The medical and functional burden of surviving childhood ependymoma: A population-based study in Ontario, Canada.

BACKGROUND: Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort. METHODS: All individuals younger than 18 years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5 years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared. RESULTS: Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10 years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p = .0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p < .0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p < .0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p < .0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p < .0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p < .0001) compared to controls. CONCLUSIONS: Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health.

Intracranial ependymomas in pediatric patients: patterns of care, disparities, and survival outcomes from the National Cancer Database.

OBJECTIVE: This study aimed to extract and analyze comprehensive data from the National Cancer Database (NCDB) to gain insights into the epidemiological prevalence, treatment patterns, and survival outcomes associated with intracranial ependymomas in pediatric patients. METHODS: The authors examined data extracted from the NCDB spanning the years 2010 to 2017, with a specific emphasis on intracranial ependymomas in individuals aged 0-21 years. The study used logistic and Poisson regression, along with Kaplan-Meier survival estimates and Cox proportional hazards models, for analysis. RESULTS: Among 908 included pediatric patients, 495 (54.5%) were male, and 702 (80.6%) were White. Kaplan-Meier analysis determined overall survival (OS) rates of 97.1% (95% CI 96%-98.2%) at 1 year postdiagnosis, 89% (95% CI 86.9%-91.1%) at 3 years, 82.9% (95% CI 80.3%-85.7%) at 5 years, and 74.5% (95% CI 69.8%-79.4%) at 10 years. Grade 3 tumors predicted a more than fourfold higher mortality hazard (p < 0.001; reference = grade 2). Infratentorial localization was also associated with a 1.7-fold increase in mortality hazard (p = 0.002; reference = supratentorial). Larger maximum tumor size (> 5 cm) correlated with a lower mortality hazard (HR 0.64, p = 0.011; reference ≤ 5 cm). The vast majority of patients (85.9%, n = 780) underwent resection. Uninsured patients had over fourfold higher prolonged length of stay (LOS) odds than those privately insured (OR 4.645, p = 0.007). Radiotherapy was received by 76.1% of patients, and the highest rates of radiotherapy occurred among children aged 5-12 years (p < 0.001). Only 25.6% received chemotherapy at any point during their treatment. Peak chemotherapy use emerged within ages 0-4 years, reaching 33.6% in this age group. Kaplan-Meier analysis indicated chemotherapy was associated with significantly worse OS (p = 0.041). CONCLUSIONS: This comprehensive analysis of the NCDB provides valuable insights into the epidemiology, treatment patterns, and survival outcomes of intracranial ependymomas in pediatric patients. Higher tumor grade, infratentorial localization, and chemotherapy use was associated with worse OS, while larger tumor size correlated with lower mortality hazard. Disparities in care were identified, with uninsured patients experiencing prolonged LOS. These findings underscore the need for tailored treatment strategies based on patient and tumor characteristics and highlight the importance of addressing socioeconomic barriers to optimize outcomes for children with ependymomas.

Radiotherapy dosing in intracranial ependymoma using the national cancer database.

PURPOSE: To determine the dose-dependent effect of adjuvant radiotherapy on survival for pediatric intracranial ependymomas and explore patient and disease characteristics that experience survival benefit from higher doses. METHODS: Data was accessed from the National Cancer Database. Inclusion criteria was comprised of a diagnosis of non-metastatic intracranial ependymoma, World Health Organization (WHO) grade 2 or 3, surgical resection, adjuvant radiotherapy between 4500-6300 cGy, and non-missing survivorship data. Crude and adjusted Cox proportional hazard ratios (HRs) were calculated to estimate the associations of patient, tumor, and treatment characteristics with overall survival (OS). Kaplan-Meier (KM) estimations were used to visualize survival curves for dosing for the general cohort and by subgroups (age, resection extent, and grade). RESULTS: Of the 1154 patients who met inclusion criteria, 405 received ≤ 5400 cGy and 749 received > 5400 cGy. We found no difference in OS crude (0.95, 95% CI 0.72-1.06) or adjusted (0.88, 95% CI 0.46-1.69) HR for those receiving ≤ 5400 cGy. KM curves showed no difference in OS for dosing for the general cohort based on age, surgical extent, and grade. However, there was better OS in those with WHO grade 2 tumors compared to grade 3 regardless of dose received. CONCLUSIONS: There was no difference in OS between patients who received ≤ 5400 cGy compared to > 5400 cGy. We found improved OS in those with grade 2 tumors compared to grade 3, however there was no difference in OS based on dose received by tumor grade, age, or resection extent. Limitations in data available prevent exploring other outcomes or toxicity.

Survival Factors in 1580 Adults with Spinal Ependymoma: Insights from a Multicenter Oncology Database.

BACKGROUND: Using a multi-institutional oncology database, we investigate the survival rates and the impacts of demographic, clinical, and management characteristics on overall survival among adult patients diagnosed with spinal ependymoma. METHODS: Utilizing the SEER registry, patients with histologically or radiologically confirmed ependymomas were included. Factors impacting overall survival were analyzed using Kaplan-Meier survival curves and log-rank statistical analyses. RESULTS: A total of 1,580 patients were included. Their mean ± standard deviation age was 46.68 ± 15.96 years, and 51.1% were women. Gross total resection (GTR) was achieved in 66.4% of patients. The 5- and 10-year survival rates were 96.7% and 95.4%, respectively. A multivariable backward Cox regression showed that age ≥65 years was a significant predictor for mortality (hazard ratio [HR]: 3.93; 95% confidence interval [CI]: 2.21-7.00; P < 0.001). Likewise, tumor grade 3 (HR: 6.36; 95% CI: 1.95-20.76; P = 0.002), tumor grade 4 (HR: 7.74; 95% CI: 3.97-15.11; P < 0.001), presence of extra-neural metastasis (HR: 13.81; 95% CI: 3.67-51.96; P < 0.001), and receiving radiotherapy (HR: 2.50; 95% CI: 1.50-4.19; P < 0.001) were significant risk factors for mortality, while GTR was significantly associated with improved overall survival compared with subtotal resection or nonsurgical management (HR: 0.42; 95% CI: 0.25-0.73; P = 0.002). There were no significant effects for gender, race, marital status, income, residential area, chemotherapy, tumor size, and the presence of other benign or malignant tumors on the survival hazards (P > 0.05 for each). CONCLUSION: Early diagnosis and surgical management of spinal ependymomas, such as GTR, were associated with remarkable survival benefits. Old age, high-grade spinal ependymoma, and extra-neural metastasis were associated with worse overall survival, whereas radiotherapy's role remains unclear.

Pediatric intramedullary spinal cord tumors: A national cancer database analysis of demographics, patterns of care, and survival.

OBJECTIVE: Query the National Cancer Database (NCDB) to delineate epidemiologic frequency, care patterns, and survival outcomes of pediatric intramedullary spinal cord tumors (IMSCTs). METHODS: IMSCTs included ependymoma, astrocytoma, and hemangioblastoma. We examined data from the NCDB spanning 2004-2018, focusing on IMSCT in children aged 0-21 years. Our analysis included logistic and Poisson regression, Kaplan-Meier survival estimates, and Cox proportional hazards models. RESULTS: This study included 1066 patients aged 0-21 years. 59.4 % of patients were male, while 83.1 % were white. The most common tumor histology was ependymoma (57.5 %), followed by astrocytoma (36.1 %) and hemangioblastoma (6.4 %). 24.9 % of patients received radiotherapy, with radiotherapy utilization being highest among patients aged 6-10 years. Chemotherapy utilization was highest in patients aged 0-5 years. 87.2 % of patients underwent surgical resection, with higher rates in patients aged 16-21 years. Overall survival did not differ significantly between resected and non-resected patients (p = 0.315). Patients in rural areas had worse OS than those in metro areas (HR = 4.42, p = 0.048). Patients with astrocytoma had worse OS compared to other histologies (HR = 2.21, p = 0.003). Astrocytoma patients were over twice as likely to have prolonged LOS compared to ependymoma patients (OR = 2.204, p < 0.001). CONCLUSIONS: In summary, our analysis utilizing the NCDB database provides a comprehensive overview of demographics, care patterns, and outcomes for the largest cohort of pediatric IMSCTs to date. These insights underscore the complexity of managing IMSCTs and emphasize the need for tailored approaches to improve patient outcomes.

Predictive Factors of Long-Term Neurologic Outcome and Progression-Free Survival in Intramedullary Spinal Cord Tumors: A 10-year Single-Center Cohort Study and Review of the Literature.

BACKGROUND: Intramedullary spinal cord tumors (IMSCTs) are a rare subgroup of neoplasms, encompassing both benign, slow-growing masses, and malignant lesions; radical surgical excision represents the cornerstone of treatment for such pathologies regardless of histopathology, which, on the other hand, is a known predictor of survival and neurologic outcome postsurgery. The present study aims to investigate the relevance of other factors in predicting survival and long-term functional outcomes. METHODS: We conducted a review of current literature on functional outcomes of IMSCTs, as well as a 10-years prospective analysis of a wide cohort of patients with diagnosis of IMSCTs who underwent surgical resection at our institution. RESULTS: Our series encompasses 60 patients with IMSCTS, among which 36 ependymomas, 6 cavernous angiomas, 5 hemangioblastomas, 6 WHO Grade I-IV astrocytomas, 3 intramedullary spinal metastases and 4 miscellaneous tumors. GTR was achieved in 76,67% of patients, with high preoperative McCormick grade, syringomyelia and changes at neurophysiologic monitoring being the strongest predictors at multivariate analysis (P = 0.0027, P = 0.0017 and P = 0.001 respectively). CONCLUSIONS: Consistently with literature, preoperative neurologic function is the most important factor predicting long-term functional outcome (0.17, CI 0.069-0.57 with P = 0.0018), advocating for early surgery in the management of IMSCTs, whereas late complications such as myelopathy and neuropathic pain were present regardless of preoperative function.

Treatment Outcomes of Patients with Ependymoma Receiving Radiotherapy: A Single Institution Experience.

INTRODUCTION: This study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. METHODS: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. RESULTS: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near-total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018, for LPFS; hazard ratio = 3.20, p = 0.029, for PFS). CONCLUSION: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.

Clinical presentation and extent of resection impacts progression-free survival in spinal ependymomas.

PURPOSE: Primary treatment of spinal ependymomas involves surgical resection, however recurrence ranges between 50 and 70%. While the association of survival outcomes with lesion extent of resection (EOR) has been studied, existing analyses are limited by small samples and archaic data resulting in an inhomogeneous population. We investigated the relationship between EOR and survival outcomes, chiefly overall survival (OS) and progression-free survival (PFS), in a large contemporary cohort of spinal ependymoma patients. METHODS: Adult patients diagnosed with a spinal ependymoma from 2006 to 2021 were identified from an institutional registry. Patients undergoing primary surgical resection at our institution, ≥ 1 routine follow-up MRI, and pathologic diagnosis of ependymoma were included. Records were reviewed for demographic information, EOR, lesion characteristics, and pre-/post-operative neurologic symptoms. EOR was divided into 2 classifications: gross total resection (GTR) and subtotal resection (STR). Log-rank test was used to compare OS and PFS between patient groups. RESULTS: Sixty-nine patients satisfied inclusion criteria, with 79.7% benefitting from GTR. The population was 56.2% male with average age of 45.7 years, and median follow-up duration of 58 months. Cox multivariate model demonstrated significant improvement in PFS when a GTR was attained (p <.001). Independently ambulatory patients prior to surgery had superior PFS (p <.001) and OS (p =.05). In univariate analyses, patients with a syrinx had improved PFS (p =.03) and were more likely to benefit from GTR (p =.01). Alternatively, OS was not affected by EOR (p =.78). CONCLUSIONS: In this large, contemporary series of adult spinal ependymoma patients, we demonstrated improvements in PFS when GTR was achieved.

Impact of Molecular Subgroups on Prognosis and Survival Outcomes in Posterior Fossa Ependymomas: A Retrospective Study of 412 Cases.

BACKGROUND AND OBJECTIVES: Posterior fossa ependymomas (PFEs) are rare brain tumors classified as PF-EPN-A (PFA) and PF-EPN-B (PFB) subgroups. The study aimed to evaluate the prognosis and survival outcomes in PFEs, with a focus on the impact of molecular subgroups. METHODS: A retrospective study was conducted on 412 patients with PFEs. Kaplan-Meier survival analyses were conducted to evaluate the overall survival (OS) and progression-free survival. Cox regression analyses were conducted to assess the prognostic factors. A nomogram was developed to predict the OS rates of PFEs. RESULTS: The study revealed significant differences between PFA and PFB in patient and tumor characteristics. PFAs were associated with poorer OS (hazard ratios [HR] 3.252, 95% CI 1.777-5.950, P < .001) and progression-free survival (HR 4.144, 95% CI 2.869-5.985, P < .001). World Health Organization grade 3 was associated with poorer OS (HR 2.389, 95% CI 1.236-4.617, P = .010). As for treatment patterns, gross total resection followed by radiotherapy or the combination of radiotherapy and chemotherapy yielded the most favorable OS for PFA ( P = .025 for both), whereas gross total resection followed by radiotherapy rather than observation showed improved OS for PFB ( P = .046). The nomogram demonstrated a high degree of accuracy and discrimination capacity for the prediction of OS rates for up to 10 years. In addition, 6 cases of PFA (3.51%) with H3K27M mutations were identified. CONCLUSION: PFAs demonstrate worse prognosis and survival outcomes compared with PFBs. Both PFAs and PFBs necessitate maximal resection followed by intensive adjuvant therapies in long-term effects.

Development and validation of prognostic nomogram in ependymoma: A retrospective analysis of the SEER database.

BACKGROUND: The prognostic factors for survival in patients with ependymoma (EPN) remain controversial. The aim of this study was to establish a prognostic model for 5- and 10-year survival probability nomograms for patients with EPN. METHODS: Clinical data from the Surveillance, Epidemiology, and End Results (SEER) database were used for patients diagnosed with ependymoma between 2000 and 2018 and were randomized 7:3 into a development set and a validation set. Factors significantly associated with prognosis were screened out using the least absolute shrinkage and selection operator (LASSO) regression. The calibration chart and consistency index (C-index) are used to evaluate the discrimination and consistency of the prediction model. Decision curve analysis (DCA) was used to further evaluate the established model. Finally, prognostic factors selected by LASSO regression were evaluated using Kaplan-Meier (KM) survival curves. RESULTS: A total of 3820 patients were included in the prognostic model. Seven survival predictors were obtained by LASSO regression screening, including age, gender, morphology, location, size, laterality, and resection. The prognostic model of the nomogram showed moderate discriminative ability in the development group and the validation group, with a C-index of 0.642 and 0.615, respectively. In the development set and validation set survival curves, the prognosis index of high risk was less effective than low risk (p < 0.001). CONCLUSIONS: Our nomograms may play an important role in predicting 5 and 10-year outcomes for patients with ependymoma. This will help assist clinicians in personalized medicine.

Transcriptional profiling of paediatric ependymomas identifies prognostically significant groups.

The majority of supratentorial ependymomas in children contain oncogenic fusions, such as ZFTA-RELA or YAP1-MAMLD1. In contrast, posterior fossa (PF) ependymomas lack recurrent somatic mutations and are classified based on gene expression or methylation profiling into group A (PFA) and group B (PFB). We have applied a novel method, NanoString nCounter Technology, to identify four molecular groups among 16 supratentorial and 50 PF paediatric ependymomas, using 4-5 group-specific signature genes. Clustering analysis of 16 supratentorial ependymomas revealed 9 tumours with a RELA fusion-positive signature (RELA+), 1 tumour with a YAP1 fusion-positive signature (YAP1+), and 6 not-classified tumours. Additionally, we identified one RELA+ tumour among historically diagnosed CNS primitive neuroectodermal tumour samples. Overall, 9 of 10 tumours with the RELA+ signature possessed the ZFTA-RELA fusion as detected by next-generation sequencing (p = 0.005). Similarly, the only tumour with a YAP1+ signature exhibited the YAP1-MAMLD1 fusion. Among the remaining unclassified ependymomas, which did not exhibit the ZFTA-RELA fusion, the ZFTA-MAML2 fusion was detected in one case. Notably, among nine ependymoma patients with the RELA+ signature, eight survived at least 5 years after diagnosis. Clustering analysis of PF tumours revealed 42 samples with PFA signatures and 7 samples with PFB signatures. Clinical characteristics of patients with PFA and PFB ependymomas corroborated the previous findings. In conclusion, we confirm here that the NanoString method is a useful single tool for the diagnosis of all four main molecular groups of ependymoma. The differences in reported survival rates warrant further clinical investigation of patients with the ZFTA-RELA fusion.

Supratentorial Extraventricular Ependymomas: Imaging Features and the Added Value of Apparent Diffusion Coefficient.

OBJECTIVE: To improve the understanding and the diagnosis of intracranial ependymal tumors. METHODS: The clinical, radiological and prognostic features of 48 supratentorial extraventricular ependymomas and 74 intraventricular ependymomas were summarized and compared. RESULTS: Supratentorial extraventricular ependymomas, most often located in the frontal lobe (33.3%) and classified as grade III (75.0%), had relatively large eccentric cysts (3.07 ± 2.03 cm), significant enhancement (84.8%), low apparent diffusion coefficient (ADC) values, and associated with higher mortality (41.3%). The majority of intraventricular lesions occurred in the fourth ventricle (86.5%) and classified as grade II (78.4%), had relatively small and multiple cystic changes (1.04 ± 0.87 cm), slight or moderate enhancement (76.9%), high ADC values and associated with lower mortality (20.7%). There were few significant differences between grade II and grade III tumors in these 2 groups, respectively. Young age, high grade and low ADC values are worse prognostic indicators for patients with supratentorial extraventricular ependymomas, but not for those with intraventricular ependymomas. CONCLUSIONS: Conventional radiological features, combined with clinical manifestations and quantitative information provided by diffusion-weighted imaging, may not only enhance the diagnosis and assist in determining prognosis but also provide a better pathophysiological understanding of intracranial ependymal tumors.

Marital Status Independently Predicts Glioma Patient Mortality: A Surveillance, Epidemiology, and End Results (SEER) Analysis.

OBJECTIVE: To examine the impact of marital status on the mortality of patients with primary malignant brain tumors excluding bias from basic characteristics and treatment. METHODS: We used the Surveillance, Epidemiology, and End Results program to identify 81,277 patients diagnosed from 2000 through 2016 with the most common primary malignant brain tumors, including glioma, ependymoma, and medulloblastoma. To avoid bias, we used the propensity score matching method to match 44,854 patients with complete clinical and follow-up information. Then, we used Cox regression and Kaplan-Meier survival analysis to investigate the impact of marital status on cancer patient mortality. RESULTS: Married patients were more likely to receive surgery and adjuvant chemo- or radiotherapy than single and divorced, separated, and widowed (DSW) patients (all P < 0.001). Married patients with high grade glioma were more likely to survive longer and less likely to die of their malignance compared with single (adjusted odds ratio [OR] 1.120; 95% confidence interval [CI], 1.069 to 1.174; P < 0.001; OR 1.078; 95% CI, 1.025 to 1.133; P = 0.003; respectively), and DSW patients (OR 1.117; 95% CI, 1.074 to 1.161; P <0.001; OR 1.090; 95% CI, 1.046 to 1.136; P<0.001; respectively) (all adjusted to the married group). Similar results were identified in patients with low-grade glioma but not ependymoma and medulloblastoma. CONCLUSIONS: Even after adjusting for known confounders, married patients with high-grade glioma and low-grade glioma are at higher possibility to have a better outcome. This study highlights the potential significance that intimate support from spouse can improve glioma patient survival.

Pediatric ependymoma: A single-center experience from a developing country.

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.

Long-term outcomes of spinal ependymomas: an institutional experience of more than 60 cases.

PURPOSE: Spinal ependymomas represent the most common primary intramedullary tumors for which optimal management remains undefined. When possible, gross total resection (GTR) is often the mainstay of treatment, with consideration of radiotherapy (RT) in cases of residual or recurrent tumor. The impact of extent of resection and radiotherapy remain understudied. OBJECTIVE: Report on a large institutional cohort with lengthy follow-up to provide information on long-term outcomes and to contribute to limited data assessing the value of extent of resection and RT. METHODS: Patients with pathologically proven primary spinal ependymoma between 1990 and 2018 were identified. Kaplan-Meier estimates were used to calculate progression-free survival (PFS); local-control (LC) and overall survival (OS). Logistic regression was used to analyze variables' association with receipt of RT. RESULTS: We identified 69 patients with ependymoma of which 4 had leptomeningeal dissemination at diagnosis and were excluded. Of the remaining cohort (n = 65), 42 patients (65%) had Grade II spinal ependymoma, 20 (31%) had Grade I myxopapillary ependymoma and 3 (5%) had Grade III anaplastic ependymoma; 54% underwent GTR and 39% underwent RT. With a median follow-up of 5.7 years, GTR was associated with improved PFS. For grade II lesions, STR+RT yielded better outcomes than STR alone (10y PFS 77.1% vs 68.2%, LC 85.7% vs 50%). Degree of resection was the only significant predictor of adjuvant radiotherapy (p < 0.0001). CONCLUSION: Our findings confirm the importance of GTR in spinal ependymomas. Adjuvant RT should be utilized in the setting of a subtotal resection with expectation of improved disease-related outcomes.

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.

Tumors in the cauda equina: A SEER analysis of tumor types and predictors of outcome.

Caudaequinatumors are histologically diverse. International Classification of Diseases for Oncology (ICD-O3) confers dedicated site code (C72. 1) for cauda equina. This code is excluded during analyses of other primary spinal cord tumors. In this retrospective study, the Surveillance, Epidemiology and End Results (SEER) data for primary cauda equina tumors (PCET, C72. 1) excluding the tumors of spinal meninges (C70. 1) from 1992 to 2015 were reviewed. Demographic characteristics, tumor types, and clinical outcomes were analyzed using univariable analysis. Overall survival was estimated using Kaplan-Meier methods and compared for age, histology and treatment type. 293 patients with PCET met inclusion criteria. The most common tumors comprised schwannoma (32%), myxopapillary ependymoma (21%), malignant ependymoma (22%). The median age at diagnosis was 50 years (range < 1 year to 98 years), 57% of patients were males. 77% of the patients underwent surgery. Median follow up time for these patients was 70 months. Of the 293 patients, 250 (85%) were living at the end of 2015. The cause of death was tumor or CNS related in 15 patients. 136 patients were followed for <5 years, of which 102 were censored and 34 died (11.6%) before 5 years. Using univariable analysis, age at diagnosis (Hazard Ratio, HR 1.05; confidence interval, CI 1.03-1.07; p < 0.001), malignant tumor type (HR 2.88, CI 1.15-7.19, p = 0.0239) and absence of surgical intervention (HR 2.54, CI1.26-5.11, p = 0.0092) were predictors of increased mortality. Although most patients did well, older age and lack of surgical intervention were associated with worse survival.

Treatment trends and overall survival in patients with grade II/III ependymoma: The role of tumor grade and location.

BACKGROUND: Treatment of ependymoma (EPN) is guided by associated tumor features, such as grade and location. However, the relationship between these features with treatments and overall survival in EPN patients remains uncharacterized. Here, we describe the change over time in treatment strategies and identify tumor characteristics that influence treatment and survival in EPN. METHODS AND MATERIALS: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 Registries (1973-2016) database, we identified patients with EPN microscopically confirmed to be grade II (EPN-GII) or III (EPN-GIII) tumors between 2004-2016. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates and multivariable Cox proportional hazard models. A sub-analysis was performed by tumor location (supratentorial, posterior fossa, and spine). Change over time in rates of gross total resection (GTR), radiotherapy (RT), and chemotherapy (CS) were analyzed using linear regression, and predictors of treatment were identified using multivariable logistic regression models. RESULTS: Between 2004-2016, 1,671 patients were diagnosed with EPN, of which 1,234 (74 %) were EPN-GII and 437 (26 %) EPN-GIII. Over the study period, EPN-GII patients underwent a less aggressive treatment (48 % vs 27 %, GTR; 60 % vs 30 %, RT; 22 % vs 2%, CS; 2004 vs 2016; p < 0.01 for all). Age, tumor size, location, and grade were positive predictors of undergoing treatment. Univariate analysis revealed that tumor grade and location were significantly associated with OS (p < 0.0001 for both). In multivariable Cox regression, tumor grade was an independent predictor of OS among patients in the cohort (grade III, HR 3.89 [2.84-5.33]; p < 0.0001), with this finding remaining significant across all tumor locations. CONCLUSIONS: In EPN, tumor grade and location are predictors of treatment and overall survival. These findings support the importance of histologic WHO grade and location in the decision-making for treatment and their role in individualizing treatment for different patient populations.

A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival and ineffectiveness of current treatments across central nervous system locations and molecular subgroups.

BACKGROUND: Relapse occurs in 50% of pediatric ependymoma cases and has poor prognosis. Few studies have investigated the clinical progress of relapsed disease, and treatment lacks a standardized approach. METHODS AND MATERIALS: We analyzed 302 pediatric ependymoma cases. Tumor, demographic, and treatment variables were investigated for association with relapse risk, time to recurrence, and survival after relapse. DNA methylation profiling was performed for 135/302 cases, and predominant subgroups were EPN_PFA (n = 95) and EPN_RELA (n = 24). Chromosome 1q status was ascertained for 185/302 cases by fluorescent in-situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and DNA methylation profiles. RESULTS: Sixty-two percent of cases relapsed, with a median of two recurrences with no difference between posterior fossa and supratentorial locations (66% vs 55% relapse rate). One hundred seventeen (38%) cases relapsed within two years and five (2%) beyond 10 years. The late relapses were clinically heterogeneous. Tumor grade and treatment affected risk and time to relapse variably across subgroups. After relapse, surgery and irradiation delayed disease progression with a minimal impact on survival across the entire cohort. In the EPN_PFA and EPN_RELA groups, 1q gain was independently associated with relapse risk (subhazard ratio [SHR] 4.307, P = 0.027 and SHR 1.982, P = 0.010, respectively) while EPN_PFA had increased relapse risk compared with EPN_RELA (SHR = 0.394, P = 0.018). CONCLUSIONS: Recurrent pediatric ependymoma is an aggressive disease with poor outcomes, for which current treatments are inadequate. We report that chromosome 1q gain increases relapse risk in common molecular subgroups in children but a deeper understanding of the underlying biology at relapse and novel therapeutic approaches are urgently needed.