Ependymoma

Steven H. Lin, Ori Shokek, and Updated by Mark Edson

BACKGROUND

In children and adults, what % of brain tumors are ependymomas?

Children: 5% (3^rd most common childhood CNS tumor)

Adults: 2%

What is the median age of Dx for ependymomas?

Bimodal peak distribution, with peaks at 5 yrs and 35 yrs

What % of ependymomas arise intracranially, and how does this differ in children vs. adults? What are the most common locations?

Children: 90% intracranial (10% cord). If intracranial, the posterior fossa is the most common site (60% infratentorial [floor of 4^th ventricle], 40% supratentorial [lat ventricle]).

Adults: 75% arise in spinal canal. Of intracranial tumors, two-thirds are supratentorial and one-third are infratentorial.

What is the cell of origin for ependymomas?

Ependymomas arise from the ependymal cells lining the ventricles.

What % of primary spinal tumors is ependymoma?

∼20% (meningiomas comprise 33%, spinal nerve tumors 27%)

What genetic syndrome is associated with spinal cord ependymoma?

Spinal cord ependymoma is associated with NF-2.

What % of ependymoma pts present with CSF seeding? What features predispose to seeding?

5%–10%; infratentorial location, high-grade tumors, and LF predispose to CSF seeding.

What is the WHO classification of ependymoma?

Grade I: myxopapillary and subependymoma

Grade II: classic ependymoma

Grade III: anaplastic

Grade IV: ependymoblastoma

Where do grade IV ependymomas generally arise?

Grade IV ependymomas usually arise in the supratentorium.

What is the classical pathologic feature of ependymomas?

Perivascular pseudorosettes are a classical pathologic feature of ependymomas.

What defines malignant ependymomas on pathology?

Greater number of mitoses, cellular atypia, and more necrosis

Which histopathologic subtype is most commonly found in the lumbosacral spinal cord?

Myxopapillary ependymomas usually arise in the conus/filum region of the spinal cord.

What is the typical presentation of ependymomas?

Depends on location. If infratentorial: CN deficits, ↑ ICP; if supratentorial: seizures, focal deficits

With what neurologic deficits are spinal cord ependymoma pts likely to present?

Sensory deficits (vs. cord astrocytomas, which present with pain/motor deficits)

WORKUP/STAGING

What is the workup for ependymoma?

Ependymoma workup: H&P, basic labs, CSF cytology/sampling, and MRI brain/spinal cord

When is LP contraindicated?

LP is contraindicated with a posterior fossa tumor with surrounding mass effect.

When should spinal MRI or CSF cytology be obtained after resection?

2 wks (10–14 days) postop to avoid false+.

TREATMENT/PROGNOSIS

What is the Tx paradigm for ependymoma?

Traditional ependymoma Tx paradigm: max safe resection with adj RT for children >3 yo (adj chemo if <3 yo)

Under what circumstances should CSI be done for ependymomas?

CSI should be done if +CSF, +MRI neuroaxis, and ependymoblastoma histology. For all others, local RT is sufficient.

What evidence supports the omission of CSI for anaplastic ependymomas after resection if there is no evidence of neuroaxial involvement?

Multiple retrospective reviews reveal the following: LR is the primary pattern of failure (>90%) regardless of field size; spinal seeding is uncommon without LR; and prophylaxis with CSI or WBRT does not affect survival when compared to local RT.

What is the role of chemo in ependymoma? What is the response rate?

Traditionally, chemo is utilized for <3 yo to delay RT and for salvage (cisplatin, VP-16, temozolomide, nitrosoureas). The response rate typically is 5%–15%. However, a new prospective study from St. Jude’s Children’s Hospital (Merchant TE et al., Lancet Oncol 2009), which included many pts <3 yo (78%) treated with maximal safe resection and postoperative conformal RT to 59.4 Gy with 10-mm margin around postop bed, suggests that RT can be given safely and effectively for pts <3 yo. The 7-yr OS was 81%, EFS was 69%, and LC rate was 87.3% (cumulative LF rate is 16.3%). Therefore, young age should not preclude pts from receiving high-dose RT after surgery, except for infants <1 yo. Current protocols require postop RT in completely resected infratentorial ependymoma starting at age 18 mos. If STR, chemo may be used to see if GTR is possible with 2^nd-look surgery after 2 cycles of chemo.

What is the single most important favorable prognostic factor in ependymoma?

Completeness of surgical resection (correlates closely with LC for ependymomas)

What is the difference in 5-yr OS between GTR and STR for ependymomas?

75% vs. 35% (similar for low-grade vs. high-grade ependymomas)

What ependymoma locations are most amenable to GTR? Least?

Spinal (GTR ∼100%) > supratentorial (80%) > infratentorial

What is given to children <3 yo after STR for ependymoma?

2 cycles of chemo can be used as a bridge Tx to see if GTR can be achieved. RT can be deferred with chemo until >18 mos, based on the St. Jude’s trial (Merchant TE et al., Lancet Oncol 2009) and SEER analysis (Koshy M et al., J Neurooncol 2011). Both suggest that postop RT in children <3 yo improves survival.

What types of chemo are typically used for ependymoma?

Cisplatin, cyclophosphamide, and etoposide are typical chemo agents for ependymoma.

What is the dose and volume of RT to be used if no CSI is given for ependymomas?

Preop GTV + 1–2-cm margin to 54–59.4 Gy (54 Gy for children <18 mos and >18 mos with GTR)

How is ependymoblastoma treated? What is the total dose to spine lesions vs. cranial lesions?

Treat like high-risk medulloblastoma/PNET: CSI 36 Gy + vincristine +/– carboplatin, boost to cavity/gross Dz. 45–50.4 Gy if spine and 54–59.4 Gy if cranial → vincristine/Cytoxan/prednisolone 6 wks after RT.

How is infratentorial ependymoma managed?

Max safe resection followed by involved field postop RT to a dose of 54–59.4 Gy.

How is supratentorial ependymoma managed?

If not anaplastic (i.e., if grades I–II), observation after max GTR is acceptable.

How is recurrent ependymoma managed?

If no prior RT: surgery → RT

If prior RT: surgery → stereotactic RT or chemo

Which phase II study showed min neurocognitive decrement with conformal/small RT fields?

St. Jude’s study ACNS0121 (Merchant TE et al., JCO 2004): 88 pts, 33 pts with grade 3. 3-yr PFS was 74%. IQ testing was stable after 2 yrs.

What is a major reason infratentorial lesions should get adj RT, regardless of histologic grade?

Difficulty with complete resection due to proximity to floor of 4^th ventricle, or laterally protrusion through foramen of Luschka and involvement of CN nerves or CNS vessels → higher LR if infratentorial without RT

Which recent studies showed a benefit with adj RT after GTR for posterior fossa ependymomas?

Rogers L et al.: 10-yr LC GTR/RT 100% vs. 50% GTR alone. Nonsignificant benefit in 10-yr OS GTR (67%), GTR/RT (83%). (J Neurosurg 2005)

Merchant TE et al.: 5.3-yr median follow-up update from the phase II study ACNS0121. All rcvd conformal RT to 59.4 Gy for NTR/all sites and grade, and for R0 infratentorial lesions of all histologies. Well-differentiated lesions after GTR were observed. Chemo for STR, then evaluated for surgery and RT. 7-yr OS was 81%, LC was 87.3%, and EFS was 69.1%. Median age 2.9 yrs, with 78% of the pts <3 yo. (Lancet Oncol 2009)

When is RT used in spinal ependymomas?

When resection is incomplete or anaplastic histology (Kaiser data: Volpp PB et al., IJROBP 2007)

What fields/doses are used for spinal ependymomas?

Include 2 vertebral bodies/sacral nerve roots above and below tumor to 45 Gy (boost if below cord to 50.4–59.4 Gy)

What molecular profile is associated with poor outcomes in ependymoma?

Overexpression of erbB-2/erbB-4 is associated with poor outcomes in ependymoma.

Do young children or young adults with ependymoma have a worse prognosis?

Children. Age <4 yrs is a poor prognostic factor.

Which ependymoma lesions have a poorer prognosis: supratentorial or infratentorial?

Supratentorial (↑ high grade and more STR) (Mansur DB et al., IJROBP 2005)

What are the 5- and 10-yr OS rates for pts with grades II–III ependymomas?

70% and 55%, respectively (Mansur DB et al., IJROBP 2005); no difference between grade II and grade III tumors (p = 0.71)