Approach Considerations
The treatment recommendations for oligodendrogliomas are based largely on studies completed prior to the use of 1p/19q as a definitive marker for the disease. Currently, the standard treatment is maximum safe surgical resection, followed by either observation in “low-risk” patients (patients with gross total resection who are younger than 40 years) and upfront radiation and chemotherapy with either PCV or temozolomide in “high-risk” patients (patients with either subtotal resection or age older than 40 years). These recommendations may change with newer studies as 1p/19q co-deletion may prove to be a factor contributing to “low risk” of recurrence.
Medical Care
Medical and surgical treatment of oligodendrogliomas depends on the presence or absence of symptoms, location and biological aggressiveness of the tumor, extent of possible surgical resection, age of the patient, and histopathology and degree of anaplasia. Treatment options vary from conservative treatment of some patients with serial imaging studies and no intervention to aggressive multimodal treatment including surgical resection, radiotherapy, and chemotherapy in others.
Patients with low-grade gliomas, which include grade 2 oligodendrogliomas, have classically been stratified into “high risk” and “low risk” categories, with risk referring to risk of tumor progression or recurrence. “Low-risk” patients have a better prognosis than “high-risk” patients. See Prognosis.
“Low-risk” patients can sometimes defer treatment with radiation and chemotherapy with radiographic and clinical surveillance only, while “high-risk” patients have shown benefit with upfront adjuvant treatment. [3] Notably, this risk stratification is debated, especially now in the era of precision medicine and genetic markers for diagnosis.
Anti-epileptic medications are used in patients who have had seizures; empiric anti-epileptic therapy is not recommended.
Radiation therapy
The CODEL trial is investigating patients with grade 3 oligodendrogliomas, 1p/19q co-deleted. Investigators initially compared treatment with RT alone, RT plus concomitant and adjuvant temozolomide, and temozolomide alone. Interim analysis revealed that patients who received RT had significantly increased survival compared to patients who received TMZ alone without RT. For this reason, radiotherapy in combination with chemotherapy rather than chemotherapy alone is recommended in patients undergoing upfront treatment. [7] However, this trial is currently ongoing comparing with modified treatment arms and should establish the comparative efficacy of RT plus adjuvant PCV versus RT plus concomitant and adjuvant temozolomide.
Shaw et al found that for oligodendroglioma patients with 2-year survival (more benign tumors), the probability of overall survival for an additional 5 years was 74% with combination therapy compared to 59% with radiotherapy alone. [8]
One study suggests that patients with oligodendroglioma are at higher risk of developing radiation necrosis (RN). Of the cohort of 319 patients, 41 patients were identified as having RN (12.9%): 28 patients (21.3%) with oligodendroglioma and 13 (6.9%) with astrocytoma (HR 3.42, p < 0.001). Patients with oligodendroglioma who received > 54 Gy had a higher incidence (31.2%) than those receiving ≤ 54 Gy (14.3%, HR 6.9, p = 0.002). [9]
Chemotherapy
The role of chemotherapy for the treatment of oligodendroglioma was well established by several studies using nitrosourea-based therapy. [10] Most used procarbazine, lomustine (CCNU), and vincristine, a combination chemotherapy regimen (ie, PCV) developed by Levin and coworkers. [11] The RTOG 9802 trial investigated the use of radiation therapy alone versus radiation therapy followed by PCV in patients with grade 2 gliomas who were “high risk” as defined above (at the time, 1p/19q co-deletion status was not a requirement for differentiation of oligodendrogliomas from other gliomas). The rate of progression-free survival was 51% at 10 years in the radiation + PCV group versus 21% in the radiation only group. [4] For this reason, combination chemotherapy and radiation therapy is advised.
Several studies have evaluated the role of temozolomide as second-line chemotherapy for recurrent oligodendroglioma and showed a response rate of about 25% for patients relapsing after PCV therapy. The EORTC study evaluated temozolomide as a first-line chemotherapy for recurrent oligodendroglial tumors and showed a response rate of 54%, with 39% of patients remaining free from progression at 12 months. [12] . A subsequent EORTC study investigated the response rate of “high risk” grade 2 gliomas to either radiation therapy or neoadjuvant temozolomide and although there was a progression-free survival benefit for patients who received RT, this benefit did not reach statistical significance. [13] The more recent CODEL trial evaluated patients with grade 3 oligodendrogliomas, 1p/19q co-deleted. They initially compared treatment with RT alone, RT plus concomitant and adjuvant temozolomide, and temozolomide alone. Interim analysis revealed that patients who received RT had significantly increased survival compared to patients who received TMZ alone without RT. Future results from this trial will help guide chemotherapeutic treatment for these tumor types. [7]
Preliminary findings from a phase III study reported by Cairncross et al, comparing radiation therapy versus chemotherapy plus radiation in patients with newly diagnosed anaplastic glioma, showed overall similar survival in both groups (4.8 y for radiotherapy plus chemotherapy group vs 4.5 y for radiotherapy alone). However, disease progression-free interval was longer for the combined therapy group (2.6 y vs 1.9 y for radiotherapy alone group). [14]
Targeted therapy
As oligodendrogliomas are by definition IDH-mutated, investigations into IDH-targeted therapies have been undertaken. Enasidenib and ivosidenib are medications currently used for IDH-mutant acute myeloid leukemia. It is currently unclear how IDH mutations contribute to glioma formation and growth. Studies are currently ongoing investigating the use of this targeted therapy in IDH-mutated gliomas.
Surgical Care
Historically, surgery has been the mainstay of treatment for oligodendrogliomas. The extent of resection depends in large part on the location of the tumor and its proximity to "eloquent" brain areas. If possible, the goal is total resection of the tumor. In patients who undergo gross total resection and have features of low risk for recurrence (age< 40), no further treatment may be necessary, but the patient must be followed closely for clinical or radiologic recurrence. In patients with high risk for recurrence (subtotal resection, age > 40), upfront treatment with radiation therapy and chemotherapy is advised.
Long-Term Monitoring
Further inpatient care
After the initial surgical resection and rehabilitation, the patient may require further inpatient care depending on the development of complications from either therapy or tumor recurrence. Appropriate intervention also depends on the nature of complications (eg, surgery for recurrence, steroid therapy for increased vasogenic edema).
Inpatient and outpatient medications
Patients with seizures require appropriate seizure medications even after surgery. Over time, the dose of the medications can be reduced, depending on the frequency of seizures.
Transfer
Transfer depends on the residual neurological deficit. The patient may be fully ambulatory or may need appropriate transfer arrangements (eg, cane, wheelchair).
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Classic histologic image of oligodendroglioma. This image shows monomorphous tumoral proliferation that consists of round, regular cells with a small, central, hyperchromatic nucleus surrounded by clear cytoplasm. Few calcifications are present.
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Smear preparation of anaplastic oligodendroglioma. This image reveals increased nuclear pleomorphism and vascular proliferation.
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Contrast-enhanced computed tomography scan in a 44-year-old man with a 3-year history of epileptic seizures. This image reveals a calcified hypoattenuating lesion that is invading the corpus callosum.
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Computed tomography scan of a low-grade oligodendroglioma. This image reveals a well-demarcated, left frontal hypoattenuating lesion with a small calcification.
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Sagittal gadolinium-enhanced T1-weighted magnetic resonance image of a low-grade oligodendroglioma. This image demonstrates no contrast enhancement.
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Oligodendrogliomas. This tumor exhibits oligodendroglial-type nuclei and scanty eosinophilic fibrillar cytoplasm amidst a mucinous background. Such tumors may be considered oligoastrocytomas.
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Oligodendrogliomas. The classic appearance of the oligodendroglioma is that of a round to oval, water-clear cytoplasm ringing about round to lobulated nuclei. The chromatin appearance is finely threadlike to smudgy, often associated with pointlike basophilic chromocenters, rather than nucleoli.
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Oligodendrogliomas. The cellular density is moderate to high, and the fried-egg appearance dominates the histologic features.
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Oligodendrogliomas. Oligodendrogliomas with vascular proliferation and significant mitotic activity are best considered to be anaplastic oligodendrogliomas (World Health Organization [WHO] grade III).
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Oligodendrogliomas. Anaplastic oligodendrogliomas frequently take on eosinophilic cytoplasm and hyperchromasia of the nuclei. Such tumors may demonstrate necrosis among its diagnostic features.
