Anaplastic Glioma
  • 25% of high-grade gliomas in adults
  • Young to middle adulthood
  • Anaplastic astrocytomas
  • Anaplastic oligodendrogliomas
  • Anaplastic mixed oligoastrocytomas, correspond to WHO grade III. Histologically, these tumors have nuclear atypia and mitotic activity, without necrosis or neovascularization. On imaging, anaplastic gliomas may show enhancement and necrosis similar to GBM or appear nonenhancing like grade II gliomas. They display clinical and biologic heterogeneity.

Overall, patients with anaplastic astrocytoma have a median survival of approximately 3 years following diagnosis. Prognostic factors include age at diagnosis, mental status, and performance status (see Table 32.4). Patients with anaplastic oligodendroglioma have a better prognosis, particularly those with tumor containing the chromosome changes characterized by loss of heterozygosity of 1p and 19q for whom median survival is approximately 5 to 7 years (27,254). The prognosis for patients with a mixed tumor, anaplastic oligoastrocytoma, varies depending on the dominant histological cell type (55).
Molecular Genetics
Allelic loss of 1p and 19q is thought to be an early genetic alteration in the transformation and progression of oligodendrogliomas. Combined 1p and 19q deletions have been found in 63% of patients with anaplastic oligodendroglioma and 52% of patients with mixed anaplastic oligoastrocytoma, whereas astrocytic tumors have a low incidence (8% to 11%) of combined 1p and 19q deletions (224). Deletions in 1p and 19p have been associated with longer progression-free survival and chemo- and radiosensitivity (8,28,224).
This has been confirmed in two recent phase III trials. RTOG 94-02 assessed 1p and 19q status in 206/289 enrolled patients (71%) with anaplastic oligodendroglioma/oligoastrocytoma randomized to receive chemotherapy with procarbazine, CCNU, and vincristine (PCV) followed by radiotherapy or radiotherapy alone (27). Combined loss of 1p and 19q was present in 43% of patients in the PCV plus radiotherapy arm and 50% in the radiotherapy alone arm. Combined loss of 1p and 19q resulted in a longer median survival time of >7 years versus 2.8 years (p <.001). There was no effect of tumor genotype on overall survival by treatment. The addition of PCV to radiotherapy did not improve survival for any patient subgroup. However, there was a lower risk of progression in patients with 1p and 19q deletions after treatment with PCV plus radiotherapy, providing indirect evidence that allelic loss of 1p and 19q may be predictive for chemotherapy response.
In EORTC 26951 368 patients with anaplastic oligodendroglioma/oligoastrocytoma were randomized to receive radiotherapy followed by PCV or radiotherapy alone (254). Patients with codeletions of 1p and 19q had significantly longer overall survival irrespective of treatment, but in contrast to the RTOG trial, the addition of PCV did not result in a better outcome compared to radiotherapy alone. Presence of 1p or 19q loss was found to be the most important predictor of outcome, with a hazard ratio of 0.27, confirming that patients with loss of 1p or 19q represent a unique biologic subset.
Treatment
The current standard of care for patients with anaplastic gliomas is maximal surgical resection followed by postoperative radiotherapy (259). The radiotherapy target volume and dose are the same as for GBM.
Chemotherapy
Adjuvant chemotherapy has been justified on the basis of prospective trials and a meta-analysis showing a small long-term survival benefit in patients with anaplastic glioma treated with alkylating agents (231,259). However, because treatment is associated with significant toxicity and because of the marginal
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survival benefit, the use of chemotherapy has not been universally adopted.