Sequential improvement in paediatric medulloblastoma outcomes in a low-and-middle-income country setting over three decades

Johann Riedemann,Anthony Figaji,Tracy Kilborn,Komala Pillay,Clare Stannard,Jeannette Parkes,Alan Davidson

doi:10.4102/sajo.v5i0.174

Abstract

Background: Medulloblastoma (MB) is the commonest malignant brain tumour of childhood. Accurate clinical data on paediatric MB in the low-and-middle-income countries (LMIC) setting are lacking. Sequential improvements in outcomes seen in high-income countries are yet to be reflected in LMICs.Aim: The aim of this study was quantification of paediatric MB outcomes in the LMIC setting over three decades of advances in multidisciplinary intervention.Setting: Cape Town, South Africa.Methods: This was a retrospective study of 136 children with MB diagnosed between 1985 and 2015. The modified Chang criteria were used for risk stratification. The primary objective of this study was overall survival (OS), quantified by analysis of epidemiological, clinical and pathological data.Results: OS improved significantly during the most recent decade (2005–2015) when compared with the preceding two decades (1985–1995 and 1995–2005). Despite reduced-dose craniospinal irradiation (CSI) for standard risk cases, OS was significantly greater than during the preceding two decades. High-risk disease was identified in 71.4% of cases and was associated with significantly inferior OS compared with standard-risk cases. Improved OS was positively correlated with the therapeutic era, three-dimensional (3D) conformal radiotherapy technique, older age at diagnosis, classic and desmoplastic histology, extent of resection and absence of leptomeningeal spread on imaging.Conclusion: Advances in multidisciplinary management of MB in our combined service are associated with improved survival. Access to improved imaging modalities, advances in surgical techniques, increased number of patients receiving risk-adapted combination chemotherapy or radiotherapy, as well as CSI using a linear accelerator with 3D planning, are considered as contributing factors.

Highlights

Brain and central nervous tumours are rare in children but result in mortality and morbidity that is disproportionate to incidence rates
Because of the constraints associated with the duration of this study, we were unable to determine the origin of the cerebrospinal fluid (CSF) samples, and results reflect either intraoperative cisternal puncture or day 14 post-operative lumbar puncture samples
Age-adjusted analysis of our data indicated that 59% of patients under the age group 3–15 years were of high risk, which is in line with other low-and-middle-income countries (LMIC) reports documenting high-risk frequencies of 50% – 60%

Summary

Introduction

Brain and central nervous tumours are rare in children but result in mortality and morbidity that is disproportionate to incidence rates They constitute the leading cause of paediatric cancerassociated deaths worldwide, despite lower incidence rates in comparison with haematological malignancies.[1]. Medulloblastoma (MB) is the most common malignant paediatric brain tumour, comprising a group of histologically and molecularly diverse posterior fossa tumours, pathologically described as undifferentiated, small round blue cells with mild-to-moderate nuclear pleomorphism and high mitotic counts. These tumours are of embryonic origin and are believed to have originated from progenitor cell lineages present during early brain development. Sequential improvements in outcomes seen in high-income countries are yet to be reflected in LMICs

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