Pediatric versus Adult Medulloblastoma: Towards a Definition That Goes beyond Age

Abstract

Medulloblastoma is a rare malignant brain tumor that predominantly affects children but also occurs in adults. The incidence declines significantly after age 15, and distinct tumor molecular features are seen across the age spectrum. Standard of care treatment consists of maximal safe surgical resection followed by adjuvant radiation and/or chemotherapy. Adjuvant treatment decisions are based on individual patient risk factors and have been informed by decades of prospective clinical trials. These trials have historically relied on arbitrary age cutoffs for inclusion (age 16, 18, or 21, for example), while trials that include adult patients or stratify patients by molecular features of disease have been rare. The aim of this literature review is to review the history of clinical trials in medulloblastoma, with an emphasis on selection criteria, and argue in favor of rational and inclusive trials based on molecular features of disease as opposed to chronological age. We performed a scoping literature review for medulloblastoma and clinical trials and include a summary of those results. We also discuss some of the significant advances made in understanding the molecular biology of medulloblastoma within the past decade, most notably the identification of four distinct subgroups based on gene expression profiling. We will also cite the recent experiences of childhood leukemia and the emergence of tissue-agnostic therapies as examples of successes of rationally designed, inclusive trials translating to improved clinical outcomes for patients across the age spectrum. Despite the prior trial history and recent molecular advances outcomes remain poor for ~30% of medulloblastoma patients. We believe that defining patients by the specific molecular alterations their tumors harbor is the best way to ensure they can access potentially efficacious therapies on clinical trials.

Medulloblastoma and other neoplasms in patients with heterozygous germline SUFU variants: A scoping review

“…This scoping review also highlights the importance of evaluating molecular phenotypes when describing patients with cancer predisposition syndromes. It is clear that molecular alterations that drive medulloblastoma and BCNS can help predict clinical outcomes; as such, it is no longer appropriate to group diseases simply based on the tissue of origin or general phenotype (Wooley & Penas‐Prado, 2021). Moving forward, international databases of patients with cancer predisposition need to be established to allow for large prospective studies that capture the full spectrum of neoplasms to better understand which cancers patients are at an elevated risk of developing.…”

“…management of patients with cancer predisposition requires access to highly specialized care and unequal access will continue to be a substantial obstacle to optimizing patient care and research initiatives in this field (Wooley & Penas-Prado, 2021).…”

Adult's Medulloblastoma

“…Overtime, many guidelines for the classification of CNS tumors were published. As the interest for medulloblastomas has grown and evolved, they were reviewed as a distinct subtype of embryonal tumors and four separate histological subsets were admitted (classic, desmoplastic, extensive nodularity, and large cell) [5].…”

Adult Medulloblastoma: Updates on Current Management and Future Perspectives

“…Examining data from the Surveillance, Epidemiology, and End-Results (SEER) database from 1973 through 2007, MB is the second most common of all pediatric central nervous system (CNS) tumors (accounting for about 20% of the total CNS tumors in the pediatric age group), with a bimodal peak at age 3 to 4 years and at age 8 to 10 years [ 3 , 4 ]. Age of MB onset is variable, from birth to adolescence, but the incidence rate dramatically declines after age 15 [ 5 ].…”

“…In adult neuro-oncology practice, therefore, MB is a very rare condition, representing only 0.4–1% of all adult CNS tumors, with an incidence of 0.6–1 case per million per year [ 4 ]: this population, which is the topic of this review and for readability purposes will be called “adult MB”, is an “orphan” entity, being that the main therapeutic protocols were extrapolated from experiences in children, while prospective randomized clinical trials specifically designed for adult patients are very rare [ 5 , 6 , 7 , 8 , 9 , 10 ].…”