Assisted reproductive technology use and outcomes in childhood cancer survivors.

BACKGROUND: Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. METHODS: Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. RESULTS: Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10 years [range, 0-20 years]; median years of follow-up after age 18 years, 11 years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p = .39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p = .33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000 mg/m2 vs. none; RR, 1.04; 95% CI, 0.52-2.05). CONCLUSIONS: Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population.

Social participation of school-aged survivors of pediatric brain tumors: A daily diary report.

BACKGROUND: Difficulties with social functioning are common among survivors of pediatric brain tumors. Social participation is an understudied measure of social functioning that is associated with emotional health across the lifespan. This paper uses a diary method to assess the social participation of survivors of pediatric brain tumors in middle childhood. PROCEDURE: Survivors of pediatric brain tumors (N = 47; age 10.6 ± 1.4 years; 51.1% male, 89.4% White) who were 5.3 (SD = 2.4, range: 2-9.9) years post therapy completed a daily diary assessment of social interaction (5-7 days) and an objective measure of facial affect recognition. The participant's caregiver completed the NIH Toolbox Emotion Measures and a background information questionnaire. RESULTS: Overall, frequency and quality of reported social interactions were low for survivors, with a large subset of survivors (n = 16, 34%) endorsing fewer than 10 social interactions over the course of a typical school week, and almost half of parents (48.9%) reporting that their child participates in zero social activities outside of school during a typical week. Participants engaged in more positive social participation exhibited stronger social skills (facial affect recognition (F(2,44)  = 4.85, p < .05). CONCLUSIONS: School-aged survivors of pediatric brain tumors seemed to be infrequently engaged in social participation and quality interaction with peers. More specifically, the interactions most commonly reported on the diary assessment are not indicative of friendship development and maintenance. Survivors of pediatric brain tumors would likely benefit from interventions designed to increase quality time spent with peers.

Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

Predictors of low and very low bone mineral density in long-term childhood acute lymphoblastic leukemia survivors: Toward personalized risk prediction.

BACKGROUND: Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10 years after diagnosis. We investigated risk factors for low BMD in long-term cALL survivors. METHODS: We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event-free survival. Median time since diagnosis was 15.1 years. RESULTS: Prevalence of low DXA-derived BMD (Z-score ≤-1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and between 3.7% and 5.8% for very low BMD (Z-score ≤-2). Males had a higher prevalence of low BMD than females for all three outcomes (26%-32% vs. 18%-21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment-related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN-BMD site. CONCLUSION: Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow-up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.

Neurological hospitalisations in childhood cancer survivors treated before 2001: findings from the French Childhood Cancer Survivor Study cohort.

PURPOSE: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). METHODS: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. RESULTS: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5-31.2 and RHR = 5.1, 95%CI 4.4-5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7-13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7-3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3-4.7) compared to those who did not receive radiotherapy. CONCLUSIONS: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals.

Respiratory dysfunction in childhood cancer survivors: A single institution study.

BACKGROUND: Recently, while the overall survival rate of childhood cancer has improved, research has highlighted a high incidence of comorbidities in childhood cancer survivors (CCSs). However, it is likely that many asymptomatic comorbidities go unnoticed. The purpose of the current study was to identify comorbidities unique to Japanese CCSs through comparisons with a general population that underwent comparable comprehensive medical checkups. METHODS: The patient group included CCSs who had completed their cancer treatment, were aged 16 years or older, and underwent the comprehensive medical checkups at the University of Tsukuba Hospital between 2018 and 2020. The control group included members of the general population who underwent comprehensive medical checkups at the same hospital in 2018. RESULTS: Seventeen CCSs and 59 controls were included. Among the CCSs, the median ages at medical checkup and diagnosis were 22.1 years (range, 16-39) and 8.7 years (range, 1.3-14.8), respectively. Incidence of abnormalities in respiratory function, hearing function, and body mass index was higher in CCSs (52.9%, p = 0.013; 17.6%, p < 0.001; and 41.2%, p = 0.080, respectively) compared with controls. CONCLUSION: Asymptomatic pulmonary dysfunction was detected in the comprehensive medical checkup as a unique comorbidity in CCSs. Because the odds ratio of mortality due to respiratory failure is high in CCSs, as previously reported, we believe that detection of pulmonary dysfunction and the promotion of a healthy lifestyle are important. The evaluation of the pulmonary function may not typically be included in routine clinical visits, but it could be necessary for comprehensive medical evaluation in CCSs.

Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap. METHODS: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease. RESULTS: Survivors (N = 837; median [range] age, 25 [17-58] years, age diagnosed, 1 [0-21] years) were compared to sibling controls (N = 728; age, 32 [16-43] years). Survivors had higher risk of impaired task efficiency (≤1 year relative risk [RR], 1.48; 95% confidence interval [CI], 1.08-2.03; >1 year RR, 1.58; 95% CI, 1.22-2.06) and emotional regulation (≤1 year RR, 1.51; 95% CI, 1.07-2.12; >1 year RR, 1.44; 95% CI, 1.06-1.95). Impaired task efficiency associated with platinum exposure (≤1 year RR, 1.74; 95% CI, 1.01-2.97), hearing loss (≤1 year RR, 1.95; 95% CI, 1.26-3.00; >1 year RR, 1.56; 95% CI, 1.09-2.24), cardiovascular (≤1 year RR, 1.83; 95% CI, 1.15-2.89; >1 year RR, 1.74; 95% CI, 1.12-2.69), neurologic (≤1 year RR, 2.00; 95% CI, 1.32-3.03; >1 year RR, 2.29; 95% CI, 1.64-3.21), and respiratory (>1 year RR, 2.35; 95% CI, 1.60-3.45) conditions. Survivors ≤1 year; female sex (RR, 1.54; 95% CI, 1.02-2.33), cardiovascular (RR, 1.71; 95% CI, 1.08-2.70) and respiratory (RR, 1.99; 95% CI, 1.14-3.49) conditions associated impaired emotional regulation. Survivors were less likely to be employed full-time (p < .0001), graduate college (p = .035), and live independently (p < .0001). CONCLUSIONS: Neuroblastoma survivors report neurocognitive impairment impacting adult milestones. Identified health conditions and treatment exposures can be targeted to improve outcomes. PLAIN LANGUAGE SUMMARY: Survival rates continue to improve in patients with neuroblastoma. There is a lack of information regarding neurocognitive outcomes in neuroblastoma survivors; most studies examined survivors of leukemia or brain tumors. In this study, 837 adult survivors of childhood neuroblastoma were compared to siblings from the Childhood Cancer Survivorship Study. Survivors had a 50% higher risk of impairment with attention/processing speed (task efficiency) and emotional reactivity/frustration tolerance (emotional regulation). Survivors were less likely to reach adult milestones such as living independently. Survivors with chronic health conditions are at a higher risk of impairment. Early identification and aggressive management of chronic conditions may help mitigate the level of impairment.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

Adherence to healthy diet and risk of cardiovascular disease in adult survivors of childhood cancer in the St. Jude Lifetime Cohort: a cross-sectional study.

BACKGROUND: Whether diet has beneficial effects on cardiovascular disease (CVD) in childhood cancer survivors as in the general population is unknown. Therefore, we examined associations between dietary patterns and risk of CVD in adult survivors of childhood cancer. METHODS: Childhood cancer survivors, 18-65 years old in the St Jude Lifetime Cohort (1882 men and 1634 women) were included in the analysis. Dietary patterns were defined by the adherence to the Healthy Eating Index (HEI)-2015, Dietary Approaches to Stop Hypertension (DASH), and alternate Mediterranean diet (aMED) based on a food frequency questionnaire at study entry. CVD cases (323 in men and 213 in women) were defined as participants with at least one grade 2 or higher CVD-related diagnosis at baseline. Multivariable logistic regression adjusted for confounders was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. RESULTS: Greater adherence to HEI-2015 (OR=0.88, 95% CI: 0.75-1.03, per 10 score increment), DASH (OR=0.85, 95% CI: 0.71-1.01, per 10 score increment), and aMED (OR=0.92, 95% CI: 0.84-1.00, each score increment) were, albeit trending towards significance, associated with a lower risk of CVD in women. HEI-2015 was associated with a non-significantly lower risk of CVD in men (ORQ5 vs. Q1=0.80, 95% CI: 0.50-1.28). These dietary patterns were also associated with a lower risk of CVD in survivors with high underlying CVD risk. CONCLUSIONS: As recommended to the general population, a diet rich in plant foods and moderate in animal foods needs to be a part of CVD management and prevention in childhood cancer survivors.

Response-shift effects in childhood cancer survivors: A prospective study.

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.

Clinician perceptions of Passport for Care, a web-based clinical decision support tool for survivorship care plan delivery.

BACKGROUND: The Children's Oncology Group Long-Term Follow-Up Guidelines provide exposure-based risks and recommendations for late effects screening of survivors of childhood cancer. Passport for Care (PFC) is a web-based clinical decision support tool for generating a personalized survivorship care plan (SCP) derived from the Guidelines and user-entered exposures. We assessed PFC clinician user practices and perceptions of PFC impact on clinic workflow, guidelines application, and survivor shared decision-making. PROCEDURE: A 35-item REDCap survey was emailed to all PFC users (n = 936) in 146 current and former PFC user clinics. Anonymous responses were permitted. Results were summarized and compared with a 2012 survey. RESULTS: Data were available from 148 respondents representing 64 out of 146 PFC user clinics (minimum clinic response rate 44%, excluding 49 anonymous responses). Generation of a personalized SCP was the most common application of PFC, followed by determination of surveillance recommendations and use as a survivor database. Twenty-five respondents (17%) felt data entry was a significant or insurmountable barrier to PFC application. Sixty-nine percent of respondents attributed PFC with a very high/high impact on guidelines adherence in their clinical practice, compared with 40% who attributed PFC with having a significant impact on adherence in 2012 (p < .001). CONCLUSION: The survey results provide valuable insights on patterns of SCP delivery and Survivor Clinic workflow. User-perceived benefits to PFC included facilitating clinician ability to follow guidelines recommendations in clinical practice. Importantly, some barriers to resource utilization were also identified, suggesting a need for user-informed adaptations to further improve uptake.

Perceived barriers and facilitators to physical activity in childhood cancer survivors and their parents: A large-scale interview study from the International PACCS Study.

BACKGROUND: Physical activity (PA) may reduce risks of late effects in childhood cancer survivors, yet many have low activity levels. Using the WHO's International Classification of Functioning, Disability, and Health for Children and Youths (ICF-CY) as a conceptual framework, we aimed to identify perceived barriers and facilitators to PA in young survivors and their parents. DESIGN/METHODS: We conducted individual, semi-structured interviews with 63 survivors, aged 9-18 years, ≥1-year off treatment, and 68 parents, recruited from three pediatric oncology departments in Norway and Denmark. Interviews were analyzed inductively using thematic analysis to identify barriers and facilitators to PA, which were mapped onto the ICF-CY model components; body function/structures, activities, participation, and environmental and personal factors. RESULTS: Two-thirds of the survivors described how treatment-related impairments of bodily functions (e.g., fatigue, physical weakness, reduced lung capacity) caused physical limitations, reducing opportunities to participate in PA, especially team sports and school physical education. This resulted in a perceived ability gap between survivors and peers, reducing motivation for PA. These PA barriers were moderated by environmental factors that facilitated or further hindered PA participation (family, peer, and school support). Similarily, personal factors also facilitated (acceptance, motivation, goal setting) or hindered (anxiety, low motivation, and lack of trust) PA participation. CONCLUSION: Treatment-related long-term or late effects represented significant barriers to PA as their functional consequences reduced survivors' capacities and capabilities to be active. Environmental and personal factors acting as facilitators or further barriers to PA were identified. Applying the ICF-CY framework in clinical practice could help to enable PA participation.

Healthcare utilization and cost barriers among U.S. childhood cancer survivors.

BACKGROUND: To evaluate healthcare utilization and cost barrier patterns among childhood cancer survivors (CCS) compared with noncancer controls. PROCEDURE: Using the 2014-2019 Behavioral Risk Factor Surveillance System, we identified CCS < 50 years and matched controls. We used chi-squared tests to compare characteristics between the two groups. Logistic regression analyses were used to assess the likelihood of having a checkup, receiving influenza vaccine, and experiencing healthcare cost barriers (being unable to see the doctor due to cost) during the past 12 months. Conditional models accounted for the matching. RESULTS: We included 231 CCS and 692 controls. CCS had lower household income (p < 0.001), lower educational attainment (p = 0.021), more chronic health conditions (p < 0.001), and a higher proportion of being current smokers (p = 0.005) than controls. Both groups had similar rates of having a checkup and influenza vaccine; however, a quarter of CCS experienced healthcare cost barriers compared with 13.9% in controls (p = 0.001; regression findings: adjusted odds ratio (aOR) = 1.72, 95% confidence interval (CI): 1.11-2.65). Compared with the youngest CCS group (18-24 years), CCS ages 25-29 years were five times more likely to experience healthcare cost barriers (aOR = 4.79; 95% CI, 1.39-16.54). Among CCS, current smokers were less likely to have a checkup (aOR = 0.46; 95% CI, 0.23-0.94). Uninsured CCS were less likely to have a checkup (aOR = 0.33; 95% CI, 0.14-0.75) and ∼8 times more likely to experience healthcare cost barriers (aOR = 8.28; 95% CI, 3.45-19.88). CONCLUSION: CCS being 25-29 years, uninsured, or current smokers encounter inferior outcomes in healthcare utilization and cost barriers. We suggest emphasis on programs on care transition and smoking cessation for CCS.

Multifaceted support for quality of life in childhood cancer survivors: Questionnaire survey.

BACKGROUND: Along with improvements in curative treatment for childhood cancer, childhood cancer survivors (CCSs) often face numerous problems such as late complications of cancer treatment, social issues at school, struggles in employment, and financial difficulties. These children have received a wide range of support from the medical, educational, and administrative sectors. However, it was unclear how this multifaceted support contributed to quality of life (QOL) of CCSs in Japan. METHODS: The subjects were 46 CCSs of 16 years of age or older at the time of the survey, who had been diagnosed and treated for pediatric cancer. A self-administered questionnaire survey was conducted to investigate the in-hospital status during treatment, adjustment when returning to school, and administrative social support. The QOL of CCSs was also evaluated by the Medical Outcome Study 36-Item Short-Form Health Survey. RESULTS: Twenty-four CCSs answered the questions. The respondents who had experienced school-life problems tended to have lower role/social QOL scores (p = 0.046), whereas the CCSs who had experienced administrative counseling tended to have lower physical QOL scores (p = 0.036). The mental QOL scores tended to be higher in respondents who were informed of the exact diagnosis of cancer during hospitalization. The role/social QOL scores tended to be lower in respondents who advanced to their preferred career path. CONCLUSIONS: It is essential for three stakeholders-health-care providers, education offices, and public administrative agencies-to collaborate to share long-term psychosocial issues or concerns related to employment or daily living that CCSs may encounter, and to establish a coordinated approach to support CCSs.

The Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis examined long-term glomerular dysfunction in childhood cancer survivors.

This investigation aimed to evaluate glomerular dysfunction among childhood cancer survivors in comparison with matched controls from the general population. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis, a nationwide cross-sectional cohort study, 1024 survivors five or more years after diagnosis, aged 18 or more 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. In addition, 500 age- and sex-matched controls from Lifelines, a prospective population-based cohort study in the Netherlands, participated. At a median age of 32.0 years (interquartile range 26.6-37.4), the glomerular filtration rate was under 60 ml/min/1.73m2 in 3.7% of survivors and in none of the controls. Ten survivors had kidney failure. Chronic kidney disease according to age-thresholds (glomerular filtration rate respectively under 75 for age under 40, under 60 for ages 40-65, and under 40 for age over 65) was 6.6% in survivors vs. 0.2% in controls. Albuminuria (albumin-to-creatinine ratio over3 mg/mmol) was found in 16.2% of survivors and 1.2% of controls. Risk factors for chronic kidney disease, based on multivariable analyses, were nephrectomy (odds ratio 3.7 (95% Confidence interval 2.1-6.4)), abdominal radiotherapy (1.8 (1.1-2.9)), ifosfamide (2.9 (1.9-4.4)) and cisplatin over 500 mg/m2 (7.2 (3.4-15.2)). For albuminuria, risk factors were total body irradiation (2.3 (1.2-4.4)), abdominal radiotherapy over 30 Gy (2.6 (1.4- 5.0)) and ifosfamide (1.6 (1.0-2.4)). Hypertension and follow-up 30 or more years increased the risk for glomerular dysfunction. Thus, lifetime monitoring of glomerular function in survivors exposed to these identified high risk factors is warranted.

Differences in the approaches of cancer specialists toward adolescent and young adult cancer care.

BACKGROUND: This study investigated the medical care of adolescent and young adult (AYA) cancer patients and compared approaches toward AYA cancer care by pediatric and adult cancer specialists. METHODS: An Internet survey was conducted among 1,305 specialists (192 pediatric and 1,109 adult) in 2016. RESULTS: The rate of awareness of the term "AYA" was lower for adult specialists than for pediatric specialists. The departments that are responsible for caring for AYA cancer patients change when they reach 20 years of age. For the treatment of AYA patients, both pediatric and adult specialists preferred a multidisciplinary team as a top priority issue. A special ward or hospital rooms for AYA was required mostly for AYA patients under 24, and the needs for special wards or rooms for AYA was higher in pediatric specialists than in adult specialists. However, for AYA patients over 25, about 60% of adult specialists and 35% of pediatric specialists believed that no special care was required. As for desirable follow-up protocols for pediatric cancer AYA survivors, half of the specialists considered that they should be conducted mainly by pediatric specialists in cooperation with adult specialists, and 30% to 40% of the specialists considered that transition to the corresponding adult medicine department would be preferable. CONCLUSIONS: There were obvious differences in medical care and support for AYA cancer patients according to their age, particularly under the age of 20 or 24, and according to whether the onset of disease occurred during the AYA period or whether it was secondary to pediatric cancers. For each aspect, appropriate programs would require close cooperation between pediatric and adult specialists.

Recovery of lymphocyte subpopulations is incomplete in the long-term setting in pediatric solid tumor survivors.

BACKGROUND: Childhood cancer survivors (CCSs) may have comorbidities including a long-term abnormality in the immune system. Immune reconstitution in CCSs after treatment for acute leukemia has been reported previously, while analyses of immune reconstitution in CCSs with solid tumors have been limited. METHODS: Childhood cancer survivors who received chemotherapy for solid tumors and who visited University of Tsukuba Hospital between November 2019 and March 2021 were included the study. Peripheral blood was collected for flow cytometry analysis. RESULTS: Forty-nine samples from 35 CCSs (18 male, 17 female) were included in the study. High-dose chemotherapy and cerebral spinal irradiation were conducted in 14 CCSs (40%) and in five CCSs (14%), respectively. The median time between the completion of chemotherapy and the collection of the present samples was 15.0 months (range, 0-286 months). The total lymphocyte count, B cells, and CD8-positive T cells recovered to the normal range of controls (NR-CTLs) in 0 (0%), four (66.7%), and four (66.7%) of six samples at 0-3 months after the completion of chemotherapy, and in three (60%), four (80%), and three (60%) of five samples at 3-12 months after the completion of chemotherapy, respectively. Meanwhile, CD4-positive T cells remained lower than NR-CTLs in 0 (0%) of six samples, one (20%) of five samples, and seven (63.7%) of 11 samples at 0-3, 3-12 and 12-60 months after the completion of chemotherapy, respectively. CONCLUSIONS: Recovery to the NR-CTLs was rapidly achieved in B cells and CD8-positive T cells, while the recovery was slower and incomplete in CD4-positive T cells. Careful observation of infection in long-term follow-up clinics is needed.

Long-term follow-up of surgical outcomes for patients with Wilms tumor and neuroblastoma.

BACKGROUND: There are minimal data on long-term surgical outcomes of patients who have undergone resection for Wilms tumor (WT) and neuroblastoma (NB). METHODS: A retrospective review of patients in a long-term survivor clinic between the years 1967 and 2016 in a pediatric tertiary care hospital (>5 years posttreatment) was performed. RESULTS: Eighty-six survivors of WT and 86 survivors of NB who had ongoing follow-up in the survivors' clinic were identified. The median age at diagnosis was 2.5 years (range, 0.4-15.7 years) with a mean follow-up of 22.3 years (±10.4 years) for WT. The median age at diagnosis for patients with NB was 0.9 years (range, 0.1-8.6 months); mean follow-up of 21.7 years (±7.9 years). Twelve patients with WT (14.0%) had at least 1 repeat laparotomy, 11.1% for bowel obstruction, at a median of 3 months from initial surgery. Twelve patients (14.0%) with NB required laparotomy and 8.1% for bowel obstruction, at a median of 12 years after initial surgery. The incidence of hypertension in patients with WT who had undergone nephrectomy was not outside of population norms. Patients who underwent thoracotomy for a NB have a higher incidence of scoliosis and Horner syndrome. CONCLUSIONS: Small bowel obstruction requiring laparotomy is significantly higher than the literature norms for both tumor patient populations and typically occurs in the early postoperative period for patients with WT and remotely in patients with NB. The long-term surgical complications of patients who underwent resection for NB and WT clearly merit follow-up and patient education within multidisciplinary long-term survivorship clinics.

Validation of questionnaire-reported chest wall abnormalities with a telephone interview in Swiss childhood cancer survivors.

BACKGROUND: Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors. METHODS: We investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors. RESULTS: Forty-eight of 2382 (95%CI 2-3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16-20 years; OR 2.5, 95%CI 1.0-6.1), lymphoma (OR 3.8, 95%CI 1.2-11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0-30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0-4.2), surgery to the chest (OR 4.5, 95%CI 1.8-11.5), or chemotherapy (OR 2.9, 95%CI 1.0-8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors. CONCLUSION: It is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Perceptions and knowledge of air pollution and its health effects among caregivers of childhood cancer survivors: a qualitative study.

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.