Early disc degeneration in radiotherapy-treated childhood brain tumor survivors.

BACKGROUND: Childhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls. METHODS: In this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5-33.1), 67 survivors (mean age 28.4, range 16.2-43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration. RESULTS: Childhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05). CONCLUSIONS: Signs of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.

Sleep Disturbance and Its Association With Sluggish Cognitive Tempo and Attention in Pediatric Brain Tumor Survivors.

Background: Pediatric brain tumor (PBT) survivors are at risk for developing sleep disturbances. While in other pediatric populations sleep disturbance has been associated with worse cognitive functioning, it is unclear to what extent this relationship generalizes to PBT survivors. The aim of the current study was to assess the relationship between sleep disturbance and aspects of cognition, including sluggish cognitive tempo (SCT) as well as attention and working memory. Materials and Methods: Eighty-three PBT survivors 6-18 years of age who were at least 3 months post-treatment were included in the present cross-sectional study. Level of sleep disturbance was measured as a composite score reflecting various sleep problems as rated by caregivers. Cognitive measures included caregiver-ratings of sluggish cognitive tempo and attention problems, as well as performance-based cognitive measures assessing attention and executive functioning. Hierarchical regression analysis was used to assess associations between sleep and cognition. Results: Of all caregivers, 32.5% reported one or more sleep disturbances as "very/often true" and over 68% of caregivers rated at least one sleep-related item as "somewhat true." Of all cognitive variables, scores were most frequently impaired for SCT (30%). A higher level of sleep disturbance was associated with worse SCT and parent-rated attention problems. Associations between sleep and performance-based cognitive measures assessing attention and working memory were not statistically significant. Conclusion: Findings of the current study highlight the importance of further investigation into the relationship between sleep and cognition in PBT survivors, which may assist efforts to maximize cognitive outcome and health-related quality of life in PBT survivors. The current study additionally suggests further investigation of SCT in this population is warranted, as it may be more sensitive to detecting possible associations with sleep disturbance relative to discrete measures that assess cognitive performance under ideal circumstances.

Neuropsychological Screening in Pediatric Multidisciplinary Clinics: Group Characteristics and Predictive Utility.

OBJECTIVE: To evaluate the feasibility of administering caregiver-report neuropsychological screening measures in pediatric multidisciplinary clinics (MDCs) and investigate predictive utility for cognitive and academic difficulties on follow-up testing. METHOD: The Pediatric Perceived Cognitive Functioning (Peds PCF) and Colorado Learning Difficulties Questionnaire (CLDQ) were administered to caregivers of youth with history of brain tumor (BT), non-central nervous system (CNS) cancer, or Fontan circulation as part of routine neuropsychological consultation in MDCs from 2017 to 2019. We examined cross-sectional differences on screening measures, and relationships between screening and intellectual and academic test performance in a subset who presented for follow-up neuropsychological evaluation. Receiver operating characteristic (ROC) curve analysis was used to identify suggested cut scores on screening measures for predicting who would most benefit from further evaluation. RESULTS: Screening was completed with 192 families. Children with history of non-CNS cancer (n = 29) had fewer parent-reported cognitive and academic concerns compared with either BT (n = 88) or Fontan (n = 75) groups. Peds PCF and CLDQ scores were related to intellectual and academic test performance in the group presenting for neuropsychological evaluation (n = 68). ROC curve analysis identified cut scores across screening measures with maximal sensitivity and specificity for detecting neuropsychological difficulties. CONCLUSIONS: It is feasible to utilize parent rating measures during neuropsychological consultation in pediatric MDCs. The Peds PCF and CLDQ demonstrated sensitivity to intellectual and academic difficulties in children with significant medical histories. Screening may be a helpful tool for pediatric neuropsychologists and other professionals during MDC consultation to inform clinical management.

Fertility preservation in childhood and adolescent female tumor survivors.

OBJECTIVE: To assess the proportion of female childhood and adolescent tumor survivors who could benefit from oocyte cryopreservation. DESIGN: Case series of female childhood and adolescent tumor survivors referred for fertility counseling. SETTING: A referral cancer center and an infertility unit of an academic hospital. PATIENT(S): Young female childhood and adolescent tumor survivors who received gonadotoxic treatments. INTERVENTION(S): Patients were prescribed tests of ovarian reserve and a personalized counseling was given. Oocyte cryopreservation was considered in subjects aged ≥18 years who were diagnosed with diminished ovarian reserve (DOR) (antimüllerian hormone level <2 ng/mL or total antral follicle count ≤10). MAIN OUTCOME MEASURE(S): Rate of women with DOR who stored their oocytes. RESULT(S): Ninety out of 126 evaluated women completed the assessments. We documented preserved ovarian reserve, DOR, and premature ovarian insufficiency in 36 (40%), 35 (39%), and 19 (21%) cases, respectively. Overall, 13 subjects with DOR were eligible for oocyte cryostorage, of whom 9 (69%) underwent the procedure. Considering the whole cohort of evaluated young women (n = 90), the rate of those who had egg freezing was 10%. Finally, nine women started seeking pregnancy after the counseling (six with DOR), and seven of them became pregnant. When the data were analyzed separately according to most gonadotoxic treatments, considerable differences emerged but the evidence did not support the idea that counseling should be restricted to particular subgroups of women. CONCLUSION(S): Ovarian reserve impairment is common in female childhood and adolescent tumor survivors. Postcancer oocyte cryopreservation may be part of the armamentarium of fertility preservation options.

Impact of COVID-19 on adolescent and emerging adult brain tumor survivors and their parents.

BACKGROUND: The COVID-19 pandemic has prompted unprecedented challenges, contributing to greater difficulties among families of children with special health care needs, such as pediatric brain tumor survivors. We examined the impact of the pandemic on psychosocial functioning of adolescent and emerging adult survivors and their parents. We hypothesized that COVID-19 disruptions and survivor social connectedness would be associated with survivor-reported posttraumatic stress and family outcomes, including family functioning, parenting, and parent mental health. PROCEDURE: Fifty-five families (44 survivors, 48 parents) were recruited via phone and email to participate in the study. Survivors were ages 13-25 (M = 19.62, SD = 3.47) and at least 5 years post diagnosis. Parents completed the COVID-19 Exposure and Family Impact Survey (CEFIS), and survivors completed the Environmental influences on Child Health Outcomes (ECHO) COVID-19 child self-report form, which assessed pandemic impacts on their psychosocial functioning. RESULTS: Parents reported a mean of 7.52 (SD = 2.83) disruptions to their families' lives. The pandemic negatively affected survivors' life satisfaction (Mdiff  = 0.46, t(44) = 3.96, p < .001), with 92% reporting reduced social connectedness (n = 39). Total disruptions due to COVID-19 and survivor social connectedness predicted survivor-reported posttraumatic stress, above and beyond survivors' pre-pandemic psychosocial risk. Most parents reported positive changes in their parenting (n = 31, 67.4%) and family cohesion (n = 30, 66.7%). However, they also reported worsened mood (n = 28, 62.3%) and increased anxiety (n = 31, 71.1%). CONCLUSIONS: Parents and survivors reported positive and negative impacts of COVID-19, which had downstream consequences on survivor psychosocial functioning. Follow-up care should consider potential adverse effects on social connectedness and stress symptoms.

Executive functions and social skills in pediatric brain tumor survivors.

Pediatric brain tumor survivors (PBTSs) may experience impairment in executive functions and social competence, but their interrelation is not well understood. This study aimed to address the specificity of this relationship. PBTSs (n = 91) were on average 11.21 years old, 5 years from diagnosis, and 48.4% female. One parent and PBTS completed the Social Skills Rating System (subscales: Cooperation, Assertiveness, Empathy, Self-Control, and Total), and parents also completed the Behavior Rating Inventory of Executive Function (General Executive Composite [GEC], Metacognition [MI], and Behavioral Regulation [BRI] indices) and the (Withdrawal scale). Based on proxy reports, more PBTSs had deficits in Cooperation, Assertiveness and Responsibility skills relative to normative data. MI was more consistently associated with parent reported social skills deficits than BRI. PBTSs reported fewer deficits in social skills relative to normative data across all scales; none of the correlations between PBTSs reported social skills and executive functions were significant. Time since diagnosis and proxy reported lower total social skills predicted greater withdrawal. These findings highlight the importance of assessing differential perspectives of PBTSs social competence, and that metacognitive strategies may bear particular importance for the social skills of PBTSs.

Sublethal whole-body irradiation causes progressive premature frailty in mice.

There is an unmet need to develop and validate therapies that can treat or at least prevent premature therapy-induced frailty, multi-morbidity and mortality in long-term tumour survivors. In an approach to develop a first mouse model for therapy-induced long-term frailty, we irradiated male C57Bl/6 mice at 5-6 months of age sub-lethally with 3 × 3 Gy (whole body) and assessed subsequent frailty for up to 6 months using a Rockwood-type frailty index (FI). Frailty scorers were trained to obtain excellent inter- and intra-observer reproducibility. Irradiated mice developed progressive frailty approximately twice as fast as controls. This was premature frailty; it was phenotypically identical to that in non-irradiated mice at higher age. As expected, frailty was associated with decreased cognition and predicted mortality. In irradiated mice, frailty and neuromuscular performance, measured by Rotarod and Hanging Wire tests, were not associated with each other, probably because of long-term decreased body weights after irradiation. We conclude that progressive frailty following sub-lethal irradiation comprises a sensitive and easy to use test bed for interventions to stop premature ageing in long-term tumour survivors.