Rare Central Nervous System Tumors Research Articles

Construction and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Primary Anaplastic Oligodendroglioma

Anaplastic oligodendroglioma (AOD) is a rare high-grade central nervous system tumor. The current research on prognostic prediction of AOD remains limited. This study aimed to identify prognostic factors and establish the nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with AOD. Patients diagnosed with AOD between 1992 and 2020 were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. We performed univariate and multivariate Cox regression analyses to identify independent prognostic factors based on the training group. KM survival curves were used to compare the impact of various independent factors on patient prognosis. For OS and CSS, the nomograms were constructed, and verified by the validation group. C-index, ROC curves, calibration curves, and DCA were used to assess the discrimination, consistency and clinical value of the nomograms. A total of 1202 AOD patients were enrolled, being randomly divided into training (n=841) and validation (n=361) groups (7:3 ratio). Univariate and multivariate Cox analysis identified four significant independent factors (tumor site, age, surgery, chemotherapy). For OS and CSS, C-index were 0.731 (0.705-0.757) and 0.728 (0.701-0.754) in the training group, 0.688 (0.646-0.731) and 0.684 (0.639-0.729) in the validation group, respectively. ROC curves and Calibration curves showed good discrimination and consistency, respectively. In addition, the DCA curves showed the nomograms have good clinical benefits. We successfully established the nomograms to predict the OS and CSS for AOD patients. The nomograms showed good performance in prognostic prediction, assisting clinicians in evaluating patient prognosis and personalizing treatment plans.

Genetically Distinct Oligosarcoma Arising from Oligodendroglioma: Systematic Review & Illustrative Case Example

BackgroundOligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and aggressive clinical phenotype. We present a systematic review and illustrative case example emphasizing the clinical and prognostic features of this unusual and unfavorable neuro-oncologic disease. MethodsSystematic literature review and illustrative case report. ResultsA 41-year-old man who had undergone two neurosurgical resections for a WHO grade II oligodendroglioma (Ki-67=5-10%, 1p/19q co-deleted, IDH2 mutated), without adjuvant chemoradiation, presented with seizures seven years after resection. An extra-axial mass was identified adjacent to the resection cavity, in which gross total resection was achieved. Pathology confirmed WHO grade IV oligosarcoma (Ki-67=20%). Adjuvant chemoradiation was initiated, with disease control observed over 6 months of follow-up.7 publications met inclusion criteria. Oligosarcoma has been confirmed in 36 lesions, arising in 35 patients; 5 were primary oligosarcoma, while 31 occurred in the setting of prior resected oligodendroglioma or oligoastrocytoma. Features shared by these lesions include re–gain of H3K27me3 expression, 1p/19q codeletion, homozygous deletion of CDKN2A/B, loss of 6q, loss of NF1 and YAP1, and attenuation of CpG island methylator (G-CIMP). Median survival after oligosarcoma diagnosis was 1.3 years (range, 0-5.2; n=35). ConclusionOligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.

Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors

PurposeMultidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers.MethodsWe retrospectively reviewed records from virtual MTBs held between 04/2020–03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions.ResultsDuring 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions.ConclusionVirtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Whole-exome sequencing has revealed novel genetic characteristics in intracranial germ cell tumours in the Chinese.

Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.

Epidemiology and survival of patients with spinal meningiomas: a large retrospective cohort study.

Spinal meningiomas (SMs) are relatively rare central nervous system tumors that usually trigger neurological symptoms. The prevalence of SMs is increasing with the aging of the global population. This study aimed to perform a systematic epidemiologic and survival prognostic analysis of SMs to evaluate their public health impact and to develop a novel method to estimate the overall survival at 3-year, 5-year, and 10-year in patients with SMs. Five thousand one hundred fifty eight patients with SMs were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Firstly, descriptive analysis was performed on the epidemiology of SMs. Secondly, these individuals were randomly allocated to the training and validation sets in a ratio of 7:3. Kaplan-Meier method and Cox regression analysis were utilized in the training set to identify independent prognostic factors and to construct a nomogram for survival prognosis. Subsequently, the discriminative power, predictive performance, and clinical utility of the nomogram were evaluated by receiver operating characteristic curve and decision curve analysis. Finally, a mortality risk stratification system and a web-based dynamic nomogram were constructed to quantify the risk of mortality in patients with SMs. The annual age-adjusted incidence rates of SMs increased steadily since 2004, reaching a rate of 0.40 cases per 100000 population in 2019, with a female-to-male ratio of ~4:1. The age groups of 50-59, 60-69, and 70-79 years old were the most prevalent ages for SMs, accounting for 19.08, 24.93, and 23.32%, respectively. In addition, seven independent prognostic factors were identified to establish a prognostic nomogram for patients with SMs. The decision curve analysis and receiver operating characteristic curve indicated that the nomogram had high clinical utility and favorable accuracy. Moreover, the mortality risk stratification system effectively divided patients into low-risk, middle-risk, and high-risk subgroups. SMs are relatively rare benign spinal tumors prevalent in the white elderly female population. Clinicians could use the nomogram to personalize the prediction of the overall survival probability of patients with SMs, categorize these patients into different mortality risk subgroups, and develop personalized decision-making plans. Moreover, the web-based dynamic nomogram could help to further promote clinical application and assist clinicians in providing personalized counseling, timely monitoring, and clinical assessment for patients.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.

INNV-27. LOW/ULTRA-LOW RADIO FREQUENCY MAGNETIC FIELD THERAPIES FOR THE TREATMENT OF CNS TUMORS: RGBM AND DIPG – PAST AND CURRENT RESULTS USING THE EMULATE THERAPEUTICS INC. TECHNOLOGY

Abstract EMulate Therapeutics, Inc. (EMTx) has developed a technology that emulates the effects of chemical compounds, via an alternating magnetic field. Our research has led to the development of a radio frequency energy (RFE) signal (A1A) that emulates the effects of paclitaxel. Pre-clinical and animal studies demonstrate an effect in slowing down and inhibiting tumor growth. EMTx has developed a portable medical device that allows for continuous delivery of our A1A signal for up to 14 hours before recharging. The device can be used in combination with current best-supportive-care (BSC) and new investigational treatments. Our technology has been tested in recurrent glioblastoma (rGBM) with very encouraging results in overall survival (OS), especially in combination with BSC. Phase II OS alone was equivalent to BSC (7.2 months BSC OS vs. 7.0 months A1A alone OS) and a considerably improved OS when combined with conventional drug treatment (7.2 months BSC OS versus 10.0 months A1A + BSC OS). EMTx is in the process of seeking humanitarian device exemption (HDE) from the US Food & Drug Administration (FDA) for the Hælo® therapeutic system, our pediatric treatment option. Diffuse intrinsic pontine gliomas (DIPG) are a rare pediatric central nervous system (CNS) tumor. Survival is measured in under 12 months, with no clinical trials demonstrating a significant increase in overall survival in 20 years (9 months median survival post radiation therapy). EMTx’s compassionate use program demonstrated safety and suggested a clinical benefit, with 12 of 14 patients surviving more than 12 months. EMTx is committed to run and complete a pivotal pediatric trial for children diagnosed with DMG/DIPG. The trial will recruit study patients from both the US and India. A total of 35-40 patients will be recruited to participate in this pediatric neuro-oncology trial, which will be a best-supportive-care + single therapy (Hælo®) clinical trial.

A rare case of large retropharyngeal pre-vertebral chordoma presented as oropharyngeal swelling

Posterior oropharyngeal swelling can result from various pathologies, including chordomas. Chordoma is a notochordal remnant origin tumor. It is a rare bone and central nervous system tumor, especially in the cervical region. Chordoma is a tumor with properties such as slowly growing and frequently recur in most patients. This case report aims to comprehensively understand the clinical presentation and radiological features of a rare C2 retropharyngeal pre-vertebral chordoma. A 24-year-old male with a two-year history of dysphagia presented with progressively worsening symptoms, including dyspnea, dysphonia, and weight loss. On examination, a large mass was observed in the posterior oropharynx. Radiologically, a large soft tissue mass involves the C2 vertebral body, extending into the pre-vertebral soft tissue and compromising the airway. The mass appears hypointense in T1 weighted images, heterogeneously hyperintense in T2, and shows heterogeneous contrast enhancement. The chordoma was confirmed through histopathological analysis, showing characteristic physaliferous cells within a myxoid stroma. Posterior oropharyngeal masses require prompt and accurate evaluation. Radiological evaluation is crucial in identifying the tumor's origin, extent, and vascularity, aiding in diagnosis and treatment planning. Surgical resection is the primary treatment, but chordomas have a high recurrence rate even after complete removal. Radiotherapy can improve survival and reduce recurrence. This case highlights the importance of multidisciplinary collaboration in providing individualized care for rare chordoma presentations.

A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.

Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.

Neuroepithelial tumor with EWSR1::PATZ1 fusion: A literature review.

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET.

FRI337 Progressive Suprasellar Chordoid Glioma Presenting With Panhypopituitarism, Diabetes Insipidus And Encephalopathy

Abstract Disclosure: J.D. Gatillo: None. M.D. Maningat-Goco: None. F.K. Co: None. Chordoid glioma is a rare central nervous system neoplasm of uncertain origin, with most cases seen at anterior wall or roof of the third ventricle. It is described as a perplexing lesion as it tends to mimic benign lesions at the onset but eventually some develop with threatening complications. We present a case of a 39 year old Filipino, female, who initially presented with a 1- year history of memory lapses, behavioral changes, and blurring of vision. MRI showed 4.3 x 3 x 4.2 cm heterogeneously enhancing suprasellar mass and was initially worked-up as pituitary macroadenoma. The imaging also showed heterogeneously enhancing extra-axial lesion along the right anteromedial temporal convexity. She underwent pterional craniotomy and sub temporal craniectomy with excision biopsy of tumor. Histopathology confirmed the diagnosis of chordoid glioma WHO Grade 2. However, only a few days after the surgery, she began to experience emotional lability and more behavioral changes. She then received oral Temozolomide for 4 cycles and whole brain radiotherapy for 32 cycles. Approximately 10 months since diagnosis was made, patient eventually developed seizures and manifested progressive drowsiness and generalized weakness. Patient was diagnosed and clinically presented with Panhypopituitarism and Diabetes Insipidus. She was maintained on levothyroxine, prednisone and desmopressin. A repeat MRI was done which showed apparent progression in the size (4.6 x 3.7 x 4.1 cm) of the heterogeneously enhancing suprasellar mass with signs of tumor infiltration and extension in the left lateral ventricle. Further, patient was treated with Bevacizumab and Nimotuzumab. Repeat MRI showed regression in size of the known suprasellar mass and improvement of symptoms. Little is still known about chordoid gliomas especially in the Asian population - their initial presentation as well as the best diagnostic approach and treatment strategy for this elusive disease. There is no formally recognized treatment protocol for chordoid glioma, and postoperative mortality and morbidity is high. More case reports are needed in order to ascertain the best diagnostic and treatment strategy for patients with chordoid glioma and its endocrine complications. Presentation: Friday, June 16, 2023

P21.05.B CAPTURING EVOLVING DEFINITIONS OF 12 SELECT RARE CNS TUMORS: A TIMELY REPORT FROM CBTRUS AND NCI-CONNECT

Abstract BACKGROUND Histopathology-specific incidence, prevalence, and survival are essential population-based cancer statistics that describe cancer burden. The National Cancer Institute’s Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) aims to improve understanding of tumor biology and patient outcomes for 12 selected rare brain and other central nervous system (CNS) tumor types to improve approaches to care and treatment. These types included atypical teratoid/rhabdoid tumor, brainstem and midline gliomas, choroid plexus tumors, ependymomas, high grade meningiomas, gliomatosis cerebri, medulloblastoma, oligodendrogliomas, pineal region tumors, pleomorphic xanthoastrocytomas, CNS embryonal tumors, NEC/NOS and primary CNS sarcoma. The analysis aimed to estimate the incidence (new cases per year), prevalence (currently living cases), and survival rates for these selected rare brain and other CNS tumor types. MATERIAL AND METHODS The Central Brain Tumor Registry of the United States (CBTRUS) data, which contains data from the Centers for Disease Control and Preventions National Program of Cancer Registries (NPCR) and National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) data, from 2008-2019 were used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race/ethnicity, and age. Incidence time trends were calculated for diagnosis years 2004-2019. NPCR survival data from 2001-2018 were used to calculate relative survival (RS) estimates. Estimated prevalence counts as of December 31, 2019 were estimated using incidence from CBTRUS and overall survival rates from SEER. RESULTS Overall AAAIR for all 12 subtypes combined was 1.51 per 100,000 population, with the highest subtype-specific incidence in ependymomas (AAAIR=0.41/100,000). Overall, most subtypes were more common in males and people who are non-Hispanic White. Incidence of all subtypes varied by age. Ependymomas were most prevalent with 19,339 cases; followed by oligodendrogliomas with 15,070 cases. Time trends in incidence varied by subtype, with significant decreases in incidence of gliomatosis cerebri, CNS embryonal tumor, and primary CNS sarcoma. RS for all subtypes combined at 1, 5, and 10 years was 86.6%, 71.9%, and 65.3%, respectively. Ependymomas had the highest RS (1-year=96.1%, 5-years=90.6%, 10-years=86.6%) and primary CNS sarcomas had the lowest RS (1-year=48.2%, 5-years=7.7%, 10-years=5.2%). CONCLUSION Incidence, prevalence, and survival patterns for these 12 selected rare cancer subtypes varied significantly by type. Population based data are critical to guiding effective design of and accrual expectations for clinical trials in rare cancers.

Ependymoma in WHO Classification of Tumours 5th Edition

Ependymoma is a rare central nervous system tumor that occurs in all age groups and is one of the most common childhood malignant brain tumors. Until the 3rd edition of the WHO Classification of Brain Tumours, ependymoma was classified based solely on histologic findings, but advances in molecular analysis led to the incorporation of molecular information into the diagnosis of ependymoma for the first time in the 2016 WHO Classification, 4th edition. However, the low correlation between tumor grade and survival prognosis remained a problem. Unlike other malignant brain tumors, ependymoma is genetically and epigenetically characterized with few identified point mutations. Methylation profiling was found to classify ependymoma into distinct subgroups, and the 2021 WHO Classification, 5th Edition, adopted new classifications by histologic findings, genetic alterations, methylation patterns, and anatomic location. This new classification includes 10 diagnostic entities: 1)supratentorial subependymoma; 2)supratentorial ependymoma, ZFTA-fusion positive; 3)supratentorial ependymoma, YAP1-fusion positive; 4)posterior fossa subependymoma; 5)posterior fossa group A ependymoma; 6)posterior fossa group B ependymoma; 7)spinal subependymoma; 8)spinal ependymoma; 9)spinal myxopapillary ependymoma; and 10)spinal ependymoma, MYCN-amplified. The previously accepted term "anaplastic ependymoma" was dropped. As with other CNS tumors, a new classification was introduced based on an integrated diagnosis that incorporates histologic and molecular diagnosis. In this article, we summarize the molecular classification of ependymoma in the WHO Classification of Brain Tumours, 5th edition.

Surgical epidemiology of spinal cord tumors at Dr. Kariadi Hospital, Semarang, Indonesia

Link of Video Abstract: https://youtu.be/JhROjWPKuAc Background: Primary spinal cord tumors are rare central nervous system tumors that could develop at any age and have different management strategies based on the histopathological types. However, there is a lack of literature in Indonesia regarding the epidemiology and surgical treatment of patients with spinal cord tumors. This study aims to review and address the incidence of primary spinal cord tumors in Dr. Kariadi Hospital, Semarang. Methods: A retrospective descriptive study was conducted using medical records of patients with spinal cord tumors at Dr. Kariadi Hospital, Semarang, Central Java, from 2019 to 2022. The frequency of each tumor, classified by gender, age, histologic type, anatomical position, and location based on vertebral segment, was analyzed to provide a descriptive result. Data were analyzed using SPSS version 25.0 for Windows. Results: A total of 125 patients were identified with the mean age of patients being 43.95 ± 15.28 years old and a slight predominance of males (52.00%). Schwannoma (26.40%) and meningioma (24.80%) were the two most common histological types of tumors. Most of the tumor was intradural extramedullary (47.20%) and at the level of thoracic vertebrae (46.80%). The histologic type of the tumors was found to be associated with the patient’s age and the tumor’s anatomical position. Conclusion: The incidence of spinal cord tumors in Dr. Kariadi Hospital, Semarang, is dominated by meningioma and schwannoma, mostly located at the thoracal level with an intradural extramedullary position. There is a significant association between the histological type of tumor and the patient's age and the location of the tumor

Differences in survival prognosticators between children and adults with H3K27M-mutant diffuse midline glioma.

H3K27M-mutant diffuse midline glioma (DMG) is a rare and aggressive central nervous system tumor. The biological behavior, clinicopathological characteristics, and prognostic factors of DMG have not yet been completely uncovered, especially in adult patients. This study aims to investigate the clinicopathological characteristics and identify prognostic factors of H3K27M-mutant DMG in pediatric and adult patients, respectively. A total of 171 patients with H3K27M-mutant DMG were included in the study. The clinicopathological characteristics of the patients were analyzed and stratified based on age. The Cox proportional hazard model was used to determine the independent prognostic factors in pediatric and adult subgroups. The median overall survival (OS) for the entire cohort was 9.0 months. Significant differences were found in some clinicopathological characteristics between children and adults. The median OS was also significantly different between the pediatric and adult subgroups, with 7.1 months for children and 12.3 months for adults (p < 0.001). In the overall population, the multivariate analysis identified adult patients, single lesion, concurrent chemoradiotherapy/radiotherapy, and intact ATRX expression as independent favorable prognostic factors. In the age-stratified subgroups, the prognostic factors varied between children and adults, with intact ATRX expression and single lesion being independent favorable prognostic factors in adults, while infratentorial localization was significantly associated with worse prognosis in children. The differences in clinicopathological features and prognostic factors between pediatric and adult patients with H3K27M-mutant DMG suggest the need for further clinical and molecular stratification based on age.

Latest classification of ependymoma in the molecular era and advances in its treatment: a review.

Ependymoma is a rare central nervous system (CNS) tumour occurring in all age groups and is one of the most common paediatric malignant brain tumours. Unlike other malignant brain tumours, ependymomas have few identified point mutations and genetic and epigenetic features. With advances in molecular understanding, the latest 2021 World Health Organization (WHO) classification of CNS tumours divided ependymomas into 10 diagnostic categories based on the histology, molecular information and location; this accurately reflected the prognosis and biology of this tumour. Although maximal surgical resection followed by radiotherapy is considered the standard treatment method, and chemotherapy is considered ineffective, the validation of the role of these treatment modalities continues. Although the rarity and long-term clinical course of ependymoma make designing and conducting prospective clinical trials challenging, knowledge is steadily accumulating and progress is being made. Much of the clinical knowledge obtained from clinical trials to date was based on the previous histology-based WHO classifications, and the addition of new molecular information may lead to more complex treatment strategies. Therefore, this review presents the latest findings on the molecular classification of ependymomas and advances in its treatment.

A demographic and socioeconomic analysis of risk factors in meningeal melanomatosis.

e14019 Background: Meningeal melanomatosis (MM) is a rare and aggressive central nervous system neoplasm that normally occurs in the leptomeningeal melanocytes. Meningeal melanomatosis represents only 0.06% to 0.1% of all primary brain tumors, but it is accompanied with a very poor prognosis with data showing a mean survival of 10 weeks after diagnosis. Despite intrathecal chemotherapy treatment, only a modest positive effect on survival was observed. Limited research has been done. In this study, demographic factors in patients diagnosed with MM from the National Cancer Database (NCDB) were analyzed to elucidate potentially valuable insights regarding its epidemiology. Methods: A retrospective cohort study using data collected between 2004–2020 from the NCDB included 137 patients with a histologically confirmed diagnosis of MN. The descriptive analysis included an examination of demographic factors such as sex, age, race, Hispanic status, insurance coverage, type of medical facility, and Charleson-Deyo score. Primary site was also analyzed. Results: A total of 137 patients were identified with a diagnosis of MM between 2004 – 2020. The most common primary sites of MM were the meninges, not otherwise specified (NOS) (43.8%), spinal meninges (29.2%) and cerebral meninges (19.0%). In the dataset, 50.4% of diagnosed patients were male. The average age of diagnosis was 51.4 years (SD = 21.5, range = 0 – 90 years). The majority of the individuals (73.7%) had a Charlson-Deyo comorbidity score of 0. Most of the individuals diagnosed with MM were non-Hispanic (83.9%) and 87.6% of patients with diagnosed MM were White. Among the 115 patients with available data for median household income, 37.4% were in the top income quartile. A greater proportion of patients, 54.7%, had private insurance compared to those without insurance or those insured through Medicare or Medicaid. The majority of patients resided in metropolitan counties with a population exceeding 250,000 (71.8%) For patients with documented treatment facility type (N = 99), 56.6% of patients were treated in an academic/research program. Conclusions: This first NCDB analysis fills a crucial void in the existing knowledge on MM. MM affected males and females equally, contrary to published literature which suggested a slight predominance in males. The most common primary sites of diagnosis were the meninges NOS, spinal meninges and cerebral meninges, which supports findings in the literature. This is a novel description of the socioeconomic factors of MM patients in the literature, showing that these patients tend to have higher incomes and reside in densely populated metropolitan areas, and are more likely to receive treatment in an academic medical facility. Additional research is imperative to elucidate the influence of demographic and socioeconomic factors on the diagnosis, treatment options, and overall survival outcomes for patients with MM.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors.

Establishing novel therapies for rare central nervous system (CNS) tumors is arduous due to challenges in conducting clinical trials in rare tumors. Immunotherapy treatment has been a rapidly developing field and has demonstrated improvements in outcomes for multiple types of solid malignancies. In rare CNS tumors, the role of immunotherapy is being explored. In this article, we review the preclinical and clinical data of various immunotherapy modalities in select rare CNS tumors, including atypical meningioma, aggressive pituitary adenoma, pituitary carcinoma, ependymoma, embryonal tumor, atypical teratoid/rhabdoid tumor, and meningeal solitary fibrous tumor. Among these tumor types, some studies have shown promise; however, ongoing clinical trials will be critical for defining and optimizing the role of immunotherapy for these patients.

216 Indications and Outcome of Endoscopic Transorbital Surgery for Trigeminal Schwannoma Based on the Classification: A multicenter Study With 50 cases (Korean Society of Endoscopic Neurosurgery - 009)

INTRODUCTION: Trigeminal schwannoma is a rare central nervous system tumor and involves multi-compartmental skull base. Recently, endoscopic transorbital approach (ETOA) has been emerging technique as a minimally invasive surgery. METHODS: Between Sep. 2016 and Feb. 2022, we performed ETOA in 50 patients with trigeminal schwannoma at four tertiary hospitals. There were 15 men and 35 women with the mean age of 46.9 years. All tumors were classified type A (mainly involving the middle cranial fossa), type B (mainly posterior cranial fossa), type C (dumbbell-shaped tumor involving middle and posterior fossa), type D (Extracranial type). Type D tumors were also classified the ophthalmic division (D1), maxillary division (D2), mandibular division (D3). RESULTS: In this study, overall gross or near total resection was performed in 45 of 50 patients (90.0%). Median follow-up period was 21.9 months ranging from 1 to 61.7 months. There was no regrowing or recurrence during the follow-up period. Based on the classification, there were 17 tumors with type A, 1 type B, 19 type C and 13 type D. In particular, seven tumors were belong to D1, one D2, and five D3. For type A tumors, GTR/NTR was achieved with ETOA in 16 of 17 patients (94.1%). 18 of 20 patients with type C received GTR/NTR. For type D tumors, GTR was achieved in 5 of 7 patients who underwent ETOA. CONCLUSIONS: This study showed that trigeminal schwannomas can be effectively treated with a minimally invasive ETOA in all types of tumor except tumors mainly involving posterior fossa (type B). Especially, trigeminal schwannoma involving orbit (D1) or infratemporal fossa (D3) can be successfully removed with ETOA alone or combined ETOA with the endoscopic endonasal approach.