Low-Grade Glioma

Approximately 3000 new cases of low-grade glioma (LGG) will be diagnosed annually in the United States. LGG includes Grade 1 and Grade 2 glioma and represents a heterogeneous group of tumors, historically. Pilocytic Grade I astrocytoma is the most common Grade I lesion and Grade II lesions are diffuse astrocytoma and oligodendroglioma, which comprise the majority of adult LGG. The pathologic criteria for diagnosis of LGG have been updated per the World Health Organization 2021 classification system. With the 2021 WHO Classification of Tumors of the Central Nervous System (CNS) fifth edition update, diffuse LGG (Grade 2 lesions) is distinguished by genetic characteristics on molecular testing alone or in combination with histologic features. All adult glioma are now classified as astrocytoma, IDH mutant; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted; and glioblastoma, IDH wild type. IDH1 (R132) mutation is the most common IDH mutation in LGG. TP53 mutations along with ATRX mutations are found in the majority of Grade 2 astrocytomas. 1p/19q co-deletions define the diagnosis of oligodendrogliomas and are mutually exclusive from TP53 mutations. Grading is within the category and has moved beyond histology alone to determine grade, where the homozygous deletion of CDKN2A/B is sufficient for the diagnosis of a Grade 4 lesion regardless of histological features. The terms anaplastic astrocytoma and IDH mutant glioblastoma are no longer a component of the WHO Classification. Herein, we will focus on LGG defined as astrocytoma, IDH mutant, Grade 2 tumors, as well as, oligodendroglioma, IDH mutant, and Grade 2 tumors. Seizure is the most common presenting symptom for patients with Grade 2 glioma, with occasional lesions discovered incidentally or with patients presenting with focal neurologic deficits. Diffuse Grade 2 gliomas are most commonly found in patients in their later 30s to early 40s. Grade 2 lesions are poorly circumscribed on magnetic resonance imaging (MRI) and have minimal enhancement, with significant edema best seen on T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequencing. Primary therapy includes maximal safe resection versus observation in select cases. Adjuvant options include radiation therapy (RT) versus observation after resection with RT at the time of progression. RT can improve symptomatology and improve progression-free survival (PFS). Dosing is generally 50.4–54 Gy delivered in 28–30, 1.8 Gy daily fractions. For high-risk patients, defined as age older than 40 or age under 40 with subtotal resection (STR), the addition of procarbazine, CCNU, and vincristine (PCV) to RT has been shown to improve overall survival (OS). Temozolomide (TMZ) can be used alone in select patients, but more typically is used in combination with RT. Further prospective work is needed to clarify the optimal timing and intensity of therapy, weighing the side effects of early intervention with the potential survival benefit.