Treatment for childhood solid tumors may lead to an increased risk for gonadal dysfunction/infertility. Discussion of risk should occur at diagnosis, any changes in therapy, and during survivorship. Gonadotoxic therapies were abstracted from 32 Children’s Oncology Group (COG) phase III, frontline solid tumor protocols, in use from 2000-2022. Risk for gonadal dysfunction/infertility was assessed based on gonadotoxic therapies, sex, and pubertal status and assigned as minimal, significant, and high following the Oncofertility Consortium Pediatric Initiative Network (PIN) risk stratification. Most protocols (65.6%, 21/32) contained at least one therapeutic arm with a high level of increased risk. Solid tumor therapies present challenges in risk stratification due to response-adjusted therapy and the need to account for radiation field in the risk assessment. This guide hopes to serve as a tool to assist in standardizing gonadotoxic risk assessments across disciplines and improve referral for fertility services and reproductive health counseling for patients receiving COG based solid tumor therapy.

BACKGROUND Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness and reduce risk of cardiovascular disease. PROCEDURE Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose <1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were 1) 60% enrollment of approached patients, 2) 80% completion of weekly phone calls and 3) 80% completion of the RT intervention and FU1 assessments. Acceptability was measured by recommendation of the intervention to an AYA HCT survivor. RESULTS Twenty of 31 (65%) eligible AYAs enrolled. Two participants failed to complete baseline measurements (1=scheduling barriers, 1=passive refusal) and 4 participants who completed baseline assessments did not receive the intervention (2=medical reasons, 2=no longer interested). Of the 13 who received the intervention, 11 (85%) completed FU1 and completed 88.5% of coaching calls. LBM (kg) increased or remained unchanged in 9/9 participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4,1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. CONCLUSIONS A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

Background: Pediatric patients who undergo hematopoietic cell transplant (HCT) are at risk for neurocognitive impairments; however, long-term studies are lacking. Procedure: Eligible survivors (HCT at age <21y and ≥1y post-HCT) completed a 60-question survey of neurocognitive function and quality of life, which included the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ) and the Neuro-Quality of Life Cognitive Function Short Form (Neuro-QoL). Baseline demographic and transplant characteristics were retrieved from the institutional research database. Analyses of risk factors included univariate comparisons and multivariable logistic regression. Results: Participants (n=199, 50.3% female, 53.3% acute leukemia, 87.9% allogeneic transplants) were surveyed at median age of 37.8 years (range 18-61) at survey and median 27.6 years (range 1-46) from transplant. On the CCSS-NCQ, 18.9-32.5% of survivors reported impairments (Z-score >1.28) in task efficiency, memory, emotional regulation, or organization, compared with expected 10% in the general population (all p<0.01). Certain co-morbidities were associated with impaired CCSS-NCQ scores. However, survivors reported average Neuro-QoL (T-score 49.6±0.7) compared with population normative value of 50 (p=0.52). In multivariable regression, impaired Neuro-QoL (T-score <40) was independently associated with hearing issues (OR 4.79, 95% CI 1.91-12.0), history of stroke or seizure (OR 5.22, 95% CI 1.73-15.7), and sleep disturbances (OR 6.90, 95% CI 2.53-18.9). Conclusions: Although long-term survivors of pediatric HCT reported higher rates of impairment in specific neurocognitive domains, cognitive quality of life was perceived as similar to the general population. Subsets of survivors with certain co-morbidities had substantially worse neurocognitive outcomes.