Search

Background: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses. Methods: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study‐Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m2), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two‐step cluster analyses were performed to examine sociodemographic‐related, health‐related, cancer‐related, and treatment‐related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors. Results: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p <.001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users. Conclusions: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors. The results of this study indicate a higher prevalence of physical inactivity in childhood cancer survivors compared with sibling controls and the Dutch population, emphasizing the necessity for personalized health behavior interventions in childhood cancer survivors. These findings can be used in clinical practice to create awareness and to identify subgroups of childhood cancer survivors who need special attention regarding health behaviors. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate how cumulative burden of clinically relevant, self‐reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications. Methods: The authors invited 5925 5‐year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self‐reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30‐year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30‐year MCC, and compared the ranking to levels of care according to existing risk stratifications. Results: At median 18.5 years after 5‐year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30‐year MCC = 0.79; 95% confidence interval [CI], 0.74–0.85 vs. 30‐year MCC = 0.29; 95% CI, 0.25–0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30‐year MCC often did not correspond with levels of care in existing risk stratifications. Conclusions: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity. Survivors of childhood cancer experience a high cumulative burden of clinically relevant outcomes. Choices for survivorship care should extend beyond primary tumor and treatment parameters and should also consider including the current morbidity of childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Treatment‐related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. Methods: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. Results: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p <.001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p =.86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p <.001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p =.001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p =.001). Conclusions: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists. This study showed that two‐thirds of male survivors of childhood cancer who had a desire for children fathered a biological child and that children of 90% of male survivors were conceived spontaneously. Compared with male siblings, more male survivors consulted a reproductive specialist because of not siring a pregnancy; however, both the application of and birth rates after assisted reproductive techniques in survivors were lower. [ABSTRACT FROM AUTHOR]

Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed 7–32 months after childhood cancer diagnosis in 6/6 consecutive patients biopsied for progressive chronic kidney disease (CKD) of unknown cause between 2018 and 2021. The morphometry of nuclear size distribution and markers for DNA damage (γH2AX), cell‐cycle arrest (p21+, Ki67−), and nuclear lamina decay (loss of lamin B1), identified karyomegaly and senescence features in TECs. Polyploidy was assessed by chromosome fluorescence in situ hybridization (FISH). In all six patients the number of p21‐positive TECs far exceeded the typically small numbers of truly karyomegalic cells, and p21‐positive TECs contained less lysozyme, testifying to defective resorption, which explains the consistently observed low‐molecular‐weight (LMW) proteinuria. In addition, polyploidy of TEC was observed to correlate with loss of lysozyme staining. Importantly, in the five patients with the largest nuclei, the percentage of p21‐positive TECs tightly correlated with estimated glomerular filtration rate loss between biopsy and last follow‐up (R2 = 0.93, p < 0.01). We conclude that cellular senescence is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with KIN and appears to be a prevalent cause of otherwise unexplained CKD and LMW proteinuria in children treated with DNA‐damaging and cell stress‐inducing therapy including ifosfamide. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background. Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective. We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods. All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell–Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells < 9 cells/µL was defined as abnormal. Results. We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/µL, p = 0.06) or TBI (55 cells/µL, p = 0.03) compared to CCS who received splenectomy (20 cells/µL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/µL vs. 44 cells/µL). Conclusion. Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: Vincristine is an integral component of treatment for children with cancer. Its main dose‐limiting side effect is vincristine‐induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1‐hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short‐term outcomes (median follow‐up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1‐hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow‐up 20 months), which includes treatment outcome as a secondary objective (follow‐up 3 years). Methods: VIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric‐modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed. Results: Forty‐five participants per randomization group were included. There was no significant effect of 1‐hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one‐hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one‐hour group and one patient in the push group relapsed. Two patients in the one‐hour group died. Conclusion: 1‐hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1‐hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile. Vincristine is an integral component of treatment for children with cancer. Its main dose‐limiting side effect is vincristine‐induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of one‐hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. We found that in patients receiving concurrent azoles, one‐hour infusion may be less toxic. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic had global catastrophic effects on the management of non‐communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic's impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP‐RTSG‐UMBRELLA study, as compared with data from a historical SIOP‐RTSG trial (2005–2009). Methods: The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic's severity and impact on societies. Clinical and tumour data were extracted from the SIOP‐RTSG‐UMBRELLA study and from historical SIOP‐RTSG trials. Results: During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID‐9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID‐19 (599 cm3 vs. 459 and 514 cm3), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID‐19 restrictions may have caused children to reach care later. Conclusion: The COVID‐19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer‐term impact on clinical outcomes will be kept under review. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)‐LATER cohort (diagnosed 1963–2001) part 2 (attained age ≥18 years, diagnosed <18 years, ≥5 years since diagnosis) completed the Rosenberg Self‐Esteem Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Self‐Rating Scale for Post‐Traumatic Stress Disorder, and the Short Form‐36 (Health Related Quality of Life). CCS' scores were compared with references using analysis of variances and logistic regression analysis, controlling for age and sex (p <.05). Risk factors for worse psychosocial outcomes were assessed with regression analyses (p <.05). Results: CCS, N = 1797, mean age 35.4 years, 49.0% female, all ≥15 years since diagnosis, participated. Three percent reported posttraumatic stress disorder because of childhood cancer and 36.6% experienced clinical distress. CCS did not differ from references on self‐esteem and anxiety but were less depressed (d = −.25), and scored poorer on all health‐related quality of life scales, except for bodily pain (.01 ≤ d ≥ −.36). Female sex, lower educational attainment, not being in a relationship, and being unemployed were negatively associated with almost all psychosocial outcomes. Except for a central nervous system tumor diagnosis, few medical characteristics were associated with psychosocial outcomes. Conclusion: CCS appear resilient regarding mental health but have slightly poorer health‐related quality of life than references. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. Future studies should address additional factors in explaining CCS' psychosocial functioning, such as coping, social support, and physical late effects. Adult childhood cancer survivors appear resilient regarding mental health but have slightly poorer health‐related quality of life than reference patients. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor Study LATER study: 1317 male CCSs and 407 male sibling controls completed a questionnaire addressing the desire for children. Logistic regression analyses were used to explore the independent association between survivorship status and the desire for children. Furthermore, additional analyses were performed to identify which cancer‐related factors were associated with the desire for children in male CCSs. Results: After adjustments for the age at assessment, the percentage of men who had a desire for children was significantly lower among CCSs compared with the siblings (74% vs. 82%; odds ratio [OR], 0.61; 95% CI, 0.46–0.82; p =.001). The association between survivorship status and the desire for children was attenuated after adjustments for marital status, level of education, and employment status (OR, 0.83; 95% CI, 0.61–1.14; p =.250). The percentage of men who had an unfulfilled desire for children remained significantly higher among CCSs compared with the siblings after adjustments for sociodemographic factors (25% vs. 7%; OR, 5.14; 95% CI, 2.48–10.64; p <.001). Conclusions: The majority of male CCSs have a desire for children. The likelihood of having to deal with an unfulfilled desire for children is 5 times higher among CCSs compared with their siblings. This insight is important for understanding the needs and experienced problems of CCSs regarding family planning and fertility issues. Male survivors of childhood cancer report a lower desire for children in comparison with male siblings, and this can be explained by differences in marital status, level of education, and employment status. The likelihood of having to deal with an unfulfilled desire is 5 times higher among male survivors compared with siblings, and cancer diagnosis, allogeneic hematopoietic stem cell transplantation, and cancer treatment are associated with an unfulfilled desire for children. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the significant increase in overall survival rates of childhood cancer, more awareness has been raised for the long-term consequences of treatment, including infertility. Currently, patients and their families are offered information regarding the risk of gonadal damage by paediatric oncologists and fertility counselling by fertility specialists regarding fertility preservation. However, the experiences of childhood cancer patients with oncofertility care are underreported. The available evidence reported in this review shows that female patients and survivors are variably satisfied with fertility information and report challenges in communication. They prefer to receive general information at diagnosis and detailed information later. Regrets are reported after refusal of fertility preservation. Patients and survivors are concerned about future children's health, effect on relationships and lack of control over fertility. With the results from this review, (international) standards for information for paediatric cancer patients and families may be developed to improve fertility information and counselling for current and future childhood cancer patients and survivors. Background: Childhood cancer patients and their families are increasingly offered oncofertility care including information regarding their risk of gonadal damage by paediatric oncologists, fertility counselling by fertility specialists and fertility preservation options. However, experiences regarding oncofertility care are underreported. We aimed to summarize the available evidence of experiences of female childhood cancer patients and survivors regarding oncofertility care. Methods: Manuscripts were systematically identified using the PubMed and Embase database. From, respectively, 1256 and 3857 manuscripts, 7 articles were included and assessed, including risk of bias assessment. Outcome measures included data describing experiences of female childhood cancer patients and survivors, regarding fertility information, counselling and/or preservation. Results: Female patients and survivors are variably satisfied with fertility information, report challenges in communication with healthcare professionals and prefer to receive general information at diagnosis and detailed fertility information later. Regrets after fertility counselling are underreported, but are associated with refusing fertility preservation. Lastly, regardless of counselling, female patients and survivors report fertility concerns about their future children's health and effect on relationships. Conclusion: Currently, the satisfaction with oncofertility care varies and female patients or survivors report regrets and concerns regardless of receiving fertility information or counselling. These results may help to improve the content of fertility information, communication skills of healthcare professionals and timing of counselling. [ABSTRACT FROM AUTHOR]

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

Objective: To describe health‐related quality of life (HRQoL), post‐traumatic stress and post‐traumatic growth of parents of long‐term survivors of childhood cancer (CCS) and study associated factors. Methods: Parents of survivors of the Dutch Childhood Cancer Survivor Study LATER cohort below 30 years and diagnosed 1986–2001 were invited to complete the TNO‐AZL Questionnaire for Adult's HRQoL (e.g., sleep and aggressive emotions), Self‐Rating Scale for Post‐traumatic Stress Disorder, Post‐traumatic Growth Inventory, and Illness Cognition Questionnaire. HRQoL domain scores were compared to references using Mann‐Whitney U tests. Correlations between post‐traumatic stress, growth and HRQoL were evaluated. Medical characteristics of their child and illness cognitions were studied as associated factors of HRQOL, post‐traumatic stress and growth. p < 0.05 was considered statistically significant. Results: Parents (n = 661 of n = 448 survivors, 56% female, mean time since child's diagnosis: 21.3 [SD: 3.3] years) reported better HRQoL in social functioning and aggressive emotions than references (r =.08–0.17). Mothers additionally reported better HRQoL in pain, daily activities, sexuality, vitality, positive and depressive emotions (r =.07–0.14). Post‐traumatic stress was symptomatic in 3%, and associated with worse HRQoL (r = −0.27–0.48). Post‐traumatic growth was positively associated to post‐traumatic stress and better HRQoL (r = 0.09–0.12). Cancer recurrence was associated to better HRQoL (β = 0.37–0.46). Acceptance illness cognitions were associated to better (β = 0.12–0.25), and helplessness to worse outcomes (β = 0.14–0.38). Conclusions: HRQoL of parents of young adult survivors of CCS is comparable to references or slightly better. Only a small proportion reports symptomatic post‐traumatic stress. Improving acceptance and reducing feelings of helplessness may provide treatment targets for parents with psychosocial problems. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at risk of kidney dysfunction. Recently, the shrunken pore syndrome (SPS) has been described, which is characterized by selectively impaired filtration of larger molecules like cystatin C, while filtration of smaller molecules like creatinine is unaltered. It has been associated with increased mortality, even in the presence of a normal estimated glomerular filtration rate (eGFR). The aim of this study was to evaluate the prevalence of SPS in CCS exposed to potentially nephrotoxic therapy. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 Renal study, a nationwide cross-sectional cohort study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study, treated between 1963-2001 with nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide or hematopoietic stem cell transplantation participated, and 500 age- and sex-matched controls form Lifelines. SPS was defined as an eGFRcys/eGFRcr ratio <0.6 in the absence of non-GFR determinants of cystatin C and creatinine metabolism (i.e. hyperthyroidism, corticosteroids, underweight). Three pairs of eGFR-equations were used; CKD-EPIcys/CKD-EPIcr, CAPA/LMR, and FAScys/FASage. Median age was 32 years. Although an eGFRcys/eGFRcr ratio <0.6 was more common in CCS (1.0%) than controls (0%) based on the CKD-EPI equations, most cases were explained by non-GFR determinants. The prevalence of SPS in CCS was 0.3% (CKD-EPI equations), 0.2% (CAPA/LMR) and 0.1% (FAS equations), and not increased compared to controls. CCS treated with nephrotoxic therapy are not at increased risk for SPS compared to controls. Yet, non-GFR determinants are more common and should be taken into account when estimating GFR. [ABSTRACT FROM AUTHOR]

Simple Summary: Salivary gland dysfunction is an underestimated late effect in childhood cancer survivors (CCS). The objective of this cross-sectional study, part of the multidisciplinary multicenter Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2), was to assess the prevalence of and risk factors for hyposalivation and xerostomia in CCS with a long-term follow-up exceeding 15 years. From February 2016 until March 2020, 292 CCS were included. The prevalence of hyposalivation was 32% and the prevalence of xerostomia was 9.4%. Hyposalivation and xerostomia did not correlate significantly. Risk factors for hyposalivation were female gender and a higher dose of radiotherapy (>12 Gy) to the salivary glands. Screening for hyposalivation during long-term follow-up in CCS is recommended in order to provide optimal oral supportive care aimed to improve oral health. Background: Limited data are available on the risk factors of salivary gland dysfunction in long-term childhood cancer survivors (CCS). The objective of this cross-sectional study, part of the multidisciplinary multicenter Dutch CCS Study Late Effects 2 (DCCSS LATER 2), was to assess the prevalence of and risk factors for hyposalivation and xerostomia in CCS. Methods: From February 2016 until March 2020, 292 CCS were included. Data with regard to gender, age at study, diagnosis, age at diagnosis, and treatment characteristics were collected, as well as the unstimulated (UWS) and stimulated whole salivary flow rate (SWS). Xerostomia was assessed with the Xerostomia Inventory (XI) questionnaire. Multivariable Poisson regression analyses were used to evaluate the association between potential risk factors and the occurrence of hyposalivation. Results: The minimum time between diagnosis and study enrollment was 15 years. The prevalence of hyposalivation was 32% and the prevalence of xerostomia was 9.4%. Hyposalivation and xerostomia were not significantly correlated. Risk factors for hyposalivation were female gender and a higher dose of radiotherapy (>12 Gy) to the salivary gland region. Conclusion: Considering the importance of saliva for oral health, screening for hyposalivation in CCS is suggested in order to provide optimal oral supportive care aimed to improve oral health. [ABSTRACT FROM AUTHOR]

Background: Some children with central nervous system (CNS) and solid tumors are at risk to develop ototoxicity during treatment. Up to now, several risk factors have been identified that may contribute to ototoxicity, such as platinum derivates, cranial irradiation, and brain surgery. Comedication, like antibiotics and diuretics, is known to enhance ototoxicity, but their independent influence has not been investigated in childhood cancer patients. Recommendations for hearing loss screening are missing or vary highly across treatment protocols. Additionally, adherence to existing screening guidelines is not always optimal. Currently, knowledge is lacking on the prevalence of ototoxicity. Objective: The aim of the Study on Prevalence and Determinants of Ototoxicity During Treatment of Childhood Cancer (SOUND) is to determine the feasibility of audiological testing and to determine the prevalence and determinants of ototoxicity during treatment for childhood cancer in a national cohort of patients with solid and CNS tumors. Methods: The SOUND study is a prospective cohort study in the national childhood cancer center in the Netherlands. The study aims to include all children aged 0 to 19 years with a newly diagnosed CNS or solid tumor. Part of these patients will get audiological examination as part of their standard of care (stratum 1). Patients in which audiological examination is not the standard of care will be invited for inclusion in stratum 2. Age-dependent audiological assessments will be pursued before the start of treatment and within 3 months after the end of treatment. Apart from hearing loss, we will investigate the feasibility to screen patients for tinnitus and vertigo prevalence after cancer treatment. This study will also determine the independent contribution of antibiotics and diuretics on ototoxicity. Results: This study was approved by the Medical Research Ethics Committee Utrecht (Identifier 20-417/M). Currently, we are in the process of recruitment for this study. Conclusions: The SOUND study will raise awareness about the presence of ototoxicity during the treatment of children with CNS or solid tumors. It will give insight into the prevalence and independent clinical and cotreatment-related determinants of ototoxicity. This is important for the identification of future high-risk patients. Thereby, the study will provide a basis for the selection of patients who will benefit from innovative otoprotective intervention trials during childhood cancer treatment that are currently being prepared. Trial Registration: Netherlands Trial Register NL8881; https://www.trialregister.nl/trial/8881 International Registered Report Identifier (IRRID): DERR1-10.2196/34297 [ABSTRACT FROM AUTHOR]

Background: 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. Methods: CCSs from the Dutch Childhood Cancer Survivor Study LATER cohort (1963‐2001) part 2, who were 18 years old or older (time since diagnosis ≥ 5 years), were invited to complete the TNO‐AZL Questionnaire for Adult Health‐Related Quality of Life. Domain scores and proportions of CCSs with impaired HRQOL (score < 25th percentile of the reference scores) were compared with references via Mann‐Whitney U tests and logistic regression analyses corrected for age and sex (P <.004). Interactions of group with sex were included if they were significant (P <.05). Moreover, medical determinants were analyzed with multivariable logistic regression analyses. Results: HRQOL scores for 1766 CCSs (mean age, 35.9 years [standard deviation, 9.4 years]; male, 51%; response rate, 71%) differed from references on most domains with small effect sizes. Both male and female CCSs were more often impaired in gross and fine motor functioning, cognitive functioning, sleep, and vitality with odds ratios (ORs) > 1.4. In addition, female CCSs were more often impaired in daily activities, pain, and sexuality (ORs, 1.4‐1.9) and were less often aggressive (OR, 0.6). CCCs of central nervous system (CNS) tumors, bone tumors, and retinoblastoma and those with cranial, abdominopelvic, or lower extremity radiotherapy were at increased risk of impairment in 1 or more domains. Conclusions: Dutch adult CCSs, especially females, have impaired HRQOL in several domains; this is most pronounced in cognitive functioning. The vulnerabilities of subgroups at risk, such as CCSs of CNS tumors, were confirmed. Surveillance of HRQOL and multidisciplinary survivor care are recommended. Lay Summary: The health‐related quality of life in a Dutch nationwide cohort of 1766 survivors of childhood cancer was studied.Survivors of childhood cancer were found to have lower health‐related quality of life in several domains (eg, motor functioning and vitality) in comparison with the general population.They most often reported low cognitive functioning (eg, memory and attention).Females had low health‐related quality of life in more domains than males.Survivors of brain tumors had low health‐related quality of life in most domains.Monitoring health‐related quality of life regularly and collaborating between disciplines in survivor care is recommended. Dutch adult survivors of childhood cancer, especially females and central nervous system tumor survivors, have impaired health‐related quality of life in several domains; this is most pronounced in cognitive functioning. Surveillance of health‐related quality of life and multidisciplinary survivor care are recommended. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: In this study, 2810 CCSs (5‐year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12‐65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer‐ and treatment‐related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses. Results: In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P <.001). In adolescent CCSs and sibling controls (<18 years old), the prevalence of CF was 10.9% and 3.2%, respectively. Female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.73‐2.62), unemployment (OR, 2.18; 95% CI, 1.67‐2.85), having 1 or more health problems (OR for 1‐2, 1.48; 95% CI, 1.18‐1.87; OR for >2, 2.20; 95% CI, 1.50‐3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17‐2.60) were significantly associated with CF in adult CCSs. Conclusions: This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs. One in 4 childhood cancer survivors reports chronic fatigue. Current health problems increase the risk of reporting chronic fatigue. [ABSTRACT FROM AUTHOR]

Background: Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated for use in childhood cancer survivors (CCS). The aim of the current study was to present norm values and psychometric properties of the Checklist Individual Strength (CIS) and Short Fatigue Questionnaire (SFQ) in a nationwide cohort of CCS. Methods: In total, 2073 participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort. Normative data, construct validity, structural validity, and internal consistency were calculated for the CIS and SFQ. In addition, reliability and a cutoff score to indicate severe fatigue were determined for the SFQ. Results: Correlations between CIS/SFQ and vitality measures asking about fatigue were high (>0.8). Correlations between CIS/SFQ and measures of different constructs (sleep, depressive emotions, and role functioning emotional) were moderate (0.4-0.6). Confirmatory factor analysis resulted in a four-factor solution for the CIS and a one-factor solution for the SFQ with Cronbach's alpha for each (sub)scale showing good to excellent values (>0.8). Test-retest reliability of the SFQ was adequate (Pearson's correlation = 0.88; ICC = 0.946; weighted Cohen's kappa item scores ranged 0.31-0.50) and a cut-off score of 18 showed good sensitivity and specificity scores (92.6% and 91.3%, respectively). Conclusion: The current study shows that the SFQ is a good instrument to screen for severe fatigue in CCS. The CIS can be used as a tool to assess the multiple fatigue dimensions in CCS. [ABSTRACT FROM AUTHOR]

Background: Ototoxicity is a common adverse event of cisplatin treatment. The authors investigated the development of cisplatin‐induced hearing loss (CIHL) over time in children with cancer by age and examined the influence of other clinical characteristics on the course of CIHL. Methods: Data from Canadian patients with childhood cancer were retrospectively reviewed. Hearing loss was graded according to International Society of Pediatric Oncology criteria. The Kaplan‐Meier method was applied to estimate the cumulative incidence of CIHL for the total cohort and according to age. Cox regression models were used to explore the effects of independent variables on CIHL development up to 3 years after the start of therapy. Results: In total, 368 patients with 2052 audiological assessments were included. Three years after initiating therapy, the cumulative incidence of CIHL was highest in patients aged ≤5 years (75%; 95% confidence interval [CI], 66%‐84%), with a rapid increase observed to 27% (95% CI, 21%‐35%) at 3 months and to 61% (95% CI, 53%‐69%) at 1 year, compared with patients aged >5 years (48%; 95% CI, 37%‐62%; P <.001). The total cumulative dose of cisplatin at 3 months (per 100 mg/m2 increase: hazard ratio [HR], 1.20; 95% CI, 1.01‐1.41) vincristine (HR, 2.87; 95% CI, 1.89‐4.36) and the total duration of concomitantly administered antibiotics (>30 days: HR, 1.85; 95% CI, 1.17‐2.95) further influenced CIHL development over time. Conclusions: In young children, the cumulative incidence of CIHL is higher compared with that in older children and develops early during therapy. The course of CIHL is further influenced by the total cumulative dose of cisplatin and other ototoxic (co‐)medication. These results highlight the need for audiological monitoring at each cisplatin cycle. In young children, the cumulative incidence of cisplatin‐induced hearing loss is higher compared with that in older children and develops early during therapy. The course of cisplatin‐induced hearing loss development over time is further influenced by the total cumulative dose of cisplatin, vincristine treatment, and total duration of concomitantly administered antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: Vincristine (VCR) is a chemotherapeutic agent used in the treatment of pediatric oncology patients, but its main toxicity is VCR‐induced peripheral neuropathy (VIPN). However, whether VIPN has an effect on health‐related quality of life (HR‐QoL) in children during treatment is unknown. Therefore, the aim of our study was to investigate the association between VIPN and HR‐QoL in children starting treatment for cancer. Methods: Measurements of VIPN were performed using two tools: Common Terminology Criteria for Adverse Events (CTCAE) and pediatric‐modified Total Neuropathy Score (ped‐mTNS). Assessment of HR‐QoL was done with self‐ and proxy assessment of the Cancer and Generic module of the Pediatric Cancer Quality of Life Inventory™ (PedsQL). Results: In total, N = 86 children were included. HR‐QoL of children with VIPN (n = 67%, 76%) was significantly lower in comparison with children without VIPN: estimated Total score of PedsQL Generic (proxy) 84.57; β = −8.96 and 95% confidence interval (CI) −14.48 to −3.43; p = 0.002, estimated PedsQL Generic Total score (self‐reported): 85.16, β = −8.38 (95% CI: −13.76 to −3.00); p = 0.003. Similar results were found in the Pain and Hurt domain of the PedsQL Cancer (pain: estimated score [proxy]: 85.28, β = −9.94 [95%CI: −16.44 to −3.45], p = 0.003; hurt: estimated score [self‐report] 97.57, β = −19.15 [95%CI: −26.82 to −11.48], p < 0.001). Conclusion: VIPN results in a significant reduction of HR‐QoL in children under treatment for a malignancy, which means that VIPN is important for the well‐being of pediatric oncology patients. Therefore, this study underlines the importance of optimizing treatment with VCR, thereby aiming to reduce VIPN while maintaining efficacy. [ABSTRACT FROM AUTHOR]

Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up. Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [β-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin). Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0–25.0) and 23.5 (IQR 14.0–30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0–17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T- and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers β-CTX and PINP remained stable. Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Trial Registration: This follow-up study was registered in The Netherlands Trial Register under no. NL3280 (www.trialregister.nl/trial/3280). [ABSTRACT FROM AUTHOR]

Summary: Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta‐analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF‐alpha, IL‐1, IL‐6, apolipoprotein B (apoB), and lipoprotein(a) [lp(a)]) in survivors and adult non‐cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS‐2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta‐analysis showed OR for hyperuricemia of 2.94 (age‐/sex‐adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications. [ABSTRACT FROM AUTHOR]

Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort. [ABSTRACT FROM AUTHOR]

Background: A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER fatigue study is to examine the prevalence of and factors associated with CRF, proposing a model which discerns predisposing, triggering, maintaining and moderating factors. Triggering factors are related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms. Maintaining factors are daily life- and psychosocial factors which may perpetuate fatigue once triggered. Moderating factors might influence the way fatigue symptoms express in individuals. Predisposing factors already existed before the diagnosis, such as genetic factors, and are thought to increase the vulnerability to develop fatigue. Methodology of the participant inclusion, data collection and planned analyses of the DCCSS LATER fatigue study are presented.Results: Data of 1955 CCS and 455 siblings was collected. Analysis of the data is planned and we aim to start reporting the first results in 2022.Conclusion: The DCCSS LATER fatigue study will provide information on the epidemiology of CRF and investigate the role of a broad range of associated factors in CCS. Insight in associated factors for fatigue in survivors experiencing severe and persistent fatigue may help identify individuals at risk for developing CRF and may aid in the development of interventions. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer patients often remain uninformed regarding their potential risk of gonadal damage. In our hospital we introduced a five step standard oncofertility care plan for all newly diagnosed female patients aiming to identify, inform and triage 100% of patients and counsel 100% of patients at high risk (HR) of gonadal damage. This observational retrospective study (PEARL study) evaluated the use of this standard oncofertility care plan in the first full year in a national cohort. Methods: The steps consist of 1)timely (preferably before start of gonadotoxic treatment) identification of all new patients, 2)triage of gonadal damage risk using a standardized gonadal damage risk stratification tool, 3)informing all patients and families, 4)counseling of a selected subset of girls, and 5) fertility preservation including ovarian tissue cryopreservation (OTC) in HR patients using amended Edinburgh criteria. A survey of the medical records of all girls newly diagnosed with cancer the first year (1-1-2019 until 31-12-2019) was conducted. Results: Of 261 girls, 228 (87.4%) were timely identified and triaged. Triage resulted in 151 (66%) low(LR), 32 (14%) intermediate(IR) and 45 (20%) high risk(HR) patients. Ninety-nine families were documented to be timely informed regarding gonadal damage risk. In total, 35 girls (5 LR, 5 IR, 25 HR) were counseled by an oncofertility expert. 16/25 HR patients underwent fertility preservation (1 ovariopexy + OTC, oocyte cryopreservation (1 with and 1 without OTC) and 13 OTC). Fertility preservation did not lead to complications or delay of cancer treatment in any patient. Conclusion: We timely identified and triaged most girls (88%) with cancer with a high risk of gonadal damage to be counseled for fertility preservation. We aim to optimize the oncofertility care plan and the standardized gonadal damage risk stratification tool based on this experience and these may be of value to other pediatric oncology centers. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1–39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3–24.7) years. The median cumulative dose of 131I administered was 7.4 (IQR 3.7–13.0) GBq/200.0 (IQR 100.0–350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0–3.7) μg/L vs. 1.6 (IQR 0.6–3.1) μg/L, respectively, p = 0.244]. The cumulative dose of 131I was not associated with AMH levels in DTC survivors (rs = 0.210, p = 0.130). Conclusions: Female survivors of DTC who received 131I treatment during childhood do not appear to have major abnormalities in reproductive characteristics nor in predictors of ovarian failure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Purpose: Diminished reproductive function can be a major late effect of childhood cancer treatment. This study evaluates the changes, and occurrence of possible recovery, in gonadal function markers in children treated for cancer. Methods: Gonadal function markers were measured before (T0), directly after (T1), and 1 year after (T2) end of treatment of childhood cancer. Anti-Müllerian hormone (AMH) was measured in girls and inhibin B in boys and compared to reference populations. Repeated measures analysis of variance and t-tests were employed for data analysis. Results: Baseline gonadal function markers (T0) at diagnosis were available in 129 girls and 150 boys. Paired gonadal function markers were available in 49 girls and 54 boys for T0–T1, and in 27 girls and 32 boys for T1–T2. Gonadal function markers were significantly lower than the reference population at each time point (p < 0.001). Post-menarcheal girls showed a decrease in AMH between T0 and T1 (standard deviation scores [SDS] −0.72 to −1.32, p = 0.007), and in the boys cohort, a decrease in inhibin B (SDS −1.14 to −1.43, p = 0.045) was observed. Impaired gonadal function levels (<5th percentile) at T1 were observed in 15 of 27 (56%) girls and in 15 of 32 (47%) boys. However, gonadal function had recovered at T2 in seven girls and six boys. Conclusion: Our data suggest that gonadal function is already compromised at diagnosis and is further decreased by childhood cancer treatment. Nevertheless, about half of the children with gonadal impairment recovered over time. Evaluation of gonadal function markers before 1 year after end of treatment may therefore be unreliable. [ABSTRACT FROM AUTHOR]

Study Question: Do children conceived by ART have an increased risk of cancer?Summary Answer: Overall, ART-conceived children do not appear to have an increased risk of cancer.What Is Known Already: Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce.Study Design, Size, Duration: A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001.Participants/materials, Setting, Methods: All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]).Main Results and the Role Of Chance: The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children.Limitations, Reasons For Caution: Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare.Wider Implications Of the Findings: Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos.Study Funding/competing Interest(s): This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests. [ABSTRACT FROM AUTHOR]

Hypogonadism after treatment for childhood cancer is a recognized complication and its cause may be subdivided into primary gonadal failure and central hypogonadism. Here, we provide an overview of the risk factors for the development of hypogonadism, assessment and potential interventions and give a summary of the current recommendations for management and follow-up of hypogonadism in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors. [ABSTRACT FROM AUTHOR]

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

Objective: The impact of childhood differentiated thyroid carcinoma (DTC) on psychosocial development has not yet been studied. The aim of this study was to evaluate the achievement of psychosocial developmental milestones in long-term survivors of childhood DTC. Design and methods: Survivors of childhood DTC diagnosed between 1970 and 2013 were included. Reasons for exclusion were age <18 or >35 years at follow-up, a follow-up period <5 years or diagnosis with DTC as a second malignant neoplasm. Survivors gathered peer controls of similar age and sex (n = 30). A comparison group non-affected with cancer (n = 508) and other childhood cancer survivors (CCS) were also used to compare psychosocial development. To assess the achievement of psychosocial milestones (social, autonomy and psychosexual development), the course of life questionnaire (CoLQ) was used. Results: We included 39 survivors of childhood DTC (response rate 83.0%, mean age at diagnosis 15.6 years, and mean age at evaluation 26.1 years). CoLQ scores did not significantly differ between survivors of childhood DTC and the two non-affected groups. CoLQ scores of childhood DTC survivors were compared to scores of other CCS diagnosed at similar ages (n = 76). DTC survivors scored significantly higher on social development than other CCS, but scores were similar on autonomy and psychosexual developmental scales. Conclusions: Survivors of childhood DTC showed similar development on social, autonomy, and psychosexual domains compared to non-affected individuals. Social development was slightly more favorable in DTC survivors than in other CCS, but was similar on autonomy and psychosexual domains. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is no adequate prevention or treatment for both oral and gastrointestinal mucositis induced by chemotherapy and/or radiotherapy. Supportive care of symptoms plays a primary role during mucositis in the pediatric clinical setting. We aimed to get insight in the currently used feeding strategies in clinical practice in pediatric cancer patients with chemotherapy-induced mucositis.Methods: A prospective observational study was performed to identify feeding strategies after chemotherapy courses causing mucositis in almost all patients at the University Medical Center Groningen (UMCG), the Academic Medical Center Amsterdam (AMC), and the Princess Maxima Center Utrecht (PMC). Consecutive patients, aged 0-18 years, either diagnosed with B cell non-Hodgkin lymphoma (B-NHL) or scheduled for autologous stem cell transplantation (SCT) between April 2015 and September 2016 were included in this study. In addition to the observational study in the Netherlands, an international online questionnaire was conducted for pediatric oncology centers.Results: A total of 13 patients were included, after 21 chemotherapy courses. No nutritional support was administered after 23.8% courses, tube feeding after 19.0% of the courses, TPN in 19.0% of courses, and 38.1% received a combination of tube feeding and TPN. The international survey revealed that 63.2% of the centers administered tube feeding as first choice, 31.6% administered only TPN as first choice, and one center administered a combination as first choice.Conclusions: There is a variability in feeding strategies in the clinical practice both in the Netherlands as well as worldwide. This study is a basis for future studies in this important clinical field to develop clinical trials comparing tube feeding and TPN both in adult and pediatric patients. [ABSTRACT FROM AUTHOR]

Study Question: Are Inhibin B and testosterone levels reduced in boys with newly diagnosed cancer prior to therapy?Summary Answer: Pretreatment serum levels of Inhibin B and testosterone are significantly reduced in boys with newly diagnosed cancer, compared to reference values.What Is Already Known: Disease-related gonadal impairment has been demonstrated in girls and young women diagnosed with cancer, prior to therapy.Study Design, Size, Duration: We conducted a descriptive study in boys newly diagnosed with cancer between January 2006 and February 2014.Participants/materials, Setting, Methods: Serum Inhibin B and testosterone levels were determined in 224 boys, up to the age of 18 years, with newly diagnosed cancer prior to therapy. Hormone levels were compared with age-matched reference values. The cohort consisted of patients with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lym-phoma (NHL), nephroblastoma, neuroblastoma and sarcoma.Main Results and the Role Of Chance: This study demonstrates reduced serum levels of Inhibin B in boys with newly diagnosed cancer, compared to reference values (standard deviation score (SDS) -0.9, P < 0.001). Median Inhibin B level in patients was 103.5 ng/l (range 20-422). Of all patients, 78.6% showed Inhibin B levels below the 50th percentile, and 58.5% had Inhibin B levels below the 25th percentile. Serum testosterone levels were significantly lower than the reference range population (SDS -1.2, P < 0.001). Median testosterone level in pubertal patients was 7.3 nmol/l (range 0.1-23.6). No correlation with clinical signs of general illness and hormone levels were observed.Limitations, Reasons For Caution: In this study, reproductive hormone levels were compared with age-matched reference values. Future studies may compare reproductive hormone levels with case controls.Wider Implications Of the Findings: Future longitudinal studies are necessary to determine whether pretreatment impaired gonadal function at the time of cancer diagnosis is an important determinant of ultimate recovery of spermatogenesis after treatment and later on in adulthood.Study Funding/competing Interests: W.v.D. was supported by the Pediatric Oncology Center Society for Research (KOCR), Rotterdam, The Netherlands. A.-L.L.F.v.d.K. was supported by EU FP7 PanCare LIFE study. The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objective: The Psychosocial Assessment Tool (PAT) was developed to screen for psychosocial risk in families of a child diagnosed with cancer. The current study is the first describing the cross-cultural adaptation, reliability, validity, and usability of the PAT in an European country (Dutch translation).Methods: A total of 117 families (response rate 59%) of newly diagnosed children with cancer completed the PAT2.0 and validation measures.Results: Acceptable reliability was obtained for the PAT total score (α = .72) and majority of subscales (0.50-0.82). Two subscales showed inadequate internal consistency (Social Support α = .19; Family Beliefs α = .20). Validity and usability were adequate. Of the families, 66% scored low (Universal), 29% medium (Targeted), and 5% high (Clinical) risk.Conclusions: This study confirms the cross-cultural applicability, reliability, and validity of the PAT total score. Reliability left room for improvement on subscale level. Future research should indicate whether the PAT can be used to provide cost-effective care. [ABSTRACT FROM AUTHOR]

Background: Fertility preservation care for children, adolescents, and young adults (CAYAs) with cancer is not uniform among practitioners. To ensure high-quality care, evidence-based clinical practice guidelines (CPGs) are essential. The authors identified existing CPGs for fertility preservation in CAYAs with cancer, evaluated their quality, and explored differences in recommendations.Methods: A systematic search in PubMed (January 2000-October 2014); guideline databases; and Web sites of oncology, pediatric, and fertility organizations was performed. Two reviewers evaluated the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II). From high-quality CPGs, the authors evaluated concordant and discordant areas among the recommendations.Results: A total of 25 CPGs regarding fertility preservation were identified. The average AGREE II domain scores (scale of 0%-100%) varied from 15% on applicability to 100% on clarity of presentation. The authors considered 8 CPGs (32%) to be of high quality, which was defined as scores ≥60% in any 4 domains. Large variations in the recommendations of the high-quality CPGs were observed, with 87.2% and 88.6%, respectively, of discordant guideline areas among the fertility preservation recommendations for female and male patients with cancer.Conclusions: Only approximately one-third of the identified CPGs were found to be of sufficient quality. Of these CPGs, the fertility preservation recommendations varied substantially, which can be a reflection of inadequate evidence for specific recommendations, thereby hindering the ability of providers to deliver high-quality care. CPGs including a transparent decision process for fertility preservation can help health care providers to deliver optimal and uniform care, thus improving the quality of life of CAYAs with cancer and cancer survivors. Cancer 2016;122:2216-23. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

Gooskens SL, Braakman E, van den Boom AL, So-Osman C, de Winter F, Pieters R, van den Heuvel-Eibrink MM. Peripheral stem cell harvest using regular chemotherapy schedules in childhood cancer. Abstract: Prediction of the best moment for the harvest of PBSCs after standard chemotherapy followed by filgrastim in children with cancer is difficult. We retrospectively analyzed the moment of harvesting of 152 procedures in 94 patients. The start of apheresis was guided by WBC count and CD34+ cell measurement in peripheral blood. We defined the first day of filgrastim administration, after completion of mobilizing chemotherapy, as day 1. Median time to harvest in different subgroups is as follows: neuroblastoma 11 days (range, 6-29 days), Ewing's sarcoma nine days (range, 7-15 days), brain tumor 10 days (range, 7-15 days), relapsed Wilms' tumor 16 days (range, 9-20 days), and extracranial GCT seven days (range, 6-14 days). Patients harvested after cyclophosphamide priming (time to harvest within a range of 8-9 days) were analyzed as a separate group. The optimal moment for harvesting in different types of tumors was highly variable, although most consistent in patients diagnosed with Ewing's sarcoma or brain tumors and after cyclophosphamide priming. [ABSTRACT FROM AUTHOR]

The authors discuss the importance of palliative care, treatment that afford relief from disease but not cure, in children with cancer. Topics mentioned include the contribution of general practitioner (GP) in palliative care, the children health management, and the symptoms suffered by children with cancer at the end of life including fatigue, poor appetite, and pain.

Background: Despite a significant number of studies on female fertility following childhood, adolescent, and young adult (CAYA) cancer, studies establishing precise (dose-related) estimates of treatment-related risks are still scarce. Previous studies have been underpowered, did not include detailed treatment information, or were based on self-report only without any hormonal assessments. More precise assessments of who is at risk for sub- or infertility are needed. Objective: The objective of our study is to describe the design and methods of 2 studies on female fertility (a cohort study and a nested case-control study) among female survivors of CAYA cancer performed within the European PanCareLIFE project. Methods: For the cohort study, which aims to evaluate the overall risk of fertility impairment, as well as the risk for specific subgroups of female CAYA cancer survivors, 13 institutions from 9 countries provide data on fertility impairment. Survivors are defined as being fertility impaired if they meet at least one of 8 different criteria based on self-reported and hormonal data. For the nested case-control study, which aims to identify specific treatment-related risk factors associated with fertility impairment in addition to possible dose-response relationships, cases (fertility impaired survivors) are selected from the cohort study and matched to controls (survivors without fertility impairment) on a 1:2 basis. Results: Of the 10,964 survivors invited for the cohort study, data are available from 6619 survivors, either questionnaire-based only (n=4979), hormonal-based only (n=72), or both (n=1568). For the nested case-control study, a total of 450 cases and 882 controls are identified. Conclusions: Results of both PanCareLIFE fertility studies will provide detailed insight into the risk of fertility impairment following CAYA cancer and diagnostic- or treatment-related factors associated with an increased risk. This will help clinicians to adequately counsel both girls and young women, who are about to start anticancer treatment, as well as adult female CAYA cancer survivors, concerning future parenthood and to timely refer them for fertility preservation. Ultimately, we aim to empower patients and survivors and improve their quality of life. [ABSTRACT FROM AUTHOR]

Anthracyclines and radiotherapy involving the heart region are cardiotoxic, but the potential cardiotoxicity of vincristine remains unknown. We assessed cardiac function in vincristine-treated >5-year childhood cancer survivors (CCS). We cross-sectionally compared echocardiograms of 101 vincristine-treated CCS (median age 35 years [range: 17–53], median vincristine dose 63 mg/m2) from the national Dutch Childhood Cancer Survivor Study, LATER cohort, to 101 age- and sex-matched controls. CCS treated with anthracyclines, radiotherapy involving the heart region, cyclophosphamide or ifosfamide were excluded. Twelve CCS (14%) versus four controls (4%; p 0.034) had a decreased left ventricular ejection fraction (LVEF; men <52%, women <54%). Mean LVEF was 58.4% versus 59.7% (p 0.050). Global longitudinal strain (GLS) was abnormal in nineteen (24%) CCS versus eight controls (9%; p 0.011). Mean GLS was 19.0% versus 20.1% (p 0.001). No ≥grade 2 diastolic dysfunction was detected. In multivariable logistic regression analysis CCS had higher risk of abnormal GLS (OR 3.55, p 0.012), but not abnormal LVEF (OR 3.07, p 0.065), than controls. Blood pressure and smoking history contributed to variation in LVEF, whereas obesity and diastolic blood pressure contributed to variation in GLS. Cumulative vincristine dose was not associated with either abnormal LVEF or abnormal GLS in multivariable models corrected for age and sex (OR per 50 mg/m2: 0.88, p 0.85 and 1.14, p 0.82, respectively). Vincristine-treated long-term CCS showed an abnormal GLS more frequently than controls. Their risk for future clinical cardiac events and the role of risk factor modification should be further elucidated. [Display omitted] • Echocardiographic GLS measurement may detect cardiac dysfunction in an early stage • Vincristine-treated childhood cancer survivors show reduced GLS • No dose-response relation was present between vincristine dose and LVEF or GLS • Diastolic blood pressure and body mass index contributed to lower GLS • Whether these survivors are at risk for cardiovascular events should be elucidated [ABSTRACT FROM AUTHOR]

Infertility is a serious early, as well as late, effect of childhood cancer treatment. If addressed in a timely manner at diagnosis, fertility preservation measures can be taken, preferably before the start of cancer treatment. However, pediatric oncologists might remain reluctant to offer counseling on fertility-preservation methods, although infrastructure to freeze ovarian tissue has become available and is currently considered standard care for pre- and postpubertal girls at high risk of gonadal damage. More importantly, risk factors have been identified for cancer treatment-related impairment of gonadal function, and the first successful pregnancies have been reported after autotransplanted ovarian tissue, which has been harvested from children. Additionally, great progress has been made in the field of ex vivo maturation of oocytes in frozen ovarian tissue, which provides opportunities for those at risk of ovarian micrometastasis. Hence, it is time to counsel girls at risk and make every effort to cryopreserve their ovarian tissue, now more than ever before. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU.Design: A nationwide, multicenter, retrospective, observational study.Setting: Eight PICUs of a tertiary care hospitals in the Netherlands.Patients: Pediatric cancer and hematopoietic stem cell transplant patients (cancer and noncancer) who received continuous renal replacement therapy from January 2006 to July 2017 in the Netherlands.Interventions: None.Measurement and Main Results: Of 1,927 PICU admissions of pediatric cancer and hematopoietic stem cell transplant patients, 68 of 70 evaluable patients who received continuous renal replacement therapy were included. Raw PICU mortality was 11.2% (216/1,972 admissions). PICU mortality of patients requiring continuous renal replacement therapy was 54.4% (37/68 patients). Fluid overload (odds ratio, 1.08; 95% CI, 1.01-1.17) and need for inotropic support (odds ratio, 6.53; 95% CI, 1.86-23.08) at the start of continuous renal replacement therapy were associated with PICU mortality. Serum creatinine levels increased above 150% of baseline 3 days before the start of continuous renal replacement therapy. Urine production did not reach the critical limit of oliguria. In contrast, body weight (fluid overload) increased already 5 days prior to continuous renal replacement therapy initiation.Conclusions: PICU mortality of pediatric cancer and hematopoietic stem cell transplant patients requiring continuous renal replacement therapy is sadly high. Fluid overload at the initiation of continuous renal replacement therapy is the most important and earliest predictor of PICU mortality. Our results suggest that the most commonly used criteria of acute kidney injury, that is, serum creatinine and urine production, are not useful as a trigger to initiate continuous renal replacement therapy. This highlights the urgent need for prospective studies to generate recommendations for effective therapeutic interventions at an early phase in this specific patient population. [ABSTRACT FROM AUTHOR]

Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7–31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79–24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16–21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31–8.04], p = 0.01) was significantly associated with PICU mortality. PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial. [ABSTRACT FROM AUTHOR]