What is the standard system for glioma staging and treatment?

Glioma Staging and Treatment System

The 2000 World Health Organization (WHO) classification is the standard for diagnosis and histoprognostic grading of glioma, which categorizes tumors based on histological type and malignancy grade from WHO grade I-IV. 1

Diagnostic Approach

Imaging

• MRI should be performed with and without intravenous contrast medium as the primary diagnostic tool, preferred over CT scanning 1
• Required imaging sequences include T1-weighted (with and without contrast medium), T2-weighted MR images and/or fluid-attenuated inversion recovery (FLAIR) 1
• Three-dimensional scans should be taken using the same technique and converted to digital format for possible subsequent dosimetric studies 1
• Additional imaging options include functional MRI, diffusion imaging, perfusion studies, and proton MR spectroscopy 1
• PET or SPECT scans can be considered in clinical trial settings 1

Histological Confirmation

• Histological confirmation is mandatory as neuroradiological investigations are not sufficiently specific 1
• The surgeon must ensure samples are representative of the lesion, particularly from areas of contrast enhancement 1
• Sample quality must be sufficient to allow histological diagnosis (type and grade) and molecular-biological/cytogenetic investigations 1
• Samples should be processed immediately by the pathologist with appropriate fixation methods 1

WHO Classification System

Histological Grading

• WHO Grade I: Benign, slow-growing tumors (e.g., pilocytic astrocytoma) with circumscribed growth and favorable prognosis 2, 3, 4
• WHO Grade II: Low-grade diffuse gliomas with infiltrative growth pattern and potential for malignant transformation 2, 3, 4
• WHO Grade III: Anaplastic gliomas with increased mitotic activity and cellular atypia 2, 3
• WHO Grade IV: Glioblastoma, the most aggressive form with necrosis and/or microvascular proliferation 2, 3, 5

Molecular Classification

• IDH-mutant, 1p/19q co-deleted tumors (mostly oligodendroglial morphology) - best prognosis 2, 3
• IDH-mutant, 1p/19q non-co-deleted tumors (mostly astrocytic histology) - intermediate outcome 2, 3
• IDH wild-type tumors (mostly higher WHO grade III or IV) - poor prognosis 2, 3

Treatment Approach by Tumor Type

Pilocytic Astrocytoma (WHO Grade I)

• Complete surgical resection significantly improves survival and often cures patients 1
• If complete resection is achieved, simple clinical follow-up is indicated 1
• For incomplete resection, annual follow-up with clinical and MRI assessment should be undertaken 1
• When progression occurs after incomplete resection, radiotherapy and/or chemotherapy can be considered 1

Diffuse Low-Grade Gliomas (WHO Grade II)

• Optimal surgical resection should be attempted when feasible 1
• For IDH-mutant astrocytomas, treatment options include observation, radiotherapy, or chemotherapy based on risk factors 1
• For oligodendrogliomas (IDH-mutant, 1p/19q co-deleted), treatment may include observation or radiotherapy followed by PCV (procarbazine, lomustine, vincristine) or temozolomide 1

Anaplastic Gliomas (WHO Grade III)

• Maximal safe resection should be attempted 1
• For anaplastic astrocytomas, standard treatment includes radiotherapy followed by temozolomide 1
• For anaplastic oligodendrogliomas, radiotherapy followed by PCV improves long-term survival 5

Glioblastoma (WHO Grade IV)

• Maximal safe surgical resection should be performed whenever feasible 1, 6
• Standard treatment includes fractionated radiotherapy (60 Gy in 2-Gy fractions) with concurrent temozolomide (75 mg/m² daily) followed by adjuvant temozolomide (150-200 mg/m², 5 out of 28 days) 1, 6, 7
• For elderly patients (≥70 years), hypofractionated radiotherapy (40 Gy in 15 fractions) with or without temozolomide based on MGMT promoter methylation status is recommended 1, 6

Radiation Therapy Guidelines

• Clinical tumor volume (CTV) should include a safety margin of 20 mm outside the gross tumor volume (GTV) 1, 8
• This safety margin can be reduced depending on grade, histological type, and tumor volume 1, 8
• Non-coplanar focalized multiple beam (3-5) should be used to minimize dose to non-diseased brain 1, 8
• All fields should be irradiated the same day with fractionated doses of 1.8-2 Gy per fraction, five times per week 1, 8
• Total dose should be adapted according to histological type and grade, not exceeding 60 Gy 1, 8

Follow-up Monitoring

• After surgical removal, MRI should be performed within 72 hours to assess residual tumor 1
• MRI is preferable to CT scanning for follow-up of disease progression 1
• Clinical and imaging follow-up should be performed at 2-3 month intervals initially, with potential for longer intervals in stable cases 1, 6
• Pseudoprogression should be considered if MRI changes are noted within 6-9 months after radiotherapy 6

Prognostic Factors

• Favorable prognostic factors include younger age, good performance status, extent of resection, and molecular markers such as MGMT promoter methylation and IDH mutation 6, 5
• Molecular testing should include MGMT promoter methylation status and IDH mutation status to guide treatment decisions 6, 5

Common Pitfalls and Caveats

• Pseudoprogression can occur within 3 months of chemoradiotherapy and should not be misinterpreted as treatment failure 1
• Clinical and/or radiological deterioration in the 2 months after radiotherapy should be interpreted with caution 8
• Patients over 50 years and/or with vascular disease have increased risk for late neurological complications 8
• Review of histology by an expert committee is recommended for difficult samples and in clinical trials 1