Showing papers by "Cécile M. Ronckers published in 2023"

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

Abstract: 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).

Psychosocial outcomes in long‐term Dutch adult survivors of childhood cancer: The DCCSS‐LATER 2 psycho‐oncology study

Abstract: This study compares a comprehensive range of psychosocial outcomes of adult childhood cancer survivors (CCS) to general population‐based references and identifies sociodemographic and medical risk factors.

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

Abstract: 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).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.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 than in comparison groups (12% and 12%, respectively). The OHIP-14 score was significantly correlated with the number of self-reported oral health problems (r = .333, p<0.0005) and dental problems (r = .392, p <0.0005). In multivariable analysis, CCS with a shorter time since diagnosis (10-19 years vs. ≥30 years) had a 1.47-fold higher risk of ≥1 oral health problem.Though the perceived oral health is relatively good, oral complications following childhood cancer treatment are prevalent in CCS. This underlines that attention to impaired oral health and awareness on this topic is mandatory and regular visits to the dentist should be a part of long-term follow-up care.

Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer: DCCSS-LATER 2 psycho-oncology study.

Abstract: OBJECTIVE To describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes. METHODS Siblings of survivors (diagnosed <18 years old, between 1963 and 2001, >5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests. Associations of siblings' sociodemographic and CCS' cancer-related characteristics with the outcomes were assessed with mixed model analysis. RESULTS Five hundred five siblings (response rate 34%, 64% female, mean age 37.5, mean time since diagnosis 29.5) of 412 CCS participated. Siblings had comparable HRQoL, anxiety and self-esteem to references with no or small differences (r = 0.08-0.15, p < 0.05) and less depression. Proportions of symptomatic PTSD were very small (0.4%-0.6%). Effect sizes of associations of siblings' sociodemographic and CCS cancer-related characteristics were mostly small to medium (β = 0.19-0.67, p < 0.05) and no clear trend was found in the studied associated factors for worse outcomes. CONCLUSIONS On the very long-term, siblings do not have impaired psychosocial functioning compared to references. Cancer-related factors seem not to impact siblings' psychosocial functioning. Early support and education remain essential to prevent long-term consequences.

Childhood and adolescent cancer in Germany – an overview

Abstract: Background Childhood and adolescent cancer constitutes only a very small fraction of the cancer cases in Germany and throughout the world, but it is the most frequent cause of disease-related death in children. The diagnostic spectrum differs markedly from that of adults. More than 90% of all cases of childhood and adolescent cancer in Germany are treated according to centralised protocols or in therapy studies. Methods The main epidemiological data for this group are collected by the German Childhood Cancer Registry (GCCR) since 1980. Based on this data, three typical diagnoses and their incidence and prognosis are described in exemplary manner: Lymphoid leukaemia (LL), astrocytoma and neuroblastoma. Results Approximately 2,250 new cancers are diagnosed in children and adolescents under the age of 18 in Germany every year. In this age group, leukaemia and lymphoma account for almost 50% of all new cancer cases, predominately acute forms. Overall, the prognosis is considerably better than in adults. Conclusions There is relatively little consistent evidence available on external factors as risk factors for childhood cancer, despite decades of research. For LL, the immune system and infections are assumed to play a role, as early training of the immune system appears to be protective. To an increasing degree, research is identifying genetic risk factors for many types of childhood and adolescent cancer. The therapy is sometimes very intensive and leads to a variety of late effects for at least 75% of the survivors, which may occur soon after the primary diagnosis, but also decades later.

Central Endocrine Complications Among Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

Abstract: Children who receive cranial radiation therapy (RT) as a component of treatment for malignancy are often at risk of long-term central endocrine toxicity secondary to radiation to the hypothalamic-pituitary axis (HPA). A comprehensive analysis was performed of central endocrine late effects in survivors of childhood cancer treated with RT as part of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium.A systematic review of the risk of RT-related central endocrine effects was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 4629 publications were identified, of which 16 met criteria for inclusion in dose modeling analysis, with a total of 570 patients in 19 cohorts. Eighteen cohorts reported outcomes for growth hormone deficiency (GHD), 7 reported outcomes for central hypothyroidism (HT), and 6 reported outcomes for adrenocorticotropic hormone (ACTH) deficiency.Normal tissue complication probability modeling for GHD (18 cohorts, 545 patients) yielded D50 = 24.9 Gy (95% CI, 20.9-28.0) and γ50 = 0.5 (95% CI, 0.27-0.78). The normal tissue complication probability model fit for whole brain irradiation in children with a median age of >5 years indicated a 20% risk of GHD for patients who receive a mean dose of 21 Gy in 2-Gy fractions to the HPA. For HT, among 7 cohorts (250 patients), D50 = 39 Gy (95% CI, 34.1-53.2) and γ50 = 0.81 (95% CI, 0.46-1.35), with a 20% risk of HT in children who receive a mean dose of 22 Gy in 2-Gy fractions to the HPA. For ACTH deficiency (6 cohorts, 230 patients), D50 = 61 Gy (95% CI, 44.7-119.4) and γ50 = 0.76 (95% CI, 0.5-1.19); there is a 20% risk of ACTH deficiency in children who receive a mean dose of 34 Gy in 2-Gy fractions to the HPA.RT dose to the HPA increases the risk of central endocrine toxicity, including GHD, HT, and ACTH deficiency. In some clinical situations, these toxicities may be difficult to avoid, and counseling of patients and families with respect to anticipated outcomes is important.

Desire for children among male survivors of childhood cancer: A DCCSS LATER study

Abstract: Knowledge of the desire for children among childhood cancer survivors (CCSs) is scarce. This study evaluated the desire for children in male CCSs in comparison with male siblings.

Psychosexual development, sexual functioning and sexual satisfaction in long-term childhood cancer survivors: DCCSS-LATER 2 sexuality substudy.

Abstract: OBJECTIVES Childhood cancer may negatively impact childhood cancer survivors' (CCS) sexuality. However, this is an understudied research area. We aimed to describe the psychosexual development, sexual functioning and sexual satisfaction of CCS, and identify determinants for these outcomes. Secondarily, we compared the outcomes of a subsample of emerging adult CCS to the Dutch general population. METHODS From the Dutch Childhood Cancer Survivor Study LATER cohort (diagnosed 1963-2001), 1912 CCS (18-71 years, 50.8% male) completed questions on sexuality, psychosocial development, body perception, mental and physical health. Multivariable linear regressions were used to identify determinants. Sexuality of CCS age 18-24 (N = 243) was compared to same-aged references using binomial tests and t-tests. RESULTS One third of all CCS reported hindered sexuality due to childhood cancer, with insecure body the most often reported reason (44.8%). Older age at study, lower education, surviving central nervous system cancer, poorer mental health and negative body perception were identified as determinants for later sexual debut, worse sexual functioning and/or sexual satisfaction. CCS age 18-24 showed significantly less experience with kissing (p = 0.014), petting under clothes (p = 0.002), oral (p = 0.016) and anal sex (p = 0.032) when compared to references. No significant differences with references were found for sexual functioning and sexual satisfaction, neither among female CCS nor male CCS age 18-24. CONCLUSIONS Emerging adult CCS reported less experience with psychosexual development, but similar sexual functioning and sexual satisfaction compared to references. We identified determinants for sexuality, which could be integrated in clinical interventions for CCS at risk for reduced sexuality.

Positive and negative survivor-specific psychosocial consequences of childhood cancer: the DCCSS-LATER 2 psycho-oncology study.

Abstract: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors.CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004).CCS, N = 1713, age mean (M) 36 years, 49% female, ≥ 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact.The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support.

Health effects of ionising radiation in paediatrics undergoing either cardiac fluoroscopy or modern radiotherapy (The HARMONIC project)

Abstract: The use of ionising radiation (IR) for medical diagnosis and treatment procedures has had a major impact on the survival of paediatric patients. Although the benefits of these techniques lead to efficient health care, evaluation of potential associated long-term health effects is required. HARMONIC aims to better understand the increased risk of cancer and non-cancer effects after exposure to medical IR in children with cancer treated with modern external beam radiotherapy (EBRT) – radiation energy in MeV range – and in children with cardiac defects diagnosed and treated with cardiac fluoroscopy procedures (CFP) – radiation energy in keV range. The project investigates, among survivors of paediatric cancer, potential endocrine dysfunction, cardiovascular and neurovascular damage, health-related quality of life and second (and subsequent) primary cancer (SPC). The cardiac component builds a pooled cohort of approximately 90 000 paediatric patients who underwent CFP during childhood and adolescence to investigate cancer risk following exposure to IR and explore the potential effects of conditions predisposing to cancer. HARMONIC develops software tools to allow dose reconstruction in both EBRT and CFP to enable epidemiological investigations and future optimisation of treatments. With the creation of a biobank of blood and saliva samples, HARMONIC aims to provide a mechanistic understanding of radiation-induced adverse health effects and identify potential biomarkers that can predict these effects.

Temporal patterns of childhood cancer survival 1991 to 2016: A nationwide register‐study based on data from the German Childhood Cancer Registry

Abstract: Childhood cancer is the leading disease‐related cause of death among under 15 year olds in Europe. Since primary preventive measures are lacking, improving survival probabilities and long‐term well‐being remain primary goals. With this report, we provide the first long‐term assessment and interpretation of patterns in childhood cancer survival in Germany, covering a period of 30 years. Using data from the German Childhood Cancer Registry, we assessed temporal patterns of cancer survival among children (0‐14 years) diagnosed in Germany from 1991 to 2016, by cancer type, age at diagnosis and sex. We calculated overall survival (OS) and average annual percentage changes of the respective 5‐year OS estimates. OS improved across all cancer types, age groups as well as for boys and girls over time. Five‐year OS for all childhood cancers combined increased from 77.8% in 1991‐1995 to 86.5% in 2011‐2016, with stronger improvements during the early 1990s. The most pronounced survival improvement was seen for acute myeloid leukaemia, at 2% annually and 5‐year OS recently reaching 81.5%. Survival improvements for some diagnoses such as neuroblastoma, renal tumours and bone tumours have flattened out. Tremendous enhancements in diagnostics, treatment and supportive care have affected average survival improvements for most cancer types. Recently, survival improvements have decelerated overall and for some cancer types, it plateaued at an unsatisfactory level. As not all children benefited equally from the survival improvements, personal factors (eg, socioeconomic circumstances, health literacy, access to care) likely affect individual prognosis and warrant further investigation.

A comprehensive review of 30 years of pediatric clinical trial radiotherapy dose constraints

Abstract: Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which has led to variations in constraints over the years. In this study, we identify these variations in dose constraints within pediatric trials both in the United States and in Europe used in the past 30 years.

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

Abstract: PURPOSE Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION To our knowledge, we demonstrate—for the first time—that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

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

Abstract: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side‐effects of two dimensional planned radiotherapy.