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1. Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Author

Drechsel, K. C. E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W. R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C. H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J. L., van Dulmen-den Broeder, E., and Veening, M. A.

Published
2023
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5. Questionnaire- and linkage-based outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER study part 1.

Author

Teepen, J.C., Kok, J.L., Feijen, E.A.M., Loonen, J.J., Heuvel-Eibrink, M.M. van den, Pal, H.J. van der, Tissing, W.J.E., Bresters, D., Versluys, B., Grootenhuis, M.A., Louwerens, M., Neggers, S.J., Santen, H.M. van, Vries, Andrica de, Janssens, G.O., Hartogh, J.G. den, Leeuwen, F.E. van, Hollema, N., Streefkerk, N., Kilsdonk, E., Heiden-van der Loo, M., Dulmen-den Broeder, E. van, Ronckers, C.M., Kremer, L.C.M., Teepen, J.C., Kok, J.L., Feijen, E.A.M., Loonen, J.J., Heuvel-Eibrink, M.M. van den, Pal, H.J. van der, Tissing, W.J.E., Bresters, D., Versluys, B., Grootenhuis, M.A., Louwerens, M., Neggers, S.J., Santen, H.M. van, Vries, Andrica de, Janssens, G.O., Hartogh, J.G. den, Leeuwen, F.E. van, Hollema, N., Streefkerk, N., Kilsdonk, E., Heiden-van der Loo, M., Dulmen-den Broeder, E. van, Ronckers, C.M., and Kremer, L.C.M.

Abstract

Item does not contain fulltext, 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

6. Clinical evaluation of late outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER 2 study.

Author

Feijen, E.A.M., Teepen, J.C., Dulmen-den Broeder, E. van, Heuvel-Eibrink, M.M. van den, Heiden-van der Loo, M., Pal, H.J. van der, Vries, A.C.M. de, Louwerens, M., Bresters, D., Versluys, B., Ridder, H. de, Veening, M., Leeuwen, F.E. van, Grootenhuis, M., Maurice-Stam, H., Santen, H.M. van, Neggers, S.J., Pluijm, S., Hartogh, J. den, Ronckers, C.M., Tissing, W.J.E., Groot-Loonen, J.J., Kremer, L.C.M., Feijen, E.A.M., Teepen, J.C., Dulmen-den Broeder, E. van, Heuvel-Eibrink, M.M. van den, Heiden-van der Loo, M., Pal, H.J. van der, Vries, A.C.M. de, Louwerens, M., Bresters, D., Versluys, B., Ridder, H. de, Veening, M., Leeuwen, F.E. van, Grootenhuis, M., Maurice-Stam, H., Santen, H.M. van, Neggers, S.J., Pluijm, S., Hartogh, J. den, Ronckers, C.M., Tissing, W.J.E., Groot-Loonen, J.J., and Kremer, L.C.M.

Abstract

Item does not contain fulltext, BACKGROUND: Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer Survivor Study (DCCSS) cross-sectional clinical study (LATER 2 study). PROCEDURE: From the multi-center DCCSS LATER cohort of 6165 five-year survivors diagnosed during 1963-2001, we invited 4735 eligible survivors in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome-specific subprojects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research-defined measurements (physical examination, clinical tests, questionnaires). Furthermore, blood/saliva samples were taken for deoxyribonucleic acid (DNA) extraction. RESULTS: In total, 2519 (53.2%) survivors participated in the LATER 2 study. When comparing participants with nonparticipants, we observed that males, CNS survivors, and those treated with surgery only were less likely to participate. Of the participating survivors, 49.3% were female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8-54.7 years) and median attained age was 34.4 years (range 15.4-66.6 years). CONCLUSIONS: The high-quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and physical and psychosocial health outcomes and factors for early recognition of those health outcomes in long-term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.

Published
2023

7. High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency

Author

Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., Vasen, H.F.A., Ghorbanoghli, Z., Kouwen, M.C.A. van, Versluys, B., Bonnet, D., Devalck, C., Tinat, J., Januszkiewicz-Lewandowska, D., Costas, C.C., Cottereau, E., Hardwick, J.C.H., Wimmer, K., Brugieres, L., Colas, C., and Vasen, H.F.A.

Abstract

Contains fulltext : 294692.pdf (Publisher’s version ) (Closed access), BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme. METHODS: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients. RESULTS: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive. CONCLUSION: The study suggests a beneficial effect of surveillance of the digestive tract and brains.

Published
2023

8. Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study

Author

Penson, A., Walraven, I., Bronkhorst, E., Grootenhuis, M. A., Maurice-Stam, H., de Beijer, I., van der Heiden-van der Loo, M., Tissing, W. J.E., van der Pal, H. J.H., de Vries, A. C.H., Bresters, D., Ronckers, C. M., van den Heuvel-Eibrink, M. M., Neggers, S., Versluys, B. A.B., Louwerens, M., Pluijm, S. M.F., Blijlevens, N., van Dulmen-den Broeder, E., Kremer, L. C.M., Knoop, H., Loonen, J., Penson, A., Walraven, I., Bronkhorst, E., Grootenhuis, M. A., Maurice-Stam, H., de Beijer, I., van der Heiden-van der Loo, M., Tissing, W. J.E., van der Pal, H. J.H., de Vries, A. C.H., Bresters, D., Ronckers, C. M., van den Heuvel-Eibrink, M. M., Neggers, S., Versluys, B. A.B., Louwerens, M., Pluijm, S. M.F., Blijlevens, N., van Dulmen-den Broeder, E., Kremer, L. C.M., Knoop, H., and Loonen, J.

Abstract

Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). Patients and methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the ‘fatigue severity subscale’ of the Checklist Individual Strength (‘CIS-fatigue’). CF was defined as scoring ≥35 on the ‘CIS-fatigue’ and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.

Published
2023

9. Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Author

Drechsel, K. C.E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W.R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C.H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J.L., van Dulmen-den Broeder, E., Veening, M. A., Drechsel, K. C.E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W.R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C.H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J.L., van Dulmen-den Broeder, E., and Veening, M. A.

Abstract

Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion:HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

Published
2023

10. Frailty and sarcopenia within the earliest Dutch childhood cancer survivor cohort (n=2,003)

Author

Atteveld, J.E. van, Winter, D.T.C. de, Pluimakers, V.G., Fiocco, M., Nievelstein, R.A.J., Hobbelink, M.G.G., Kremer, L.C.M., Ronckers, C.M., Grootenhuis, M.A., Maurice-Stam, H., Tissing, W.J.E., Vries Andrica, C.H. de, Loonen, J.J., Dulmen-den Broeder, E. van, Pal, H.J. van der, Pluijm, S., Heiden-van der Loo, M. van der, Versluys, B., Louwerens, M., Bresters, D., Santen, H.M. van, Hoefer, I., Berg, S.A.A., van den, Hoeijmakers, J.H.J., Neggers, S.J.C.M.M., and Heuvel-Eibrink, M.M. van den

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

12. Support needs of Dutch young adult childhood cancer survivors

Author

Erp, L., Maurice-Stam, H., Kremer, L., Tissing, W., Pal, H., Beek, L., Vries, A., Den Heuvel-Eibrink, M., Versluys, B., Heiden-Van Loo, M., Marloes van Gorp, Huizinga, G., Grootenhuis, M., Paediatric Oncology, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Child and Adolescent Psychiatry & Psychosocial Care, Pediatrics, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Adult, Health Services Needs and Demand, Adolescent, Psychosocial support, Survivorship care, Social Support, Survivorship, Young Adult, Cancer Survivors, Oncology, SDG 3 - Good Health and Well-being, Neoplasms, Surveys and Questionnaires, Quality of Life, Humans, Original Article, Child, Childhood cancer, Needs, Young adults
Abstract

Background Studies about support needs of young adult childhood cancer survivors (YACCS) previously focused mainly on information needs. This study assessed support needs and associated factors (sociodemographic, medical, and psychosocial functioning) in Dutch YACCS. Methods YACCS (aged 18–30, diagnosed ≤ 18 years, time since diagnosis ≥ 5 years) cross-sectionally filled out a questionnaire regarding their need for various types of support (concrete information, personal counseling, and peer contact) in eight domains (physical consequences of childhood cancer, social-emotional consequences, relationships and sexuality, fertility, lifestyle, school and work, future perspective, insurance and mortgage), and questionnaires assessing health-related quality of life (PedsQL-YA), anxiety and depression (HADS), and fatigue (CIS-20R). Descriptive statistics were used to describe support needs. Linear regression was used to identify characteristics associated with support needs. Results One hundred fifty-one YACCS participated (response = 40%). Most YACCS reported a need for support in one or more domains (88.0%, N = 133). More than half of the participants reported a need for concrete information in the domains lifestyle, fertility, and physical consequences of childhood cancer and 25–50% in the domains insurance and mortgages, future perspective, and social-emotional consequences of childhood cancer. In the domains lifestyle and physical as well as emotional consequences of childhood cancer, 25–50% reported a need for counseling. Overall need for support was positively associated with middle (β = 0.26, p = 0.024) and high (β = 0.35, p = 0.014) compared to low educational attainment and (sub)clinical anxiety (β = 0.22, p = 0.017), and negatively associated with social functioning (β = − 0.37, p = 0.002) in multivariate analyses. Conclusion YACCS report the strongest need for support, for concrete information, in the domains lifestyle, fertility, and physical consequences of childhood cancer. Associated factors were mostly socioeconomic and psychosocial in nature. Psychosocial care should be an integral part of survivorship care for YACCS, with screening for psychosocial problems, information provision including associated emotional consequences and support if necessary (psycho-education) and tailored interventions, and adequate referrals to more specialized care if necessary.

Published
2022

13. Support needs of Dutch young adult childhood cancer survivors

Author

PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, van Erp, L M E, Maurice-Stam, H, Kremer, L C M, Tissing, W J E, van der Pal, H J H, Beek, L, de Vries, A C H, van den Heuvel-Eibrink, M M, Versluys, B A B, van der Heiden-van der Loo, M, van Gorp, M, Huizinga, G A, Grootenhuis, M A, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, van Erp, L M E, Maurice-Stam, H, Kremer, L C M, Tissing, W J E, van der Pal, H J H, Beek, L, de Vries, A C H, van den Heuvel-Eibrink, M M, Versluys, B A B, van der Heiden-van der Loo, M, van Gorp, M, Huizinga, G A, and Grootenhuis, M A

Published
2022

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

Author

Teepen, JC, Kok, JL, Kremer, LC, Tissing, WJ, Van den Heuvel - Eibrink, Marry, Loonen, JJ, Bresters, D, van der Pal, HJ, Versluys, B, van Dulmen-den Broeder, E, Nijsten, Tamar, Hauptmann, M, Hollema, N, Dolsma, WV, van Leeuwen, FE, Ronckers, CM, Caron, HN, Daniels, LA, Bruggink, AH, Grootenhuis, MA, den Hartogh, JG, te Loo, M, Jaspers, MWM, Neggers, S.J.C.M.M., Schaapveld, M, Pediatrics, Dermatology, Internal Medicine, Epidemiology and Data Science, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, CCA - Cancer Treatment and quality of life, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, Gerontology, Cancer Research, 2ND MALIGNANCIES, Neoplasms, Radiation-Induced, NETHERLANDS, BASAL-CELL CARCINOMA, Cohort Studies, 0302 clinical medicine, Cancer Survivors, Risk Factors, Neoplasms, 030212 general & internal medicine, Young adult, Child, Melanoma, Articles, Middle Aged, SUBSEQUENT, COMPETING RISKS, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, MALIGNANT NEOPLASMS, Carcinoma, Squamous Cell, Female, SQUAMOUS-CELL, Cohort study, Adult, Adolescent, Drug-Related Side Effects and Adverse Reactions, Childhood cancer, MEDLINE, TRANSPLANT RECIPIENTS, Radiation Dosage, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Drug Therapy, RADIATION-THERAPY, medicine, Humans, Vinca Alkaloids, Proportional Hazards Models, Radiotherapy, Proportional hazards model, business.industry, Cancer, medicine.disease, IRRADIATION, Long term risk, Carcinoma, Basal Cell, Skin cancer, business
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.

Published
2019

15. Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort

Author

Teepen, J.C., Kremer, L.C., Heiden-van der Loo, M. van der, Tissing, W.J., Pal, H.J. van der, Heuvel-Eibrink, M.M. van den, Loonen, J.J., Louwerens, M., Versluys, B., Dulmen-den Broeder, E. van, Visser, O., Maduro, J.H., Leeuwen, F.E. van, Ronckers, C.M., Bresters, D., Batenburg, L., Veening, M., Huizinga, G., Steeg, L. van der, Jaspers, M., Vries, A. de, Aleman, B.M.P., Caron, H.N., Grootenhuis, M.A., Hartogh, J.G. den, Hollema, N., Neggers, S.J.C.M.M., Postma, A., Ridder-Sluiter, J.G. de, Rutgers, E.J.T., DCOG-LATER Study Grp, Graduate School, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Paediatric Oncology, Child and Adolescent Psychiatry & Psychosocial Care, APH - Mental Health, APH - Methodology, Epidemiology and Data Science, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, CCA - Cancer Treatment and quality of life, Pediatrics, Internal Medicine, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Oncology, Male, Cancer Research, Skin Neoplasms, PROGNOSIS, Survival, Epidemiology, medicine.medical_treatment, Childhood cancer survivors, Cohort Studies, SOFT-TISSUE SARCOMAS, 0302 clinical medicine, Cancer Survivors, Neoplasms, Medicine, 030212 general & internal medicine, Sarcoma/epidemiology, Child, 2ND PRIMARY, Melanoma, Netherlands, RISK, education.field_of_study, Breast Neoplasms/epidemiology, Hazard ratio, Neoplasms, Second Primary, Sarcoma, 030220 oncology & carcinogenesis, HEALTH OUTCOMES, Skin Neoplasms/epidemiology, Female, Adult, medicine.medical_specialty, Population, Long-term complications, Second Primary/epidemiology, Breast Neoplasms, Melanoma/epidemiology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Breast cancer, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Internal medicine, PRIMARY THYROID-CANCER, Journal Article, Humans, education, business.industry, Proportional hazards model, HODGKINS-LYMPHOMA, Cancer, LONG-TERM SURVIVAL, 5-YEAR SURVIVORS, medicine.disease, Survival Analysis, Cancer registry, Subsequent malignant neoplasm, Radiation therapy, RADIATION, Neoplasms, Second Primary/epidemiology, business
Abstract

PURPOSE: Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) and a population-based sample of similar first malignant neoplasm (FMN) patients.METHODS: We assembled three case series of solid SMNs observed in a cohort of 5-year Dutch childhood cancer survivors diagnosed 1963-2001 and followed until 2014: sarcoma (n = 45), female breast cancer (n = 41), and melanoma (n = 17). Each SMN patient was sex-, age-, and calendar year-matched to 10 FMN patients in the population-based Netherlands Cancer Registry. We compared clinical and histopathological characteristics by Fisher's exact tests and survival by multivariable Cox regression and competing risk regression analyses.RESULTS: Among sarcoma-SMN patients, overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.23-2.87] and sarcoma-specific mortality (HR 1.91, 95% CI 1.16-3.13) were significantly worse compared to sarcoma-FMN patients (foremost for soft-tissue sarcoma), with 15-year survival rates of 30.8% and 61.6%, respectively. Overall survival did not significantly differ for breast-SMN versus breast-FMN patients (HR 1.14, 95% CI 0.54-2.37), nor for melanoma-SMN versus melanoma-FMN patients (HR 0.71, 95% CI 0.10-5.00). No significant differences in tumor characteristics were observed between breast-SMN and breast-FMN patients. Breast-SMN patients were treated more often with mastectomy without radiotherapy/chemotherapy compared to breast-FMN patients (17.1% vs. 5.6%).CONCLUSIONS: Survival of sarcoma-SMN patients is worse than sarcoma-FMN patients. Although survival and tumor characteristics appear similar for breast-SMN and breast-FMN patients, treatment differs; breast-SMN patients less often receive breast-conserving therapy. Larger studies are necessary to substantiate these exploratory findings.

Published
2019

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

Author

Kok, J.L., Teepen, J.C., Leeuwen, F.E. van, Tissing, W.J.E., Neggers, S.J.C.M.M., Pal, H.J. van der, Loonen, J.J., Bresters, D., Versluys, B., Heuvel-Eibrink, M.M. van den, Dulmen-den Broeder, E. van, Heiden-van der Loo, M. van der, Aleman, B.M.P., Daniels, L.A., Haasbeek, C.J.A., Hoeben, B., Janssens, G.O., Maduro, J.H., Oldenburger, F., Rij, C. van, Tersteeg, R.J.H.A., Hauptmann, M., Kremer, L.C.M., Ronckers, C.M., Berg, M.H. van den, Bruggink, A.H., Caron, H.N., Dolsma, W.V., Grootenhuis, M.A., Hartogh, J.G. den, Hollema, N., Jongmans, M.C., Jaspers, M.W.M., Postma, A., Vijver, M.J. van de, DCOG-LATER Study Group, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Paediatric Oncology, Graduate School, Epidemiology and Data Science, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, CCA - Cancer Treatment and quality of life, Radiation Oncology, Pediatrics, Radiotherapy, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, Organs at Risk, PROTOCOL, Cancer Research, Neoplasms, Radiation-Induced, meningioma, chemistry.chemical_compound, 0302 clinical medicine, Cancer Survivors, Neoplasms, Meningeal Neoplasms, Cumulative incidence, Child, radiation volume, Netherlands, education.field_of_study, Hazard ratio, Age Factors, INTENSIVE TREATMENT, TUMORS, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, CNS, radiation dose, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], RADIOTHERAPY, Adult, Risk, medicine.medical_specialty, Adolescent, childhood cancer survivors, Population, Clinical Neurology, cranial radiotherapy, Radiation Dosage, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Meningioma, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, education, TERM-FOLLOW-UP, Proportional Hazards Models, ACUTE LYMPHOBLASTIC-LEUKEMIA, SUBSEQUENT NEOPLASMS, business.industry, CENTRAL-NERVOUS-SYSTEM, Infant, Newborn, Infant, Cancer, 5-YEAR SURVIVORS, medicine.disease, Carboplatin, chemistry, Relative risk, Benign Meningioma, Neurology (clinical), Cranial Irradiation, business, Pediatric Neuro-Oncology, 030217 neurology & neurosurgery
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

17. Female reproductive function after treatment of childhood acute lymphoblastic leukemia

Author

Roshandel, R., Dijk, M. van, Overbeek, A., Kaspers, G., Lambalk, C., Beerendonk, C.C., Bresters, D., Heiden-van der Loo, M., Heuvel-Eibrink, M. van den, Kremer, L., Loonen, J.J., Pal, H. Van der, Ronckers, C., Tissing, W., Versluys, B., Leeuwen, F van, Berg, M. van den, Dulmen-den Broeder, E. van, Roshandel, R., Dijk, M. van, Overbeek, A., Kaspers, G., Lambalk, C., Beerendonk, C.C., Bresters, D., Heiden-van der Loo, M., Heuvel-Eibrink, M. van den, Kremer, L., Loonen, J.J., Pal, H. Van der, Ronckers, C., Tissing, W., Versluys, B., Leeuwen, F van, Berg, M. van den, and Dulmen-den Broeder, E. van

Abstract

Contains fulltext : 244604.pdf (Publisher’s version ) (Closed access), BACKGROUND: The aim was to evaluate self-reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. PROCEDURE: Self-reported reproductive characteristics were assessed by questionnaire among 357 adult 5-year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]-only group, CT and radiotherapy [RT] group) were analyzed. RESULTS: Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1-0.6], 0.5 [0.3-0.9], and 0.4 [0.2-0.9], respectively). Survivors in the CT-only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function. CONCLUSION: Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.

Published
2021

18. Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

Author

Perk, M.E.M. van der, Broer, L., Yasui, Y., Robison, L.L., Hudson, M.M., Laven, J. S. E., Pal, H.J. van der, Tissing, W.J., Versluys, B., Bresters, D., Kaspers, G.J., Vries, A.C.M. de, Lambalk, C.B., Overbeek, A., Loonen, J.J., Beerendonk, C.C.M., Byrne, J., Berger, C., Clemens, E., Dirksen, U., Winther, J. Falck, Fosså, S.D., Grabow, D., Muraca, M., Kaiser, M., Kepák, T., Kruseova, J., Modan-Moses, D., Spix, C., Zolk, O., Kaatsch, P., Krijthe, J.H., Kremer, L.C., Brooke, R.J., Baedke, J.L., Schaik, R.H. van, Anker, J.N. van den, Uitterlinden, A.G., Bos, A.M., Leeuwen, F.E. van, Dulmen-den Broeder, E. van, Kooi, A.L. Van der, Heuvel-Eibrink, M.M. van den, PanCare, L.C. On Behalf Of Th, Perk, M.E.M. van der, Broer, L., Yasui, Y., Robison, L.L., Hudson, M.M., Laven, J. S. E., Pal, H.J. van der, Tissing, W.J., Versluys, B., Bresters, D., Kaspers, G.J., Vries, A.C.M. de, Lambalk, C.B., Overbeek, A., Loonen, J.J., Beerendonk, C.C.M., Byrne, J., Berger, C., Clemens, E., Dirksen, U., Winther, J. Falck, Fosså, S.D., Grabow, D., Muraca, M., Kaiser, M., Kepák, T., Kruseova, J., Modan-Moses, D., Spix, C., Zolk, O., Kaatsch, P., Krijthe, J.H., Kremer, L.C., Brooke, R.J., Baedke, J.L., Schaik, R.H. van, Anker, J.N. van den, Uitterlinden, A.G., Bos, A.M., Leeuwen, F.E. van, Dulmen-den Broeder, E. van, Kooi, A.L. Van der, Heuvel-Eibrink, M.M. van den, and PanCare, L.C. On Behalf Of Th

Abstract

Contains fulltext : 237733.pdf (Publisher’s version ) (Open Access), BACKGROUND: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. METHODS: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1-30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6-37.4). RESULTS: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): -0.706 (-1.11--0.298), p-value = 7 × 10(-4)) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126-0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m(2) CED. CONCLUSIONS: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatme

Published
2021

19. Metabolic syndrome parameters, determinants, and biomarkers in adult survivors of childhood cancer: Protocol for the Dutch childhood cancer survivor study on metabolic syndrome (Dutch LATER METS)

Author

Pluimakers, V. (Vincent), Fiocco, M. (Marta), van Atteveld, J. (Jenneke), Hobbelink, M. (Monique), Bresters, D. (Dorine), Dulmen-den Broeder, E. (Eline) van, Heiden-Van der Loo, M. (Margriet) van der, Janssens, G.O. (Geert), Kremer, L.C.M. (Leontien), Loonen, J.J. (Jacqueline), Louwerens, M. (Marlous), van der Pal, H. (Helena), Ronckers, C. (Cécile), Van Santen, H.M. (Hanneke M.), Versluys, B. (Birgitta), Vries, A.C.H. (Andrica) de, Heuvel-Eibrink, M.M. (Marry) van den, Neggers, S. (Sebastian), Pluimakers, V. (Vincent), Fiocco, M. (Marta), van Atteveld, J. (Jenneke), Hobbelink, M. (Monique), Bresters, D. (Dorine), Dulmen-den Broeder, E. (Eline) van, Heiden-Van der Loo, M. (Margriet) van der, Janssens, G.O. (Geert), Kremer, L.C.M. (Leontien), Loonen, J.J. (Jacqueline), Louwerens, M. (Marlous), van der Pal, H. (Helena), Ronckers, C. (Cécile), Van Santen, H.M. (Hanneke M.), Versluys, B. (Birgitta), Vries, A.C.H. (Andrica) de, Heuvel-Eibrink, M.M. (Marry) van den, and Neggers, S. (Sebastian)

Abstract

Background: Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia, and hypertension. These risk factors cluster together as metabolic syndrome and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis, and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no national cohort studies on the prevalence and determinants of metabolic syndrome in childhood cancer survivors, including biomarkers and genetic predisposition, are available. Objective: The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of metabolic syndrome and its separate components, and 2) the potential diagnostic and predictive value of additional biomarkers for surveillance of metabolic syndrome in the national cohort of adult long-term survivors of childhood cancer. Methods

Published
2021
Full Text
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20. Metabolic syndrome parameters, determinants, and biomarkers in adult survivors of childhood cancer: Protocol for the Dutch childhood cancer survivor study on metabolic syndrome (Dutch LATER METS)

Author

Pluimakers, V, Fiocco, M, van Atteveld, J, Hobbelink, M, Bresters, D, van Dulmen-Den Broeder, E, van der Heiden-van der Loo, M, Janssens, GO, Kremer, L, Loonen, J, Louwerens, M, van der Pal, H, Ronckers, C, van Santen, H, Versluys, B, de Vries, A.C.H., van den Heuvel-Eibrink, M, Neggers, S.J.C.M.M., Pluimakers, V, Fiocco, M, van Atteveld, J, Hobbelink, M, Bresters, D, van Dulmen-Den Broeder, E, van der Heiden-van der Loo, M, Janssens, GO, Kremer, L, Loonen, J, Louwerens, M, van der Pal, H, Ronckers, C, van Santen, H, Versluys, B, de Vries, A.C.H., van den Heuvel-Eibrink, M, and Neggers, S.J.C.M.M.

Abstract

Background: Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia, and hypertension. These risk factors cluster together as metabolic syndrome and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis, and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no national cohort studies on the prevalence and determinants of metabolic syndrome in childhood cancer survivors, including biomarkers and genetic predisposition, are available. Objective: The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of metabolic syndrome and its separate components, and 2) the potential diagnostic and predictive value of additional biomarkers for surveillance of metabolic syndrome in the national cohort of adult long-term survivors of childhood cancer. Methods: This is a cross-sectional study based on recruitment of all survivors treated in the Netherlands between 1963 and 2002. Metabolic syndrome will be classified according to the definitions of the third Adult Treatment Panel Report of the National Cholesterol Education Program as well as the Joint Interim Statement and compared to reference data. Dual-energy x-ray absorptiometry scans were performed to assess body composition in more detail. The effect of patient characteristics, previous treatment, and genetic variation on the risk of metabolic syndrome will be assessed. The diagnostic and predictive value of novel biomarkers will be tested. Results: Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors from 7 pediatric oncology hospitals have participated. From July 2020, biomarker testing, single nucleotide polymorphism analysis, and data analysis will be performed. Conclusions: The Dutch LATER METS study will provide knowledge on clinic

Published
2021

23. Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

Author

Dijk, M van, Leeuwen, F.E. van, Overbeek, A., Lambalk, C.B., Heuvel-Eibrink, M.M. van den, Dorp, W. van, Tissing, W.J., Kremer, L.C., Loonen, J.J., Versluys, B., Bresters, D., Ronckers, C.M., Pal, H.J. van der, Beerendonk, C.C.M., Kaspers, G.J., Dulmen-den Broeder, E. van, Berg, M.H. van den, Dijk, M van, Leeuwen, F.E. van, Overbeek, A., Lambalk, C.B., Heuvel-Eibrink, M.M. van den, Dorp, W. van, Tissing, W.J., Kremer, L.C., Loonen, J.J., Versluys, B., Bresters, D., Ronckers, C.M., Pal, H.J. van der, Beerendonk, C.C.M., Kaspers, G.J., Dulmen-den Broeder, E. van, and Berg, M.H. van den

Abstract

Contains fulltext : 220530.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. METHODS: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. RESULTS: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4-0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3-3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2-2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. CONCLUSION: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated.

Published
2020

24. Risk factors associated with tinnitus in 2948 Dutch survivors of childhood cancer: a Dutch LATER questionnaire study

Author

Meijer, A.J.H.M., Fiocco, M.F., Janssens, G.O., Clemens, E., Tissing, W.J., Loonen, J.J., Dulmen-den Broeder, E. van, Vries, A.C.M. de, Bresters, D., Versluys, B., Ronckers, C.M., Kremer, L.C., Pal, H.J. van der, Neggers, S., Heiden-van der Loo, M., Stokroos, R.J., Hoetink, A.E., Grotel, M. van, Heuvel-Eibrink, M.M. van den, Meijer, A.J.H.M., Fiocco, M.F., Janssens, G.O., Clemens, E., Tissing, W.J., Loonen, J.J., Dulmen-den Broeder, E. van, Vries, A.C.M. de, Bresters, D., Versluys, B., Ronckers, C.M., Kremer, L.C., Pal, H.J. van der, Neggers, S., Heiden-van der Loo, M., Stokroos, R.J., Hoetink, A.E., Grotel, M. van, and Heuvel-Eibrink, M.M. van den

Abstract

Contains fulltext : 229315.pdf (publisher's version ) (Open Access), BACKGROUND: Tinnitus is a serious late effect of childhood cancer treatment. The aim of this study was to determine the occurrence and risk factors for tinnitus in a national cohort of childhood cancer survivors (CCS). METHODS: Data were collected within the national Dutch Childhood Oncology Group - Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort by a self-reported health questionnaire among 5327 Dutch CCS treated between 1963 and 2002. Siblings (N = 1663) were invited to complete the same questionnaire. Relevant patient characteristics and treatment factors were obtained from the Dutch LATER database. The occurrence of tinnitus in survivors was compared to siblings. To study the effect of risk factors, multivariate logistic regression models were estimated. RESULTS: In total, 2948 CCS and 1055 siblings completed the tinnitus item. Tinnitus was reported in 9.5% of survivors and in 3.7% of siblings (odds ratio [OR] 3.0, 95% confidence interval [CI] 2.9-3.1). Risk factors associated with tinnitus in CCS were total cumulative dose cisplatin ≥400 mg/m(2) (OR 2.4, 95% CI 1.4-4.0), age at diagnosis (≥10 years: OR 2.1, 95% CI 1.6-2.8), cranial irradiation/total body irradiation (TBI; OR 1.9, 95% CI 1.5-2.5), and neuro/ear, nose, throat (ENT) surgery (OR 1.8, 95% CI 1.1-2.9). Fifty-one percent of CCS with tinnitus had received treatment with either cisplatin, cranial irradiation/TBI, and/or neuro/ENT surgery. CONCLUSIONS: Tinnitus in CCS was present nearly 3 times more often than in siblings. Awareness in CCS previously treated with cisplatin, cranial irradiation/TBI, and/or neuro/ENT surgery is warranted. As only half of affected CCS had a history of these treatments, it seems that other factors might be associated with tinnitus occurrence in this population.

Published
2020

25. Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

Author

van Dijk, M. (M.), Leeuwen, F.E. (Flora) van, Overbeek, A. (Annelies), Lambalk, C.B. (Cornelius), Heuvel-Eibrink, M.M. (Marry) van den, Dorp, W. (Wendy) van, Tissing, W.J.E. (Wim), Kremer, L.C.M. (Leontien), Loonen, J.J. (Jacqueline), Versluys, B. (B.), Bresters, D. (Dorine), Ronckers, C.M. (Cécile), van der Pal, H.J. (H. J.), Beerendonk, C.C.M. (Catharina), Kaspers, G.J.L. (Gertjan), Dulmen-den Broeder, E. (Eline) van, Berg, M.H. (Marleen) van den, van Dijk, M. (M.), Leeuwen, F.E. (Flora) van, Overbeek, A. (Annelies), Lambalk, C.B. (Cornelius), Heuvel-Eibrink, M.M. (Marry) van den, Dorp, W. (Wendy) van, Tissing, W.J.E. (Wim), Kremer, L.C.M. (Leontien), Loonen, J.J. (Jacqueline), Versluys, B. (B.), Bresters, D. (Dorine), Ronckers, C.M. (Cécile), van der Pal, H.J. (H. J.), Beerendonk, C.C.M. (Catharina), Kaspers, G.J.L. (Gertjan), Dulmen-den Broeder, E. (Eline) van, and Berg, M.H. (Marleen) van den

Abstract

Purpose: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. Methods: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. Results: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. Conclusion: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated.

Published
2020
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26. Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children

Author

Uden, T., Bertaina, A., Abrahamsson, J., Ansari, M., Balduzzi, A., Bourquin, J. -P., Gerhardt, C., Bierings, M., Hasle, H., Lankester, A., Mischke, K., Moore, A. S., Nivison-Smith, I., Pieczonka, A., Peters, C., Sedlacek, P., Reinhardt, D., Stein, J., Versluys, B., Wachowiak, J., Willems, L., Zimmermann, M., Locatelli, Franco, Sauer, M. G., Locatelli F. (ORCID:0000-0002-7976-3654), Uden, T., Bertaina, A., Abrahamsson, J., Ansari, M., Balduzzi, A., Bourquin, J. -P., Gerhardt, C., Bierings, M., Hasle, H., Lankester, A., Mischke, K., Moore, A. S., Nivison-Smith, I., Pieczonka, A., Peters, C., Sedlacek, P., Reinhardt, D., Stein, J., Versluys, B., Wachowiak, J., Willems, L., Zimmermann, M., Locatelli, Franco, Sauer, M. G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%.

Published
2020

27. Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children

Author

Uden, T, Bertaina, A, Abrahamsson, J, Ansari, M, Balduzzi, A, Bourquin, J, Gerhardt, C, Bierings, M, Hasle, H, Lankester, A, Mischke, K, Moore, A, Nivison-Smith, I, Pieczonka, A, Peters, C, Sedlacek, P, Reinhardt, D, Stein, J, Versluys, B, Wachowiak, J, Willems, L, Zimmermann, M, Locatelli, F, Sauer, M, Uden, Theodor, Bertaina, Alice, Abrahamsson, Jonas, Ansari, Marc, Balduzzi, Adriana, Bourquin, Jean-Pierre, Gerhardt, Corinne, Bierings, Marc, Hasle, Henrik, Lankester, Arjan, Mischke, Kirsten, Moore, Andrew S, Nivison-Smith, Ian, Pieczonka, Anna, Peters, Christina, Sedlacek, Petr, Reinhardt, Dirk, Stein, Jerry, Versluys, Birgitta, Wachowiak, Jacek, Willems, Leen, Zimmermann, Martin, Locatelli, Franco, Sauer, Martin G, Uden, T, Bertaina, A, Abrahamsson, J, Ansari, M, Balduzzi, A, Bourquin, J, Gerhardt, C, Bierings, M, Hasle, H, Lankester, A, Mischke, K, Moore, A, Nivison-Smith, I, Pieczonka, A, Peters, C, Sedlacek, P, Reinhardt, D, Stein, J, Versluys, B, Wachowiak, J, Willems, L, Zimmermann, M, Locatelli, F, Sauer, M, Uden, Theodor, Bertaina, Alice, Abrahamsson, Jonas, Ansari, Marc, Balduzzi, Adriana, Bourquin, Jean-Pierre, Gerhardt, Corinne, Bierings, Marc, Hasle, Henrik, Lankester, Arjan, Mischke, Kirsten, Moore, Andrew S, Nivison-Smith, Ian, Pieczonka, Anna, Peters, Christina, Sedlacek, Petr, Reinhardt, Dirk, Stein, Jerry, Versluys, Birgitta, Wachowiak, Jacek, Willems, Leen, Zimmermann, Martin, Locatelli, Franco, and Sauer, Martin G

Abstract

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%.

Published
2020

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

Author

Kok, J.L., Teepen, J.C., Pal, H.J. van der, Leeuwen, F.E. van, Tissing, W.J.E., Neggers, S.J.C.M.M., Loonen, J.J., Louwerens, M., Versluys, B., Heuvel-Eibrink, M. van den, Dulmen-den Broeder, E. van, Jaspers, M.M.W., Santen, H.M. van, Heiden-van der Loo, M. van der, Janssens, G.O., Maduro, J.H., Bruggink, A.H., Jongmans, M.C., Kremer, L.C.M., Ronckers, C.M., Aleman, B.M.P., Berg, M.H. van den, Bresters, D., Caron, H.N., Clement, S.C., Daniels, L.A., Dolsma, W.V., Grootenhuis, M.A., Haasbeek, C.J.A., Hoeben, B.A.W., Hartogh, J.G. den, Hollema, N., Oldenburger, F., Postma, A., Rij, C.M. van, Tersteeg, R.J.H.A., DCOG-LATER Study Grp, Guided Treatment in Optimal Selected Cancer Patients (GUTS), CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, Internal Medicine, Radiotherapy, Graduate School, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Medical Informatics, APH - Aging & Later Life, APH - Methodology, Paediatric Oncology, and APH - Societal Participation & Health

Subjects
Oncology, Osteochondroma, Adult, Male, medicine.medical_specialty, Cancer Research, Adolescent, Uterine fibroids, Population, Benign tumor, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Cancer Survivors, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Breast Fibroadenoma, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Registries, education, Child, Original Investigation, Aged, Netherlands, education.field_of_study, Radiotherapy, business.industry, Incidence, Hazard ratio, Cancer, 5-YEAR SURVIVORS, DCOG-LATER, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, Child, Preschool, Female, business, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], NEOPLASMS, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

IMPORTANC E 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. OBJECT; VE 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], 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 CC5s (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 llafter total body irradiation (HR, 37.4; 95% CI, 14.8-94.7). Nerve sheath tumors (n = 55) were associated with radiotherapy (HR at 31years of age, 2.9; 95% CI, 1.5-5.5) and a crude indicator of neurofibromatosis type lor 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

31. Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors

Author

Loo, L. van de, Berg, M.H. van den, Overbeek, A., Dijk, M van, Damen, L., Lambalk, C.B., Ronckers, C.M., Heuvel-Eibrink, M.M. van den, Kremer, L.C., Pal, H.J. van der, Laven, J.S., Tissing, W.J., Loonen, J.J., Versluys, B., Bresters, D., Kaspers, G.J., Leeuwen, F.E. van, Broeder, E. van Dulmen-den, Loo, L. van de, Berg, M.H. van den, Overbeek, A., Dijk, M van, Damen, L., Lambalk, C.B., Ronckers, C.M., Heuvel-Eibrink, M.M. van den, Kremer, L.C., Pal, H.J. van der, Laven, J.S., Tissing, W.J., Loonen, J.J., Versluys, B., Bresters, D., Kaspers, G.J., Leeuwen, F.E. van, and Broeder, E. van Dulmen-den

Abstract

Contains fulltext : 202764.pdf (publisher's version ) (Closed access), OBJECTIVE: To evaluate whether abdominal-pelvic radiotherapy for childhood cancer impairs uterine function and increases the risk of pregnancy complications and adverse pregnancy outcomes. DESIGN: Nested cohort study. SETTING: Not applicable. PATIENT(S): Childhood cancer survivors previously exposed to abdominal-pelvic radiotherapy (RT-exposed CCSs) as part of their treatment for childhood cancer. INTERVENTION(S): Radiotherapy-exposed CCSs (n = 55) were age- and parity-matched to nonirradiated CCSs (non-RT-exposed CCSs; n = 110) and general population controls (n = 110). MAIN OUTCOME MEASURES: Uterine volume, pregnancy complications, and pregnancy outcomes. RESULT(S): Among nulligravidous participants, median (interquartile range) uterine volume was 41.4 (18.6-52.8) mL for RT-exposed CCSs, 48.1 (35.7-61.8) mL for non-RT-exposed CCSs, and 61.3 (49.1-75.5) mL for general population controls. Radiotherapy-exposed CCSs were at increased risk of a reduced uterine volume (<44.3 mL) compared with population controls (odds ratio [OR] 5.31 [95% confidence interval 1.98-14.23]). Surprisingly, the same was true for non-RT-exposed CCSs (OR 2.61 [1.16-5.91]). Among gravidous participants, RT-exposed CCSs had increased risks of pregnancy complications, preterm delivery, and a low birth weight infant compared with population controls (OR 12.70 [2.55-63.40], OR 9.74 [1.49-63.60], and OR 15.66 [1.43-171.35], respectively). Compared with non-RT-exposed CCSs, RT-exposed CCSs were at increased risk of delivering a low birth weight infant (OR 6.86 [1.08-43.75]). CONCLUSION(S): Uterine exposure to radiotherapy during childhood reduces adult uterine volume and leads to an increased risk of pregnancy complications and adverse pregnancy outcomes. Preconceptional counseling and appropriate obstetric monitoring is warranted.

Published
2019

32. Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort

Author

Teepen, JC, Kremer, LC, te Loo, M, Tissing, WJ, van der Pal, HJ, Van den Heuvel - Eibrink, Marry, Loonen, JJ, Louwerens, M, Versluys, B, van Dulmen-den Broeder, E, Visser, O, Maduro, JH, van Leeuwen, FE, Ronckers, CM, Bresters, D, Batenburg, L, Veening, M, Huizinga, G, van der Steeg, L, Jaspers, M, Vries, AC, Aleman, BMP, Caron, HN, Grootenhuis, MA, den Hartogh, JG, Hollema, N, Neggers, S.J.C.M.M., Postma, A, de Ridder-Sluiter, JG, Rutgers, EJT, Teepen, JC, Kremer, LC, te Loo, M, Tissing, WJ, van der Pal, HJ, Van den Heuvel - Eibrink, Marry, Loonen, JJ, Louwerens, M, Versluys, B, van Dulmen-den Broeder, E, Visser, O, Maduro, JH, van Leeuwen, FE, Ronckers, CM, Bresters, D, Batenburg, L, Veening, M, Huizinga, G, van der Steeg, L, Jaspers, M, Vries, AC, Aleman, BMP, Caron, HN, Grootenhuis, MA, den Hartogh, JG, Hollema, N, Neggers, S.J.C.M.M., Postma, A, de Ridder-Sluiter, JG, and Rutgers, EJT

Published
2019

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

Author

Teepen, J.C., Kok, J.L., Leeuwen, F.E. van, Tissing, W.J., Dolsma, W.V., Pal, H.J. van der, Loonen, J.J., Bresters, D., Versluys, B., Heuvel-Eibrink, M.M. van den, Dulmen-den Broeder, E. van, Berg, M.H. van den, Loo, M. te, Hauptmann, M., Jongmans, M.C.J., Overbeek, L.I., Vijver, M.J. van de, Kremer, L.C., Ronckers, C.M., Teepen, J.C., Kok, J.L., Leeuwen, F.E. van, Tissing, W.J., Dolsma, W.V., Pal, H.J. van der, Loonen, J.J., Bresters, D., Versluys, B., Heuvel-Eibrink, M.M. van den, Dulmen-den Broeder, E. van, Berg, M.H. van den, Loo, M. te, Hauptmann, M., Jongmans, M.C.J., Overbeek, L.I., Vijver, M.J. van de, Kremer, L.C., and Ronckers, C.M.

Abstract

Item does not contain fulltext, 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/m(2); HR = 3.85, 95% CI = 1.45 to 10.26 for >/=480 mg/m(2); 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 aden

Published
2018

34. Reproductive intentions and use of reproductive health care among female survivors of childhood cancer

Author

Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., Van Dulmen-Den Broeder, E., Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., and Van Dulmen-Den Broeder, E.

Published
2018

35. Reproductive intentions and use of reproductive health care among female survivors of childhood cancer

Author

Speerpunt Child Health, Child Health, Longziekten onderzoek 1, PMC Medisch specialisten, Zorg en O&O, SCT patientenzorg, Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., Van Dulmen-Den Broeder, E., Speerpunt Child Health, Child Health, Longziekten onderzoek 1, PMC Medisch specialisten, Zorg en O&O, SCT patientenzorg, Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., and Van Dulmen-Den Broeder, E.

Published
2018

36. Long-term effect of childhood cancer treatment on ovarian function markers: final results of the DCOG-LATER VEVO study

Author

Overbeek, A., Berg, M. van den, Lambalk, C., Kaspers, G., Bresters, D., Heuvel-Eibrink, M. van den, Kremer, L., Loonen, J., Tissing, W., Versluys, B., Hauptmann, M., Twisk, J., Leeuwen, F. van, Dulmen-den Broeder, E. van, Amsterdam Reproduction & Development, CCA - Treatment and quality of life, VU University medical center, ACS - Atherosclerosis & ischemic syndromes, Pediatrics, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Epidemiology and Data Science, and APH - Quality of Care

Published
2017

37. Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy

Author

Teepen, J.C., Leeuwen, F.E. van, Tissing, W.J., Dulmen-den Broeder, E. van, Heuvel-Eibrink, M.M. van den, Pal, H.J. van der, Loonen, J.J., Bresters, D., Versluys, B., Neggers, S.J.C.M.M., Jaspers, M.W.M., Hauptmann, M., Heiden-van der Loo, M. van der, Visser, O., Kremer, L.C.M., Ronckers, C.M., DCOG LATER Study Grp, CCA - Cancer Treatment and Quality of Life, Paediatric Oncology, Graduate School, APH - Quality of Care, CCA -Cancer Center Amsterdam, APH - Societal Participation & Health, APH - Aging & Later Life, Medical Informatics, ARD - Amsterdam Reproduction and Development, CCA - Cancer Treatment and quality of life, Epidemiology and Data Science, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Pediatrics, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Time Factors, Lymphoma, medicine.medical_treatment, Soft Tissue Neoplasms, Central Nervous System Neoplasms, Li-Fraumeni Syndrome, 0302 clinical medicine, TUMOR-INDUCTION, Medicine, Registries, Child, IARC TP53 DATABASE, Netherlands, Leukemia, NESTED CASE-CONTROL, Incidence, Absolute risk reduction, Neoplasms, Second Primary, Sarcoma, Chemoradiotherapy, Middle Aged, COMPETING RISKS, ALKYLATING-AGENTS, Adult Survivors of Child Adverse Events, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Adolescent, Antineoplastic Agents, Bone Neoplasms, Breast Neoplasms, Risk Assessment, Young Adult, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, RADIATION-THERAPY, Internal medicine, Humans, BREAST-CANCER, Ifosfamide, SPRAGUE-DAWLEY RATS, SECONDARY SARCOMAS, Cyclophosphamide, Aged, Proportional Hazards Models, HODGKINS-DISEASE, Gynecology, business.industry, Infant, Newborn, Infant, Cancer, medicine.disease, Cancer registry, Radiation therapy, 030104 developmental biology, Standardized mortality ratio, Doxorubicin, Nested case-control study, business
Abstract

Purpose Childhood cancer survivors (CCSs) are at increased risk for subsequent malignant neoplasms (SMNs). We evaluated the long-term risk of SMNs in a well-characterized cohort of 5-year CCSs, with a particular focus on individual chemotherapeutic agents and solid cancer risk. Methods The Dutch Childhood Cancer Oncology Group–Long-Term Effects After Childhood Cancer cohort includes 6,165 5-year CCSs diagnosed between 1963 and 2001 in the Netherlands. SMNs were identified by linkages with the Netherlands Cancer Registry, the Dutch Pathology Registry, and medical chart review. We calculated standardized incidence ratios, excess absolute risks, and cumulative incidences. Multivariable Cox proportional hazard regression analyses were used to evaluate treatment-associated risks for breast cancer, sarcoma, and all solid cancers. Results After a median follow-up of 20.7 years (range, 5.0 to 49.8 years) since first diagnosis, 291 SMNs were ascertained in 261 CCSs (standardized incidence ratio, 5.2; 95% CI, 4.6 to 5.8; excess absolute risk, 20.3/10,000 person-years). Cumulative SMN incidence at 25 years after first diagnosis was 3.9% (95% CI, 3.4% to 4.6%) and did not change noticeably among CCSs treated in the 1990s compared with those treated earlier. We found dose-dependent doxorubicin-related increased risks of all solid cancers ( Ptrend < .001) and breast cancer ( Ptrend < .001). The doxorubicin-breast cancer dose response was stronger in survivors of Li-Fraumeni syndrome–associated childhood cancers (leukemia, CNS, and non-Ewing sarcoma) versus survivors of other cancers ( Pdifference = .008). In addition, cyclophosphamide was found to increase sarcoma risk in a dose-dependent manner ( Ptrend = .01). Conclusion The results strongly suggest that doxorubicin exposure in CCSs increases the risk of subsequent solid cancers and breast cancer, whereas cyclophosphamide exposure increases the risk of subsequent sarcomas. These results may inform future childhood cancer treatment protocols and SMN surveillance guidelines for CCSs.

Published
2017

38. Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors

Author

Clemens, E., Vries, A.C. de, Zehnhoff-Dinnesen, A.A., Tissing, W.J., Loonen, J.J., Pluijm, S.F., Dulmen-den Broeder, E. van, Bresters, D., Versluys, B., Kremer, L.C., Pal, H.J. van der, Neggers, S.J., Grotel, M. van, Heuvel-Eibrink, M.M. van den, Clemens, E., Vries, A.C. de, Zehnhoff-Dinnesen, A.A., Tissing, W.J., Loonen, J.J., Pluijm, S.F., Dulmen-den Broeder, E. van, Bresters, D., Versluys, B., Kremer, L.C., Pal, H.J. van der, Neggers, S.J., Grotel, M. van, and Heuvel-Eibrink, M.M. van den

Abstract

Contains fulltext : 175119.pdf (publisher's version ) (Open Access), Cisplatin and carboplatin are effective antineoplastic agents. They are also considered to be potentially highly ototoxic. To date, no long-term follow-up data from well-documented cohorts with substantial numbers of childhood cancer survivors (CCS) with platinum-related hearing loss are available. Therefore, in this study, we studied the reversibility of ototoxicity from discontinuation of treatment onwards in a national cohort of platinum-treated survivors with hearing loss at the end of cancer treatment. Of the 168 CCS with follow-up audiograms, we longitudinally evaluated the course of hearing function in 61 CCS who showed hearing impairment at discontinuation of treatment according to the Munster criteria (>20 dB at >/=4-8 kHz). Survivors were treated with platinum (median total cumulative dose cisplatin: 480 mg/m2 and median total cumulative dose carboplatin: 2520 mg/m2). Median follow-up time was 5.5 years (range: 1.0-28.8 years). The results showed that none of these survivors revealed improvement of hearing function even till 28.8 years after discontinuation of treatment (grade <2b during long-term follow-up). An increase in hearing loss with two or three Munster degrees was observed in five of 61 survivors after 1.6-19.6 years. Overall, this indicates that ototoxicity after platinum treatment may be irreversible and that longitudinal clinical audiological monitoring and care is required in long-term survivors of childhood cancer on a large scale.

Published
2017

39. Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors

Author

Clemens, Eva, de Vries, A.C.H., Zehnhoff-Dinnesen, AA, Tissing, WJE, Loonen, JJ, Pluijm, Saskia, van Dulmen-den Broeder, E, Bresters, D, Versluys, B, Kremer, LCM (Leontien), van der Pal, HJ, Neggers, S.J.C.M.M., van Grotel, M, Van den Heuvel - Eibrink, Marry, Clemens, Eva, de Vries, A.C.H., Zehnhoff-Dinnesen, AA, Tissing, WJE, Loonen, JJ, Pluijm, Saskia, van Dulmen-den Broeder, E, Bresters, D, Versluys, B, Kremer, LCM (Leontien), van der Pal, HJ, Neggers, S.J.C.M.M., van Grotel, M, and Van den Heuvel - Eibrink, Marry

Published
2017

43. Lowest numbers of primary CD8+ T cells can reconstitute protective immunity upon adoptive immunotherapy

Author

Stemberger, C., Graef, P., Odendahl, M., Albrecht, J., Doessinger, G., Anderl, F., Buchholz, V.R., Gasteiger, G., Schiemann, M., Grigoleit, G.U., Schuster, F.R., Borkhardt, A., Versluys, B., Tonn, T., Seifried, E., Einsele, H., Germeroth, L., Busch, D.H., and Neuenhahn, M.

Abstract

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols. To establish a lower limit for successful adoptive T-cell therapy, we conducted low-dose CD8(+) T-cell transfers in the well-established murine Listeria monocytogenes (L.m.) infection model. Major histocompatibility complex-Streptamer-enriched antigen-specific CD62L(hi) but not CD62L(io) CD8(+) memory T cells proliferated, differentiated, and protected against L.m. infections after prophylactic application. Even progenies derived from a single CD62L(hi) L.m.-specific CD8(+) T cell could be protective against bacterial challenge. In analogy, low-dose transfers of Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients led to strong pathogen-specific T-cell expansion in a compassionate-use setting. In summary, low-dose adoptive T-cell transfer (ACT) could be a promising strategy, particularly for prophylactic treatment of infectious complications after allo-HSCT.

Published
2014

44. PO-0771: Temporal changes in pediatric radiation oncology: DCOG LATER childhood cancer survivor study

Author

Kok, J., primary, Dolsma, W., additional, Van Dulmen-den Broeder, E., additional, Van den Heuvel-Eibrink, M., additional, Loonen, J., additional, Tissing, W., additional, Bresters, D., additional, Versluys, B., additional, Van der Pal, H., additional, Neggers, S., additional, Hollema, N., additional, Van der Heiden-van der Loo, M., additional, Van Leeuwen, F., additional, Oldenburger, F., additional, Aleman, B., additional, Janssens, G., additional, Maduro, J., additional, Tersteeg, R., additional, Van Rij, C., additional, Daniels, L., additional, Haasbeek, C., additional, Caron, H., additional, Kremer, L., additional, and Ronckers, C., additional

Published
2016
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45. OC-0542: Benign tumours among long-term childhood cancer survivors: a DCOG LATER record linkage study

Author

Kok, J., primary, Teepen, J., additional, Van der Pal, H., additional, Dolsma, W., additional, Van Dulmen-den Broeder, E., additional, Van den Heuvel-Eibrink, M., additional, Loonen, J., additional, Tissing, W., additional, Bresters, D., additional, Versluys, B., additional, Neggers, S., additional, Van der Heiden-van der Loo, M., additional, Van Leeuwen, F., additional, Caron, H., additional, Oldenburger, F., additional, Janssens, G., additional, Maduro, J., additional, Tersteeg, R., additional, Van Rij, C., additional, Daniels, L., additional, Haasbeek, C., additional, Gijsbers-Bruggink, A., additional, Kremer, L., additional, and Ronckers, C., additional

Published
2016
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47. Reproductive intentions and use of reproductive health care among female survivors of childhood cancer.

Author

Dijk, van, den Berg, M. H. van, Overbeek, A., Lambalk, C. B., den Heuvel-Eibrink, M. M. van, Tissing, W. J., Kremer, L. C., van der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J. L., van Leeuwen, F. E., van Dulmen-den Broeder, E., van Dijk, M, van den Berg, M H, van den Heuvel-Eibrink, M M, and DCOG LATER-VEVO study group

Subjects
CHILDHOOD cancer, REPRODUCTIVE health services, CANCER patients, WOMEN patients, REPRODUCTIVE health, CANCER treatment, ATTITUDE (Psychology)
Abstract

Study Question: Do female childhood cancer survivors (CCSs) express a decreased desire to have children and do they use reproductive health care more often compared to women without a history of cancer?Summary Answer: Overall, no difference was found in the desire to have children between CCSs and controls, whereas CCSs consult a fertility specialist more often, at a younger age, and sooner after their first attempt at conceiving.What Is Known Already: Female CCSs may face a shorter than anticipated reproductive window as a result of their cancer treatment. Little is known about their desire to have children and use of reproductive health care, especially in relation to their former cancer treatment.Study Design, Size, Duration: This study is part of the DCOG LATER-VEVO study, a nationwide retrospective cohort study on female fertility in Dutch CCSs. In total, 1749 CCSs and 1673 controls were invited for the study. Data collection took place between January 2008 and May 2014.Participants/materials, Setting, Methods: Data on the desire to have children and use of reproductive health care were collected by questionnaire. The control group consisted of sisters from CCSs and females from the general population. In total, 1106 (63%) CCSs and 818 (49%) controls completed the questionnaire.Main Results and the Role Of Chance: Overall, no difference was found in the desire to have children between CCSs and controls (86% and 89%, respectively). However, survivors of a CNS tumour were less likely to desire children and CCSs without biological children at time of study were more likely to report that their desire to have children was unfulfilled because of medical reasons (9%), compared to controls (1%). In total, 12% of CCSs ever consulted a fertility specialist compared to 10% of controls (OR = 1.7, 95% CI: 1.3-2.4). Mean (SD) age at time of their first visit was 27.7 (4.4) years for CCSs and 29.9 (3.9) years for controls (P < 0.01). In total, 43% of CCSs consulted a fertility specialist within 12 months after they had started trying to achieve a pregnancy, compared to 27% of controls. Risk factors for consulting a fertility specialist included a previous diagnosis of renal tumour, leukaemia, lymphoma or a CNS tumour, and treatment with alkylating chemotherapy, gonadotoxic radiotherapy or both. In total, 70% of CCSs reported a female factor as cause of subfertility compared to 34% of controls (OR = 4.5, 95% CI: 2.3-8.7) and in this specific group, CCSs seemed more likely to use fertility treatment (OR = 2.9, 95% CI: 1.0-8.2).Limitations, Reasons For Caution: Because of the low number of CCSs who used fertility treatment, we were not able to look at specific diagnoses and treatment types associated with using fertility treatment. Nevertheless, we were able to identify diagnostic- and treatment-related risk factors for consulting a fertility specialist. Details regarding consultations with a fertility specialist and fertility treatment were based on self-report and may therefore be subject to recall bias.Wider Implications Of the Findings: Decisions about parenthood affect all CCSs. It's important to evaluate reproductive intentions and function timely after cancer treatment, so CCSs can be adequately counselled regarding family planning and fertility treatment.Study Funding/competing Interest(s): This work was supported by the Dutch Cancer Society (Grant no. VU 2006-3622) and the Children Cancer Free Foundation (Project no. 20).Trial Registration Number: NTR2922. [ABSTRACT FROM AUTHOR]

Published
2018
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49. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer

Author

Overbeek, A. (Annelies), Berg, M.H. (Marleen) van den, Kremer, L.C.M. (Leontien), Heuvel-Eibrink, M.M. (Marry) van den, Tissing, W.J.E. (Wim), Loonen, J.J. (Jacqueline), Versluys, B. (Birgitta), Bresters, D. (Dorine), Kaspers, G.J.L. (Gertjan), Lambalk, C.B. (Cornelius), Leeuwen, F.E. (Flora) van, Dulmen-den Broeder, E. (Eline) van, Beerendonk, C.C.M. (Catharina), Bökkerink, J.P. (Jos), Bos, C. (Cor) van den, Dorp, W. (Wendy) van, Engelen, M.P. (M.) van, Huizinga, G.A. (G.), Jaspers, M.W.M. (Monique), Laven, J.S.E. (Joop), Louwerens, M. (Marlous), Pal, H.J.H. (Heleen) van der, Ronckers, C.M. (Cécile), Simons, A.H.M., Tonch, N. (Nino), Verkerk, E.C.M. (E. C M), Overbeek, A. (Annelies), Berg, M.H. (Marleen) van den, Kremer, L.C.M. (Leontien), Heuvel-Eibrink, M.M. (Marry) van den, Tissing, W.J.E. (Wim), Loonen, J.J. (Jacqueline), Versluys, B. (Birgitta), Bresters, D. (Dorine), Kaspers, G.J.L. (Gertjan), Lambalk, C.B. (Cornelius), Leeuwen, F.E. (Flora) van, Dulmen-den Broeder, E. (Eline) van, Beerendonk, C.C.M. (Catharina), Bökkerink, J.P. (Jos), Bos, C. (Cor) van den, Dorp, W. (Wendy) van, Engelen, M.P. (M.) van, Huizinga, G.A. (G.), Jaspers, M.W.M. (Monique), Laven, J.S.E. (Joop), Louwerens, M. (Marlous), Pal, H.J.H. (Heleen) van der, Ronckers, C.M. (Cécile), Simons, A.H.M., Tonch, N. (Nino), and Verkerk, E.C.M. (E. C M)

Abstract

Background: Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.Methods: The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.Discussion: The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatri

Published
2012
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50. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

Author

Overbeek, A (Annelies), van den Berg, MH, Kremer, LCM (Leontien), Van den Heuvel - Eibrink, Marry, Tissing, WJE, Loonen, JJ, Versluys, B, Bresters, D, Kaspers, GJL, Lambalk, CB, van Dulmen-Den Broeder, E, Overbeek, A (Annelies), van den Berg, MH, Kremer, LCM (Leontien), Van den Heuvel - Eibrink, Marry, Tissing, WJE, Loonen, JJ, Versluys, B, Bresters, D, Kaspers, GJL, Lambalk, CB, and van Dulmen-Den Broeder, E

Published
2012

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