Physician, patient, and caregiver support for a formal certification in pediatric neuro-oncology: A survey-based report from the SNO pediatrics working group.

Background: Although CNS tumors are the most common pediatric cancer in the United States, most physicians caring for these patients are not formally certified in the subspecialty. To determine support for developing a formal certification process in pediatric neuro-oncology, the Society for Neuro-Oncology's Pediatrics Special Interest Track Training and Credentialing working group performed a cross-sectional survey-based study of physicians and patients/caregivers of children with a CNS tumor history. Methods: Surveys were built in Survey Monkey and were available for 3 months. The physician survey had 34 questions and was open to doctors currently caring for pediatric neuro-oncology patients. The patient/caregiver survey had 13 questions. Both surveys were completed anonymously. Results: The physician survey was completed by 193 participants, the majority of whom self-identified as oncologists. Only 5.6% of survey participants had ever been board-certified in neuro-oncology; the majority of participating physicians were either unaware that this certification existed or thought they were not eligible due to training in pediatrics rather than neurology or internal medicine. Almost half of the self-identified pediatric neuro-oncologists had not completed any specific clinical neuro-oncology training. Over 75% of physicians were supportive of the implementation of a formal certification process in pediatric neuro-oncology. A total of 30 participants completed the patient/caregiver survey. Although the majority of survey participants were highly satisfied with their oncologist, 70% would have been more comfortable if their oncologist had been specifically certified in pediatric neuro-oncology. Conclusions: There is support from physicians, patients, and caregivers to establish a formal certification process in pediatric neuro-oncology.

Long-term health and social function in adult survivors of paediatric astrocytoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Although paediatric astrocytoma has an excellent 5-year survival rate, survivors remain at risk for morbidity and late mortality. This study aimed to estimate the risk of late mortality, chronic conditions, poor health status and social impairment in ageing paediatric astrocytoma survivors. METHODS: We longitudinally evaluated 1182 5-year astrocytoma survivors diagnosed between 1970 and 1986 and 4023 siblings enrolled in a retrospective cohort study. Kaplan-Meier estimates of late mortality and cumulative incidence of serious chronic conditions were estimated. Cox regression models provided hazard ratios (HRs) with 95% confidence intervals (CIs) for development of chronic conditions, and generalised linear models provided relative risks (RRs) of the poor health status and social outcomes. RESULTS: At 30 years from diagnosis, cumulative late mortality was 22.1% (CI 20.0-24.3%), primarily due to disease progression or recurrence. Compared with siblings, survivors were at increased risk of serious chronic conditions (HR 4.6, CI 3.8-5.5). Survivors reported higher rates of poor general health (RR 3.3, CI 2.8-3.8), poor mental health (RR 1.9, CI 1.7-2.1), functional impairment (RR 9.0, CI 7.7-10.5) and activity limitation (RR 3.6, CI 3.1-4.2) and lower rates of college graduation (RR 0.75, CI 0.69-0.82), marriage (RR 0.62, CI 0.58-0.66), employment (RR 0.75, CI 0.72-0.79) and household income ≥$40,000 (RR 0.68, CI 0.64-0.73). Even survivors without radiation exposure had elevated risk of chronic conditions, poor health status and social impairment compared with siblings. CONCLUSIONS: Survivors of paediatric astrocytoma are at high risk for long-term complications of their disease and its treatment. They require lifelong monitoring for late effects.

Long-term outcomes of primarily metastatic juvenile pilocytic astrocytoma in children.

OBJECTIVE Primarily metastatic juvenile pilocytic astrocytoma (JPA) is rare, likely representing 2%-3% of all cases of JPA. Due to the rarity of primarily metastatic JPA, there is currently no standard treatment paradigm and the long-term outcomes are not fully known. The goal of this case series was to add to the current understanding of this disease process. METHODS The authors searched a comprehensive database of pediatric patients with brain and spinal cord tumors treated at Lucile Packard Children's Hospital from 1997 to 2016 and identified 5 patients with primarily metastatic JPA. A retrospective chart review was performed and details of the patients' treatment and clinical course were recorded for further analysis. RESULTS For the 5 patients with primarily metastatic JPA, the mean follow-up period was 12.3 years. All patients in our series had biopsies or subtotal resections and upfront treatment. Three patients were treated with chemotherapy alone, one was treated with chemotherapy and radiotherapy, and one was treated with radiotherapy alone. Four patients had stable disease after initial treatment, and one patient had multiple episodes of progressive disease but underwent successful salvage therapy and has had stable disease for 19 years. One patient died of an intracerebral hemorrhage 10 years following initial radiation treatment believed to be secondary to radiation vasculopathy. CONCLUSIONS Evaluation of the entire neuraxis should be performed in all instances of initial JPA diagnosis to properly assess for primarily metastatic disease. Many patients with primarily metastatic JPA will have stable disease after upfront treatment, although the higher rate of stable disease found in this series relative to other reports is likely secondary to the small sample size.

An Investigation of Connections between Birth Defects and Cancers Arising in Adolescence and Very Young Adulthood.

This study investigated the relationship between birth defects and cancer in adolescents and very young adults using California's population-based registries. Although overall cancer risk was elevated among individuals with chromosomal birth defects, this was not observed in those with nonchromosomal birth defects, as was demonstrated previously in younger children.

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.

BACKGROUND: p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children. METHODS: Children aged 3-21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose. RESULTS: Of the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles. CONCLUSIONS: This phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose.