Steven H. Lin and Ori Shokek
In children and adults, what % of brain tumors are ependymomas?
1. Children: 10%
2. Adults: 5%
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?
1. Children: 90% intracranial (10% cord). If intracranial, the posterior fossa is the most common site (60% infratentorial [floor of 4th ventricle], 40% supratentorial [lat ventricle]).
2. Adults: ~67% are supratentorial, and ~33% are infratentorial.
What is the cell of origin for ependymomas?
Ependymomas arise from the ependymal cells lining the ventricles.
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?
10%–15%; infratentorial location, high-grade tumors, and LF predispose to CSF seeding.
Which histologic subtypes of ependymoma are considered grades 1, 2, 3, and 4?
1. Grade 1: myxopapillary and subependymoma
2. Grade 2: classic ependymoma
3. Grade 3: anaplastic
4. Grade 4: ependymoblastoma
Where do grade 4 ependymomas generally arise?
Grade 4 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 type of ependymomas commonly arise in the conus/filum region of the 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)
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 mass.
When should spinal MRI or CSF cytology be obtained after resection?
2 wks (14 days) postop to avoid postsurgical artifacts
What is the Tx paradigm for ependymoma?
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 (CDDP, VP-16, temozolomide, nitrosoureas). The response rate typically is 5%–15%. However, a new prospective study out of St. Jude's Children's Hospital (Merchant TE et al., Lancet Oncol 2009) that 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 to receive high-dose RT after surgery, except for infants <1 yo.
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?
Chemo is typically used as a bridge Tx. RT is deferred until >3 yo.
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 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?
Infratentorial ependymoma management: max resection. At the Johns Hopkins Hospital, regardless of histologic grade, all get postop RT to involved fields and a dose of 59.4 Gy.
How is supratentorial ependymoma managed?
If not anaplastic (i.e., if grades 1–2), observation after max GTR is acceptable.
How is recurrent ependymoma managed?
1. If no prior RT: surgery → RT
2. If prior RT: surgery → stereotactic RT or chemo
Which phase II study showed min neurocognitive decrement with conformal/small RT fields?
St. Jude 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 4th ventricle, CNS vessels → higher LR if infratentorial without RT
What study suggested a benefit to hyperfractionation for ependymomas?
POG 9132; better EFS with 1.2 Gy bid to 69.6 Gy
Which recent studies showed a benefit with adj RT after GTR for posterior fossa ependymomas?
Rogers L et al., J Neurosurg 2005: 10-yr OS GTR (67%), GTR/RT (83%)
Merchant TE et al., Lancet Oncol 2009: update from the phase II study ACNS0121. All rcv 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. 10-yr OS was 75%, LC was 87%, and EFS was 69%. Median age 2.9 yrs, with 78% of the patients <3 yo.
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 45–50.4 Gy (boost if below cord to 54–59.4 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 et al., IJROBP 2005)
What are the 5- and 10-yr OS rates for pts with grade 2–3 ependymomas?
70% and 55%, respectively (Mansur et al., IJROBP 2005); no difference between grade 2–3 tumors (p = 0.71)
What % of ependymoma pts eventually die of their Dz?
50% of ependymoma pts eventually die of their Dz.
How long of a follow-up is required for pts with ependymoma?
At least 10 yrs, because late recurrences of >12 yrs after surgery can occur.
What imaging is required during the follow-up for ependymoma pts?
Craniospinal MRI q6mos for the 1st 2 yrs, then annually
What is a commonly used dose constraint for the spinal cord?
45 Gy is the usual dose constraint for the spinal cord.
What is a commonly used dose constraint for the chiasm?
50.4 Gy is the usual dose constraint for the chiasm.