What is the best adjuvant treatment for a 32‑year‑old female with WHO grade 3 astrocytoma, IDH‑1 mutated, after 90 % gross‑total resection?

Treatment Recommendation for Grade 3 IDH-Mutant Astrocytoma

This 32-year-old female with grade 3 IDH-mutant astrocytoma after 90% resection should receive involved-field radiotherapy (54-60 Gy in 1.8-2 Gy fractions) followed by adjuvant temozolomide chemotherapy. 1

Standard of Care Based on Guidelines

The EANO guidelines explicitly state that the standard of care for IDH-mutant astrocytomas, WHO grade 3 includes resection as feasible or biopsy followed by involved field radiotherapy and maintenance temozolomide (CATNON trial). 1 This is a strong recommendation with moderate evidence quality.

Specific Treatment Protocol

Radiotherapy:

• Dose: 54-60 Gy delivered in 1.8-2 Gy fractions
• Target: Involved-field radiotherapy (not whole brain)
• Consider intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to minimize long-term cognitive effects, particularly important given her young age 2

Chemotherapy:

• Temozolomide as maintenance therapy following radiotherapy
• Standard dosing: 150-200 mg/m² for 5 days out of every 28-day cycle
• Duration: Typically 6-12 cycles based on tolerance and response 3

Why Temozolomide Over PCV for Grade 3

While PCV (procarbazine, lomustine, vincristine) is the standard for grade 2 IDH-mutant astrocytomas requiring treatment 1, temozolomide is specifically recommended for grade 3 IDH-mutant astrocytomas based on the CATNON trial results. 1 This distinction is critical—grade matters for chemotherapy selection in astrocytomas.

The guidelines show that radiotherapy followed by temozolomide improves outcomes in patients with non-codeleted grade 3 IDH-mutant astrocytoma, with overall survival extending up to 10 years. 3

Important Considerations for This Patient

Age and Extent of Resection:

• At 32 years old with 90% resection, she has favorable prognostic factors
• However, grade 3 disease mandates adjuvant therapy—observation alone is NOT appropriate for grade 3, even with near-gross total resection 1
• The 10% residual disease further supports the need for immediate adjuvant treatment

Timing:

• Treatment should begin within 4-6 weeks post-surgery
• Do not delay—early initiation of radiotherapy and chemotherapy is standard

Emerging Option: Vorasidenib

The 2025 ASCO-SNO rapid update introduced vorasidenib as a conditional recommendation, but only for grade 2 IDH-mutant astrocytomas where radiation and chemotherapy can be deferred. 4 This patient has grade 3 disease and requires immediate treatment, making vorasidenib inappropriate as first-line therapy. Vorasidenib may be considered at recurrence if standard therapy fails.

Common Pitfalls to Avoid

1. Do not defer treatment based on young age and near-complete resection—grade 3 requires immediate adjuvant therapy
2. Do not use PCV instead of temozolomide for grade 3 astrocytoma—this is specific to grade 2 disease
3. Do not use radiotherapy alone without chemotherapy—combined modality improves survival
4. Do not consider vorasidenib as first-line therapy for grade 3 disease—it is only for grade 2 with deferred treatment

Monitoring During Treatment

• Liver function tests every 2 weeks for first 2 months if any IDH inhibitor is considered later
• MRI surveillance every 3-6 months during and after treatment 1
• Neurological examination at each visit
• Monitor for radiation-induced cognitive changes, particularly important given her age

At Progression

If disease progresses after initial therapy, options include:

• Nitrosourea-based chemotherapy
• Temozolomide rechallenge
• Re-resection if feasible
• Consider ivosidenib (IDH-1 inhibitor) for recurrent disease 5