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The molecular characteristics of glioma patients, such as 1p/19q codeletion, MGMT promoter region methylation, and IDH1/IDH2 mutations, carry important information for tumor classification, biological behavior, and the prediction of patient survival. We sought to address the clinical characteristics of brain tumor patients in the Taiwanese population. Our aim was to compare the H&E-based classification and the 2016 WHO classification in glioma patients. 192 patients were recruited in this study including glioblastomas (GBMs) and lower-grade gliomas (LGGs). We performed assays to determine the statuses of 1p/19q codeletion, MGMT promoter methylation, and IDH mutations in tumors and assessed their associations with survival time. We also compared the difference between H&E and WHO 2016 classification. Using the H&E classification, the overall survival time (OST) was associated with IDH status in astrocytoma and oligoastrocytoma patients but not in oligodendroglioma and GBM patients. However, OST showed no significant correlation with MGMT promoter methylation in all the groups. Furthermore, no significant association was observed between 1p/19q codeletion and OST in GBM patients. Using the WHO 2016 classification, our results indicated that astrocytoma and oligodendroglioma patients with mutant IDH showed a significantly prolonged OST than patients with wild-type IDH. However, only oligodendroglioma patients with MGMT hypermethylation demonstrated statistically significant difference. Prognostic factors, including the age at diagnosis, IDH mutations, MGMT promoter methylation, and 1p/19q codeletion, could independently predict patient survival. Based on the WHO 2016 classification of glioma, the new histological groups provide a better and objective method to categorize glioma patients and predict patient survival.

Oligodendroglioma is the second most common primary intra-axial brain tumor. These tumors are diffusely infiltrating and composed of well-differentiated cells that resemble normal oligodendrocytes. Typically, oligodendrogliomas develop in the fourth-fifth decades of life and usually involve the cerebral hemispheres. Genome sequence profiling has ushered in a new era of cancer research that has led to the systematic clustering and cataloguing of oligodendrogliomas not based on histopathology but based on molecular phenotype. For patients with oligodendroglioma, treatment decisions and prognosis are predicated on these molecular findings, as well as other factors including location, size, grade, and extent of surgical resection. Anaplastic oligodendrogliomas, pediatric oligodendrogliomas and spinal cord oligodendrogliomas are much less common entities. Based on the most recent WHO guidelines, oligoastrocytoma is no longer a clinical entity and is not discussed in this chapter.

Anaplastic oligodendrogliomas have long attracted interest because of their sensitivity to chemotherapy, in particular in the subset of 1p/19q co-deleted tumors. Recent molecular studies have shown that all 1p/19q co-deleted tumors have IDH mutations and most of them also have TERT mutations. Because of the presence of similar typical genetic alterations in astrocytoma and glioblastoma, the current trend is to diagnose these tumors on the basis of their molecular profile. Further long-term follow-up analysis of both EORTC and RTOG randomized studies on (neo)adjuvant procarbazine, lomustine, vincristine (PCV) chemotherapy have shown that adjuvant chemotherapy indeed improves outcome, and this is now standard of care. It is also equally clear that benefit to PCV chemotherapy is not limited to the 1p/19q co-deleted cases; potential other predictive factors are IDH mutations and MGMT promoter methylation. Moreover, a recent RTOG study on low-grade glioma also noted an improved outcome after adjuvant PCV chemotherapy, thus making (PCV) chemotherapy now standard of care for all 1p/19q co-deleted tumors regardless of grade. It remains unclear whether temozolomide provides the same survival benefit, as no data from well-designed clinical trials on adjuvant temozolomide in this tumor type are available. Another question that remains is whether one can safely leave out radiotherapy as part of initial treatment to avoid cognitive side-effects of radiotherapy. The current data suggest that delaying radiotherapy and treatment with chemotherapy only may be detrimental for overall survival.

The infiltrative or “diffuse” gliomas include astrocytomas and oligodendrogliomas. Taken together, these are the most frequent primary neoplasms of the central nervous system parenchyma. These tumors are difficult to manage clinically, in large part because of their widespread invasiveness, their strong tendency toward biologic progression, and the resistance of many of these neoplasms to conventional adjuvant therapies. The WHO classification currently divides diffuse gliomas into astrocytomas and oligodendrogliomas and includes criteria for their grading. The category of “oligoastrocytoma” is no longer supported, since these lesions have been demonstrated to represent either astrocytomas or oligodendrogliomas at the molecular genetic level. Diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III), and glioblastoma (GBM; WHO grade IV) form a malignancy continuum for the diffusely infiltrating astrocytomas. The diffusely infiltrative astrocytomas of adults are now subdivided based on the mutational status of isocitrate dehydrogenase-1 or -2 (IDH1/2) genes into either IDH-mutant or IDH-wildtype for each grade. Another form of diffuse high-grade astrocytoma that most often occurs in the pediatric population is characterized by histone H3F3 mutations and occurs either in the midline (K27 codon mutations) or in the cerebral hemispheres (G34 codon mutations). The oligodendrogliomas include WHO grade II and III designations and are defined histologically and by the presence of IDH mutations and the codeletion of the entire 1p and 19q chromosomal arms.

Oligoastrocytomas are tumors consisting of areas of cells with the morphologic characteristics of oligodendroglioma intermingled with areas where the morphology of the cells is astrocytic. In most, the cells are diffusely mixed. Tumors with separate areas of oligodendroglial and astrocytic cells are not common. Oligoastrocytomas have an incidence between 2 and 10% of all gliomas. At present, there seems to be two main categories of oligoastrocytoma. Those that have 1p and 19q deletions and those with TP53 mutations. The former, typical of pure oligodendroglioma, suggest oligodendroglial lineage. TP53 mutations are typical of astrocytomas, suggesting that those oligoastrocytomas may be derived from astrocytic precursor cells. This chapter focuses on studies in which there has been an attempt to analyze chemotherapy of oligoastrocytomas separately from oligodendrogliomas. It reviews several studies on use of various chemotherapeutic agents including procarbazine, lomustine [1,(2-chloroethyl)-3-cyclohexyl-1-nitrosurea, CCNU], and vincristine (PCV), temozolomide (TMZ), and other chemotherapy regimens in anaplastic and low-grade oligoastrocytomas.

Primary brain tumors, accounting for fewer than 2% of all cancers, are among the most costly to society. Low-grade gliomas represent 10% of these primary tumors. The descriptive names that we apply reflect microscopic appearances and immunohistochemical staining characteristics as well as locations within the nervous system. The terminology is confusing, and the names do not reflect biological behavior, response to therapy, prognosis, or molecular alterations. Astrocytic tumors predominate (diffuse astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma), followed by oligodendroglial (oligodendroglioma) and mixed glial tumors (oligoastrocytoma). Tumors of mixed glial-neuronal populations also occur (ganglioglioma, desmoplastic infantile astrocytoma, ganglioglioma). Least common are growths in proximity to the ventricles and choroid plexus (choroid plexus papilloma), the ependyma (ependymoma, myxopapillary ependymoma), subependymoma, and neuroepithelial tumors of unknown origin (dysembryoplastic neuroepithelial tumor, chordoid glioma of the third ventricle). Some of these tumors are discussed elsewhere in Part VII of this book. Central to this chapter and to the care of afflicted patients are two tenets. First, low-grade glioma is a descriptive term and does not imply a benign clinical course. A "benign" infiltrating astrocytoma of the brainstem can lead to disability and death; a similar lesion in the optic chiasm causes blindness, and intramedullary spinal low-grade glioma can produce irreversible paraplegia. Second, because many patients survive their tumors, the clinician must weigh the gains of therapy against the side effects of surgery, irradiation, and chemotherapy.