Lowgrade Gliomas

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Low-grade gliomas are a heterogeneous group of brain tumors that have varied pathology and location. Included in this group are WHO grade 1 and 2 tumors, pilocytic astrocytomas, fibrillary, gemis-tocytic, and mixed variants. Less common are the pleomorphic xanthroastrocytomas and subependymal giant cell astrocytomas [9]. Optic pathway gliomas are also considered to be low-grade gliomas and are discussed separately in the next section.

Pilocytic astrocytomas (WHO grade I) are the most common histopathologic grouping of the low-grade gliomas. They are characterized by compact and spongy regions consisting of elongated cells surrounding spongy loose areas in which stellate astrocytes are observed. Necrosis, hemorrhage, and Rosenthal fibers may be found. They are often micro-cystic or may have a single large cyst with a tumor nodule. The diffuse astrocytoma (fibrillary pattern) has meningeal fibrils which impact a firm consistency to the tumor. Mitoses are absent and there is no endothelial proliferation. Gemistocytic astrocytomas have homogeneous, lightly eosinophilic cytoplasm. They have a tendency to dedifferentiate into glio-blastoma multiforme [10].

Surgery is the treatment of choice for these tumors. For patients with a total excision, prognosis is excellent. For some patients, tumor location or size can preclude complete surgical excision. In these instances, additional treatment may be necessary for progressive or symptomatic patients. Treatment options for these patients include radiation therapy or chemotherapy. Side effects from radiation therapy can be detrimental to young children, and can negatively affect intellectual functioning, growth, and endocrino-logic function [11]. The role of chemotherapy in the treatment of progressive or symptomatic low-grade tumors in young children has, therefore, been expanded in an effort to spare them the effects of radiation therapy. In a Phase II Children's Oncology Group randomized study, patients with progressive

Pea Sized Brain Tumors Mri Top Skull
FIGURE 36.1 MRI scan of a seven-year-old patient with low-grade astrocytoma. Top: MRI done at diagnosis. Bottom: MRI done after treatment with vincristine/carboplatin for one year.

or recurrent brain tumors were randomized to receive either carboplatin or iproplatin. Patients were given carboplatin 560 mg/m2 at four week intervals or iproplatin 270 mg/m2 at three week intervals. Twenty-four patients on the study had low-grade astrocytic neoplasms. Overall, 71 per cent of the patients with low-grade astrocytomas had response to these agents. It was noted that patients treated with carboplatin had sustained stable disease (median 40+ months) as compared with iproplatin (median 7 months). Major toxicities of therapy included myelosuppression, particularly thrombocytopenia, and ototoxitity [12]. Results from this study confirmed the potential use of carboplatin in future chemotherapy regimens for low-grade gliomas.

Vincristine and carboplatin have also been used together for the treatment of low-grade gliomas (Fig. 36.1). Twenty-three children with recurrent and thirty-seven children with newly diagnosed low-grade gliomas were treated with a ten week induction of weekly carboplatin (175 mg/m2) and vincristine (1.5 mg/m2) followed by maintenance treatment with the same drugs. Fifty-two percent of the children with recurrent disease had an objective response to treatment and 62 per cent of newly diagnosed patients had an objective response. Hematologic toxicity, specifically thrombocytopenia, was the most common therapy induced toxicity, resulting in one patient being removed from the study. Six children had allergic reactions, presumably to the carbo-platin [13]. Follow-up studies confirmed a 3-year progression-free survival rate of 74 per cent in newly diagnosed children less than five years old. Older patients demonstrated only a 39 per cent progressionfree survival rate. There was no difference in response in those patients with Neurofibromatosis Type I. A current study in the Children's Oncology Group randomizes patients to receive either vincristine/ carboplatin or thioguanine/procarbazine/CCNU/ vincristine for progressive or symptomatic tumors in children less than ten years old. Results from this study are still pending. More recently, temozolomide has shown promising results in adult patients with gliomas. Although more commonly used in high-grade gliomas, the efficacy of temozolomide is being evaluated in the low-grade gliomas.

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