Adolescents and young adults with brain tumors in the context of molecular advances in neuro‐oncology

Abstract

Adolescents and young adults (AYA) comprise a specific group of oncology patients with a distinct biological and epidemiological spectrum of central nervous system neoplasms. It has been well documented that they differ clinically, especially in relation to prognosis and chemotherapy tolerance; however, the underlying reasons for this are unclear. Recent advances in the genomics of both childhood and adult brain tumors have provided new explanations and insights into the previously described age-dependent heterogeneity. Herein, we summarize the current state of the AYA population in neuro-oncology, specifically how biological advances can help personalize therapy for this unique group of patients.

Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost

“…Recently, it has been shown that childhood posterior fossa ependymoma (PFE) is not a single entity but rather is comprised of at least 2 distinct molecular variants, group A (PFA) and group B (PFB), with distinct epigenetics, demographics, and outcomes . Although PFA represents nearly all infants with posterior fossa ependymoma, PFB is prevalent in adults and with a near equal distribution in adolescence . A recent retrospective study across 820 cases of PFE has shown that the molecular subgroup is the most powerful predictor of outcome, and even within the PFA group, upfront postsurgical external‐beam RT and a complete surgical resection are reported to be strong predictors of a good outcome .…”

“…4 Although PFA represents nearly all infants with Cancer June 1, 2019 posterior fossa ependymoma, PFB is prevalent in adults and with a near equal distribution in adolescence. [5][6][7][8][9] A recent retrospective study across 820 cases of PFE has shown that the molecular subgroup is the most powerful predictor of outcome, and even within the PFA group, upfront postsurgical external-beam RT and a complete surgical resection are reported to be strong predictors of a good outcome. 2 Although RT was uniform in the majority of cases in this study, chemotherapy regimens were not, including infants treated with delayed RT prior to disease progression.…”

A comparative analysis of clinicopathological features and survival among early adolescents/young adults and children with low-grade glioma: a report from the Children’s Oncology Group

“…Although these disparities remain poorly understood, they are indicators of potential differences in cancer and host biology, receipt of appropriate therapy, and health behaviors among AYAs. Knowledge about these disparities is important for improving clinical care and informing additional research in this at-risk population [8, 9]. …”

“…However, little is known about the biology and clinical behavior of LGG among AYAs. In young children versus older adults, LGGs exhibit contrasting biological and clinical features [9]. Most pediatric LGG are characterized by BRAF and other RAS/RAF pathway alterations, are unlikely to transform to high-grade glioma, and are associated with excellent long-term overall survival (OS) [11].…”

“…Most pediatric LGG are characterized by BRAF and other RAS/RAF pathway alterations, are unlikely to transform to high-grade glioma, and are associated with excellent long-term overall survival (OS) [11]. In contrast, RAS/RAF pathway alterations are rare in adult LGG, which is typified by IDH1/2 and ATRX mutations/alterations, a high incidence of malignant transformation, and a more guarded prognosis [9, 12, 13]. Whether LGG among AYAs has more in common with pediatric or adult LGG phenotype, or whether it is a third biological entity distinct from both, has not been established [14].…”