Is there a role for Gamma Knife (stereotactic radiosurgery) in the further treatment of a 19-year-old boy with a recurrent right frontal lobe ependymoma (grade 3) after surgery and proton therapy (56.8 Gy)?

Gamma Knife Radiosurgery for Recurrent Grade 3 Frontal Lobe Ependymoma

Yes, Gamma Knife stereotactic radiosurgery has a definitive role as part of the re-irradiation strategy for this patient, but only after maximal surgical re-resection is attempted first. 1

Treatment Algorithm: Sequential Approach

Step 1: Surgical Re-resection (First Priority)

• Re-operation must be the initial treatment for recurrent grade 3 ependymoma in the operative bed, as repeat surgery is associated with significantly improved prognosis 1
• Among patients with recurrent ependymoma, 5-year event-free survival after re-operation is 19% with gross total resection versus only 8% without repeat surgery 1
• The extent of resection at recurrence is the single most critical prognostic factor determining survival 1
• Obtain post-operative MRI within 48-72 hours to document extent of resection 2

Step 2: Staging Before Re-irradiation Planning

• Wait at least 2-3 weeks post-surgery before performing craniospinal MRI with contrast and CSF cytology to assess for metastatic disease 2
• This staging is mandatory before finalizing the radiation plan, as disseminated disease would alter the treatment field 1, 2

Step 3: Re-irradiation Strategy (Including Gamma Knife)

Re-irradiation achieves durable responses and should be administered even after complete resection in grade 3 ependymomas 1, 2

Two Re-irradiation Options:

Option A: Fractionated Stereotactic Radiotherapy

• Use focal fractionated re-irradiation with doses of 54-60 Gy to the tumor bed 1, 2
• This approach showed 5-year progression-free survival of 37.5% in one series 3

Option B: Gamma Knife Stereotactic Radiosurgery (SRS)

• Gamma Knife SRS achieved 5-year local control of 66% in skull base chordomas (similar radioresistant tumors) with median margin dose of 15.0 Gy 3
• For recurrent anaplastic ependymomas specifically, stereotactic radiosurgery provided 76% local control at 3 years with minimal toxicity 4
• Minimum effective dose: 21 Gy in 3 fractions or 25 Gy in 5 fractions - lesions receiving these doses or higher did not recur within 1 year 4
• No grade ≥2 toxicity was observed with this approach 4

Critical Dose Reconstruction Requirement:

• The radiation plan must be based on accurate reconstruction of the previous proton therapy dose distribution (56.8 Gy), with consideration of tissue recovery over the 23-month interval 2
• Re-irradiation can be delivered with curative intent if adequate coverage can be achieved without exceeding estimated dose constraints on organs at risk 2

Step 4: Chemotherapy (Only After Exhausting Local Options)

• Chemotherapy should be considered only when both surgical and radiotherapy options have been exhausted 1, 2
• In chemo-naïve patients with recurrent grade II/III ependymoma, temozolomide shows 22% response rate with median progression-free survival of 9.69 months 1
• Responses occur only in chemotherapy-naïve patients and typically appear delayed 1

Critical Pitfalls to Avoid

• Do not proceed directly to Gamma Knife without attempting surgical resection - the extent of resection is the most powerful predictor of survival at recurrence 1
• Do not start radiotherapy before completing staging workup (craniospinal MRI and CSF cytology at 2-3 weeks post-op), as this may result in inadequate treatment fields if metastatic disease is present 2
• Do not use single-fraction doses below 21 Gy or hypofractionated doses below 25 Gy/5 fractions for Gamma Knife treatment, as lower doses showed local recurrence within 1 year 4
• Do not assume chemotherapy is an alternative to re-irradiation - it is a third-line option only 1, 2

Evidence Supporting Gamma Knife in This Context

The evidence specifically demonstrates that stereotactic radiosurgery (including Gamma Knife) is effective for recurrent ependymomas after prior conventional radiotherapy 4. The 76% local control rate at 3 years with minimal toxicity makes this a viable option, particularly given that this patient has already received proton therapy and the 23-month interval allows for some normal tissue recovery 2, 4.

The optimal approach combines maximal surgical resection followed by Gamma Knife radiosurgery at doses ≥21 Gy/3 fractions, with chemotherapy reserved only if both local treatment modalities fail. 1, 4