Eline Broeder - Academia.edu (original) (raw)

Papers by Eline Broeder

Research paper thumbnail of Self-reported outcomes on oral health and oral health-related quality of life in long-term childhood cancer survivors—A DCCSS-LATER 2 Study

Supportive Care in Cancer

Purpose The present study aimed to determine the prevalence of self-reported oral problems and th... more Purpose The present study aimed to determine the prevalence of self-reported oral problems and the oral health–related quality of life (OHRQoL) in childhood cancer survivors (CCS). Methods Patient and treatment characteristics of CCS have been collected in a cross-sectional study, part of the multidisciplinary DCCSS-LATER 2 Study. To assess self-reported oral health problems and dental problems, CCS filled out the ‘Toegepast-Natuurwetenschappelijk Onderzoek’ (TNO) oral health questionnaire. OHRQoL was assessed by the Dutch version of the Oral Health Impact Profile-14 (OHIP-14). Prevalences were compared with two comparison groups from the literature. Univariable and multivariable analyses were performed. Results A total of 249 CCS participated in our study. The OHIP-14 total score had a mean value of 1.94 (sd 4.39), with a median score of 0 (range 0–29). The oral problems ‘oral blisters/aphthae’ (25.9%) and ‘bad odor/halitosis’ (23.3%) were significantly more often reported in CCS t...

Research paper thumbnail of Female reproductive function after treatment of childhood acute lymphoblastic leukemia

Yearbook of Paediatric Endocrinology, 2021

Background: The aim was to evaluate self-reported reproductive characteristics and markers of ova... more 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%

Research paper thumbnail of Increased health‐related quality of life impairments of male and female survivors of childhood cancer: DCCSS LATER 2 psycho‐oncology study

Cancer, 2021

The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch ad... more The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and to study medical determinants.

Research paper thumbnail of Social outcomes in adult survivors of childhood cancer compared to the general population: linkage of a cohort with population registers

Psycho-Oncology, 2015

Background and objective Self-reported data show differences in social outcomes (not being marrie... more Background and objective Self-reported data show differences in social outcomes (not being married/having a registered partnership; not living independently; using social benefits) for childhood cancer survivors compared with their peers. We aimed to determine differences in these social outcomes between survivors and the general population using national register data and explored associated risk factors. Methods We performed medical record linkage between a single-centre cohort of 1768 ≥5year survivors of childhood cancer (diagnosed 1966-2001) and two national registers (1999-2011), and obtained a random reference sample matched on gender and year of birth per survivor. We used multivariable logistic regression to calculate in adult survivors of childhood cancer (born before 1990) the odds of the specified social outcomes at the end of follow-up in both groups. Within the survivors, we analysed risk factors for the social outcomes. Results We retrieved data from 1283 adult childhood cancer survivors and 25082 reference persons. Survivors had higher odds (odds ratio; 95% confidence interval) of not being married (1.2;1.07-1.42), not living independently (1.7;1.41-2.00) and using social benefits (2.3;1.98-2.69) compared with reference persons. Radiotherapy to head and/or neck, and an original central nervous system tumour diagnosis negatively influenced all social outcomes examined in childhood cancer survivors. Conclusions National register data show differences between social outcomes in childhood cancer survivors and the general population, especially for survivors treated with radiotherapy to head and/or neck and those originally diagnosed with central nervous system tumours. Development and implementation of effective targeted support strategies to improve social outcomes of childhood cancer survivors needs consideration.

Research paper thumbnail of Collaborative Research in Childhood Cancer Survivorship: The Current Landscape

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 24, 2015

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk f... more Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salien...

Research paper thumbnail of Factors influencing childhood cancer patients to participate in a combined physical and psychosocial intervention program: Quality of Life in Motion

Psycho-oncology, Jan 6, 2014

For a multi-center randomized trial investigating the effects of a 12-week physical and psychosoc... more For a multi-center randomized trial investigating the effects of a 12-week physical and psychosocial intervention program for children with cancer, we invited 174 patients (8-18 years old) on treatment or within 1 year after treatment; about 40% participated. Reasons for non-participation were investigated. Eligible patients received written and verbal information about the study. Those declining to participate were asked to complete questionnaires concerning: reasons for non-participation, daily physical activity, health-related quality of life (HrQoL), and behavioral problems. Participants completed the same questionnaires at baseline (excluding 'reasons for non-participation'). Of 174 eligible patients, 106 did not participate; of these, 61 (57.5%) completed the one-time survey. The main reasons for non-participation as reported by the parents were 'too time consuming' and 'participation is too demanding for my child', while children most frequently report...

Research paper thumbnail of Applicability and evaluation of a psychosocial intervention program for childhood cancer patients

Supportive Care in Cancer, 2015

The purpose of this study is to explore the applicability of a psychosocial intervention in child... more The purpose of this study is to explore the applicability of a psychosocial intervention in childhood cancer patients. This individualized structured psychosocial program to enhance social-emotional functioning and coping with disease-related effects includes six sessions for children and two sessions for parents. This program was part of a combined intervention with physical exercise. Questionnaires are used to evaluate completion of the psychosocial intervention, coping and satisfaction with the psychosocial intervention by patients and psychologists, and ranking of the individual topics by patients, parents, and psychologists. Of the 30 patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who participated in the psychosocial intervention, two dropped out due to medical complications and one due to lack of time; 90 % completed the psychosocial intervention. Overall, patients liked participation in the intervention (4.2 on a 5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10-point scale; SD 1.3). Psychologists rated the intervention on several points (e.g., clarity of the manual and content of the intervention), and mean scores ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations were suggested by patients and psychologists, including customizing according to age and a more patient-tailored approach. This psychosocial intervention for childhood cancer patients appears to be applicable. Future studies need to establish whether this intervention combined with a physical exercise intervention actually improves psychosocial functioning of childhood cancer patients. When proven effective, this combined intervention can be offered to childhood cancer patients and may enhance their physical health and quality of life.

Research paper thumbnail of Fertility studies in female childhood cancer survivors: selecting appropriate comparison groups

Reproductive BioMedicine Online, 2014

Little information is available on the use of appropriate comparison groups for studies investiga... more Little information is available on the use of appropriate comparison groups for studies investigating late effects of childhood cancer. Two comparison groups in a nationwide study on reproductive function and ovarian reserve in female childhood cancer survivors were recruited (The Dutch Childhood Oncology Group Long-Term Effects After Childhood Cancer Cohort Study). Experiences of this process are reported. Two types of comparison groups were used: sisters of participating survivors and controls from the general population. A total of 352 out of 580 (61%) of the participating survivors who had a sister gave permission to invite them for the study. The participation rate of sisters was much higher than control participants from the general population (74% versus 21%, respectively), whereas considerably more effort was involved in recruiting controls from the general population. Participants in this group were significantly older and more highly educated than sister controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for both groups). No significant differences were observed between both types of comparison groups in several fertility-related characteristics, suggesting minimal bias owing to selective participation. Researchers setting up a study to investigate late effects among survivors of childhood cancer should carefully consider the advantages and disadvantages of using various types of comparison groups.

Research paper thumbnail of Alpe d’HuZes Cancer Rehabilitation (A-CaRe) Research: Four Randomized Controlled Exercise Trials and Economic Evaluations in Cancer Patients and Survivors

International Journal of Behavioral Medicine, 2011

Background Previous studies showed that exercise in cancer patients is feasible and may reduce fa... more Background Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content. Purpose This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) programme. Method A-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity Laurien Buffart and Mai Chinapaw share first authorship since they have equally contributed to this manuscript.

Research paper thumbnail of Validity of self-reported data on pregnancies for childhood cancer survivors: a comparison with data from a nationwide population-based registry

Human Reproduction, 2012

To what degree do records registered in the Netherlands Perinatal Registry (PRN) agree with self-... more To what degree do records registered in the Netherlands Perinatal Registry (PRN) agree with self-report in a study questionnaire on pregnancy outcomes in childhood cancer survivors (CCSs)? summary answer: This study suggests that self-reported pregnancy outcomes of CCSs agree well with registry data and that outcomes reported by CCSs agree better with registry data than do those of controls. what is known already: Many studies have shown that childhood cancer treatment may affect fertility outcomes in female CCSs; however, these conclusions were often based on questionnaire data, and it remains unclear whether self-report agrees well with more objective sources of information. study design, size, duration: In an nationwide cohort study on fertility (inclusion period January 2008 and April 2011, trial number: NTR2922), 1420 CCSs and 354 sibling controls were invited to complete a questionnaire regarding socio-demographic characteristics and reproductive history. In total, 879 CCSs (62%) and 287 controls (81%) returned the questionnaire. participants/materials, setting, methods: The current validation study compared the agreement between pregnancy outcomes as registered in the PRN and self-reported outcomes in the study questionnaire. A total of 589 pregnancies were reported in CCSs, and 300 pregnancies in sibling controls, of which 524 could be linked to the PRN. main results and the role of chance: A high intra-class correlation coefficient (ICC) was found for birthweight (BW) (0.94 and 0.87 for CCSs and controls, respectively). The self-reported BWs tended to be higher than reported in the PRN. For gestational age (GA), the ICC was high for CCSs (0.88), but moderate for controls (0.49). CCSs overestimated GA more often than controls. The Kappa values for method of conception and for method of delivery were moderate to good. Multilevel analyses on the mean difference with regard to BW and GA showed no differences associated with time since pregnancy or educational level.

Research paper thumbnail of Comment on: Li HW, Wong CY, Yeung WS, Ho PC, Ng EH. Serum anti-Mullerian hormone level is not altered in women using hormonal contraceptives. Contraception 2011;83:582–5

Research paper thumbnail of Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

BMC Neurology, 2012

Background Prophylaxis to prevent relapses in the central nervous system after childhood acute ly... more Background Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction. Methods Resting state eyes-closed magnetoencephalography (MEG) recordings were obtaine...

Research paper thumbnail of A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

BMC Cancer, 2012

Background Advances in childhood cancer treatment over the past decades have significantly improv... more 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 ...

Research paper thumbnail of Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer

BMC Cancer, 2010

Background: Childhood cancer and its treatment have considerable impact on a child's physical and... more Background: Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective. Methods: This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group. Discussion: Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care.

Research paper thumbnail of Prevalence and risk factors of cancer‐related fatigue in childhood cancer survivors: A DCCSS LATER study

Cancer

Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The pr... more Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer‐related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs.

Research paper thumbnail of Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors: A Dutch LATER study

European Journal of Cancer

Research paper thumbnail of Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function

Human Reproduction

STUDY QUESTION Do genetic variations in the DNA damage response pathway modify the adverse effect... more STUDY QUESTION Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood c...

Research paper thumbnail of Large variation in assessment and outcome definitions to describe the burden of long‐term morbidity in childhood cancer survivors: A systematic review

Research paper thumbnail of The involvement of primary care physicians in care for childhood cancer survivors

Pediatric Blood & Cancer

Dorine Bresters3 Eline van Dulmen-den Broeder3,4 Margriet van der Heidenvan der Loo5 Marry M. van... more Dorine Bresters3 Eline van Dulmen-den Broeder3,4 Margriet van der Heidenvan der Loo5 Marry M. van den Heuvel-Eibrink3,

Research paper thumbnail of Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors

Fertility and Sterility

Objective: To evaluate whether abdominal-pelvic radiotherapy for childhood cancer impairs uterine... more 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 ¼ 55) were age-and parity-matched to nonirradiated CCSs (non-RT-exposed CCSs; n ¼ 110) and general population controls (n ¼ 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. Radiotherapyexposed 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]).

Research paper thumbnail of Self-reported outcomes on oral health and oral health-related quality of life in long-term childhood cancer survivors—A DCCSS-LATER 2 Study

Supportive Care in Cancer

Purpose The present study aimed to determine the prevalence of self-reported oral problems and th... more Purpose The present study aimed to determine the prevalence of self-reported oral problems and the oral health–related quality of life (OHRQoL) in childhood cancer survivors (CCS). Methods Patient and treatment characteristics of CCS have been collected in a cross-sectional study, part of the multidisciplinary DCCSS-LATER 2 Study. To assess self-reported oral health problems and dental problems, CCS filled out the ‘Toegepast-Natuurwetenschappelijk Onderzoek’ (TNO) oral health questionnaire. OHRQoL was assessed by the Dutch version of the Oral Health Impact Profile-14 (OHIP-14). Prevalences were compared with two comparison groups from the literature. Univariable and multivariable analyses were performed. Results A total of 249 CCS participated in our study. The OHIP-14 total score had a mean value of 1.94 (sd 4.39), with a median score of 0 (range 0–29). The oral problems ‘oral blisters/aphthae’ (25.9%) and ‘bad odor/halitosis’ (23.3%) were significantly more often reported in CCS t...

Research paper thumbnail of Female reproductive function after treatment of childhood acute lymphoblastic leukemia

Yearbook of Paediatric Endocrinology, 2021

Background: The aim was to evaluate self-reported reproductive characteristics and markers of ova... more 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%

Research paper thumbnail of Increased health‐related quality of life impairments of male and female survivors of childhood cancer: DCCSS LATER 2 psycho‐oncology study

Cancer, 2021

The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch ad... more The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and to study medical determinants.

Research paper thumbnail of Social outcomes in adult survivors of childhood cancer compared to the general population: linkage of a cohort with population registers

Psycho-Oncology, 2015

Background and objective Self-reported data show differences in social outcomes (not being marrie... more Background and objective Self-reported data show differences in social outcomes (not being married/having a registered partnership; not living independently; using social benefits) for childhood cancer survivors compared with their peers. We aimed to determine differences in these social outcomes between survivors and the general population using national register data and explored associated risk factors. Methods We performed medical record linkage between a single-centre cohort of 1768 ≥5year survivors of childhood cancer (diagnosed 1966-2001) and two national registers (1999-2011), and obtained a random reference sample matched on gender and year of birth per survivor. We used multivariable logistic regression to calculate in adult survivors of childhood cancer (born before 1990) the odds of the specified social outcomes at the end of follow-up in both groups. Within the survivors, we analysed risk factors for the social outcomes. Results We retrieved data from 1283 adult childhood cancer survivors and 25082 reference persons. Survivors had higher odds (odds ratio; 95% confidence interval) of not being married (1.2;1.07-1.42), not living independently (1.7;1.41-2.00) and using social benefits (2.3;1.98-2.69) compared with reference persons. Radiotherapy to head and/or neck, and an original central nervous system tumour diagnosis negatively influenced all social outcomes examined in childhood cancer survivors. Conclusions National register data show differences between social outcomes in childhood cancer survivors and the general population, especially for survivors treated with radiotherapy to head and/or neck and those originally diagnosed with central nervous system tumours. Development and implementation of effective targeted support strategies to improve social outcomes of childhood cancer survivors needs consideration.

Research paper thumbnail of Collaborative Research in Childhood Cancer Survivorship: The Current Landscape

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 24, 2015

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk f... more Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salien...

Research paper thumbnail of Factors influencing childhood cancer patients to participate in a combined physical and psychosocial intervention program: Quality of Life in Motion

Psycho-oncology, Jan 6, 2014

For a multi-center randomized trial investigating the effects of a 12-week physical and psychosoc... more For a multi-center randomized trial investigating the effects of a 12-week physical and psychosocial intervention program for children with cancer, we invited 174 patients (8-18 years old) on treatment or within 1 year after treatment; about 40% participated. Reasons for non-participation were investigated. Eligible patients received written and verbal information about the study. Those declining to participate were asked to complete questionnaires concerning: reasons for non-participation, daily physical activity, health-related quality of life (HrQoL), and behavioral problems. Participants completed the same questionnaires at baseline (excluding 'reasons for non-participation'). Of 174 eligible patients, 106 did not participate; of these, 61 (57.5%) completed the one-time survey. The main reasons for non-participation as reported by the parents were 'too time consuming' and 'participation is too demanding for my child', while children most frequently report...

Research paper thumbnail of Applicability and evaluation of a psychosocial intervention program for childhood cancer patients

Supportive Care in Cancer, 2015

The purpose of this study is to explore the applicability of a psychosocial intervention in child... more The purpose of this study is to explore the applicability of a psychosocial intervention in childhood cancer patients. This individualized structured psychosocial program to enhance social-emotional functioning and coping with disease-related effects includes six sessions for children and two sessions for parents. This program was part of a combined intervention with physical exercise. Questionnaires are used to evaluate completion of the psychosocial intervention, coping and satisfaction with the psychosocial intervention by patients and psychologists, and ranking of the individual topics by patients, parents, and psychologists. Of the 30 patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who participated in the psychosocial intervention, two dropped out due to medical complications and one due to lack of time; 90 % completed the psychosocial intervention. Overall, patients liked participation in the intervention (4.2 on a 5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10-point scale; SD 1.3). Psychologists rated the intervention on several points (e.g., clarity of the manual and content of the intervention), and mean scores ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations were suggested by patients and psychologists, including customizing according to age and a more patient-tailored approach. This psychosocial intervention for childhood cancer patients appears to be applicable. Future studies need to establish whether this intervention combined with a physical exercise intervention actually improves psychosocial functioning of childhood cancer patients. When proven effective, this combined intervention can be offered to childhood cancer patients and may enhance their physical health and quality of life.

Research paper thumbnail of Fertility studies in female childhood cancer survivors: selecting appropriate comparison groups

Reproductive BioMedicine Online, 2014

Little information is available on the use of appropriate comparison groups for studies investiga... more Little information is available on the use of appropriate comparison groups for studies investigating late effects of childhood cancer. Two comparison groups in a nationwide study on reproductive function and ovarian reserve in female childhood cancer survivors were recruited (The Dutch Childhood Oncology Group Long-Term Effects After Childhood Cancer Cohort Study). Experiences of this process are reported. Two types of comparison groups were used: sisters of participating survivors and controls from the general population. A total of 352 out of 580 (61%) of the participating survivors who had a sister gave permission to invite them for the study. The participation rate of sisters was much higher than control participants from the general population (74% versus 21%, respectively), whereas considerably more effort was involved in recruiting controls from the general population. Participants in this group were significantly older and more highly educated than sister controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for both groups). No significant differences were observed between both types of comparison groups in several fertility-related characteristics, suggesting minimal bias owing to selective participation. Researchers setting up a study to investigate late effects among survivors of childhood cancer should carefully consider the advantages and disadvantages of using various types of comparison groups.

Research paper thumbnail of Alpe d’HuZes Cancer Rehabilitation (A-CaRe) Research: Four Randomized Controlled Exercise Trials and Economic Evaluations in Cancer Patients and Survivors

International Journal of Behavioral Medicine, 2011

Background Previous studies showed that exercise in cancer patients is feasible and may reduce fa... more Background Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content. Purpose This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) programme. Method A-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity Laurien Buffart and Mai Chinapaw share first authorship since they have equally contributed to this manuscript.

Research paper thumbnail of Validity of self-reported data on pregnancies for childhood cancer survivors: a comparison with data from a nationwide population-based registry

Human Reproduction, 2012

To what degree do records registered in the Netherlands Perinatal Registry (PRN) agree with self-... more To what degree do records registered in the Netherlands Perinatal Registry (PRN) agree with self-report in a study questionnaire on pregnancy outcomes in childhood cancer survivors (CCSs)? summary answer: This study suggests that self-reported pregnancy outcomes of CCSs agree well with registry data and that outcomes reported by CCSs agree better with registry data than do those of controls. what is known already: Many studies have shown that childhood cancer treatment may affect fertility outcomes in female CCSs; however, these conclusions were often based on questionnaire data, and it remains unclear whether self-report agrees well with more objective sources of information. study design, size, duration: In an nationwide cohort study on fertility (inclusion period January 2008 and April 2011, trial number: NTR2922), 1420 CCSs and 354 sibling controls were invited to complete a questionnaire regarding socio-demographic characteristics and reproductive history. In total, 879 CCSs (62%) and 287 controls (81%) returned the questionnaire. participants/materials, setting, methods: The current validation study compared the agreement between pregnancy outcomes as registered in the PRN and self-reported outcomes in the study questionnaire. A total of 589 pregnancies were reported in CCSs, and 300 pregnancies in sibling controls, of which 524 could be linked to the PRN. main results and the role of chance: A high intra-class correlation coefficient (ICC) was found for birthweight (BW) (0.94 and 0.87 for CCSs and controls, respectively). The self-reported BWs tended to be higher than reported in the PRN. For gestational age (GA), the ICC was high for CCSs (0.88), but moderate for controls (0.49). CCSs overestimated GA more often than controls. The Kappa values for method of conception and for method of delivery were moderate to good. Multilevel analyses on the mean difference with regard to BW and GA showed no differences associated with time since pregnancy or educational level.

Research paper thumbnail of Comment on: Li HW, Wong CY, Yeung WS, Ho PC, Ng EH. Serum anti-Mullerian hormone level is not altered in women using hormonal contraceptives. Contraception 2011;83:582–5

Research paper thumbnail of Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

BMC Neurology, 2012

Background Prophylaxis to prevent relapses in the central nervous system after childhood acute ly... more Background Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction. Methods Resting state eyes-closed magnetoencephalography (MEG) recordings were obtaine...

Research paper thumbnail of A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

BMC Cancer, 2012

Background Advances in childhood cancer treatment over the past decades have significantly improv... more 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 ...

Research paper thumbnail of Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer

BMC Cancer, 2010

Background: Childhood cancer and its treatment have considerable impact on a child's physical and... more Background: Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective. Methods: This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group. Discussion: Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care.

Research paper thumbnail of Prevalence and risk factors of cancer‐related fatigue in childhood cancer survivors: A DCCSS LATER study

Cancer

Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The pr... more Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer‐related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs.

Research paper thumbnail of Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors: A Dutch LATER study

European Journal of Cancer

Research paper thumbnail of Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function

Human Reproduction

STUDY QUESTION Do genetic variations in the DNA damage response pathway modify the adverse effect... more STUDY QUESTION Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood c...

Research paper thumbnail of Large variation in assessment and outcome definitions to describe the burden of long‐term morbidity in childhood cancer survivors: A systematic review

Research paper thumbnail of The involvement of primary care physicians in care for childhood cancer survivors

Pediatric Blood & Cancer

Dorine Bresters3 Eline van Dulmen-den Broeder3,4 Margriet van der Heidenvan der Loo5 Marry M. van... more Dorine Bresters3 Eline van Dulmen-den Broeder3,4 Margriet van der Heidenvan der Loo5 Marry M. van den Heuvel-Eibrink3,

Research paper thumbnail of Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors

Fertility and Sterility

Objective: To evaluate whether abdominal-pelvic radiotherapy for childhood cancer impairs uterine... more 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 ¼ 55) were age-and parity-matched to nonirradiated CCSs (non-RT-exposed CCSs; n ¼ 110) and general population controls (n ¼ 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. Radiotherapyexposed 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]).