Background Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type-1) optic pathway and hypothalamic glioma (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. Methods We present results from children with recurrent/progressive OPHGs treated on a PBTC phase 2 trial evaluating efficacy of selumetinib, (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase 2 dose (25mg/m 2 /dose BID) for a maximum of 26 courses. Results Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%) and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia and rash. Conclusions Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS and visual outcomes.

Purpose Cognitive dysfunction is a major concern for children with brain tumors. A valid, user-friendly screening tool could facilitate prompt referral for comprehensive neuropsychological assessments and therefore early intervention. Applications of the pediatric perceived cognitive function item bank (pedsPCF) such as computerized adaptive testing can potentially serve as such a tool given its brevity and user-friendly nature. This study aimed to evaluate whether pedsPCF was a valid indicator of cerebral compromise using the criterion of structural brain changes indicated by leukoencephalopathy grades. Methods Data from 99 children (mean age =12.6 years) with brain tumors and their parents were analyzed. Average time since diagnosis was 5.8 years; time since last treatment was 4.3 years. Leukoencephalopathy grade (range: 0–4) was based on white matter damage and degree of deep white matter volume loss shown on MRI. Parents of patients completed the pedsPCF. Scores were based on the US general population-based T-score metric (mean=50; standard deviation=10). Higher scores reflect better function. Results Leukoencephalopathy grade distributions were as follows: 36 grade 0; 27 grade 1; 22 grade 2; 13 grade 3, and 1 grade 4. The mean pedsPCF T-score was 48.3 (SD=8.3; range: 30.5 to 63.7). The pedsPCF scores significantly discriminated patients with different leukoencephalopathy grades, F=4.14, p=0.0084. Effect sizes ranged from 0.09 (grade 0 versus 1) to 1.22 (grade 0 versus 3 / 4). Conclusions This study demonstrates that the pedsPCF is a valid indicator of leukoencephalopathy and provides support for its use as a screening tool for more comprehensive neurocognitive testing.

No abstract

No abstract

No abstract