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Ependymoma is the third most common brain tumor in children, accounting forapproximately 10% of primary central nervous system (CNS) neoplasms. It is a neuroepithelial tumor that arises within, or adjacent to, the ependymal lining of the ventricular system or the central canal of the spinal cord. It tends to invade locally, even if histological appearance is benign. Approximately 90% of tumors are intracranial, with up to 70% occurring in the posterior fossa.

With surgery and radiotherapy, the overall 5-year survival rate is approximately 55%; however, survival rates of up to 80% can be achieved. Individual prognosis is most dependent on age and the extent of resection. The role of chemotherapy for infants and patients with postoperative residual disease is currently under investigation.

Ependymomas typically arise from the ependymal lining of the ventricular system, most often the floor, roof, or lateral recesses of the fourth ventricle. Approximately one third are supratentorial, arising from the surface of the lateral or third ventricles; however, they may be entirely extraventricular. They may also occur in the central canal of the spinal cord and in the filum terminale, although the latter site is uncommon in children. Histologically, ependymoma can be broadly separated into two major subsets, low-grade (benign) and high grade (anaplastic). Low-grade ependymoma is well differentiated and lacks mitosis and vascularity. High-grade ependymoma is poorly differentiated and has a high mitotic index, necrosis, calcifications, and endothelial proliferation. Both histological subtypes are locally invasive into adjacent brain. Those in the posterior fossa frequently infiltrate the brain stem, and as many as one third may project through the foramina to involve the medulla and upper spinal cord. Spread via cerebrospinal fluid (CSF) throughout the subarachnoid space is reported, primarily with the higher-grade tumors. Extraneural metastases to liver, lung, or bone are rare.

Mortality/Morbidity: Five-year survival rates: Overall survival rate is approximately 55%. Age and the extent of tumor resection are significant independent predictors of outcome. Five-year survival rate is 25% for infants younger than 1 year, 46% for children aged 1-4 years, and greater than 70% for those older than 5 years. For the minority of patients in whom complete tumor resection can be achieved, survival rates of 60-80% have been reported following local radiation. In those with partial resection or biopsy only, fewer than 30% respond to currently available best therapy, regardless of age or tumor histology.

Postoperative irradiation of brain ependymomas. Analysis of 33 cases.

Di Marco A, Campostrini F, Pradella R, Reggio M, Palazzi M, Grandinetti A, Garusi GF.Acta Oncol 1988;27(3):261-7

Radiation Oncology Department, Presidio Ospedaliero di Borgo, Trento, Verona, Italy.

Treatment and final outcome of 33 patients with brain ependymoma were reviewed. All patients had been operated, but the surgical removal was incomplete in the great majority of cases. Radiation therapy was subsequently performed using one of the following techniques; a) partial brain irradiation against the primary involved areas in 17 cases, b) whole brain irradiation plus boost against primary involved sites in 6 cases and c) total craniospinal irradiation in 7 cases. Three patients were not eligible for the present study because of underdosage. Five- and 10-year survival rates were 48 and 38% respectively.

Intracranial ependymoma in the adult patient: successful treatment with surgery and radiotherapy.

Donahue B, Steinfeld A.  J Neurooncol 1998 Apr;37(2):131-3

Division of Radiation Oncology, NYU Medical Center, New York, USA.

Ependymoma is an uncommon intracerebral tumor in adults. Since the site of origin frequently prevents complete surgical removal, adjunctive radiotherapy is used to destroy residual disease. We present our experience in treating 10 adults with intracranial ependymoma.Five men and 5 women were treated in the past 16 years. The median age was 38 (range 24-69). All had contrast enhanced CT or MRI showing the extent of the tumor. One patient had total excision while the remainder had subtotal removal. Radiation therapy was delivered to the tumor bed with a 1-2 cm margin of normal tissue generally at 180-200 centiGray (cGy) per treatment once a day. Total dose ranged from 5400 to 7200 cGy. Two patients received experimental treatment with 100 cGy delivered twice a day for total of 6800 and 7200 cGy respectively. Four patients received initial treatment to a large field with a subsequent boost to the tumor bed. One patient received his entire course of treatment via this large field. RESULTS: With a median follow-up of 64 months, 7 patients are alive and free of disease while 2 died of intercurrent disease, without evidence of tumor, at 7 and 9 years following treatment. Another patient died 1 1/2 years after treatment of unknown causes. CONCLUSION: We conclude that postoperative radiotherapy is effective in preventing regrowth of intracranial ependymoma following subtotal resection in adults. Treatment fields should cover the initial tumor bed with a 1-2 cm margin to avoid long term radiation damage.

Considerations in the radiation treatment of intracranial ependymoma. Prognosis in 24 own cases and results in published series after different techniques of radiation treatment.

Glanzmann C, Horst W, Schiess K, Friede R. Strahlentherapie 1980 Feb;156(2):97-101

The course of 24 patients with intracranial ependymomas after surgical and radiotherapeutic treatment from the years 1954 to 1978 is analysed. The survival rate after 5 and ten years is about 40%. Patients with well differentiated ependymoma, who were irradiated with tumor doses of at least 4000 rad in 4 weeks with inclusion of the whole brain for a part of the dose had a 5-year survival rate well above 50%. In patients with well-differentiated supra or infratentorial ependymomas, prophylactic irradiation of the whole spinal axis is not indicated. Patients with high-grade malignant ependymomas are irradiated by a treatment technique similar to that in patients with medulloblastomas, and additive chemotherapy is administered thereafter.

Intracranial ependymoma long term outcome, patterns of failure.

Kovalic JJ, Flaris N, Grigsby PW, Pirkowski M, Simpson JR, Roth KA.  J Neurooncol 1993 Feb;15(2):125-31

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
63110.

We analyzed 31 patients with intracranial ependymoma, all verified by secondary neuropathology review. There were 12 patients with ependymomas and 19 patients with anaplastic ependymoma by the WHO classification. Eight patients received craniospinal irradiation, 22 patients received cranial irradiation alone, and one patient was treated with chemotherapy alone. The median follow-up time was 11 years. The 5- and 10-year progression-free survivals (PFS) were 60% and 48%. Those with anaplastic tumors had a decreased 10 year PFS over those with low grade lesions: 26% vs. 55% (p = 0.02). Delivering spinal irradiation in addition to cranial irradiation did not improve outcome. There were relapses in 16 patients. All patients relapsed at the primary intracranial sites with no spinal failures. Patients treated with whole brain irradiation had decreased 10 year PFS over those treated with local fields: 19% vs. 64% (p = 0.006). Those patients treated to > or = 50 Gy had an improved long-term PFS (p = 0.04).  With PFS as the endpoint, only extent of cranial irradiation (favoring local fields) and pathology (favoring low grade ependymoma) were significant prognosticators. We conclude that carefully outlined local field irradiation is the therapy of choice, and elective spinal irradiation is of questionable benefit.

The significance of radiotherapy treatment duration in intracranial ependymoma.

Paulino AC, Wen BC.  Int J Radiat Oncol Biol Phys 2000 Jun 1;47(3):585-9

Department of Radiology, The University of Iowa College of Medicine and the Children's Hospital of Iowa, Iowa City 52242, USA.

From 1965 to 1997, 34 patients with intracranial ependymoma were seen and treated with postoperative radiotherapy (RT). There were
26 male and 8 female patients with a median age of 14 years (range, 18 months to 60 years). Tumor location was infratentorial in 23 (67.6%) and supratentorial in 11 (32.4%). Pathology was low-grade in 25 (73.5%) and high-grade in 9 (26.5%). Two (5.9%) patients had M+ disease at initial diagnosis. Gross total resection was achieved in 12 (35.3%), subtotal resection in 19 (55. 9%), and biopsy alone in 3 (8.8%). Median RT dose to the primary site was 5400 cGy (range, 4500 cGy to 6600 cGy). The entire neuraxis was treated in 14 (41.2%), whole brain in 9 (26.5%), and the primary site alone in 11 (32.4%). Median radiotherapy treatment duration was 43 days (range, 26 to 122 days). Patients treated with craniospinal RT were more likely to have treatment duration of > or =50 days. Median follow-up was 108 months (range, 24 to 252 months). RESULTS: The 5-, 10-, and 15-year overall survival rates were 71.5%, 63.3%, and 55.4%. Local control rates at 5, 10, and 15 years were 61.8%, 57.7%, and 57.7%. For patients with RT treatment duration <50 days, the 5-, 10-, and 15-year overall survivals were 85.5%, 78.9%, and 65.7% whereas for those with treatment duration > or = 50 days, the corresponding rates were 45.5%, 36.4%, and 36.4% (p = 0.01, log-rank test). Local control rate at 5, 10, and 15 years was 70.6% for patients with RT treatment duration <50 days and 45.5%, 36.4%, and 36.4% for patients with RT treatment duration > or =50 days (p = 0.05, log-rank test). The most common site of failure was local, found in 13 (38.2%) patients.

Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients.

Shaw EG, Evans RG, Scheithauer BW, Ilstrup DM, Earle JD.  Int J Radiat Oncol Biol Phys 1987 Oct;13(10):1457-62

In 33 patients undergoing operation and postoperative irradiation for intracranial ependymomas between January 1963 and December 1983, the tumor was grade 1 or 2 in 26 (79%) patients and grade 3 or 4 in 7 (21%). Operation consisted of only biopsy in 1 (3%), subtotal removal of tumor in 28 (85%), and gross total resection in 4 (12%). All patients received brain irradiation with a median dose of 4800 cGy. Seventeen (52%) patients also received spinal axis irradiation (median dose, 3000 cGy) which included 5 with high-grade tumors and 12 with low-grade infratentorial tumors. The relapse-free and overall survival rates at 5 years were 61% and 62%, respectively. Prognostic factors analyzed for statistically significant survival differences included age, sex, hydrocephalus, site, grade, extent of operation, extent of brain field, spinal axis irradiation, and brain dose. Grade was the only significant factor found: the 5-year survival of patients with low-grade ependymomas, 71%, was significantly better (p less than 0.04) than that of patients with high-grade ependymomas, 29%. Among the 31 patients evaluable for patterns of failure, treatment failed in 12 (39%) (10 only in the brain, 1 in the brain and spinal cord, and 1 only in the spine). All but one of the brain failures were at the site of the original primary lesion. Treatment failed in 4 of the 6 (67%) patients with high-grade tumor but in only 8 of the 25 (32%) with low grade tumor. Among the 7 low-grade infratentorial ependymomas treated with brain irradiation only, there was 1 treatment failure (in the spine; salvaged with further irradiation). Among the 12 patients with low-grade infratentorial tumors who received spinal axis irradiation, treatment failed in 1 (8%) (in the spine and also in the brain; patient subsequently died of disease). Nineteen (58%) patients remain alive; all but 2 of the patients who had recurrence died of their disease. This retrospective study suggests that: (a) patients with high-grade tumors have significantly poorer survival compared with those with low-grade tumors; (b) the main cause of death in ependymoma patients is intracranial failure at the primary site; and (c) craniospinal axis irradiation may not be necessary for patients with low-grade infratentorial ependymoma (localized irradiation alone may be adequate).

Intracranial ependymoma: results of radiotherapy at the University of Kentucky.

Chin HW, Maruyama Y, Markesbery W, Young AB.  Cancer 1982 Jun 1;49(11):2276-80

Sixteen patients with intracranial ependymoma received radiation treatment at the Department of Radiation Medicine, University of Kentucky, between 1962 and 1974. The majority of intracranial tumors occurred in children and had an infratentorial location; most adult tumors were supratentorial and adults had a greater tendency for high-grade malignant tumors. The overall five-year survival rate was 37% with 50% failure within three years. Survival appeared to be closely related to grade of tumor. Therefore, tumors were classified as ependymoma (well-differentiated) or ependymoblastoma (anaplastic, poorly differentiated). Five-year survival rate in patients with ependymoma tumors was 71% and with ependymoblastoma 11%. The data and a literature review indicate that radical radiotherapy of the ependymoma produces good patient survival; the ependymoblastoma is not adequately controlled with radical radiotherapy alone an adjuvant therapy may be necessary.

Stereotactic radiosurgery for recurrent ependymoma.

Stafford SL, Pollock BE, Foote RL, Gorman DA, Nelson DF, Schomberg PJ.  Cancer 2000 Feb 15;88(4):870-5

Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905,

Patients with recurrent intracranial ependymomas were evaluated to assess local control, overall survival, and complications from stereotactic radiosurgery (SRS). METHODS: Twelve patients (with a total of 17 tumors) with recurrent ependymoma underwent SRS. Local failure was defined as tumor progression within the prescription isodose volume, and marginal failure was defined as tumor progression adjacent to the SRS prescription isodose volume. Tumor progression away from the prescription volume was considered distant failure. Eleven of the 12 patients had undergone previous resection and external beam radiation therapy (46-56 Grays [Gy]; median, 54 Gy) before radiosurgery, and 1 patient had failure after complete resection alone. Age at SRS ranged from 5-56 years (median, 29 years). Three patients were female. The marginal tumor dose was 12-24 Gy (median, 18 Gy). One to 14 isocenters (median, 4 isocenters) were utilized to irradiate volumes of 0.3-15.5 cm(3) (median, 3.2 cm(3)). RESULTS: The duration of follow-up ranged from 2.5-60 months (median, 22.5 months). The median overall survival after SRS was 3.4 years (range, 1.4-5 years). In-field local control was achieved in 14 of the 17 tumor sites and estimated 3-year local control was 68%. There were two in-field failures and one marginal failure. Distant failure occurred in two patients. Two patients developed treatment-related complications after SRS. CONCLUSIONS: SRS provides good local tumor control for patients with recurrent intracranial ependymoma and may have a favorable impact on survival. SRS should be evaluated more extensively in the initial treatment of patients with ependymoma to minimize local failure after surgical management.

Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy.

Vanuytsel LJ, Bessell EM, Ashley SE, Bloom HJ, Brada M.  Int J Radiat Oncol Biol Phys 1992;23(2):313-9

Neuro-oncology Unit, Royal Marsden Hospital, Sutton, Surrey, UK.

Ninety-three patients with primary intracranial ependymoma were treated at the Royal Marsden Hospital, between 1952 and 1988, with postoperative radiotherapy. The survival probability at 5, 10, and 15 years was 51%, 42% and 31%, respectively, and the corresponding progression free survival (PFS) probability, 41%, 38%, and 30%. Tumor grade was the single most important prognostic factor for survival and PFS with gender of lesser prognostic significance. Treatment parameters were stratified for grade. In patients with low grade tumors survival and PFS were better following complete macroscopic excision compared to incomplete surgery. The extent of resection had no significant influence on survival or PFS in patients with high grade tumors. Extent of irradiation did not influence PFS, irrespective of tumor grade, while patients with high grade tumors had marginally better survival following extensive irradiation compared to more limited radiotherapy. The main problem in the treatment of ependymoma remains local progression which was the cause of death in all but two patients. New treatment strategies should focus on improvement of local control, especially in incompletely resected low grade tumors and all high grade tumors. The use of spinal irradiation is unlikely to significantly improve treatment results.

Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation.

Wallner KE, Wara WM, Sheline GE, Davis RL.  Int J Radiat Oncol Biol Phys 1986 Nov;12(11):1937-41

Twenty patients with intracranial ependymoma (16) or anaplastic ependymoma (4) received post-operative radiation therapy at the University of California, San Francisco from 1959 through 1981. No patient received prophylactic spinal irradiation. The actuarial survival at 5, 10, and 15 years for 15 patients with ependymoma who received greater than 45 Gy was 67, 57, and 46%, respectively. Only one patient (7%) developed clinically recognized spinal metastases; this patient was eventually shown to have tumor at the primary site, within the irradiated volume. Six of 11 patients treated with partial brain irradiation had an intracranial recurrence, versus 1 of 4 patients treated with whole brain irradiation. Three patients were autopsied after failing partial brain irradiation for an ependymoma and the site of failure was within the irradiated volume of each patient. Partial brain irradiation was used to treat 4 patients with anaplastic ependymoma. One developed a local recurrence within the irradiated volume. The other three survived longer than 10 years. At UCSF, most patients with low grade ependymomas are presently treated with partial brain irradiation, but whole brain plus spinal irradiation is used for anaplastic tumors.