Oligodendroglioma

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Abstract

Oligodendrogliomas (OD) are rare, diffusely infiltrating tumors, arising in the white matter of cerebral hemispheres, and displaying better sensitivity to treatment and prognosis than other gliomas. Favorable prognostic factors are low-grade, combined loss of 1p/19q, younger age, good performance status, and frontal localization. Low-grade OD usually present with seizures, whereas high-grade tumors often present with focal deficits, increased intracranial pressure or cognitive deficits. Treatment may be deferred until progression in young patients with low-grade OD presenting with seizures only. Patients with enhancing lesions, mass effect, focal deficits or increased intracranial pressure should be treated without delay. Treatment consists of resection as extensive and as safe possible. Postoperative radiotherapy is indicated for large, unresectable, or incompletely resected tumors; focal deficits; anaplastic tumors; or enhancing lesions. Adjuvant PCV chemotherapy increased progression-free survival but does not improve survival as compared to PCV given at recurrence. Chemotherapy with either PCV or temozolomide constitutes a standard for recurrent/progressive disease.

Section snippets

Incidence, age at presentation

Oligodendroglioma (OD) constitutes 5–20% of all glial tumors and about 1500 new cases are diagnosed in Europe each year. OD is a rare tumor with an annual incidence rate of 0.2 per 100,000 people in Europe [1]. They are predominantly a tumor of adulthood, with a peak incidence between the fourth and sixth decade of life. About 55% of all cases are between 40 and 64 years of age. In Europe, the annual incidence is 0.4 per 100,000 for this age group [1]. Low-grade OD tends to arise in slightly

Histology

Most OD arises in the white matter of cerebral hemispheres, predominantly in the frontal lobes. They can arise, however, throughout the CNS, including infratentorial sites and the spinal cord. They diffusely infiltrate brain tissue but, in contrast to astrocytoma, areas of remarkable sharp borders with surrounding brain tissue can often be found. The current WHO definition of oligodendroglioma is “a well-differentiated, diffusely infiltrating tumor of adults, typically located in the cerebral

Diagnosis

The clinical signs and symptoms of OD are unspecific, and depend on the localization and progression of the tumor. They may present with seizures, cognitive deficits, or focal deficits. Low-grade OD tend to present with seizures, whereas patients with high-grade tumors often present with focal deficits, increased intracranial pressure or cognitive deficits early in the course of the disease. On magnetic resonance imaging (MRI), low-grade ODs show increased signal intensity on T2-weighted images

Staging

Similarly to other astrocytomas, OD tend to remain localized to the CNS. Extra-CNS metastasis (especially bone metastasis) has been described but this is very rare and occurs in the occasional patient only at later stages of the disease. Leptomeningeal spread is less rare, but again usually does not develop until the time of recurrence. Therefore, there is no need for routine specific staging procedures (like craniospinal axis imaging or CSF sampling). In patients with recurrent disease the

Histology

Pure oligodendroglial tumors have a better prognosis than astrocytic tumors of the same grade; the prognosis of mixed oligoastrocytoma appears to be in between these histologies. Most likely, this is the result of underlying genetics (absence or presence of 1p/19q co-deletion; see below). Despite the relatively favorable clinical prognosis of OD, the outcome is ultimately fatal for virtually all patients.

Tumor grade

Prior to the era of genetics, tumor grade was the single most important prognostic factor

Long-term sequelae

Cognitive and focal neurological deficits may have a great impact on long-term survivors of brain tumors, regardless of the histology and grade of the tumors. Memory loss, apathy, concentration difficulties and personality changes may have a profound effect even in those patients who appear to have a Karnofsky performance status of 100. Surgery in so-called silent areas may contribute to cognitive deficits. Less clear are the late effects of radiation therapy on cognitive function. Radiotherapy

Follow-up

No general guidelines for the follow-up of OD can be given, these should be tailored to the individual patient taking tumor grade, genotype, previous treatments and remaining treatment options into account. Low-grade glioma patients should be followed, even if the lesion is stable for many years. At some point in time, progression will occur and treatment should be installed before irreversible deficits occur. To avoid significant undetected progression, it is recommended to make follow-up

Conclusions

Oligodendroglioma, in particular with 1p/19q loss have a more indolent clinical behaviour, are more sensitive to treatment and have a better overall prognosis compared to astrocytoma or non-1p/19q deleted oligodendroglial tumors of similar grade. This implies that more treatment options are available, but also that delayed side effects of treatment are a potential issue. Because of the better outcome and the relative rarity of the disease studies into this tumor type are very difficult and

Reviewers

Dr. Roger Stupp, Multidisciplinary Oncology Center, CHUV, Vaud University Hospital, 46, rue du Bugnon, CH-1011 Lausanne, Switzerland

Prof. Pierre-Yves Dietrich, Department of Oncology, University Hospital of Geneva, Rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland

Acknowledgments

The authors thank the members of the EUROCARE Working Group for permitting the survival analysis from the EUROCARE dataset.

Martin J van den Bent is head of the neuro-oncology unit of the Daniel den Hoed Cancer Center in Rotterdam, the Netherlands, and chair of the European Organisation of Research and Treartment of Cancer (EORTC) Brain Tumor Group. He has conducted several clinical trials on oligodendroglial tumors.

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    Martin J van den Bent is head of the neuro-oncology unit of the Daniel den Hoed Cancer Center in Rotterdam, the Netherlands, and chair of the European Organisation of Research and Treartment of Cancer (EORTC) Brain Tumor Group. He has conducted several clinical trials on oligodendroglial tumors.

    Michele Reni is coordinator of the clinical research and vice director of the Medical Oncology Unit, San Raffaele Scientific Institute, Milan, Italy.

    Gemma Gatta is Assistant Researcher in the Unit of Epidemiology of Istituto Nazionale Tumori, Milan, Italy. She is involved in projects with population-based cancer registries on incidence, survival and prevalence.

    Charles J. Vecht (1947) is a neurologist–oncologist at the Medical Centre The Hague in The Netherlands, where he is the coordinator of the Hospital Neuro-oncology Program. Dr. Vecht's clinical research focuses mainly on primary brain tumors with a special interest for epilepsy associated with cancer.

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