Adjuvant radiotherapy versus observation after gross total resection of WHO grade II ependymoma: a systematic review and individual-participant data meta-analysis.

BACKGROUND: The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location. METHODS: PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old). RESULTS: Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation. CONCLUSIONS: Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.

Brainstem toxicity after proton or photon therapy in children and young adults with localized intracranial ependymoma: A French retrospective study.

BACKGROUND AND PURPOSE: Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data. MATERIAL AND METHODS: We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data. RESULTS: Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 53­60). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.0­9.4) after radiation therapy, and median offset at 7.6 months (range: 3.7­7.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy. CONCLUSION: Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified.

Incorporating variable RBE in IMPT optimization for ependymoma.

PURPOSE: To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization. METHODS: This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LETd ) and dose; (3) variable RBE optimization (VarRBEopt) using a recent phenomenological RBE model developed by McNamara et al.; and (4) hybrid RBE optimization (hRBEopt) assuming constant RBE for the target and variable RBE for organs at risk. By normalizing each plan to obtain the same target coverage in either constant or variable RBE, we compared dose, LETd , LET-weighted dose, and equivalent uniform dose between the different optimization approaches. RESULTS: We found that the LETopt plans consistently achieved increased LET in tumor targets and similar or decreased LET in critical organs compared to other plans. On average, the VarRBEopt plans achieved lower mean and maximum doses with both constant and variable RBE in the brainstem and spinal cord for all 10 patients. To compensate for the underdosing of targets with 1.1 RBE for the VarRBEopt plans, the hRBEopt plans achieved higher physical dose in targets and reduced mean and especially maximum variable RBE doses compared to the ConstRBEopt and LETopt plans. CONCLUSION: We demonstrated the feasibility of directly incorporating variable RBE models in IMPT optimization. A hybrid RBE optimization strategy showed potential for clinical implementation by maintaining all current dose limits and reducing the incidence of high RBE in critical normal tissues in ependymoma patients.

Challenges in Treating Childhood Infratentorial Ependymoma: A Low- and Middle-Income Country Experience.

PURPOSE: Patients and physicians in low- and middle-income countries (LMICs) face challenges owing to limited expertise and suboptimal access to appropriate diagnostic and treatment modalities. We report our experience in treating posterior fossa ependymoma (PFE) at MAHAK, a charity organization in Iran whose radiation oncology department is the only one exclusively dedicated to childhood cancer in the whole country. METHODS AND MATERIALS: Pediatric patients with PFE referred to MAHAK between November 2008 and January 2016 were identified. Details on investigations and management done before referral were collected. Management at MAHAK and patient outcomes were analyzed. RESULTS: Of 80 patients diagnosed as having ependymoma, 54 with PFE were identified. Forty-three patients received adjuvant radiation therapy, and 11 were irradiated initially after recurrence. At a median follow-up of 5.1 years (range, 0.3-9.7 years), the latter group had the worst outcome, with a 5-year overall survival (OS) rate of 27% (95% CI, 7%-54%). Patients who started radiation therapy within 77 days after initial surgery had a better outcome compared with those who started later (5-year OS: 74% vs 32%; P = .05). Compliance with follow-up recommendations was poor. Only 22% of the patients had at least 2 IQ test assessments, and 50% showed some decline over time. Three cases of growth hormone deficiency were detected, but none of the patients received replacement therapy. CONCLUSIONS: Access to pediatric neurosurgery, anesthesia, and timely radiation therapy are among the most challenging obstacles to be overcome in LMICs. Our series confirmed that chemotherapy is not an appropriate option for delaying radiation therapy, especially in young children. The importance of long-term follow-up should be acknowledged by the parents and medical team.

Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma.

PURPOSE: We developed and tested a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources similar to those for regular intensity-modulated proton therapy (IMPT) plans and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries. METHODS: Our IMPAT planning method consists of a geometry-based energy selection step with major scanning spot contributions as inputs computed using ray-tracing and single-Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle such that each target voxel is covered by sufficient scanning spots as specified by the planner, with dose contributions above the specified threshold. Finally, IMPAT plans are generated by robustly optimizing scanning spots of the selected energy layers using a commercial proton treatment planning system (TPS). The IMPAT plan quality was assessed for four ependymoma patients. Reference three-field IMPT plans were created with similar planning objective functions and compared with the IMPAT plans. RESULTS: In all plans, the prescribed dose covered 95% of the clinical target volume (CTV) while maintaining similar maximum doses for the brainstem. While IMPAT and IMPT achieved comparable plan robustness, the IMPAT plans achieved better homogeneity and conformity than the IMPT plans. The IMPAT plans also exhibited higher relative biological effectiveness (RBE) enhancement than did the corresponding reference IMPT plans for the CTV in all four patients and brainstem in three of them. CONCLUSIONS: The proposed method demonstrated potential as an efficient technique for IMPAT planning and may offer a dosimetric benefit for patients with ependymoma or tumors in close proximity to critical organs. IMPAT plans created using this method had elevated RBE enhancement associated with increased linear energy transfer (LET) in both targets and abutting critical organs.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

PURPOSE: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT. METHODS: Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis. RESULTS: All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED. CONCLUSION: For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.

Conformal Radiation Therapy for Ependymoma at Age ≤3 Years: A 25-Year Experience.

PURPOSE: Adjuvant radiation therapy (RT) affects survival after surgery for young children (age <3 years) diagnosed with intracranial ependymoma. Conformal photon RT promised to spare normal tissue and was introduced more than 25 years ago to improve outcomes for these vulnerable patients. Long-term results for those first treated with conformal methods provide valuable information and serve as a comparison against newer methods. METHODS AND MATERIALS: Between 1997 and 2018, 101 patients <3.1-years-old were treated with conformal and intensity modulated photon therapy after definitive surgery for intracranial ependymoma. The median age at RT was 2.1 years and the time from diagnosis to the start of RT was 10 weeks. The extent of resection was gross-total in 82%, and 38% underwent more than 1 attempt at resection. The total prescribed dose was 54 to 59.4 Gy at 1.8 Gy per fraction. RESULTS: The 10-year event-free and overall survivals were 58.5% ± 5.0% and 72.6% ± 4.5%, respectively, with a median follow-up of 18.4 years (range, 4.2-23.3 years). Tumor progression occurred in 34 patients with a median time of 1.6 years. Death occurred in 34 patients from ependymoma (n = 24), secondary malignancy (n = 6), necrosis (n = 2), shunt failure (n = 1), and anaphylactic reaction (n = 1). Twenty-three patients developed a secondary tumor including 6 cases of fatal high-grade glioma. Of the surviving cohort and those ≥18 years old, 98% obtained a high school diploma, 64% had a current driver's license, 89% were students or employed full or part time, 32% were living independently, and 70% received higher education or training. CONCLUSIONS: Long-term results of children treated using photon conformal RT after surgery demonstrate that adjuvant RT resulted in long-term disease control and functional independence. These results point to the need for new treatment strategies to improve tumor control and provide investigators hope that newer RT methods will further reduce complications.

Infantile metastatic ependymoma with a novel molecular profile and favorable outcome to intensive chemotherapy without irradiation: Case-based review.

Ependymal tumors are the third most common brain tumor under 14 years old. Even though metastatic disease is a rare event, it affects mostly young children and carries an adverse prognosis. The factors associated with dissemination and the best treatment approach have not yet been established and there is limited published data on how to manage metastatic disease, especially in patients under 3 years of age. We provide a review of the literature on clinical characteristics and radiation-sparing treatments for metastatic ependymoma in children under 3 years of age treated. The majority (73%) of the identified cases were above 12 months old and had the PF as the primary site at diagnosis. Chemotherapy-based approaches, in different regimens, were used with radiation reserved for progression or relapse. The prognosis varied among the studies, with an average of 50%-58% overall survival. This study also describes the case of a 7-month-old boy with metastatic posterior fossa (PF) ependymoma, for whom we identified a novel SPECC1L-RAF1 gene fusion using a patient-centric comprehensive molecular profiling protocol. The patient was successfully treated with intensive induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic progenitor cell rescue (AuHSCR). Currently, the patient is in continuous remission 5 years after his diagnosis, without radiation therapy. The understanding of the available therapeutic approaches may assist physicians in their management of such patients. This report also opens the perspective of newly identified molecular alterations in metastatic ependymomas that might drive more chemo-sensitive tumors.

Multifocal and Multiphasic Demyelinating Lesions After Radiation for Ependymoma in a Pediatric Population.

Radiation treatment is widely used to address unresectable intracranial tumors. Owing to the nature of therapy, healthy tissue and diseased regions will be affected. New insights have shown that not only does this impact brain parenchyma but it causes changes in fluid status, myelination, and the integrity of the blood-brain barrier. This alters how peripheral and central immune systems interact, perpetuating neuroinflammation. Rare case reports in the adult literature have described multifocal, multiphasic demyelinating lesions after radiation. Here we describe 2 pediatric cases of relapsing demyelination after and in conjunction with radiation therapy for ependymoma, consistent with a multiple sclerosis phenotype. Insights into the underpinnings of multiple sclerosis show peripheral inflammation, blood-brain barrier disruption, and antigenic mimicry stimulating neuroinflammation. Here we investigate the role that radiation, tumor burden, and systemic inflammation may play in creating demyelinating disorders. We strive to elucidate common pathophysiology between radiation-induced brain injury and multiple sclerosis.

Evaluation of dose, volume, and outcome in children with localized, intracranial ependymoma treated with proton therapy within the prospective KiProReg Study.

BACKGROUND: Radiotherapy (RT) of ependymoma in children is an important part of the interdisciplinary treatment concept. However, feasibility and dose concepts are still under investigation, particularly in very young children. The aim of this study was to evaluate the standard dose and volume of proton therapy (PT) in children with ependymoma. METHODS: In this analysis, 105 patients with localized, intracranial ependymoma under the age of 18 years treated with PT between 2013 and 2018 were included. Patient characteristics, treatment, outcome, and follow-up data were analyzed using descriptive statistics, Kaplan-Meier, and Cox regression analysis. RESULTS: The median age of patients at PT was 2.8 years (0.9-17.0 years). The molecular subgroup analysis was performed in a subset of 50 patients (37 EP-PFA, 2 EP-PFB, 7 EP-RELA, 2 EP-YAP, 2 NEC [not elsewhere classified]). The median total dose was 59.4 Gy (54.0-62.0 Gy). The median follow-up time was 1.9 years. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 93.7%, 74.1%, and 55.6%, respectively. Within univariable analysis, female gender and lower dose had a positive impact on OS, whereas age ≥4 years had a negative impact on OS and PT given after progression had a negative impact on PFS. In the multivariable analysis, multiple tumor surgeries were associated with lower PFS. New ≥3° late toxicities occurred in 11 patients. CONCLUSION: For children with localized ependymoma, PT was effective and well tolerable. Multiple surgeries showed a negative impact on PFS.

Lumbar Laminoplasty for Resection of Myxopapillary Ependymoma of the Conus Medullaris: 2-Dimensional Operative Video.

Myxopapillary ependymomas are slow-growing tumors that are located almost exclusively in the region of the conus medullaris, cauda equina, and filum terminale of the spinal cord. Surgical intervention achieving a gross total resection is the main treatment modality. If, however, a gross total resection cannot be achieved, surgery is augmented with radiation therapy. In this video, we present the case of a 27-yr-old male with persistent back pain and radiculopathy who was found to have a myxopapillary ependymoma that was adherent to the conus. Preoperative imaging demonstrated that the tumor was displacing the conus and nerve roots ventrally. A laminoplasty at L1-L2 was performed with near-total resection because of the intimate involvement of neural tissue. The key features of the video include performing laminoplasty and rationale, and performing maximum safe tumor resection with a combination of bipolar cautery, suction, and ultrasonic aspiration augmented with frequent stimulation, gel foam pledgets intradurally, and achieving a watertight closure of the dura and fascia. The patient tolerated the surgery well without any complications. Given his gross residual disease along the conus and young age, he was at a high risk for continued tumor growth without adjuvant therapy, with a recurrence rate of roughly 33% to 45% in patients who underwent subtotal resection. With the addition of adjuvant radiation therapy, the recurrence rate is 20% to 29%.1,2 He was discharged to home with a plan for conventional fractionated external beam radiation. At the most recent follow-up, he reported decreased back pain and radiculopathy. Appropriate patient consent was obtained.

Proton Therapy for Pediatric Ependymoma: Mature Results From a Bicentric Study.

PURPOSE: To report the long-term efficacy and toxicity of proton therapy for pediatric ependymoma. METHODS AND MATERIALS: Between 2000 and 2019, 386 children with nonmetastatic grade 2/3 intracranial ependymoma received proton therapy at 1 of 2 academic institutions. Median age at treatment was 3.8 years (range, 0.7-21.3); 56% were male. Most (72%) tumors were in the posterior fossa and classified as World Health Organization grade 3 (65%). Eighty-five percent had a gross total or near total tumor resection before radiation therapy; 30% received chemotherapy. Median radiation dose was 55.8 Gy relative biologic effectiveness (RBE) (range, 50.4-59.4). RESULTS: Median follow-up was 5.0 years (range, 0.4-16.7). The 7-year local control, progression-free survival, and overall survival rates were 77.0% (95% confidence interval [CI], 71.9%-81.5%), 63.8% (95% CI, 58.0%-68.8%), and 82.2% (95% CI, 77.2%-86.3%), respectively. Subtotal resection was associated with inferior local control (59% vs 80%; P < .005), progression-free survival (48% vs 66%; P < .001), and overall survival (70% vs 84%; P < .05). Male sex was associated with inferior progression-free (60% vs 69%; P < .05) and overall survival (76% vs 89%; P < .05). Posterior fossa tumor site was also associated with inferior progression-free (59% vs 74%; P < .05) and overall survival (79% vs 89%; P < .01). Twenty-one patients (5.4%) required hearing aids; of these, 13 received cisplatin, including the 3 with bilateral hearing loss. Forty-five patients (11.7%) required hormone replacement, typically growth hormone (38/45). The cumulative incidence of grade 2+ brain stem toxicity was 4% and occurred more often in patients who received >54 GyRBE. Two patients (0.5%) died of brain stem necrosis. The second-malignancy rate was 0.8%. CONCLUSION: Proton therapy offers disease control commensurate with modern photon therapy without unexpected toxicity. The high rate of long-term survival justifies efforts to reduce radiation exposure in this young population. Independent of radiation modality, this large series confirms extent of resection as the most important modifiable factor for survival.

Grade III intradural extramedullary anaplastic ependymoma managed with near-complete resection and adjuvant radiotherapy: a case report.

INTRODUCTION: Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review. CASE PRESENTATION: A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resected specimen had immunoreactivity for EMA/Vimentin/CD56/CD99/S-100/GFAP, with a Ki-67 index of ~35%. These factors led to the diagnosis of anaplastic ependymoma. Seven weeks postoperatively he received adjuvant radiotherapy to the whole brain and the whole spinal cord. He recovered as an independent ambulator without recurrence 1 year postoperatively. DISCUSSION: Because of their rarity, there are no clear treatment or adjuvant therapy guidelines for spinal anaplastic ependymoma. Adjuvant radiotherapy to the whole brain and spinal cord was necessarily indicated after near-total resection. Although the patient's condition has not recurred 1 year after surgery, careful and serial follow-up is necessary for this individual.

Clinical outcomes in a large pediatric cohort of patients with ependymoma treated with proton radiotherapy.

BACKGROUND: Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy (RT). Proton RT (PRT) enables superior sparing of critical structures compared with photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT. METHODS: One hundred fifty patients (<22 y) with World Health Organization grades II/III ependymoma were treated with PRT between January 2001 and January 2019 at Massachusetts General Hospital. Demographic, tumor, and treatment-related characteristics were analyzed. Event-free survival (EFS), overall survival (OS), and local control (LC) were assessed. RESULTS: Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n = 145) at 7 years were 63.4%, 82.6%, and 76.1%. Fifty-one patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. One hundred sixteen patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR. CONCLUSION: PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with >54 Gray relative biological effectiveness (GyRBE) versus ≤54 GyRBE.

Outcomes following limited-volume proton therapy for multifocal spinal myxopapillary ependymoma.

PURPOSE: Spinal myxopapillary ependymoma (MPE) often presents with a multifocal distribution, complicating attempts at resection. There remains no standard approach to irradiating these patients. We report disease control and toxicity in pediatric patients with multifocal spinal MPE treated with limited-volume proton therapy. MATERIALS/METHODS: Twelve patients (≤21 years old) with multifocal spinal MPE were treated between 2009 and 2018 with limited-volume brain-sparing proton therapy. Median age was 13.5 years (range, 7-21). Radiotherapy was given as adjuvant therapy after primary surgery in five patients (42%) and for recurrence in seven (58%). No patient received prior radiation. Eleven patients (92%) had evidence of gross disease at radiotherapy. Eleven patients received 54 GyRBE; one received 50.4 GyRBE. Treatment toxicity was graded per the CTCAEv4.0. We estimated disease control and survival using the Kaplan-Meier product-limit method. RESULTS: The median follow-up was 3.6 years (range, 1.8-10.6). The five-year actuarial rates of local control, progression-free survival, and overall survival were 100%, 92%, and 100%, respectively. One patient experienced an out-of-field recurrence in the spine superior to the irradiated region. No patients developed in-field recurrences. Following surgery and irradiation, one patient developed grade three spinal kyphosis and one patient developed grade 2 unilateral L5 neuropathy. CONCLUSION: 54 GyRBE to a limited volume appears effective for disseminated spinal MPE in both the primary and salvage settings, sparing children the toxicity of full craniospinal irradiation. Compared with historical reports, this approach using proton therapy improves the therapeutic ratio, resulting in minimal side effects and high rates of disease control.

Survival after therapy for pediatric ependymoma in a tertiary care center in Saudi Arabia.

BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes and effectiveness of different treatment modalities in children with intracranial ependymoma. OBJECTIVE: Study the characteristics of pediatric ependymoma and outcomes of treatment modalities in Saudi Arabia. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS AND METHODS: Children with intracranial ependymoma who were younger than 14 years of age and treated between 2006 and 2015 were included in the study. Patients with prior radiation, chemo-therapy, or surgical resection at other centers were excluded. MAIN OUTCOME MEASURES: Kaplan-Meier survival curves were used to estimate the event-free (EFS) and overall survival (OS) rates of the patients. SAMPLE SIZE: 22. RESULTS: Of the 22 children, 4 (18.2%) were less than three years old. All intracranial ependymomas had upfront surgical resection of the primary tumor. Gross total resection was achievable in 9 (42.9%) cases and subtotal resection in another 9 (42.9%). Near-total resection was done in 3 (14.3%) cases. Median time from surgery to start of radiotherapy was 62 days. RT was given to 17 (77.3%) patients. Both mean and median RT dose was 55.8 Gy. Only 5 (22.7%) of the children received chemotherapy. The median duration of follow-up was 5.38 years and the median time for EFS was 2.27 years. The cumulative OS rate of the study was 44.5%. The cumulative EFS survival rate of the study was 18.6%. Among demographic, pathological, radiological features, none had a statistically significant effect on the survival. CONCLUSIONS: The outcomes are comparable to those reported by international investigators for similar populations. Further improvements can be achieved by avoiding delays in radiation therapy and adding molecular staging. LIMITATIONS: The limited number of cases, retrospective nature, lack of molecular biology and size of the tumors. CONFLICT OF INTEREST: None.

Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma.

BACKGROUND: To determine the impact of hypothalamic-pituitary (HP) disorders on health outcomes in children and adolescents who received conformal radiation therapy (RT) for central nervous system tumors. PROCEDURE: Cohort study including 355 patients (age ≤25 years at diagnosis) treated with high-dose (50.4-59.4 Gy) RT using photons for low-grade glioma or ependymoma. Patients (median age, 6.4 years at RT) received systematic endocrine follow-up (median duration, 10.1 years; range, 0.1-19.6). Associations between HP disorders and adverse health outcomes were determined by multivariable analysis. RESULTS: Prevalence was 37.2% for growth hormone deficiency (GHD), 17.7% for gonadotropin deficiency (LH/FSHD), 14.9% for thyroid-stimulating hormone deficiency (TSHD), 10.3% for adrenocorticotropic hormone deficiency (ACTHD), and 12.6% for central precocious puberty (CPP). Hypothalamus mean dose ≥ 36 Gy was associated with higher odds of any deficiency. GHD was associated with short stature (OR 2.77; 95% CI 1.34-5.70), low bone mineral density (OR 3.47; 95% CI 1.16-10.40), and TSHD with dyslipidemia (OR 5.54; 95% CI 1.66-18.52). Patients with ACTHD and CPP had lower intelligence quotient scores, and memory scores were impaired in patients with GHD (P = 0.02). Treatment of GHD was not associated with increased risk for tumor recurrence, secondary tumors, or mortality. CONCLUSIONS: HP disorders occur frequently in patients receiving high-dose RT and are related to physical and neurocognitive well-being. Future studies are needed to assess whether further optimization of endocrine management yields better health outcomes.

Adult cerebellopontine angle ependymoma presenting as an isolated cisternal mass: A case report.

INTRODUCTION: Ependymomas represent approximately 2%-8% of all primary intracranial brain tumors. The occurrence of extra-axial posterior fossa ependymomas in adults is rare. CASE AND OUTCOMES: We report a case of extra-axial cerebellopontine (CP) angle ependymoma in an adult patient, managed through gross total resection (GTR) and adjuvant radiotherapy. At her one-year postoperative visit, the patient remained clinically stable without any symptoms or focal neurological deficit and a follow up MRI showed no evidence of tumor recurrence. DISCUSSION: Only six cases of adult cerebellopontine angle ependymomas have been reported in the English literature, with the left side affected more commonly. Including this case, the mean age of the reported cases of adult extra-axial CP angle ependymoma is 44.14 years (range 22-66 years). Men accounted for five out of seven cases (71.4%). Maximal surgical resection is the mainstay of treatment in extra-axial CP angle ependymomas. Among seven reported cases, five received GTR and two had subtotal resection (STR). Patients were followed an average of 13.6 months (range 2-30 months) and only two patients with STR died during the follow-up period (6 weeks and 2 months after surgery). Six of the seven reported cases (including this one) received adjuvant radiotherapy. CONCLUSION: Although rare, extra-axial CP angle ependymomas should be considered as a differential diagnosis to other lesions of the CPA. Radical resection, whenever possible, is usually associated with a good outcome. Adjuvant radiotherapy remains an optional treatment with an unknown impact on overall and progression-free survival.