Ependymoma

Abstract

Intracranial ependymoma is much less common in adults than in children. In adults, ependymomas are more commonly located in the spinal cord. In the World Health Organization classification of brain tumors, ependymomas are divided into four major subtypes: myxopapillary, subependymoma, classic, and anaplastic ependymomas. Molecular subgroups have been proposed based on tumor sequencing and epigenetic profiling, and the field is evolving. Subgroups include posterior fossa ependymoma groups A and B and supratentorial ependymoma with RELA or YAP fusion. Factors associated with poor prognosis include high histologic grade, incomplete surgical resection, supratentorial location, and a Karnofsky performance status ≤80. For intracranial ependymoma, mainstay of therapy is maximal safe resection, after which postoperative radiation therapy is recommended for most patients with intracranial grades II and III ependymomas to reduce the risk of local recurrence. There is a limited role for chemotherapy in patients who have bulky residual disease and recurrent or refractory tumors or for very young children. Focal radiation fields using contemporary techniques such as proton therapy, tomotherapy, or IMRT are utilized with more extensive fields indicated only if there is evidence of tumor dissemination. There can be a role for focal reirradiation or stereotactic radiosurgery for selected cases of recurrent disease.

11.1 General Principles of Simulation and Target Delineation (Table 11.1)

• Staging with spine MRI and cerebrospinal fluid sampling is essential to determine if a patient has tumor dissemination.

• CT simulation with a themoplastic mask for immobilization with 1–2.5 mm slice thickness.

• Obtain MRI with T1 pre- and post-gadolinium, T2, and FLAIR for target delineation. Ependymomas often have a mixed pattern of enhancement and may be best visualized on FLAIR sequences.

• Fuse preoperative and postoperative T2/FLAIR and post-gadolinium MRIs to help delineate target volumes.

• If biopsy only, can use preoperative MRI only.

• If patient has contraindication to MRI, can obtain CT using 1–2.5 mm slice thickness with and without contrast.

• The GTV includes the postoperative residual disease and the edge of the postoperative tumor bed. The edge of any structure in contact with the preoperative tumor should be included, but the surgical tract does not need to be included. The CTV expansion into the brain stem should be limited where invasion or infiltration is not considered likely (Fig. 11.1).

• Contemporary 3D conformal or advanced techniques such as tomotherapy, IMRT, or proton therapy can be considered.

Table 11.1 Suggested target volumes and doses

Fig. 11.1

Sagittal images for a patient with WHO grade III anaplastic ependymoma of the fourth ventricle. MRI before gross total resection shows tumor centered in the floor of the fourth ventricle (white arrow) with extension through the foramen magnum to approximately the C2 level (orange arrow). CT simulation with contrast demonstrates initial and boost contours using ACNS0831 guidelines

11.2 Dose Prescriptions

• Treatment of the brain after maximal safe resection

  • The current standard doses to the target for intracranial ependymoma are 54–59.4 Gy, and higher doses may be recommended for areas with residual macroscopic disease.

  • The extent of margin for focal radiation therapy continues to be studied with shrinking clinical target volume margins employed on completed and ongoing COG clinical trials.

• Treatment of patients with leptomeningeal dissemination

  • Patients with leptomeningeal dissemination with spinal deposits of intracranial ependymoma generally have a poor prognosis, and treatments should be individualized.

  • Given challenges in the interpretation of CSF cytology in ependymoma, cytology should be repeated in 10–14 days postoperatively to confirm results.

    • Craniospinal irradiation is typically indicated after surgery. Target volumes and doses are similar to high-risk medulloblastoma.

11.3 Treatment Planning Techniques

• Contemporary 3D CRT or advanced techniques such as IMRT, VMAT, or proton therapy may be used with the goal of sparing portions of the brain stem, supratentorial brain, hypothalamus, pituitary, optic apparatus, and cochleae (Table 11.2).

• Treatment planning aims to cover 95% of the PTV volume by 95% of the prescribed dose for photon plans and 100% of the CTV volume by 100% of the prescribed dose for proton plans (Fig. 11.2).

Table 11.2 Recommended normal tissue constraints for 1.8 Gy per fraction schemes

Fig. 11.2

Sample dose-volume histogram for the above patient with WHO grade III anaplastic ependymoma of the fourth ventricle treated with an IMRT plan. PTV2, orange; PTV1, red; brain stem, dashed green; spinal cord, dashed blue; left cochlea, dotted brown; right cochlea, dotted teal; and optic chiasm, dashed indigo

11.4 Side Effects

Please see Table 11.3.

Table 11.3 Side effects

11.5 Treatment of Recurrence

• While the long-term prognosis for patients with recurrent disease is poor, there is growing evidence that reirradiation is beneficial and has successfully provided local control in carefully selected cases. Patients treated with focal reirradiation remain at risk for development of disseminated metastases or primary site recurrence

• Data in the literature showed that stereotactic radiosurgery can be used for treatment of recurrent intracranial ependymoma; the recurrent tumor, gadolinium enhanced in most cases, alone is targeted, and the typical dose used ranged from 12 to 24 Gy (median 18 Gy) in 1 fraction; the local control rate is 70–80%, but distant failure occurs in at least one quarter of the patients.