Glioma Treatment Guidelines

Introduction to Glioma Classification and Diagnosis

Gliomas are classified according to the WHO grading system, which includes Grade I-II: Low-grade gliomas, Grade III: Anaplastic gliomas, and Grade IV: Glioblastoma multiforme (GBM) 1
Diagnosis is made through MRI imaging of the brain, tissue diagnosis via biopsy or surgical resection, and molecular testing (MGMT methylation status, 1p/19q co-deletion) 1

Tumor grade and histology, age, performance status, and neurological function influence prognosis and treatment decisions, with lower grade and younger age having better prognosis 1, 2, 3
Molecular markers such as 1p/19q co-deletion and MGMT promoter methylation status are important for treatment decisions, with 1p/19q co-deletion being favorable in oligodendrogliomas and MGMT promoter methylation predicting better response to temozolomide 1, 3, 2
Patients with 1p and 19q deletions have better prognosis and improved response to chemotherapy 3
MGMT gene promoter methylation testing may help select patients likely to benefit from temozolomide 2, 3
Young age at diagnosis (<7 years) is a significant risk factor for neurocognitive impairment 4

Maximal safe surgical resection is the initial approach for debulking and obtaining tissue for diagnosis, with post-operative MRI within 24-48 hours to assess residual disease 1, 3, 2
Goals of surgical resection include obtaining tissue for accurate diagnosis, achieving maximal tumor debulking, and improving prognosis through tumor resection 2
Consider repeat surgery for selected patients with recurrent disease 2, 3
Goal of surgical resection is gross total resection (GTR) or near-total resection (NTR) with <1.5 cm² residual disease 5

Standard treatment includes fractionated focal radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide (75 mg/m² daily) followed by adjuvant temozolomide, which has demonstrated significant improvement in median and 2-year survival 3, 2
For elderly patients (>70 years) or those with poor performance status, shorter hypofractionated regimens (e.g., 40 Gy in 15 fractions) are recommended 3
Concomitant and adjuvant temozolomide has demonstrated significant improvement in median and 2-year survival for high-grade malignancies 2, 3
Temozolomide with radiation therapy is recommended for glioblastoma 3

Radiotherapy is standard treatment, with options including radiotherapy alone, radiotherapy with concurrent and adjuvant temozolomide, and chemotherapy alone for selected patients 1, 3
PCV (procarbazine, lomustine, vincristine) chemotherapy has shown efficacy in anaplastic oligodendroglioma and oligoastrocytoma 1
Anaplastic astrocytoma is more likely to respond to chemotherapy than glioblastoma 3

Five therapeutic options can be considered, including repeat surgery, systemic chemotherapy, local chemotherapy, second-line radiotherapy, and palliative care without specific anticancer treatment 1, 3
Clinical trials are strongly recommended for patients with recurrent disease, as established options are limited 3
Consider chemotherapy for recurrent disease, including ifosfamide/paclitaxel combination which has shown increased survival (13.5 months) compared to ifosfamide alone (8.4 months) 6
Maximal safe resection should be attempted for recurrent tumors, with chemotherapy options including etoposide-containing regimens, temozolomide, and high-dose chemotherapy with autologous stem cell rescue 7

Fractionated focal radiotherapy (60 Gy, 2 Gy × 30 fractions) is standard treatment after resection or biopsy for many malignant neoplasms 2, 3
Modified approaches for specific populations include shorter hypofractionated regimens (e.g., 40 Gy in 15 fractions) for elderly patients or those with low performance status 3
Patients >70 years: 28 × 1.8 Gy (50 Gy) has shown superior outcomes to best supportive care alone 3
CSI dose: 23.4 Gy with boost to posterior fossa/tumor bed to 54 Gy 5
Higher dose CSI: 36 Gy with boost to posterior fossa/tumor bed to 54-55.8 Gy 5
Proton beam therapy is strongly recommended over conventional radiotherapy when available, particularly for pediatric patients, due to reduced radiation to normal tissues while maintaining equivalent tumor control 8

Concomitant and adjuvant temozolomide has demonstrated significant improvement in median and 2-year survival for high-grade malignancies 2, 3
Temozolomide with radiation therapy is recommended for glioblastoma 3
PCV (procarbazine, lomustine, vincristine) chemotherapy has shown efficacy in anaplastic oligodendroglioma and oligoastrocytoma 1
For Group 3 high-risk tumors: Carboplatin during radiation improves event-free survival by approximately 19% 5
Post-radiation cisplatin-based chemotherapy regimens have shown 86% 5-year survival in pediatric patients 7

Prophylaxis against Pneumocystis pneumonia (PCP) is required for all patients receiving concomitant temozolomide and radiotherapy, and regular monitoring of blood counts is necessary during treatment 1
Anticoagulant prophylaxis with low-molecular weight heparin and compression stockings is recommended for preventing perioperative thromboembolic complications 1
Liver function tests should be performed at baseline, midway through the first cycle, prior to each subsequent cycle, and after treatment completion 1
Monitor for late effects including neurocognitive deficits, endocrine dysfunction, and secondary malignancies 4
Female patients should receive fertility preservation counseling due to risk of menstrual disorders and infertility 5
Brain MRI every 3 months for first 2 years, biannual brain MRI for next 3 years, and annual brain MRI thereafter 7

Pseudoprogression, radiographic worsening 4-8 weeks after radiation, may mimic tumor progression and should be re-evaluated after 4 weeks 3
MGMT testing is important, but treatment should not be withheld based solely on unmethylated status in the absence of better alternatives 3
Elderly patients should not be excluded from treatment based on age alone, and hypofractionated radiotherapy with or without temozolomide has shown benefit in patients >70 years 3
The optimal treatment for malignant neoplasms requires a specialized multidisciplinary team approach with initial surgical resection followed by appropriate adjuvant therapy based on tumor type, grade, and stage to maximize survival outcomes 2, 3
Rebiopsy is recommended for late recurrences (>3-5 years) to rule out secondary malignancies 5
For children <3 years, radiation-sparing approaches are recommended 5
The National Comprehensive Cancer Network recommends a risk-stratified approach with maximal safe surgical resection followed by craniospinal irradiation (CSI) and adjuvant chemotherapy to optimize survival outcomes while minimizing toxicity 5
Risk stratification is critical for determining appropriate radiation and chemotherapy regimens, with factors including M0 disease (no metastasis), classic histology, and GTR or NTR 5
M+ disease (metastatic), subtotal resection (STR), large cell/anaplastic histology, and MYC amplification are also considered in risk stratification 5