What is the recommended management for adult patients with World Health Organization grade II diffuse astrocytoma or oligodendroglioma, including criteria for observation versus adjuvant radiotherapy and chemotherapy?

Management of WHO Grade 2 Astrocytoma and Oligodendroglioma

For WHO grade 2 IDH-mutant astrocytomas, offer radiotherapy (50-54 Gy) followed by adjuvant chemotherapy (PCV or temozolomide), and for WHO grade 2 IDH-mutant, 1p/19q-codeleted oligodendrogliomas, offer radiotherapy combined with PCV chemotherapy, with both tumor types allowing observation in select low-risk patients (young age, gross total resection, minimal symptoms). 1

Initial Surgical Management

Maximal safe surgical resection is the foundation of treatment for all grade 2 gliomas. 1, 2

• Pursue gross total resection whenever achievable without causing neurological deficits 1, 2
• Extent of resection directly impacts progression-free and overall survival 3, 4
• Consider re-resection before initiating adjuvant therapy if additional tumor removal could convert subtotal to gross total resection 2, 5

WHO Grade 2 IDH-Mutant Astrocytoma (1p/19q Non-Codeleted)

Standard Treatment Approach

Offer radiotherapy (50-54 Gy in 1.8-2 Gy fractions) followed by adjuvant chemotherapy with either PCV or temozolomide. 1

• The RTOG 9802 trial demonstrated that radiotherapy plus PCV increased median overall survival from 7.8 years to 13.3 years in high-risk grade 2 gliomas 1, 2
• This survival benefit was observed across histological subgroups including IDH-mutant astrocytomas 1
• Temozolomide is an acceptable alternative to PCV when toxicity concerns exist, though evidence supporting temozolomide is less robust 1

Criteria for Observation ("Watch-and-Wait")

Defer initial therapy in patients meeting ALL of the following criteria: 1

• Age < 40 years (pragmatic cutoff ~40-45 years) 1, 2
• Gross total resection achieved 1
• Asymptomatic or seizures only (no focal neurological deficits) 1, 2
• Concerns about short- and long-term treatment toxicity 1

Mandatory Treatment Indications

Proceed immediately with adjuvant therapy if ANY of the following are present: 1, 2

• Age ≥ 40 years (regardless of resection extent) 1, 2
• Incomplete/subtotal resection (any age) 1, 2
• Symptomatic disease beyond seizures (focal deficits, progressive headaches) 2

Critical Caveat About Early Radiotherapy

Early radiotherapy prolongs progression-free survival but does NOT improve overall survival compared to radiotherapy administered at progression in completely resected tumors. 1, 5 This supports observation in appropriately selected low-risk patients rather than reflexive immediate treatment.

WHO Grade 2 IDH-Mutant, 1p/19q-Codeleted Oligodendroglioma

Standard Treatment Approach

Offer radiotherapy (50-54 Gy in 1.8-2 Gy fractions) in combination with PCV chemotherapy. 1

• This recommendation carries a strong evidence base with moderate quality evidence 1
• Temozolomide is a reasonable alternative when PCV toxicity is a concern, though this is based on weaker evidence (informal consensus, low quality) 1

Criteria for Observation

Initial therapy may be deferred in select patients with: 1

• Positive prognostic factors including complete resection and younger age 1
• Concerns about treatment toxicity 1
• The decision threshold is less clearly defined than for astrocytomas, requiring individualized risk-benefit assessment 1, 6

Evidence Supporting Combined Modality Treatment

The RTOG 9802 trial provided the foundational evidence showing survival benefit from combined radiotherapy and PCV across grade 2 glioma subtypes, with benefit observed in both oligodendrogliomas and astrocytomas. 1, 2 Patients with 1p/19q codeletion derive particular benefit from combined therapy. 7

Molecular Testing Requirements

Confirm the following molecular markers before finalizing treatment decisions: 1

• IDH mutation status (IDH1 and IDH2) is essential for diagnosis and prognosis 1, 8
• 1p/19q codeletion status distinguishes oligodendroglioma from astrocytoma 1, 7
• ATRX status (ATRX loss and 1p/19q codeletion are mutually exclusive) 7
• MGMT promoter methylation provides prognostic information 8

Critical distinction: Isolated 1p deletion without 19q codeletion does NOT constitute oligodendroglioma—these tumors should be classified and treated as astrocytomas. 7

Surveillance Protocol for Observed Patients

Implement the following monitoring schedule: 2

• Clinical neurological examination every 3-6 months 2
• Brain MRI with contrast every 3-6 months 2
• Monitor seizure control and minimize corticosteroid use 2
• Assess for venous thrombotic events (common in glioma patients) 2
• Recognize pseudoprogression can occur 4-8 weeks after radiotherapy completion; repeat MRI after 4 weeks if suspected 2

Management at Progression or Recurrence

First-line treatment at progression: 1, 2, 5

• Temozolomide chemotherapy is the standard approach after initial surgery and radiotherapy 1, 2, 5
• Lomustine (nitrosourea) represents an alternative option 1, 2, 5
• Re-resection should be reconsidered, especially if gross total resection is now achievable 2, 8
• Radiotherapy is recommended at recurrence if not previously administered 8
• Re-irradiation may be considered for previously irradiated patients as it may provide benefit in progression-free and overall survival 8

Special Considerations for Elderly Patients (Age ≥ 60)

Patients over age 60 with grade 2 gliomas have worse clinical outcomes compared to younger counterparts, potentially due to increased frequency of IDH-wildtype tumors in this age group. 4 Despite this, older patients may safely undergo aggressive treatment with surgical resection and adjuvant therapy. 4 The astrocytoma IDH-wildtype subtype shows shorter progression-free survival even with similar extent of resection and adjuvant treatment rates. 4

Common Pitfalls to Avoid

• Do not use watch-and-wait strategies for patients with residual disease after incomplete resection—observation is only appropriate after gross total resection in young, minimally symptomatic patients 1, 5
• Do not classify tumors with isolated 1p deletion (without 19q codeletion) as oligodendrogliomas—these are astrocytomas and should be treated accordingly 7
• Do not reflexively administer early radiotherapy to young patients with completely resected tumors, as this does not improve overall survival despite prolonging progression-free survival 1, 5
• Do not proceed with adjuvant therapy without confirming molecular diagnosis including IDH mutation and 1p/19q codeletion status 1, 7