Background
Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain.
Patients and Methods
Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses.
Results
We describe a pooled cohort of 178 pineoblastoma cases from Children’s Oncology Group (n=82) and institutional series (n=96) over 30 years. Children <3 years of age have significantly worse survival compared to older children, with 5-year progression free survival and overall survival estimates of 13.5±5.1% and 16.2±5.3% respectively compared with 60.8±5.6% and 67.3±5.0% for ≥3 years old (both p<0.0001). Multivariable analysis showed male sex was associated with worse PFS in children <3 years of age (Hazard Ratio 3.93, 95% CI 1.80-8.55; p=0.0006), suggestive of sex specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2±9.7% (HR 2.88, 95% CI 1.52-5.45; p=0.0012) and 5-year OS of 49.8±9.1% (HR 2.87, 95% CI 1.49-5.53; p=0.0016).
Conclusion
Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.
Objective
To determine the safety, tolerability and distribution of MTX110 (aqueous panobinostat) delivered by convection enhanced delivery (CED) in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) who completed focal radiation therapy (RT).
Methods
Patients with DIPG (2-21 years) were enrolled after RT. CED of MTX110 combined with gadoteridol was completed across seven dose levels (DL) (30-90 µM; volumes ranging from 3 mL to two consecutive doses of 6 mL). An accelerated dose escalation design was used. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4-8 weeks. Quality of life (QOL) assessments were obtained at baseline, every 3 months on therapy, and end of therapy.
Results
Between May 2018-March 2020 seven patients, who received a total of 48 CED infusions, were enrolled (median age 8 years, range 5-21). Three patients experienced dose-limited toxicities. Four grade 3 treatment related adverse events were observed. Most toxicities were transient new or worsening neurologic function. Median overall survival (OS) was 26.1 months (95% CI: 14.8-not reached). Progression free survival was 4-14 months (median, 7). Cumulative percentage of tumor coverage for combined CED infusions per patient ranged from 35.6–81.0%. Increased CED infusions was negatively associated with self-reported QOL assessments.
Conclusion
Repeat CED of MTX110 with real time imaging with gadoteridol is tolerable for patients with DIPG. Median OS of 26.1 months compares favorably with historical data for children with DIPG. The results support further investigation of this strategy in a larger cohort.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.