Treatment of Recurrent Grade 3 Frontal Lobe Ependymoma
Re-operation should be the first-line treatment for this recurrent grade 3 ependymoma in the operative bed, followed by re-irradiation if gross total resection is achieved or if incomplete resection occurs. 1
Primary Treatment Approach: Surgical Re-resection
- Repeat surgery is associated with significantly improved prognosis and should be pursued aggressively. 1
- Among pediatric patients (data applicable to adults), 5-year event-free survival after re-operation is 19% with gross total resection (GTR), 14% with incomplete resection, and only 8% without repeat surgery. 1, 2
- The extent of resection at recurrence is the single most critical prognostic factor determining survival. 2, 3
- Post-operative MRI should be performed within 48-72 hours to evaluate the extent of resection. 1
Staging Before Finalizing Treatment Plan
- Obtain craniospinal MRI with contrast and CSF cytology at least 2-3 weeks post-surgery to assess for metastatic disease. 1, 2
- This staging is mandatory before finalizing the re-irradiation plan, as the presence of disseminated disease would alter the radiation field. 1
Re-irradiation Strategy
Re-irradiation achieves durable responses and should be administered using either fractionated radiotherapy or hypofractionated stereotactic approaches. 1, 2
If Gross Total Resection is Achieved:
- Re-irradiation still provides benefit even after complete resection in grade 3 ependymomas. 1
- Use focal fractionated re-irradiation with doses of 54-60 Gy to the tumor bed. 1, 4
- Stereotactic approaches with minimum doses of 21 Gy in 3 fractions or 25 Gy in 5 fractions are acceptable alternatives. 5
If Incomplete Resection:
- Focal re-irradiation is essential and shows clear survival advantage (22 months vs. 7 months without re-irradiation). 3
- Combined median dose of approximately 111.6 Gy (initial + re-irradiation) has been safely delivered in focal fractionated approaches. 6
- Re-irradiation is well-tolerated with minimal severe acute complications. 7
If Metastatic Disease is Present:
- Craniospinal irradiation (CSI) should be administered with 36 Gy to the craniospinal axis plus boost to 45-54 Gy on focal lesions. 1
- Four-year event-free survival of 53% has been achieved with CSI for metastatic recurrence. 6
Chemotherapy: Third-Line Option Only
Chemotherapy should be considered only when both surgical and radiotherapy options have been exhausted. 1, 2
Temozolomide as Preferred Agent:
- In chemo-naïve patients with recurrent grade II/III ependymoma, temozolomide shows 22% response rate, median PFS of 9.69 months, and median OS of 30.55 months. 1, 2
- Responses are observed only in chemotherapy-naïve patients and typically appear delayed. 1
- Standard dosing schedule: 150-200 mg/m² days 1-5 of 28-day cycles. 1
Alternative Chemotherapy Options:
- Temozolomide combined with lapatinib showed median PFS of 25.3 weeks for grade III ependymomas, with responses correlating to higher ErbB2 expression. 2
- Continuous oral etoposide has shown activity in small series. 2
- Platinum-based regimens have 40-50% response rates but are typically reserved for pediatric populations. 2
Critical Pitfalls to Avoid
- Do not proceed directly to chemotherapy without attempting surgical resection, as the extent of resection is the most powerful predictor of survival at recurrence. 2, 3
- Avoid radiosurgery to brainstem-adjacent lesions with doses >18 Gy, as this has resulted in significant brainstem toxicity and death. 6
- Do not assume temozolomide will be effective in heavily pretreated patients, as responses occur primarily in chemo-naïve patients. 1
- The modest activity of temozolomide relates to lack of MGMT promoter methylation in ependymoma cells. 1, 2
- Monitor for neurocognitive decline after re-irradiation, as intellectual function decline has been documented despite good tumor control. 7