Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data

Jordan R Hansford; Jie Huang; Raelene Endersby; Andrew J Dodgshun; Bryan K Li; Eugene Hwang; Sarah Leary; Amar Gajjar; Katja Von Hoff; Olivia Wells; Alison Wray; Rishi S Kotecha; David R Raleigh; Schuyler Stoller; Sabine Mueller; Steven E Schild; Pratiti Bandopadhayay; Maryam Fouladi; Eric Bouffet; Annie Huang; Arzu Onar-Thomas; Nicholas G Gottardo

doi:10.1093/noajnl/vdac056

Pediatric pineoblastoma: A pooled outcome study of North American and Australian therapeutic data

Neurooncol Adv. 2022 Apr 14;4(1):vdac056. doi: 10.1093/noajnl/vdac056. eCollection 2022 Jan-Dec.

Authors

Jordan R Hansford¹, Jie Huang², Raelene Endersby³, Andrew J Dodgshun⁴, Bryan K Li⁵, Eugene Hwang⁶, Sarah Leary⁷, Amar Gajjar⁸, Katja Von Hoff⁹, Olivia Wells¹, Alison Wray¹, Rishi S Kotecha¹⁰, David R Raleigh¹¹, Schuyler Stoller¹², Sabine Mueller¹², Steven E Schild¹³, Pratiti Bandopadhayay¹⁴, Maryam Fouladi¹⁵, Eric Bouffet¹⁶, Annie Huang⁵, Arzu Onar-Thomas², Nicholas G Gottardo³

Affiliations

¹ Children's Cancer Center, Royal Children's Hospital, Melbourne, Victoria, Australia.
² Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
³ Brain Tumor Research Program, Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
⁴ Children's Hematology/Oncology Center, Christchurch Hospital, Christchurch, New Zealand.
⁵ Division of Hematology/Oncology, Cell Biology Research Program, Arthur and Sonia Labatt Brain Tumor Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Division of Oncology, Children's National Hospital, Washington, DC, USA.
⁷ Seattle Children's Hospital, Seattle, Washington, USA.
⁸ St Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁹ Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Department of Clinical Hematology, Oncology, Blood and Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.
¹¹ Departments of Radiation Oncology and Neurological Surgery, University of California San Francisco, San Francisco, California, Australia.
¹² Department of Pediatric Oncology, University of California San Francisco, San Francisco, California, Australia.
¹³ Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA.
¹⁴ Boston Children's Hospital, Dana-Farber Children's Institute, Boston, Massachusetts, USA.
¹⁵ Department of Neuro-Oncology, Division of Hematology/Oncology, Nationwide Children's Hospital, Columbus, Ohio, USA.
¹⁶ Department of Pediatrics, The Hospital for Sick Children/University of Toronto, Toronto, Ontario, Canada.

Abstract

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 (PFS) and overall survival (OS) 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 < .0001). Multivariable analysis showed male sex was associated with worse PFS in children <3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; P = .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 = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; P = .0016).

Conclusion: Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.

Keywords: pediatrics; pineoblastoma; retrospective study.