PURPOSE: We evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma.PATIENTS AND METHODS: We conducted a prospective, single-arm, three-stage, phase II clinical trial. Six cycles of induction chemotherapy were coadministered with hu14.18K322A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose interleukin-2 (IL-2). The consolidation regimen included busulfan and melphalan. When available, an additional cycle of parent-derived natural killer cells with hu14.18K322A was administered during consolidation (n = 31). Radiation therapy was administered at the end of consolidation. Postconsolidation treatment included hu14.18K322A, GM-CSF, IL-2, and isotretinoin. Early response was assessed after the first two cycles of induction therapy. End-of-induction response, event-free survival (EFS), and overall survival (OS) were evaluated.RESULTS: Sixty-four patients received hu14.18K322A with induction chemotherapy. This regimen was well tolerated, with continuous infusion narcotics. Partial responses (PRs) or better after the first two chemoimmunotherapy cycles occurred in 42 of 63 evaluable patients (66.7%; 95% CI, 55.0 to 78.3). Primary tumor volume decreased by a median of 75% (range, 100% [complete disappearance]-5% growth). Median peak hu14.18K322A serum levels in cycle one correlated with early response to therapy ( P = .0154, one-sided t-test). Sixty of 62 patients (97%) had an end-of-induction partial response or better. No patients experienced progressive disease during induction. The 3-year EFS was 73.7% (95% CI, 60.0 to 83.4), and the OS was 86.0% (95% CI, 73.8 to 92.8), respectively.CONCLUSION: Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year EFS. These results, if validated in a larger study, may be practice changing.

PURPOSE: To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5. PATIENTS AND METHODS: Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately. RESULTS: Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size. CONCLUSION: The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.

Background and Purpose: Informal (unpaid) caregiving usually provided by family is important poststroke. We studied whether the prevalence of informal caregiving after stroke differs between Mexican Americans (MAs) and non-Hispanic Whites (NHWs). Methods: Between October 2014 and December 2018, participants in the BASIC (Brain Attack Surveillance in Corpus Christi) project in Nueces County, Texas, were interviewed 90 days after stroke to determine which activities of daily living they required help with and whether family provided informal caregiving. Ethnic differences between MAs and NHWs were determined by logistic regression. The logistic models were stratified by formal (paid) care status. Odds ratios (95% CIs) are reported with NHW as the referent group. Fisher exact tests were used to assess the association of ethnicity with relationship of caregiver and with individual activities of daily living. Results: Eight hundred thirty-one patients answered the caregiving questions. Of these, 242 (29%) received family caregiving (33% of MAs and 23% of NHWs), and 142 (17%) received paid caregiving (21% of MAs and 10% of NHWs). There were no ethnic differences in stroke severity. In logistic regression analyses, among those without formal, paid care, MAs were more likely to have informal caregiving (odds ratio, 1.75 [95% CI, 1.12–2.73]) adjusted for age, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale, and insurance. No ethnic differences in informal care were found among those who had formal care. There were no differences between ethnic groups in which family members provided the informal care. MAs were more likely to require help compared with NHWs for walking ( P <0.0001), bathing ( P <0.0001), hygiene ( P =0.0012), eating ( P =0.0004), dressing ( P <0.0001), ambulating ( P =0.0304), and toileting ( P =0.0003). Conclusions: MAs required more help poststroke than NHWs for assistance with activities of daily living. MAs received more help for activities of daily living through informal, unpaid caregiving than NHWs if they were not also receiving formal, paid care. Efforts to help minority and low-resource populations provide stroke care are needed.

Background: It is well-established that cancer treatment substantially increases risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods: We included 2,052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results: By performing multiple treatment-specific EWAS, we identified 2,894 5’-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 1,583 gene/regions associated with one or more cancer treatments at epigenome-wide significance level (P < 9×10 ⁻⁸ ). Among the treatment-associated CpGs, 298 were associated with obesity, 85 with hypercholesterolemia, 41 with hypertriglyceridemia, and four with abnormal glucose metabolism (False-Discovery-Rate-Adjusted P<0.05). We observed full mediation by methylation at five independent CpGs for association between abdominal field radiotherapy (abdominal-RT) and risk of hypertriglyceridemia, nearly full mediation (99.5%) by methylation at nine CpGs for association between abdominal-RT and hypercholesterolemia, and partial mediation (42.1%) by methylation at two CpGs for association between abdominal-RT and abnormal glucose metabolism. In addition, six CpGs partially mediated the association between brain-RT and obesity with 58.6% mediation effect, two CpGs mediated the association between glucocorticoids and obesity (32.2%) and between brain-RT and hypertriglyceridemia (15.5%). Notably, several mediator CpGs reside in the proximity of well-established dyslipidemia genes: cg17058475 (CPT1A), cg11851174 (RAI1) and cg22976567 (LMNA). Conclusions: In childhood cancer survivors, prior cancer treatments are associated with DNAm variations present decades following the exposure. Treatment-associated DNAm sites may mediate the causal pathway from specific treatment exposures to certain cardiometabolic conditions, suggesting the utility of DNAm sites as risk predictors and potential mechanistic targets for future intervention studies.

Fear of cancer recurrence (FCR) is a significant but understudied concern among parents of childhood cancer survivors. This study quantitatively characterized parental FCR and explored potential demographic and clinical correlates among parents of children treated for cancer. Parents (N = 192) completed the Fear of Cancer Recurrence Inventory-Parent Short Form (FCRI-Parent) and provided demographic information. Clinical variables were obtained from medical chart review. Associations between FCR and demographic or clinical variables were analyzed using t-tests, ANOVAs, and Pearson’s correlations. Parents reported a mean FCR score of 18.64 (SD = 8.73), with 42.2% of parents endorsing FCR above a score of 22. Parental FCR significantly varied by parent race, education, and spirituality. Higher FCR was also significantly negatively correlated with child age, time since diagnosis, and time since treatment completion. Parents of children with central nervous system tumors or hematological malignancies endorsed significantly higher FCR compared to parents of children with solid tumors. Findings build on previously identified psychosocial needs for parents of children treated for cancer by quantitatively describing parental FCR and exploring subgroups that may be at increased risk for FCR. Tailored interventions, including strategies that support spiritual coping, may help mitigate FCR among at-risk parents.