdominopelvic radiotherapy (P = .002 for trend). High-dose radiotherapy to the trunk was not associated with breast fibroadenoma (n = 45). Of 23 osseous and/or chondromatous neoplasms, 16 occurred among leukemia survivors, including 11 after total body irradiation (HR, 37.4; 95% CI, 14.8-94.7). Nerve sheath tumors (n = 55) were associated with radiotherapy (HR at 31 years of age, 2.9; 95% CI, 1.5-5.5) and a crude indicator of neurofibromatosis type 1 or 2 status (HR, 5.6; 95% CI, 2.3-13.7). Subsequent risk for benign tumors was higher than the risks for subsequent nonskin solid malignant neoplasms and for benign tumors among siblings., Conclusions and Relevance: This record linkage study uses a unique resource for valid and complete outcome assessment and shows that CCSs have an approximately 2-fold risk of developing subsequent benign tumors compared with siblings. Site-specific new findings, including for uterine leiomyoma, osteochondroma, and nervous system tumors, are important to enable early diagnosis; this information will be the first step for future surveillance guidelines that include some benign tumors in CCSs and will provide leads for in-depth etiologic studies.

Published
2019
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36. Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age.

Author

Kok JL, Teepen JC, van Leeuwen FE, Tissing WJE, Neggers SJCMM, van der Pal HJ, Loonen JJ, Bresters D, Versluys B, van den Heuvel-Eibrink MM, van Dulmen-den Broeder E, van der Heiden-van der Loo M, Aleman BMP, Daniels LA, Haasbeek CJA, Hoeben B, Janssens GO, Maduro JH, Oldenburger F, van Rij C, Tersteeg RJHA, Hauptmann M, Kremer LCM, and Ronckers CM

Subjects
Adolescent, Adult, Age Factors, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Netherlands epidemiology, Organs at Risk, Proportional Hazards Models, Risk, Young Adult, Cancer Survivors, Cranial Irradiation, Meningeal Neoplasms epidemiology, Meningioma epidemiology, Neoplasms therapy, Neoplasms, Radiation-Induced epidemiology, Radiation Dosage
Abstract

Background: Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy., Methods: The Dutch Cancer Oncology Group-Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling., Results: Among 5843 CCSs (median follow-up: 23.3 y, range: 5.0-52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.01-0.15), while increased risks were observed for CrRT doses of 20-39 Gy (HR = 1.66, 95% CI: 0.83-3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30-6.08). CCSs whose cancers were diagnosed before age 5 versus 10-17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39-4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86-3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03-unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%-15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62-7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT., Conclusion: After CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2019
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