Pineoblastoma in children less than six years of age: The Head Start I, II, and III experience

• Authors: Mohamed S Abdelbaki, Nationwide Childrens Hospital; Mohammad H Abu-Arja, Weill-Cornell College of Medicine; Tom B Davidson, Childrens Hosp Los Angeles; Jason Fangusaro, Emory University; Joseph R Stanek, Nationwide Childrens Hospital; Ira J Dunkel, Memorial Sloan Kettering Cancer Center; Girish Dhall, University of Alabama Birmingham; Sharon L Gardner, New York University; Jonathan L Finlay, Nationwide Childrens Hospital
• Journal Title: PEDIATRIC BLOOD & CANCER
• Volume: Volume 67, Number 6
• Publisher: WILEY | 2020-03-18, Pages e28252-e28252
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/pbc.28252
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Hematology; Pediatrics; autologous hematopoietic cell rescue; craniospinal irradiation; Head Start; marrow-ablative chemotherapy; pineoblastoma; PRIMITIVE NEUROECTODERMAL TUMORS; HIGH-DOSE CHEMOTHERAPY; YOUNG-CHILDREN; CELL RESCUE; INTENSIVE CHEMOTHERAPY; PROGNOSTIC-FACTORS; SYSTEM; RADIOTHERAPY; RADIATION; BRAIN

Abstract

Background: We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials. Methods: Twenty-three children were enrolled prospectively between 1991 and 2009. Treatment included maximal surgical resection followed by five cycles of intensive chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following consolidation was reserved for children over six years of age or those with residual tumor at the end of induction. Results: Median age was 3.12 years (range, 0.44-5.72). Three patients withdrew from the study treatment and two patients experienced chemotherapy-related death. Eight patients experienced progressive disease (PD) during induction chemotherapy and did not proceed to HDCx/AuHCR. Ten patients received HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation (CSI) with a median dose of 20.7 Gy (range, 18-36 Gy) with boost(s) (median dose 27 Gy; range, 18-36 Gy); three received CSI as adjuvant therapy (two post-HDCx/AuHCR) and four upon progression/recurrence. The five-year progression-free survival (PFS) and overall survival (OS) were 9.7% (95% confidence intervals [CI]: 2.6%-36.0%) and 13% (95% CI: 4.5%-37.5%), respectively. Only three patients survived beyond five years. Favorable OS prognostic factors were CSI (hazard ratio [HR] = 0.30 [0.11-0.86], P = 0.025) and HDCx/AuHCR (HR = 0.40 [0.16-0.99], P = 0.047). Conclusions: Within the HS I-III trials, CSI and HDCx/AuHCR were statistically associated with improved survival. The high PD rate during later induction cycles and following consolidation chemotherapy warrants consideration of fewer induction cycles prior to consolidation and the potential intensification of consolidation with multiple cycles of marrow-ablative chemotherapy and irradiation.