Pediatric medulloblastoma in the molecular era: what are the surgical implications? Michelle M. Kameda-Smith 1 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Pediatric brain tumors are the leading cause of childhood cancer mortality with medulloblastoma (MB) representing the most frequent malignant tumor. Although standardization of therapy resulted in a 2-fold reduction in mortality in patients with MB by 2002, it became clear that further improvements in clinical outcome would require a deeper understanding of the biology of MB. Employing the four main molecular MB subgroups (Wnt, Shh, Group 3 and Group 4), a restratification into clinicogenomic risk categories quantified an unacceptable survival for the high-risk group, urging researchers to focus their efforts towards acquiring a greater biological understanding of these children. Advancing in parallel with the molecular characterization and understanding of pediatric MB is the clinicogenomic correlations giving rise to recommendations for neurosurgical care. While unique obser- vations that distinct radiological patterns can be identified to inform the MB molecular subgroup preoperatively, current neuro- surgical practice remains maximal safe surgical resection followed by risk-adapted provision of adjuvant therapy in the context of a clinical trial. Keywords Pediatric medulloblastoma . Molecular era . Neurosurgical implications 1 Introduction Pediatric brain tumors are the leading cause of childhood can- cer mortality with medulloblastoma (MB) representing the most frequent malignant tumor [1]. Our understanding of the molecular basis of pediatric MB has increased significantly since its first description by two eminent dually trained neu- rosurgeons and neuropathologists, Drs. Percival Bailey and Harvey Cushing in 1925 [2]. Since then, multiple risk strati- fications were developed in efforts to guide and standardize clinical practice. Clinically, high-risk disease is identified by an age less than 3 years and metastasis at diagnosis or postop- erative residual disease greater than 1.5 cm 2 [3]. Over the last 30 years, a multimodal approach to disease management employing a standardized risk stratification system has made significant improvements in outcome survival (OS) for these children; however, ample potential for improvements remain [4]. Traditional treatment for children age 3 years and older involves maximal safe resection, adjuvant craniospinal irradi- ation, and chemotherapy with vincristine, cisplatin, cyclo- phosphamide, and lomustine [5]. In children under the age of 3 years, the balance between the devastating neurodevelopmental and neurocognitive side effects of radia- tion therapy and disease control prompted the neurooncological community to learn from the early experi- ences of postoperative irradiation of the developing brain [6]. In these young children, a radiation sparing, high-dose che- motherapy protocol is administered with radiation reserved for salvage therapy. While childhood MB survivorship witnessed a significant improvement nearing 80% for standard-risk pa- tients, the treatment toxicity and long-term sequelae of the current regime considerably impact their quality of life, further emphasizing the need for a deeper understanding of the biol- ogy of MB (Fig. 1)[7–13]. 2 Molecular era At the turn of the millennium, high-throughput methods for studying the genome and transcriptome became available fa- cilitating early studies to subdivide histologically similar leu- kemias into clinically and molecularly distinct groups [14]. A subsequent study by Pomeroy et al. utilized transcriptomics to * Michelle M. Kameda-Smith michelle.kameda@medportal.ca 1 Division of Neurosurgery, Department of Surgery, Hamilton General Hospital, McMaster University, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada Cancer and Metastasis Reviews https://doi.org/10.1007/s10555-020-09865-y