Brain Cancer Treatment Protocols

Safe surgical resection is the primary treatment for all grades of gliomas, a category of brain tumor whose most malignant grades are considered to be cancer. The surgical goal is gross total resection; less aggressive resection is employed for tumor potentially involving eloquent brain. Under certain circumstances, weighing risk versus benefit, expectant monitoring with serial imaging is used.

There is significant divergence of opinion on treatment approaches, particularly for grade II lesions, such as grade II astrocytoma. Radiation and chemotherapy regimens may vary among institutions. Those cited below represent treatment approaches from recent clinical trials. Seizure treatment or prophylaxis is commonly appropriate. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]}

Information about treatment and clinical trials is available at https://virtualtrials.com.

Glioma treatment recommendations based on grade

Grade I (pilocytic astrocytomas):

• These uncommon lesions are typically noninvasive and are considered benign and potentially curable by surgery; when total surgical removal is not possible, radiation therapy or expectant management is typically employed.

Grade II (low-grade infiltrative astrocytomas, oligodendroglioma, mixed gliomas):

• Surgery is recommended for grade II with maximal safe resection.

• Unfavorable prognostic factors include age > 40y, astrocytoma histology, largest dimension of tumor ≥6 cm, tumor crossing midline, and presence of neurologic deficit before resection; patients with up to 2 of these are considered low risk, while patients with 3 or more are high risk. In contrast, certain molecular features are favorable prognostic markers in grade II–III gliomas: 1p19q codeletion correlates with greatly improved progression-free and overall survival, and the presence of an IDH mutation is a strongly favorable prognostic marker for overall survival. ^[13]

• Low-risk patients should undergo observation, as well as patients who are ≤40 y; high-risk patients should be treated with fractionated external-beam radiation therapy (EBRT) or adjuvant chemotherapy. ^[13]

• The standard radiation dosage for low-grade astrocytomas is 45-54 Gy, delivered in 1.8 to 2.0 Gy fractions ^[13]

• Adjuvant therapy includes temozolomide 150-200 mg/m²/day PO on days 1-5 of a 28-d cycle for six to eight cycles ^{[14, 15]}

• Recurrences or progressive, low-grade disease (previously untreated): Temozolomide 75 mg/m² PO daily on days 1-21 or 150-200 mg/m² PO on days 1-5 of a 28-d cycle until disease progression or for a maximum of 24 cycles ^{[15, 16]}

• Postoperative radiation therapy is often employed for unresectable, residual, or recurrent tumor

• Chemotherapy is often used for low-grade oligodendrogliomas, particularly tumors with the 1p19q deletion, which is a marker for tumor susceptibility to chemotherapy ^{[1, 2, 3]}

Grade III (anaplastic astrocytoma or oligoastrocytoma):

• The standard of care is surgical resection followed by EBRT (60 Gy in 30-35 fractions) and adjuvant temozolomide, 75 mg/m²/day PO on days 1-42, usually 1-1.5 h before radiation ^{[6, 7, 8, 9]}

• Post–radiation therapy: Continue temozolomide at higher doses of 150-200 mg/m²/day PO on days 1-5 every 28 d or

• PCV (procarbazine, lomustine, vincristine): lomustine (CCNU) 90-130 mg/m² PO on day 1 plus  procarbazine 60-75 mg/m² PO on days 8-21 plus  vincristine 1.4 mg/m² IV (not to exceed 2 mg/dose) on days 8 and 29; administer every 6 wk for up to four cycles ^{[4, 5, 6, 17]} with deferred radiation therapy

Grade IV (glioblastoma):

• The standard of care is surgical resection followed by EBRT (60 Gy in 30-35 fractions) and adjuvant temozolomide 75 mg/m²/day PO on days 1-42, usually 1-1.5h before radiation ^{[6, 7, 8, 9, 18]}

• Concurrent treatment with adjuvant temozolomide and alternating electric fields is a National Comprehensive Cancer Network category 1 recommendation for treatment of newly diagnosed glioblastoma in patients 70 years of age or younger who have a good performance status (PS), and is considered a reasonable treatment option for patients older than 70 years of age with good PS. ^[13]

• Postradiation therapy: Continue temozolomide at higher doses of 150-200 mg/m²/day PO on days 1-5 every 28 d ^[19]

Recommendations for recurrent tumors

Consider the following:

• There is no standard therapy for recurrent glioma
• Patients who were spared radiation therapy or chemotherapy commonly receive these therapies at recurrence
• Numerous agents are used in cases of primary treatment failure
• Surgical debulking may be useful prior to experimental therapies
• Many clinical trials are ongoing

Current avenues available include the following:

• Antiangiogenic agents
• Tyrosine kinase inhibitors
• Cancer vaccines
• Stereotactic radiosurgery ^[18]