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Background: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS‐LATER2) cohort. Methods: In total, 2338 adult childhood cancer survivors (CCS) were cross‐sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual‐energy x‐ray absorptiometry fat% instead of waist circumference to define abdominal adiposity. Logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS and both cohorts. Demographic, lifestyle, and treatment determinants of MetS were identified through multivariable logistic regression. Results: The survivor cohort (median age, 34.7 years, median follow‐up time, 27.1 years) showed increased adjusted odds ratio (aOR) for MetS (modified National Cholesterol Education Program Adult Treatment Panel III criteria), as compared to the reference cohort (aOR, 2.07; 95% confidence interval [CI], 1.85–2.32). Compared to these criteria, the alternative method identified 57 additional survivors with MetS (395 of 2070 [19.1%] vs. 452 of 1960 [23.1%], respectively). Age (odds ratio [OR], 1.07; 95% CI, 1.04–1.10, per year increase), smoking (OR, 1.46; 95% CI, 1.04–2.04), low physical activity (OR, 1.48; 95% CI, 1.05–2.09), abdominal radiotherapy (OR, 2.13; 95% CI, 1.01–4.31; >30 Gy), cranial radiotherapy (OR, 2.89; 95% CI, 1.67–4.96; 1–25 Gy; and OR, 2.44; 95% CI, 1.30–4.47; >25 Gy), total body irradiation (OR, 6.17; 95% CI, 3.20–11.76), and underlying central nervous system tumor (OR, 1.78; 95% CI, 1.21–2.60) were associated with MetS. Conclusion: The high risk of MetS in CCS, combined with several potential modifiable factors, underscores the need for timely identification and intervention strategies to mitigate the long‐term cardiovascular risks in CCS. The prevalence of metabolic syndrome in the recruited nationwide childhood cancer survivor cohort was high and inconsistent with the chronological age, suggesting a substantial future health burden. Nonmodifiable determinants, including cranial, abdominal, and total body irradiation, as well as modifiable determinants, including smoking and physical activity, were associated with metabolic syndrome in this nationwide childhood cancer survivor cohort. [ABSTRACT FROM AUTHOR]

Background: Treatment‐related late effects can worsen over time among cancer survivors. Such worsening health states may trigger changes in internal standards, values, or conceptualization of quality‐of‐life (QOL). This "response‐shift" phenomenon can jeopardize the validity of QOL assessment, and misrepresent QOL comparisons over time. This study tested response‐shift effects in reporting future‐health concerns among childhood cancer survivors who experienced progression in chronic health conditions (CHCs). Methods: 2310 adult survivors of childhood cancer from St. Jude Lifetime Cohort Study completed a survey and clinical assessment at two or more timepoints. Based on 190 individual CHCs graded for adverse‐event severity, global CHC burden was classified as "progression" or "non‐progression". QOL was assessed using the SF‐36TM eight domains and physical‐ and mental‐component summary scores (PCS, MCS). A single global item measured concerns about future health. Random‐effects models comparing survivors with and without progressive global CHC burden (progressors vs. non‐progressors) evaluated response‐shift effects (recalibration, reprioritization, reconceptualization) in reporting future‐health concerns. Results: Compared with non‐progressors, progressors were more likely to de‐emphasize (or downplay) overall physical and mental health in evaluating future‐health concerns (p‐values<0.05), indicating recalibration response‐shift, and more likely to de‐emphasize physical health earlier rather than later in follow‐up (p‐value<0.05), indicating reprioritization response‐shift. There was evidence for a reconceptualization response‐shift with progressor classification associated with worse‐than‐expected future‐health concerns and physical health, and better‐than‐expected pain and role‐emotional functioning (p‐values<0.05). Conclusion: We identified three types of response‐shift phenomena in reporting concerns about future health among childhood cancer survivors. Survivorship care or research should consider response‐shift effects when interpreting changes in QOL over time. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence of and risk factors for hypertension in childhood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (≥1 g/m2 per single dose or ≥10 g/m2 total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic ≥140 and/or diastolic ≥90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic ≥135 and/or diastolic ≥85, night time: systolic ≥120 and/or diastolic ≥70, 24-h: systolic ≥130 and/or diastolic ≥80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Median age at cancer diagnosis was 4.7 years (interquartile range, IQR 2.4–9.2), at study 32.5 years (IQR 27.7–38.0) and follow-up 25.5 years (IQR 21.4–30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (<60 ml/min/1.73 m2) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4–8.5). Risk factors were abdominal radiotherapy ≥20 Gy and TBI. The ABPM-pilot study (n = 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy ≥20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND. • Prevalence of hypertension is comparable in childhood cancer survivors and controls. • Risk factors for hypertension are abdominal radiotherapy and total body irradiation. • Hypertension is associated with decreased glomerular filtration rate in childhood cancer survivors. • Ambulatory blood pressure monitoring has added value for childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging research suggests that survivors of childhood and adolescent cancers are at risk for morbidity and mortality associated with air pollutants. However, caregiver perceptions of the effects of air pollution are unknown. Thus, to address this gap we described caregivers’ perceptions of air pollution’s impact on general population health and specifically on childhood cancer survivors, and caregivers’ air pollution information-seeking and exposure reduction behaviors. Methods Participants were Utah residents, ≥18 years, and caregiver of a childhood cancer survivor who had completed treatment. Semi-structured interviews were conducted with caregivers to describe their perspectives on air quality, how air pollution impacts health (general population and survivor health), and their information seeking and exposure reduction behaviors. Interviews were recorded, transcribed, and analyzed through two rounds of structured coding. Results Caregivers (N = 13) were non-Hispanic white and primarily females (92.3%) between 30 and 49 years old (46.2%). Most families lived within the Wasatch Front (69.2%), the main metropolitan of Utah. Two categories emerged pertaining to caregiver’s perceptions of air pollution: 1) Limited awareness about the health effects of air pollution, and 2) Unsuccessful information seeking and minimal exposure reduction behaviors. All caregivers held negative perceptions of air pollution in Utah, but most were unaware of how pollution affects health. While some families limited air pollution exposure by avoiding outdoor activity or physically leaving the region, few practiced survivor-specific exposure reduction. Nearly half of caregivers worried about potential effects of air pollution on survivor health and wanted more information. Conclusions Despite negative perceptions of air pollution, caregivers were divided on whether air pollution could impact survivor health. Few caregivers engaged in exposure reduction for their cancer survivor. As air pollution levels increase in the U.S., continued research on this topic is essential to managing cancer survivor respiratory and cardiovascular health.

BackgroundChildhood cancer survivors (CCSs) have a lifelong increased risk of chronic health problems, most of which are associated with the curative therapies. Recent studies have suggested that prospective active screening using comprehensive assessments for CCSs is superior in identifying undiagnosed chronic health problems.MethodsTo assess the significance of active screening using comprehensive medical examinations for detecting chronic health problems in multiple organ systems in CCSs, we retrospectively compared the frequency and severity of health problems between two different cohorts of CCSs in a single institution: 110 CCSs who visited the outpatient clinic for regular follow-ups between December 2010 and December 2015 (regular follow-up group) vs. 58 CCSs who underwent comprehensive medical examinations between February 2016 and September 2019 (active screening group). CCSs were defined as patients aged ≥ 18 years who had been diagnosed as having childhood cancer ≥ 10 years before and had survived without cancer for ≥ 5 years.ResultsPatient characteristics were similar between the two groups except for primary diagnosis (more brain tumors and embryonal tumors in the active screening group) and treatment history (more alkylating agents used and surgical interventions performed in the active screening group). The prevalence and the median number of health problems were significantly higher in the active screening group than in the regular follow-up group: 93% vs. 67% and 1.0 [0.0–8.0] vs. 2.0 [0.0–7.0] respectively. In term of organ-specific health problems, pulmonary dysfunction, neurocognitive impairment, ocular abnormalities, and dental abnormalities were identified more in the active screening group, partly because these problems had not been assessed in the regular follow-up group. Nevertheless, the prevalence of grade 3–5 health problems was similar between the two groups, except for pulmonary dysfunction.ConclusionActive screening using comprehensive medical examinations was effective for identifying health problems in CCSs. Although the prevalence of severe problems identified by both approaches was similar, comprehensive medical examinations could detect overlooked problems such as severe pulmonary dysfunction, dental maldevelopment, and borderline intellectual functioning, which might have an impact on quality of life in CCSs.

Background: Survivors of childhood cancer are at lifelong risk of morbidity (such as new cancers or heart failure) and premature mortality due to their cancer treatment. These are termed late effects. Therefore, they require lifelong, risk-tailored surveillance. However, most adult survivors of childhood cancer do not complete recommended surveillance tests such as mammograms or echocardiograms. Objective: In partnership with survivors, family physicians, and health system partners, we are designing a provincial support system for high-priority tests informed by principles of implementation science, behavioral science, and design thinking. Methods: Our multiphase process was structured as follows. Step 1 consisted of a qualitative study to explore intervention components essential to accessing surveillance tests. Step 2 comprised a workshop with childhood cancer survivors, family physicians, and health system stakeholders that used the Step 1 findings and “personas” (a series of fictional but data-informed characters) to develop and tailor the intervention for different survivor groups. Step 3 consisted of intervention prototype development, and Step 4 involved iterative user testing. Results: The qualitative study of 30 survivors and 7 family physicians found a high desire for information on surveillance for late effects. Respondents indicated that the intervention should help patients book appointments when they are due in addition to providing personalized information. Insights from the workshop included the importance of partnering with both family physicians and survivorship clinics and providing emotional support for survivors who may experience distress upon learning of their risk for late effects. In our user-testing process, prototypes went through iterations that incorporated feedback from users regarding acceptability, usability, and functionality. We sought to address the needs of survivors and physicians while balancing the capacity and infrastructure available for a lifelong intervention via our health system partners. Conclusions: In partnership with childhood cancer survivors, family physicians, and health system partners, we elucidated the barriers and enablers to accessing guideline-recommended surveillance tests and designed a multifaceted solution that will support survivors and their family physicians. The next step is to evaluate the intervention in a pragmatic randomized controlled trial. [ABSTRACT FROM AUTHOR]

Purpose: Most survivors of childhood cancer experience subsequent chronic conditions but little is known about concurrent symptoms. This study seeks to identify late effect symptom clusters among young pediatric cancer survivors.Methods: Survivors ≥ 18 or parents of survivors < 18 years enrolled in an institutional cohort study indicated (yes/no) if they experienced certain symptoms after treatment. The sample was randomly divided in half for exploratory factor analyses to identify symptom clusters followed by confirmatory factor analyses. Symptoms with ≥ 10% prevalence were included. Cluster structure generalizability across subgroups was examined using congruence coefficients.Results: The sample included 579 survivors (74% non-Hispanic white, 45% leukemia, 12.8 ± 4.5 years at survey, 5.9 ± 3.5 years since therapy). Respondents averaged three symptoms. Three clusters were identified: (1) gastrointestinal: abdominal pain, diarrhea, constipation, nausea, vomiting (Cronbach's α = 0.74); (2) psychological: depression, anxiety, memory problems, anger management problems, sleep problems (α = 0.71); and (3) neurologic: problems walking, numbness/tingling, fatigue, back pain, chronic pain, weakness/inability to move legs (α = 0.71). Confirmatory factor analysis confirmed the three-cluster structure (standardized root mean square residual: 0.09; parsimonious goodness of fit: 0.96; Bentler-Bonett normed fit index: 0.95). The gastrointestinal and psychological clusters were generalizable across most subgroups while the neurologic cluster varied across age and race/ethnicity subgroups.Conclusion: Three distinct late effect symptom clusters were identified in young childhood cancer survivors with gastrointestinal and psychological clusters remaining relatively stable across subgroups. Future studies should focus on the characteristics of patients who experience these symptoms, especially those with high symptom burden, and the synergistic impact on quality of life. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that survivors of childhood and adolescent cancers are at risk for morbidity and mortality associated with air pollutants. However, caregiver perceptions of the effects of air pollution are unknown. Thus, to address this gap we described caregivers' perceptions of air pollution's impact on general population health and specifically on childhood cancer survivors, and caregivers' air pollution information-seeking and exposure reduction behaviors.Methods: Participants were Utah residents, ≥18 years, and caregiver of a childhood cancer survivor who had completed treatment. Semi-structured interviews were conducted with caregivers to describe their perspectives on air quality, how air pollution impacts health (general population and survivor health), and their information seeking and exposure reduction behaviors. Interviews were recorded, transcribed, and analyzed through two rounds of structured coding.Results: Caregivers (N = 13) were non-Hispanic white and primarily females (92.3%) between 30 and 49 years old (46.2%). Most families lived within the Wasatch Front (69.2%), the main metropolitan of Utah. Two categories emerged pertaining to caregiver's perceptions of air pollution: 1) Limited awareness about the health effects of air pollution, and 2) Unsuccessful information seeking and minimal exposure reduction behaviors. All caregivers held negative perceptions of air pollution in Utah, but most were unaware of how pollution affects health. While some families limited air pollution exposure by avoiding outdoor activity or physically leaving the region, few practiced survivor-specific exposure reduction. Nearly half of caregivers worried about potential effects of air pollution on survivor health and wanted more information.Conclusions: Despite negative perceptions of air pollution, caregivers were divided on whether air pollution could impact survivor health. Few caregivers engaged in exposure reduction for their cancer survivor. As air pollution levels increase in the U.S., continued research on this topic is essential to managing cancer survivor respiratory and cardiovascular health. [ABSTRACT FROM AUTHOR]

The population of childhood cancer survivors (CCS) has grown rapidly in recent decades. Although cured of their original malignancy, these individuals are at increased risk of serious late effects, including age-associated complications. An impaired immune system has been linked to the emergence of these conditions in the elderly and CCS, likely due to senescent immune cell phenotypes accompanied by low-grade inflammation, which in the elderly is known as “inflammaging.” Whether these observations in the elderly and CCS are underpinned by similar mechanisms is unclear. If so, existing knowledge on immunosenescent phenotypes and inflammaging might potentially serve to benefit CCS. We summarize recent findings on the immune changes in CCS and the elderly, and highlight the similarities and identify areas for future research. Improving our understanding of the underlying mechanisms and immunosenescent markers of accelerated immune aging might help us to identify individuals at increased risk of serious health complications.

Background and Summary: Thanks to increasing cure rates to currently >80%, children, adolescents, and young adults (CAYA) survive their cancer much more frequently today than decades ago. Due to their long life expectancy, CAYA cancer survivors are at a particular risk of long-term sequelae from the cancer itself or the therapy applied; this requires specific follow-up, and preventative or even therapeutic interventions. Thus, compared to the normal population, morbidity and mortality may be significantly increased. In 2 of 3 survivors, the cancer and the respective treatment can lead to late effects, even after 30 years, which require specific therapy; in about one-third of these cases, these effects are classed as severe. Applying structured follow-up could identify these late effects at an early stage and initiate immediate treatment. In 2018, a working group dealing with long-term survival after cancer detected <40 years of age was founded within the framework of the National Cancer Plan of the German Federal Ministry of Health. [ABSTRACT FROM AUTHOR]

Abstract Background Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation. Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment as the primary outcome in CCS. Methods As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent CCS cohort. Discussion This international collaboration aims to enhance knowledge of genetic variation which may be included in risk prediction models for gonadal impairment in CCS.

Background: Many childhood cancer survivors develop treatment-associated late effects emerging years or even decades after the end of treatment. Evidence-based guidelines recommend risk-adapted screening, facilitating early diagnosis and management of these sequelae. Long-term follow-up (LTFU) in specialized late effects clinics is devised to implement screening recommendations in the care of childhood cancer survivors. Objectives: To create a practical LTFU tool for the daily practice. Methods: Current guidelines and screening recommendations concerning LTFU in adult survivors of childhood cancer were reviewed and a comprehensive LTFU approach was developed. Results: A risk stratification model assigning patients to three risk groups with different screening recommendations and frequencies is presented based on current LTFU guidelines. Furthermore, a model of LTFU in a clinical multidisciplinary team is proposed. Conclusions: Although late morbidity and mortality in childhood cancer survivors have been attenuated in the last decade by reducing treatment toxicities, a high proportion of long-term survivors already is or will still be affected by treatment-associated chronic health conditions. With the knowledge of late effects and their occurrence as a consequence of specific treatment modalities, practical LTFU recommendations are essential to achieve standardized and structured LTFU care. [ABSTRACT FROM AUTHOR]

Background: Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation. Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment  as the primary outcome in CCS.Methods: As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent CCS cohort.Discussion: This international collaboration aims to enhance knowledge of genetic variation which may be included in risk prediction models for gonadal impairment in CCS. [ABSTRACT FROM AUTHOR]

Introduction The variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment. Methods A systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment. Results Twenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report. Conclusion Genetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration. [ABSTRACT FROM AUTHOR]

Purpose: Given childhood cancer survivors' risk of treatment-induced late effects, long-term follow-up care is recommended. We explored experiences with late effects-related care and preferences for long-term follow-up care among adult survivors of childhood malignant lymphoma in Norway.Methods: We conducted five focus group interviews with 34 survivors (19 females; 21 Hodgkin/13 non-Hodgkin lymphoma survivors; mean age 39 years; mean time from diagnosis 26 years). Data was analyzed using principles of thematic analysis.Results: Two main themes were identified: (1) the survivors' experiences with late effects-related care and (2) their preferences for long-term follow-up care. Most of the survivors were dissatisfied with their late effects-related care due to perceptions of poor coordination of healthcare needs in a fragmented system, combined with a perceived lack of knowledge of late effects among themselves and general practitioners (GPs). All survivors valued long-term follow-up care. Oncologists were the preferred care providers, but GPs were considered acceptable providers if they had sufficient knowledge of late effects and routine examinations, short waiting times, and improved GP-oncologist collaboration.Conclusions: Our results suggest that a shared care model of long-term follow-up care involving specialists, GPs, and the survivors themselves is likely to fulfill several of the currently unmet needs among adult survivors of childhood cancers. Improved patient education about late effects and follow-up care would aid self-management. The survivors' concerns regarding lack of sufficient knowledge of late effects among GPs suggest a need for improving access to, and dissemination of, information of late effects. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported changes in the body mass index (BMI) with time in childhood cancer survivors (CCSs) during follow-up. The limitations of these studies include that they described only a subgroup of survivors or used questionnaires with self-reported heights and weights. The goal of this study was to examine BMI in a large cohort of long-term CCSs and relate this to the BMI at diagnosis, age, sex, tumor type, treatment, and endocrine defects.Methods: All patients treated for childhood cancer at the Emma Children's Hospital/Academic Medical Center between 1966 and 1996 who had survived for at least 5 years were eligible for inclusion. For 893 CCSs with a mean follow-up of 14.9 years, the BMI at the late effects outpatient clinic was compared with the BMI for the general Dutch population.Results: For girls, an increased prevalence of obesity was found. Risk factors for developing a high BMI at follow-up were a younger age and a high BMI at diagnosis and treatment with cranial radiotherapy. A significantly increased prevalence of severe underweight was found in all adult subgroups except for females aged 26 to 45 years. An association was found between a low BMI at diagnosis and a low BMI at follow-up. No treatment-related variables could be related to changes in BMI.Conclusions: The BMI at diagnosis is one of the most important predictors for the BMI at follow-up, and this suggests an important genetic or environmental cause. Adult CCSs are at high risk for developing severe underweight at follow-up. Future studies should focus on the causes and clinical consequences of underweight. [ABSTRACT FROM AUTHOR]

Background Tumours of the central nervous system (CNS) are the most frequent solid tumours and the second most frequent type of cancer in children and adolescents. Overall survival has continuously improved in Germany, since an increasing number of patients have been treated according to standardised, multicentre, multimodal treatment recommendations, trials of the German Paediatric Brain Tumour Consortium (HIT-Network) or the International Society of Paediatric Oncology-Europe (SIOP-E) during the last decades. Today, two out of three patients survive. At least 8000 long-term childhood brain tumour survivors (CBTS) are currently living in Germany. They face lifelong disease- and treatment-related late effects (LE) and associated socioeconomic problems more than many other childhood cancer survivors (CCS). Method We review the LE and resulting special needs of this particular group of CCS. Results Despite their increasing relevance for future treatment optimisation, neither the diversity of chronic and cumulative LE nor their pertinent risk factors and subsequent impact on quality of survival have yet been comprehensively addressed for CBTS treated according to HIT- or SIOP-E-protocols. Evidence-based information to empower survivors and stakeholders, as well as medical expertise to manage their individual health care, psychosocial and educational/vocational needs must still be generated and established. Conclusion The establishment of a long-term research- and care network in Germany shall contribute to a European platform, that aims at optimising CBTSs' transition into adulthood as resilient individuals with high quality of survival including optimal levels of activity, participation and acceptance by society. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.Methods: Participants included 1996 survivors who previously received treatment for cancer at St. Jude Children's Research Hospital and who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Obesity was defined as a body mass index ≥30 kg/m(2) . The factors associated with adult obesity were identified by subgroup-specific (cranial radiation [CRT] exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific, exploratory, genome-wide association analyses using a 2-stage resampling approach with a type I error rate of 5 × 10(-6) .Results: Forty-seven percent of survivors who received CRT and 29.4% of those who did not receive CRT were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of CRT status (P < .0001). The odds of obesity were increased among survivors who received CRT who had also received glucocorticoids (P = .014) or who were younger at diagnosis (P = .013). Among the survivors who had received CRT, 166 SNPs were associated with obesity. The strongest association was observed with reference SNP rs35669975 (P = 3.3 × 10(-8) ) on segment 33.3 of the long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A (family with sequence similarity 155, member A). SNPs within the glycine receptor α3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and cadherin 18 type 2 (CDH18) genes also were identified. These genes have been implicated in neural growth, repair, and connectivity.Conclusions: Obesity in childhood cancer survivors remains associated with previous exposure to CRT and glucocorticoids. Genetic variants related to neural connectivity may modify the risk of obesity among survivors who receive CRT. Validation of these findings in independent cohorts is required. [ABSTRACT FROM AUTHOR]

With growing numbers of childhood cancer survivors, it becomes increasingly important to understand the long-term toxicities associated with cure from malignancy. Many survivors were exposed to cardiotoxic chemotherapeutic agents at young ages. Indeed, cardiotoxicity is a leading cause of treatment-related morbidity and mortality in survivors of childhood cancer, and anthracycline exposure is a leading cause of these late cardiac effects. Nonetheless, anthracyclines remain critical agents in treating many pediatric cancers. Strategies to prevent anthracycline-associated cardiotoxicity include limiting lifetime cumulative anthracycline doses and adding cardioprotectant agents, such as dexrazoxane, to anthracycline-based regimens. However, attempts to reduce the cardiotoxicity of anthracyclines must also consider their effect on anti-cancer efficacy as well as new potential toxicities. In survivors of childhood acute lymphoblastic leukemia, the data suggest that including dexrazoxane in anthracycline-based regimens can prevent heart damage, does not reduce anti-leukemic efficacy, and can be safely administered. The controversies associated with dexrazoxane exemplify the challenges of changing therapy in cancers with a relatively good chance of event-free survival in efforts to prevent long-term sequelae. Studies of very-long-term survivor cohorts will continue to inform current practices. Continued efforts are needed to minimize cardiotoxic exposures during cancer treatment, to deliver safe and effective cardioprotectant measures when cardiotoxic agents cannot be avoided, to identify patients at greatest risk of serious cardiac toxicity, and to educate providers in the optimal care of survivors. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) has been associated with the development of solid second malignant neoplasms (SMNs) in childhood cancer survivors. The aim of this study was to analyse the effect of cumulative doses of previous RT received at the SMN body region, at all other body regions and at body regions adjacent to the SMN, on the risk of developing a solid SMN. A total of 190 cases diagnosed with a solid second malignant neoplasm in 1980-2002 were matched with 368 controls with single neoplasm from the database of the German Childhood Cancer Registry (GCCR) (33,809 patients at cut-off date). The GCCR registers approximately 97 % of all childhood malignancies which occur at an age of less than 15 years in Germany since 1980. It was found that 147 (77.4 %) cases had received RT compared to 208 (56.6 %) controls with cumulative focus doses from 8 to 110 Gy. Fifty per cent of the SMNs and 60 % of RT affected the head region. RT was shown to increase the risk of a solid second tumour within the body region of radiation by 5.3 % per Gy (odds ratio 1.053; 95 % confidence interval 1.036-1.071). With increasing age at diagnosis and with more recent treatment eras, this effect decreased. Cumulative RT doses received at all other body regions or only at body regions adjacent to the SMN did not show an additional effect on the risk of developing an SMN. It is thus concluded that RT is the main risk factor for the development of SMNs within the irradiated body region. Late effects surveillance of former patients should give special attention to the originally irradiated parts of the body. [ABSTRACT FROM AUTHOR]

Objective: Family functioning appears to be a predictor of psychological distress among childhood cancer survivors and their family members; however, relatively little is known about patterns in those families that are psychologically at-risk. The purpose of this study was to identify distinct clusters of families that include childhood cancer survivors, and to evaluate differences between the clusters with respect to anxiety, depression, and post-traumatic stress symptoms (PTSS). Methods: Childhood cancer survivors and their parents (247 individuals: 88 adolescent cancer survivors, 87 mothers, and 72 fathers) completed self-report questionnaires. Perceptions of family functioning were assessed using the Family Relationship Index and its three dimensions (cohesiveness, expressiveness, and conflict), and individuals were classified into groups via a cluster analytic approach. State-trait anxiety, depression, and PTSS were assessed to all of the participants. Results: The individuals were classified into three types: One cluster featured high cohesiveness, high expressiveness, and low conflict (‘Supportive-type’, n=102); a second cluster featured low cohesiveness, low expressiveness, and high conflict (‘Conflictive-type’, n=32); and a third cluster had moderate cohesiveness, moderate expressiveness, and moderate conflict (‘Intermediate-type’, n=113). Among the three types, an analysis of variance revealed that ‘Conflictive-type’ members had the highest levels of PTSS, depression, and state–trait anxiety. Conclusions: These findings suggest that perceptions of family functioning are related to psychological distress in family members of childhood cancer survivors. A family-focused intervention might be a useful approach to targeting emotional distress in these families, particularly for families with a ‘Conflictive-type’ family member. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the health status of the oldest cancer survivors since their childhood. The study was undertaken to 107 adults who were treated for childhood cancer between 1947 and 1968. Results of the study revealed that the oldest adult cancer survivors continue to be at risk due to treatment-related complications that could shorten their life expectancy and could affect their quality of life.

The majority of children and adolescents diagnosed with cancer will achieve long-term survival after contemporary therapy. Consequent to this success are challenges inherent in coordinating lifelong health care for a group predisposed to a variety of cancer-related complications. With increasing numbers of aging adult survivors of childhood cancer, clinicians now face the additional challenge of studying delayed effects of childhood cancer in the context of organ senescence. Clinicians must also address the transition of survivor health care from the pediatric oncology setting to the adult community. Salient issues influencing health care of long-term childhood cancer survivors are summarized, and a model for monitoring late treatment effects used at a pediatric cancer facility is presented. This model is remarkable for its ability to enhance optimal delivery of long-term survivor care, facilitate the transition of survivor care from the pediatric treatment center to community providers, and support investigations of late cancer-related morbidity and mortality. [ABSTRACT FROM PUBLISHER]