Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial.

BACKGROUND: This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. METHODS: Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier. RESULTS: One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89). CONCLUSIONS: In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.

The magnitude and predictors of therapy abandonment in pediatric central nervous system tumors in low- and middle-income countries: Systematic review and meta-analysis.

BACKGROUND: Outcomes of pediatric central nervous system (CNS) tumors in low- to middle-income countries (LMIC) are poorer than their high-income counterparts. Abandonment of therapy is increasingly recognized as a key contributor to this disparity, but has been poorly quantified. We performed a meta-analysis to determine the magnitude of abandonment in pediatric CNS tumors in LMIC, and risk factors and interventions aimed at reducing this. PATIENTS AND METHODS: We searched seven databases for pediatric CNS tumor cohorts followed up from diagnosis and treated in LMIC. All languages were included. Two reviewers independently selected articles and extracted data on abandonment rates (ARs) and predictors. The authors were contacted for additional information. RESULTS: Of 50 660 publications, 643 in five languages met criteria for full review; 131 met analysis inclusion criteria. ARs were not reported in the majority, and a small number were available from the authors. Available ARs ranged from 0% to 59%, from 38 studies (2497 children in 14 countries), and these were quantitatively analyzed. Lower-middle-income countries had higher ARs than upper-middle-income countries (27%, 95% confidence interval [CI] 20%-36% vs 9%, 95% CI 6%-14%, P < 0.0001), with significant heterogeneity within each (LMIC I2  = 78%, P < 0.00001, UMIC I2  = 85%, P < 0.00001). Common predictors for abandonment included distance to treatment centers, financial hardship, and prognostic misconceptions. CONCLUSION: In LMICs, ARs are highest in lower-MICs. However, the paucity of published data limits further evaluation. Given the increasing burden of pediatric CNS tumors in LMIC, addressing deficits in abandonment reporting is critical. Consistent reporting is needed for developing interventions to improve outcomes.