Treatment transition in pediatric low-grade gliomas

Abstract

Pediatric low-grade gliomas (pLGGs) are classified as WHO CNS grade 1 benign tumors and potentially curable with complete surgical resection. However, pLGGs arising in unresectable locations, such as the optic pathway-hypothalamic region or brainstem, are difficult to treat, and tumor progression often results in serious neurological sequelae. However, patients with pLGGs have favorable overall survival. Historically, pLGGs are considered diffuse astrocytic tumors; however, advances in molecular biology have led to their recognition as distinct tumor groups, distinguished from adult diffuse gliomas. Although the diagnostic classification has been refined by advances in DNA methylation analyses, this approach remains evolving. Additionally, pLGGs frequently activate the MAPK pathway involving BRAF alterations, making them promising targets for molecular-targeted therapies.

The goals of therapeutic development for pLGGs differ substantially from those of other pediatric cancers. Usually, progression-free survival (PFS) is the primary endpoint; however, the progression of pLGGs often reflects tumor regrowth. Recognizing this conceptual difference is essential for appropriate interpretation of clinical studies. Importantly, this therapy aims for long-term control of tumor growth, as tumor growth may eventually be arrested spontaneously. Accordingly, treatment strategies are shifting from prolonged conventional chemotherapy, such as carboplatin/vincristine or vinblastine, to molecular targeted therapies with careful evaluation of adverse events and long-term sequelae of growth and development.