Radiation therapy dose escalation achieves high rates of local control with tolerable toxicity profile in pediatric and young adult patients with Ewing sarcoma.

BACKGROUND: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors ≥8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. METHODS: Eligible patients ≤30 years old with newly diagnosed EWS ≥8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. RESULTS: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. CONCLUSION: This study demonstrates that definitive RT for pediatric and young adult patients with EWS ≥8 cm provides high rates of local control, while maintaining a tolerable toxicity profile.

Germline genomic findings in children and young adults with melanocytic tumors.

In this retrospective study, we examined the prevalence and spectrum of germline variants in selected cancer predisposition genes in 38 children and young adults with melanocytic lesions at St. Jude Children's Research Hospital. Diagnoses included malignant melanoma (n = 16; 42%), spitzoid melanoma (n = 16; 42%), uveal melanoma (n = 5; 13%), and malignant melanoma arising in a giant congenital melanocytic nevus (n = 1; 3%). Six patients (15.8%) harbored pathogenic germline variants: one with bi-allelic PMS2 variants, one with a heterozygous 17q21.31 deletion, and one each with a pathogenic variant in TP53, BRIP1, ATM, or AXIN2. Overall, 15.8% of patients harbored a cancer-predisposing genetic variant.

Barriers to and Facilitators of Iron Therapy in Children with Iron Deficiency Anemia.

OBJECTIVE: To characterize barriers to and facilitators of successful iron therapy in young children with iron deficiency anemia (IDA) from an in-depth parental perspective. STUDY DESIGN: Prospective, mixed methods study of children age 9 months to 4 years with a diagnosis of nutritional IDA by clinical history and laboratory criteria and their parents. Clinical data were obtained from the electronic health record. Semistructured interviews focused on knowledge of IDA, clinical effects, experience with iron therapies, and motivation were conducted with the parent who identified as the child's primary caregiver. RESULTS: Twenty patient-parent dyads completed the study; 80% (n = 16) identified as Hispanic/Latino (white). Patients' median age was 23 months (50% male); median initial hemoglobin concentration was 8.2 g/dL and duration of oral iron therapy was 3 months. Parents' median age was 29 years (85% female); 8 interviews (40%) were conducted in Spanish. Barriers included difficulty in administering oral iron owing to side effects and poor taste. Facilitators included provision of specific instructions; support from healthcare providers and additional caregivers at home; motivation to benefit child's health, which was strengthened by strong emotional reactions (ie, stress, anxiety) to therapy and follow-up; and an appreciation of child's improvement with successful completion of therapy. CONCLUSIONS: Our findings support the need for interventions designed to promote oral iron adherence in children with IDA. Rather than focusing on knowledge content related to IDA, interventions should aim to increase parental motivation by emphasizing the health benefits of adhering to iron therapy and avoiding more invasive interventions.

Influence of valproic acid on outcome of high-grade gliomas in children.

BACKGROUND: Chemotherapy has limited effects in the treatment of high-grade gliomas (HGGs). Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, may sensitize HGGs to radiochemotherapy. As the drug has been given frequently as an antiepileptic drug, a retrospective analysis was conducted to ensure relevant information was not missed before a prospective study was launched. MATERIALS AND METHODS: An analysis of 66 pediatric patients (range, 1-19 years of age) with glioblastoma multiforme (GBM) (n=40) or anaplastic astrocytoma (AA) (n=26) was retrospectively conducted for predictors of survival and response and for effects of VPA on outcome or toxicity. RESULTS: The overall survival (OS) was better for AA (p=0.0114) and complete resection (p<0.00005) and event-free survival (EFS) was better for complete resection (p=0.0049). Nine patients received VPA (for seizure) plus further oncological treatment. The most severe adverse effect was a pulmonary embolism (n=1); no other severe side-effects were noted. The response to nonsurgical treatment after 8 weeks was: complete response (CR): 0, partial response (PR): 3, stable disease (SD): 4, progressive disease (PD): 2. Some of the patients with SD responded later resulting in best response: CR:0, PR:5, SD:2, PD:2. CONCLUSION: Treatment with VPA plus radiochemotherapy is well tolerated with an encouraging response rate.