Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. US National Cancer Institute.

Purpose: Young adult survivors of childhood and adolescent cancer are an ever-growing population of patients, many of whom remain at lifelong risk for potentially serious complications of their cancer therapy. Yet research shows that many of these older survivors have deficient health-related knowledge and are not engaging in recommended health promotion and screening practices that could improve their long-term outcomes. The purpose of this review is to address these disparities by discussing how formal transition of care from pediatric to adult-focused survivorship services may help meet the unique medical, developmental, and psychosocial challenges of these young adults. Design: Literature review and discussion. Results: This article summarizes current research documenting the medical needs of young adult survivors, their suboptimal compliance with recommended follow-up, and the rationale, essential functions, current models, and innovative approaches for transition of follow-up care. Conclusion: Systematic health care transition constitutes the standard of care for young adult survivors of childhood cancer. In developing a transitional care program, it is necessary to consider the scope of services to be provided, available resources, and other local exigencies that help determine the optimal model for use. Additional research is needed to improve health services delivery to this population. Effective advocacy is needed, particularly in the United States, to ensure the availability of uninterrupted health insurance coverage for survivorship services in young adulthood.

BACKGROUND: To evaluate tumor responses, event‐free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low‐grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV).METHODS: Non‐NF1 patients were randomized to CV or thioguanine, procarbazine, 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non‐NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS.RESULTS: A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5‐year EFS rate was 69% ± 4% for the CV‐NF1 group and 39% ± 4% for the CV–non‐NF1 group (P < .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV‐treated children without NF1. NF1 patients and non‐NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P < .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non‐NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV‐NF1 group) at a median of 7.8 years (range, 7.3‐9.4 years) after enrollment, but there were none in the non‐NF1 group.CONCLUSIONS: Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928–36. © 2016 American Cancer Society.

Patient-reported outcome (PRO) measurements linked to Common Terminology Criteria for Adverse Events (CTCAE) grading may improve symptom adverse event (AE) reporting in pediatric oncology trials. We evaluated construct validity, responsiveness, and test-retest reliability of the Ped-PRO–CTCAE measurement system for children and adolescents undergoing cancer care. A total of 482 children and adolescents (7–18 years, 41.5% not non-Hispanic white) newly diagnosed with cancer and their caregivers participated from nine pediatric oncology hospitals. Surveys were completed at 72 hours preceding treatment initiation (T1) and at follow-up (T2) approximately 7–17 days later for chemotherapy, and 4+ weeks for radiation. Psychometric analyses examined the relationship of Ped-PRO-CTCAE items (assessing 62 symptom AEs) with Patient-Reported Outcomes Measurement Information System, Memorial Symptom Assessment Scale, Lansky Play-Performance Scale, and medication use. A separate test-retest study included 46 children. Ped-PRO-CTCAE and Memorial Symptom Assessment Scale were strongly correlated across age groups at T2: 7–12 years (r = 0.62–0.80), 13–15 years (r = 0.44–0.94), and 16–18 years (r = 0.65–0.98); and over time. The Ped-PRO-CTCAE was strongly correlated with Patient-Reported Outcomes Measurement Information System Pediatric measures at T2; for example, pain interference (r = 0.70, 95% confidence interval [CI] = 0.64 to 0.76), fatigue severity (r = 0.63, 95% CI = 0.56 to 0.69), and depression severity (r = 0.76, 95% CI = 0.71 to 0.81). Ped-PRO-CTCAE items differentiated children by Lansky Play-Performance Scale and by medication use. Test-retest agreement ranged from 54.3% to 93.5%. This longitudinal study provided evidence for the construct validity and reliability of the core Ped-PRO-CTCAE symptom AE items relative to several established measures. Additional responsiveness data with clinical anchors are recommended. Incorporation of Ped-PRO-CTCAE in trials may lead to a better understanding of the cancer treatment experience.

PURPOSE: For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking. METHODS: Within the Children's Oncology Group and the Dana Farber Cancer Institute's Childhood Acute Lymphoblastic Leukemia Consortium, we evaluated four randomized trials of children with acute lymphoblastic leukemia or Hodgkin lymphoma, who received doxorubicin with or without dexrazoxane, and a nonrandomized trial of patients with osteosarcoma who all received doxorubicin with dexrazoxane. Cumulative doxorubicin doses ranged from 100 to 600 mg/m² across these five trials, and dexrazoxane was administered uniformly (10:1 mg/m² ratio) as an intravenous bolus before doxorubicin. Cardiac function was prospectively assessed in survivors from these trials, plus a matched group of survivors of osteosarcoma treated with doxorubicin without dexrazoxane. Two-dimensional echocardiograms and blood biomarkers were analyzed centrally in blinded fashion. Multivariate analyses adjusted for demographic characteristics, cumulative doxorubicin dose, and chest radiotherapy determined the differences and associations by dexrazoxane status. RESULTS: From 49 participating institutions, 195 participants were assessed at 18.1 ± 2.7 years since cancer diagnosis (51% dexrazoxane-exposed; cumulative doxorubicin dose 297 ± 91 mg/m²). Dexrazoxane administration was associated with superior left ventricular fractional shortening (absolute difference, +1.4% [95% CI, 0.3 to 2.5]) and ejection fraction (absolute difference, +1.6% [95% CI, 0.0 to 3.2]), and lower myocardial stress per B-type natriuretic peptide (–6.7 pg/mL [95% CI, –10.6 to –2.8]). Dexrazoxane was associated with a reduced risk of having lower left ventricular function (fractional shortening < 30% or ejection fraction < 50%; odds ratio, 0.24 [95% CI, 0.07 to 0.81]). This protective association was primarily seen in those treated with cumulative doxorubicin doses ≥ 250 mg/m². CONCLUSION: Among young adult-aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.