|Ahead of print
Pediatric ependymoma: A single-center experience from a developing country
Mahmoud Hammad1, Maryhan Hosny1, Ehab M Khalil2, Ahmad S Alfaar3, Mohamed Fawzy1
1 Department of Pediatric Oncology and Hematology, National Cancer Institute (NCI), Cairo University; Department of Pediatric Oncology and Hematology, Children's Cancer Hospital of Egypt (CCHE/57357), Cairo, Egypt
2 Department of Radiation Oncology and Nuclear Medicine, National Cancer Institute (NCI), Cairo University, Cairo, Egypt
3 Department of Ophthalmology, Charité-Universtätsmedizin Berlin (Charité Medical University - Berlin), Berlin; Department of Ophthalmology, University of Leipzig, Leipzig, Sachsen, Germany
|Date of Submission||28-Apr-2019|
|Date of Decision||09-Nov-2019|
|Date of Acceptance||06-May-2020|
|Date of Web Publication||10-Dec-2020|
Department of Pediatric Oncology and Hematology, National Cancer Institute (NCI), Cairo University; Department of Pediatric Oncology and Hematology, Children's Cancer Hospital of Egypt (CCHE/57357), Cairo
Source of Support: None, Conflict of Interest: None
Background: Ependymomas are the third most common pediatric central nervous system (CNS) tumors, accounting for 6–12% of brain tumors in children. Management of these tumors remains challenging and recurrence occurs in over 50% of cases, mainly when complete resection is not achieved before radiotherapy. The 5-year overall survival (OS) ranges from 39 to 64%, with a 5-year progression-free survival (PFS) rate of 23–45%. The study aimed to describe the OS and PFS rates of cases of pediatric ependymoma. It also aimed to evaluate the effects of different variables on disease outcomes. Variables examined included patient age, the extent of surgical resection, radiotherapy and chemotherapy delivered, the histopathological subtype of the tumor, primary tumor location, and extent of the disease at presentation. Last, the challenges that potentially compromise treatment outcomes in resource-limited countries were to be highlighted.
Methods: This is a retrospective cohort study, representing a single-center experience that included 47 pediatric patients treated at the National Cancer Institute, Cairo University, between January 2009 and December 2014.
Results: Median follow-up stood at 23.5 months (range: 2–77 months). The average 3-year OS and PFS rates were 43.7 and 43.3%, respectively.
Conclusion: The extent of surgical excision (maximal resection) and the adequacy of postoperative radiotherapy were the only two factors that had significantly affected the outcome. Understandably, treatment outcomes for ependymomas in developing countries still lag behind best reported outcomes, mainly due to inadequate surgical excision and postoperative radiotherapy.
Keywords: Childhood cancers, developing countries, ependymoma, radiation therapy, surgery
Key Message Safe maximal resection and postoperative radiotherapy are the only two factors that affected the outcome of pediatric ependymoma. The inferior treatment outcome reflects the paucity of specialized cancer centers in Middle East African region.
| » Introduction|| |
Ependymomas are the third most common childhood group of brain tumors. They account for 6–12% of brain tumors in children less than 18 years of age. About 90% arise within the brain in the posterior fossa. The World Health Organisation (WHO) classifies ependymal tumors into three grades (grade I–III).
Gross-total resection (GTR) of the tumor along with postoperative irradiation has become a standard treatment, resulting in the most favorable prognoses. The 5-year survival rate for patients with GTR is 80–85%. Radiation is widely applied despite that experience — albeit limited — has shown that surgery alone could be sufficient for completely resected supratentorial nonanaplastic tumors as well as for spinal myxopapillary ependymoma.,
Radiation therapy in children <3 years of age has traditionally been limited, with attempts to be delayed by the use of chemotherapy to avoid side effects. Recently, conformal radiotherapy has been used for children aged 12–36 months, with the aim of minimizing the late neurologic effects while achieving better survival. Due to limited evidence for its postoperative/postradiation phase, chemotherapy is reserved for incompletely resected ependymomas and children younger than 3 years of age.
To date, there is limited data regarding the burden of brain tumors in developing countries. Herein, we aimed to describe the overall survival (OS) and progression-free survival (PFS) of pediatric ependymomas treated at the National Cancer Institute (NCI), Egypt. We also intended to highlight some barriers to effective pediatric ependymoma management in resource-limited countries including, inadequate tumor resection and skipping postoperative radiotherapy.
| » Methods|| |
This retrospective study included 47 pediatric cases treated at the National Cancer Institute, Cairo University (NCI) between January 2009 and December 2014. Patients were followed up until September 2016. The study was approved by the institutional review board.
All of the patients underwent their surgeries outside NCI. Histopathology was reviewed internally before starting the treatment. Recurrent ependymoma and patients previously treated with chemotherapy and/or radiotherapy were excluded from this study. Data collected from records included age, gender, presenting symptoms, radiological reports, tumor site, cerebrospinal fluid (CSF) cytology, the extent of surgical resection, histopathology, as well as details of treatment.
Records indicated that patients had undergone gross total resection (GTR, >99% resection) or near total resection (NTR, >90% resection) or a subtotal resection (STR, <90% resection). Upfront biopsy rather than surgical tumor resection was performed to confirm the pathology and only in tumors that were considered to be irresectable at presentation with safe surgery being unfeasible. Following surgery, patients received adjuvant radiotherapy with or without chemotherapy.
Patients were simulated on computed tomography (CT) scanner SOMATOM and axial magnetic resonance imaging (MRI) T1-weighted images were used for fusion purposes during the planning stage. External beam 3-D conformal (3DCRT) or intensity-modulated (IMRT) radiotherapy was tailored according to the extent of tumor resection and histological grade. Gross tumor volume (GTV) included the postoperative tumor bed and residual tumor. The clinical target volume (CTV) encompassed 0.5-1cm expansion from the GTV. A planning target volume (PTV) of 0.3 (IMRT) to 0.5 cm (3DCRT) geometric margin to account for daily setup variation was constructed for 3-D treatment planning system dose (TPS) calculation (XiO and Monaco-TPS). Patients with grade II and anaplastic ependymoma received a dose of 54 and 59.6 Gy, respectively. Patients with evidence of CSF involvement through cytology or MRI seedlings were treated with craniospinal radiotherapy (CSI) to a dose of 30–36 Gy followed by tumor bed (TB) boost of 18–24 Gy with a boost dose of 5.4–9 Gray (for isolated gross spinal drop metastasis).
Neuro-oncology plans were tailored according to each patient's clinical scenario. Chemotherapy was chosen for patients with less than GTR, with a plan to conduct a second-look surgery. Chemotherapy was also chosen for children <3 years in an attempt to delay radiotherapy. Chemotherapy regimens consisted of four courses; courses (A and B) consisted of vincristine on days 1 and 8 of courses A and B, carboplatin on day 1 of courses A and B, and cyclophosphamide on days 1 and 2 of course A only. Patients received etoposide on days 1–3 of course B only.
Patients' distribution among groups was tabulated as numbers (N) and percentages (%). Pearson's χ2 test was used to compare the distribution between categorical variables and the Log-Rank test to compare survival probabilities between the subgroups. PFS was calculated from the date of diagnosis to the date of relapse, progression, or death, whichever came first. All P values were calculated as two-sided P values. P values <0.05 were considered significant.
| » Results|| |
Patient characteristics are summarized in [Table 1]. Median age at diagnosis was 4 years (range: 1–18 years). The most frequent manifestations were increased intracranial tension (n = 39, 83%), lower limb weakness (n = 21, 44.7%), visual disturbances (n = 17, 36.2%), and convulsions (n = 8, 17%).
Most patients had presented with infratentorial tumors (63.8%). The majority of cases had grade-II tumors (68.1%). CSF dissemination was detected by CSF cytology in eight patients, and spinal seedlings were detected by MRI in five others. CSF involvement was detected by both CSF cytology and MRI in one other patient. There were no available initial CSF cytology reports and MRI spine for 10 (21.3%) and 7 (14.9%) patients, respectively [Table 1].
Out of 47 cases, 32 (68.1%) patients underwent surgical resection, GTR was achieved in 8 (17%) patients, 7 cases had upfront surgery, and 1 case had GTR after three cycles of chemotherapy (second-look surgery). On the other hand, NTR and STR were conducted for 6 (12.8%) and 18 (38.3%) patients, respectively. Surgery was not feasible in 15/47 (31.9%) cases, including two cases with spinal ependymomas, where a diagnostic biopsy was the only surgical intervention conducted [Table 2].
In total, 34 patients (72.3%) were treated with radiotherapy, 22 (46.8%) of them received localized radiotherapy. In all, 11 patients (23.4%) received craniospinal irradiation, including one case with spinal ependymoma.
In total, 13 patients (27.7%), including four infants, received chemotherapy. Treating physicians managed to conduct a second-look surgery on one patient only. Seven cases (14.9%) received combined radiotherapy and chemotherapy, and six cases (12.8%) received chemotherapy without radiotherapy. Cases managed with chemotherapy alone only included two infants, two with irresectable tumors, one case due to delay in radiotherapy (unavailability), and one patient suffering from an intraspinal lesion. This last patient was subjected to radiotherapy that proved intolerable.
Out of 47 patients, 12 (25.5%) achieved complete response (CR); 8 (17%) had partial response (PR); 22 (46.8%) suffered from progressive disease; and 5 (10.6%) died early while on treatment during supportive period before response assessment.
The median follow-up time was 23.5 months (range: 2–77 months). The OS and PFS rates at three years were 43.7 and 43.3%, respectively. Surgeries achieving GTR yielded significantly better OS and PFS rates compared with those that resulted in less than GTR (P = 0.048 and 0.016, respectively) [Figure 1]. Patients who were treated with postoperative radiotherapy had better OS and PFS rates compared with those who were not (P < 0.001). Further survival analyses are shown in [Figure 1] and [Table 3]. Patients with NTR had low 3-year PFS and OS rates. This could be attributed to the incompletion of the follow-up period of a large number of patients. Three patients died between 5 and 28 months of follow-up, one was lost to follow-up after 10 months, another patient was lost to follow-up after 45 months with a progression after 27 months, and one patient remained alive but with the last follow-up reported at 29 months after diagnosis.
|Figure 1: Overall (a, c, e, g) and Progression-free (b, d, f, h) survival based on treatment. STR: Subtotal resection, NTR: Near-total resection, GTR: Gross-total resection. Circles: censored patients' status|
Click here to view
|Table 3: The 3-year outcome (OS and PFS) in relation to different prognostic factors|
Click here to view
| » Discussion|| |
The Egyptian National Population Cancer Registry has estimated that the number of cases of childhood central nervous system (CNS) tumors to have stood at 6004 in 2013. The incidence of ependymomas in Egypt is similar to other regions and accounts for 10% of all cases of pediatric CNS tumors. In two national hospital-based analyses of pediatric CNS cases, ependymomas accounted for 8.7% and 10.7 of CNS tumors, respectively.,
There have been few reports in the literature with regards to pediatric ependymomas from the Middle East African region. Comparable to the results of the current study, El-Gaidi reported a predilection for grade II (82.2%) and infra-tentorial region (71%) tumors. A past study conducted at our center reported that pediatric patients had an inferior 10-year relapse-free survival (RFS) (39%) compared with their adult counterparts (69%) (P = 0.059). Authors of that study postulated the cause of this difference in RFS to be higher percentage of high-grade tumors detected in the pediatric cases.
In this study, the percentage of patients <3 years of age stood at 23.4%. In other studies, conducted in Egypt, reported percentages of cases <5 years of age stood at 52.5% and even lower for cases ≤4 years standing at 10.7%. Although the current study found no significant differences in PFS (P = 0.4) or OS (P = 0.24) according to patient age (<3 vs ≥3 year olds), it is important to note the comparatively smaller sample size of children <3 years of age. Similarly, the AIEOP protocol reported no significant differences in the 5-year PFS rates of patients by age, yet found significant differences in OS rates between the <3 and the ≥3-year-old groups (70.3% vs 84.8%; P = .039). The authors of that study attributed the lower OS rates in younger group to the less aggressive second treatment offered at relapse.
Many authors have expressed concern about long-term toxicities of radiotherapy, and some reported that only 30% of children <3 years old received postoperative radiation. Many studies have however shown that attempts to delay radiation therapy had yielded inferior results compared with immediate postoperative radiation., One Egyptian study reported that patients <3 years of age (six cases) had tolerated radiotherapy doses that ranged from 5400 to 5940 cGy with a median of 5580 cGy delivered over 42–45 days without gaps (except for one patient). The current trend, as indicated by recent reports, is to perform multiple excisions and to repeat irradiation in infantile ependymoma cases., The less aggressive approach to radiotherapy, as detailed in our study, may be one factor that led to poorer outcomes among the <3-year-old patients. Other potential factors in this study that may explain the inferior treatment outcomes for children <3 years, where 7/11 died, was the difficulty to attempt proper resection, as only one case underwent GTR, while two and eight cases underwent NTR and less than NTR, respectively. Furthermore, four patients skipped radiation therapy due to the malfunction of radiotherapy devices, which led to tumor progression.
Among studied patients <3 years of age, supratentorial tumors stood at only 18.2%, while in patients ≥3 years of age, a larger number (21/30) presented with infratentorial lesions. No observed statistically significant difference between age at presentation and site of tumor origin (P = 0.22). Unlike our results, Massimino et al. reported a significant association between patient age at presentation and tumor location with a higher percentage of infratentorial tumors among those <3 years of age (88.9%) compared with patients ≥3 years of age (60.9%); P = 0.001.
Several reports have related that patients with supratentorial ependymomas had demonstrated better prognoses compared with patients with infratentorial location.,, To the contrary, our results and others have failed to demonstrate a significant difference in prognosis by location of tumor.,
The impact of histological grading on outcome remains an unsettled debate, and its utility may be confounded by anatomic compartment. Within our patient sample, different histological grades demonstrated no statistically significant differences in survival rates (P = 0.26 in OS and P = 0.37 for PFS). This was in contrast to other studies that have reported higher 5-year PFS and OS rates among grade II tumors (75.3 and 90.5%), compared with grade III tumors (57.0 and 73.3%) (P = 0.018 in PFS and P = 0.031 in OS). Merchant et al. also reported a 5 year 86.4% event-free survival (EFS) and 91.9% OS rates in patients with grade II tumors; and 61.3% EFS and 78.3% OS for in patients with grade III tumors (P = 0.005 and P = 0.006 in OS). In our study, 70.2% of patients suffered low-grade tumors. However, few had GTR (18.1%) and NTR (15.1%), which could explain the inferior outcome.
Surgical resection is considered the most consistent independent prognostic variable, yet GTR can be achieved only in 50–80% of patients due to inaccessible tumor locations and the risk of neurovascular injury. Due to paucity of specialized pediatric neuro-oncology centers and skilled surgeons in our region, successfully performed GTRs are uncommon. Also, long waiting lists result in further deterioration of a patient's general condition and lead to tumor progression.
In our cohort, GTR was achieved in only eight cases (17%) and NTR in six patients (12.8%). In one study with comparable results, only 23 out of 48 patients (52% were children) had gross excision. In the present study, the 3-year OS and PFS for GTR stood at 100% for each. Other studies have reported 10-year OS rates of 83% versus 43% in patients who had undergone GTR plus radiotherapy versus patient who had undergone STR plus radiotherapy. Haresh et al. reported 2-year disease-free survival rates of 55% versus 30% for patients who had undergone GTR versus those who had undergone STR, respectively, with no statistically significant differences. It is worth noting that in a previous study, GTR was achieved in 42.5% of patients; higher percentage compared with that of the current study. Our center reported in a previous study higher RFS rates in a patient group that had undergone gross resection (62%) than those with who had undergone partial resection (45%). The difference was not statistically significant however (P = 0.168).
Postoperative involved field radiotherapy is considered the standard of care for pediatric ependymoma. Our data showed significant improvement of survival rates (3-year OS and PFS) in patients who had received radiotherapy (n = 34; 72.3%) versus those who had not (P < 0.001). Comparable studies have reported 5-year OS and EFS rates at 82.9 and 64.4% for patients who had received radiotherapy compared with rates of 38.1 and 12.7% for those who had not (P = 0.018 in OS, P = 0.011 in EFS). Pejavar et al. reported that radiation therapy was a significant predictor of PFS (P = 0.045) and found significance even after adjusting for the extent of resection in a multivariate analysis (P = 0.04). McGuire et al. also found that radiotherapy was associated with improved outcome, but they demonstrated this survival benefit for infratentorial tumors only. In that study, the 5-year survival rate stood at 57.1% for patients who had received radiotherapy versus 48.2% for those who had not (P = 0.018). The lack of enough new radiotherapy modalities, whether those based on conformal or intensity-modulated photon and proton therapy, is still a barrier to the achievement of better outcomes in developing countries. Such modalities would open the gate to relatively safer irradiation therapy in the pediatric age group, with less long-term toxicities. Another stumbling block is overcrowding of treatment centers with few available machines. In many cases, one tertiary center may serve many hospitals, leading to delays or omissions of needed postoperative irradiation for patients.
There is limited evidence supporting the role of chemotherapy in the treatment of ependymoma. In our study, patients who had received chemotherapy (13/47) had worse disease outcomes compared to those who had not, with 3-year OS and PFS rates of 23.1 and 23.1% versus 51.6 and 51.5%, respectively (P = 0.042 for OS). The computed poor outcome associated with chemotherapy treatment in this study could be explained by the small patient sample size and the fact that six patients had received chemotherapy without radiotherapy. Boström et al. and others reported similar results. They stated that treatment with chemotherapy alone was associated with worse outcomes compared with those who had undergone radiation therapy alone., In the AIEOP protocol study, adding VEC (vincristine, etoposide and cyclophosphamide) chemotherapy after radiotherapy for patients with completely resected anaplastic ependymomas did not improve outcomes compared with those with completely resected classic grade II tumors. Conversely, the German Hirntumoren (HIT) trials reported better results in a subset of patients who had received adjuvant chemotherapy with a sandwich or postradiotherapy courses. Pairing with expert centers in developing countries may facilitate the successful implementation of nonconventional interventions and help foster the use of individualized treatment protocols. A study from Jordan showed a favourable impact for the integration of telemedicine in facilitating the knowledge transfer and improving patients care.
In conclusion, safe maximal resection and postoperative radiotherapy were the only two factors that affected the outcome of ependymoma in this study. Other factors, such as age, histopathologic subtypes, tumor location or grade, the use of chemotherapy, and extent of the disease showed no significant effect on survival outcomes. The importance of this study is to uncover some of the problems that are faced by developing countries with high burden of CNS tumors. Few studies have covered this area from our side. The comparatively inferior outcomes of treatment of pediatric ependymomas in general, and especially for cases <3 years of age, is a sad reflection of the paucity of specialized cancer centers with enough modern radiation equipment. It is also a reflection of the need to improve our surgical skills. Initiation of international collaboration, including telemedicine, can help improve outcomes.
The authors would like to acknowledge the help of Dr. Manar Moneer, Professor of Biostatistics, National Cancer Institute for conducting the statistical analysis of the study data and Dr. Mohamed-Ismail Rakha for language editing.
Financial support and sponsorship
Dr. AA is funded by a scholarship from The German Academic Exchange Service (DAAD).
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Andreiuolo F, Puget S, Peyre M, Dantas-Barbosa C, Boddaert N, Philippe C, et al
. Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 2010;12:1126-34.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al
. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.
Aizer AA, Ancukiewicz M, Nguyen PL, MacDonald SM, Yock TI, Tarbell NJ, et al
. Natural history and role of radiation in patients with supratentorial and infratentorial WHO grade II ependymomas: Results from a population-based study. J Neurooncol 2013;115:411-9.
Lucchesi KM, Grant R, Kahle KT, Marks AM, DiLuna ML. Primary spinal myxopapillary ependymoma in the pediatric population: A study from the surveillance, epidemiology, and end results (SEER) database. J Neurooncol 2016;130:133-40.
von Hoff K, Kieffer V, Habrand J-L, Kalifa C, Dellatolas G, Grill J. Impairment of intellectual functions after surgery and posterior fossa irradiation in children with ependymoma is related to age and neurologic complications. BMC Cancer 2008;8:15.
Merchant TE, Bendel AE, Sabin N, Burger PC, Wu S, Boyett JM. A Phase II trial of conformal radiation therapy for pediatric patients with localized ependymoma, chemotherapy prior to second surgery for incompletely resected ependymoma and observation for completely resected, differentiated, supratentorial ependymoma. Int J Radiat Oncol Biol Phys 2015;93:S1.
Lin FY, Chintagumpala M. Advances in management of pediatric ependymomas. Curr Oncol Rep 2015;17:1-7.
Children's Oncology Group. Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma [Internet]. [cited 2018 Dec 09]. Available from: https://clinicaltrials.gov/ct2/show/NCT01096368
Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in Egypt: Results of the national population-based cancer registry program. J Cancer Epidemiol 2014;2014:1-18.
Vitanza NA, Partap S. Pediatric ependymoma. J Child Neurol 2016;31:1354-66.
Ezzat S, Kamal M, El-Khateeb N, El-Beltagy M, Taha H, Refaat A, et al
. Pediatric brain tumors in a low/middle income country: Does it differ from that in developed world? J Neurooncol 2016;126:371-6.
El-Gaidi MA. Descriptive epidemiology of pediatric intracranial neoplasms in Egypt. Pediatr Neurosurg 2011;47:385-95.
El-Baradie MM, Abd-Elhameed A, Moneer MM, Lotayef MM, Nasr AM, El-Sebaee M, et al
. Ependymoma: Outcome and prognostic factors. J Egypt Natl Canc Inst 2003;15:73-81.
Massimino M, Miceli R, Giangaspero F, Boschetti L, Modena P, Antonelli M, et al
. Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma. Neuro Oncol 2016;18:1451-60.
Grill J, Le Deley M-C, Gambarelli D, Raquin M, Couanet D, Pierre-Kahn A, et al
. Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: A multicenter trial of the French Society of Pediatric Oncology. J Clin Oncol 2001;19:1288-96.
Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, et al
. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 1993;328:1725-31.
Zaghloul M, Elbeltagy M, Mousa A, Eldebawy E, Amin A. Post-operative radiotherapy for fourth ventricle ependymoma in children below 3 years old: Good preliminary results. Neuro Oncol 2012;14:i33-42.
Liu AK, Foreman NK, Gaspar LE, Trinidad E, Handler MH. Maximally safe resection followed by hypofractionated re-irradiation for locally recurrent ependymoma in children. Pediatr Blood Cancer 2009;52:804-7.
Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys 2008;71:87-97.
Vaidya K, Smee R, Williams JR. Prognostic factors and treatment options for paediatric ependymomas. J Clin Neurosci 2012;19:1228-35.
Perilongo G, Massimino M, Sotti G, Belfontali T, Masiero L, Rigobello L, et al
. Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group. Med Pediatr Oncol 1997;29:79-85.
Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: A prospective study. Lancet Oncol 2009;10:258-66.
McGuire CS, Sainani KL, Fisher PG. Both location and age predict survival in ependymoma: A SEER study. Pediatr Blood Cancer 2009;52:65-9.
Pejavar S, Polley MY, Rosenberg-Wohl S, Chennupati S, Prados MD, Berger MS, et al
. Pediatric intracranial ependymoma: The roles of surgery, radiation and chemotherapy. J Neurooncol 2012;106:367-75.
Haresh K, Gandhi A, Mallick S, Benson R, Gupta S, Sharma D, et al
. Prognostic factors and survival outcomes of intracranial ependymoma treated with multimodality approach. Indian J Med Paediatr Oncol 2017;38:420-6.
] [Full text]
Rogers L, Pueschel J, Spetzler R, Shapiro W, Coons S, Thomas T, et al
. Is gross-total resection sufficient treatment for posterior fossa ependymomas? J Neurosurg 2005;102:629-36.
Liu AP-Y, Shing MM-K, Yuen H-L, Li C-H, Ling S-C, Luk C-W, et al
. Timing of adjuvant radiotherapy and treatment outcome in childhood ependymoma. Pediatr Blood Cancer 2014;61:606-11.
Timmermann B, Kortmann R-D, Kühl J, Rutkowski S, Dieckmann K, Meisner C, et al
. Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: Results of the prospective German brain tumor trials HIT-SKK 87 and 92. Radiother Oncol 2005;77:278-85.
Boström A, Boström J, Hartmann W, Pietsch T, Feuss M, von Lehe M, et al
. Treatment results in patients with intracranial ependymomas. Cent Eur Neurosurg 2011;72:127-32.
Cage TA, Clark AJ, Aranda D, Gupta N, Sun PP, Parsa AT, et al
. A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediatr 2013;11:673-81.
Qaddoumi I, Mansour A, Musharbash A, Drake J, Swaidan M, Tihan T, et al
. Impact of telemedicine on pediatric neuro-oncology in a developing country: The Jordanian-Canadian experience. Pediatr Blood Cancer 2007;48:39-43.
[Table 1], [Table 2], [Table 3]