Pineal Region Research Articles

Surgical corridor formation by minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach in pineal region tumor surgery: A review of 11 cases

IntroductionThe pineal region is a hard-to-reach part of the brain. There is no unequivocal opinion on the choice of a surgical approach to the pineal region. The surgical approaches described differ in both trajectory (infra- and supratentorial, interhemispheric) and size of craniotomy. They have advantages and disadvantages. The minimally invasive lateral occipital infracortical supra-/transtentorial (OICST) approach we have described has all the advantages of the standard supratentorial approach and minimizes its disadvantages, namely, compression and contusion of the occipital lobe. The minimally invasive craniotomy and small surgical corridor facilitate that. MethodsWe describe 11 consecutive patients with various pineal region tumors (7 cases of pineal cysts, 2 cases of pinealocytoma, 1 case of medulloblastoma, and 1 case of meningioma) who were operated on in our hospital using the lateral OICST approach. Preoperative planning was performed using Surgical Theater®. The surgical corridor was formed using a retractor made from half of a syringe shortened according to the length of the surgical corridor. Preoperative lumbar drain was used. ResultsThe pineal region tumors were completely resected in all cases. The mean craniotomy size was 2.22 × 1.79 cm. No long-term neurological deficits were reported. ConclusionsThe use of semicircular retractors and intraoperative CSF drainage via a lumbar drain allows to form a small surgical corridor to the pineal region via minimally invasive craniotomy. This reduces traction and traumatization of the occipital lobe, as well as minimizes intra- and postoperative risks.

The TIGR triangle of the pineal region: a virtual reality anatomic study.

In this morphometric study, we describe the anatomy of the TIGR triangle, which is bordered by the tentorial surface of the cerebellum, the internal cerebral vein and vein of Galen complex, and the vein of Rosenthal. These structures define the window, or deep keyhole, to access the pineal region in non-midline supracerebellar infratentorial approaches. The posterior fossa anatomy of 16 patients was studied in virtual reality (VR), and the TIGR triangles were defined and measured with special attention on its angular orientation in the posterior fossa. The angular expanse of the posterior fossa was measured and recorded as the transverse-sigmoid junction (TSJ) angle. Because a perpendicular corridor through an anatomic aperture provides the best exposure, we studied the starting point along the TSJ angle that offers the best exposure of TIGR. In the 31 posterior fossa sides included in the study, the perpendicular trajectory through the TIGR triangle was on average 27.13° CI 95% (range: 5.97°-48.53°) from the midline. When comparing the SCIT variants, both the paramedian and lateral approaches provided near-perpendicular trajectory through the TIGR triangle in a majority of specimens. However, the modified paramedian approach, with starting point defined as TSJ angle/3, provided the most perpendicular path through the TIGR triangle. We studied the size, spatial orientation, and morphology of the TIGR triangle. Our data indicated that the best exposure of TIGR is through a modified paramedian SCIT approach, in which the starting point one third of the way from midline to the TSJ.

Spinal metastases of pineal region glioblastoma with primitive neuroectodermal features highlighting the importance of molecular diagnoses: illustrative case

BACKGROUND Glioblastoma (GBM) is the most common primary brain tumor with poor patient prognosis. Spinal leptomeningeal metastasis has been rarely reported, with long intervals between the initial discovery of the primary tumor in the brain and eventual spine metastasis. OBSERVATIONS Here, the authors present the case of a 51-year-old male presenting with 7 days of severe headache, nausea, and vomiting. Magnetic resonance imaging of the brain and spine demonstrated a contrast-enhancing mass in the pineal region, along with spinal metastases to T8, T12, and L5. Initial frozen-section diagnosis led to the treatment strategy for medulloblastoma, but further molecular analysis revealed characteristics of isocitrate dehydrogenase–wild type, grade 4 GBM. LESSONS Glioblastoma has the potential to show metastatic spread at the time of diagnosis. Spinal imaging should be considered in patients with clinical suspicion of leptomeningeal spread. Furthermore, molecular analysis should be confirmed following pathological diagnosis to fine-tune treatment strategies.

Treatment of Pineal Region Lesions in Children.

Pineal region lesions are more common in children than adults; however, therapeutic strategies for pineal region lesions in children are controversial. A retrospective study involving 54 pediatric with pineal region lesions was conducted. The therapeutic strategies for lesions and hydrocephalus were classified and analyzed. Radiotherapy of pineal region lesions was shown to result in better postoperative recovery and fewer complications in the short-term compared with lesion resection. Total resection was related to smaller lesion size, endoscopic procedures, and a better prognosis. Cerebrospinal fluid (CSF) diversion before the resection reduced hydrocephalus recurrences, whereas further lesion resection had a negative short-term influence on CSF diversion. Among the 4 therapeutic strategies to manage hydrocephalus, a third ventriculostomy (ETV) was reasonable and further resection did not have a negative impact on the ETV. The relief of hydrocephalus was also related to better postoperative recovery, a higher total resection rate, fewer complications, and a better prognosis. Logistical regression analysis indicated that lesion size and intracranial complications were predictors of outcome. For lesion treatment, total resection and radiotherapy are essential components in children. Total resection and CSF diversion before resection were beneficial, whereas further lesion resection had a negative impact on CSF diversion. For hydrocephalus treatment, ETV was shown to be the best therapeutic strategy for management of pediatric hydrocephalus. Total resection and better preoperative health status were associated with greater hydrocephalus relief. For the overall prognosis, a lack of hydrocephalus relief was associated with poor outcomes. Lesion size and intracranial complications may be the best predictors of outcome.

EPID-24. CAPTURING EVOLVING DEFINITIONS OF 12 SELECT RARE CNS TUMORS: A TIMELY REPORT FROM CBTRUS AND NCI-CONNECT

Abstract BACKGROUND Incidence, prevalence, and survival are population-based cancer statistics that describe cancer burden. The National Cancer Institute’s Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) specializes in research of 12 rare CNS tumor types to improve approaches to care and treatment. These tumors include atypical teratoid/rhabdoid tumors, brainstem and midline glioma, choroid plexus tumors, ependymoma, high grade meningioma, gliomatosis cerebri, medulloblastoma, oligodendroglioma/anaplastic oligodendroglioma, pineal region tumors, pleomorphic xanthoastrocytoma, CNS embryonal tumors, not elsewhere classified (NEC)/not otherwise specified (NOS), and primary CNS sarcoma. This study aimed to update incidence, prevalence, and survival statistics for these tumors. METHODS The Central Brain Tumor Registry of the United States (CBTRUS) database, a combined dataset of CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology and End RESULTS (SEER) data, was used to calculate average annual age-adjusted incidence rates (AAAIR) per 100,000 population overall and by sex, race-ethnicity, and age (2008-2019). NPCR data were used to calculate relative survival (RS) estimates (2008-2018). Prevalence on December 31, 2019 was estimated using annual age-specific incidence and survival from CBTRUS and SEER, respectively. RESULTS AAAIR was 1.51 per 100,000 for these tumors combined, with highest incidence in ependymomas (AAAIR=0.41/100,000). Most tumor types were more common in males, adults (ages 40+ years) or children ages < 15 years, and non-Hispanic White individuals. Ependymomas were most prevalent (19,339 cases) followed by oligodendrogliomas (15,070 cases). 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 (5-years=90.6%) and primary CNS sarcomas had the lowest RS (5-years=7.7%). CONCLUSIONS 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.

Clinicopathological spectrum of central nervous system germ cell tumors: A single-institution retrospective study.

Central nervous system germ cell tumors (CNSGCTs) though rare is the second most common extragonadal site for GCTs. To determine the clinicopathological features of CNSGCTs diagnosed at our center. A retrospective study of all histologically diagnosed CNSGCTs, during 2006-2019. The patients' data were retrieved from the hospital information systems and analyzed. Data on categorical variables were analyzed as percentages, and data on continuous variables calculated as mean. Chi-square test or Fisher's exact test was used to study association between variables. Of the total 34 cases with CNSGCT, age ranged from 1 to 27 years, majority in the second decade (19/34; 56%). Male: female (M: F) ratio was 1.6:1. Single site involvement was seen in 27 cases (27/34; 79%), whereas seven (7/34; 21%) showed bi/multifocal involvement. Among the unifocal cases, common sites involved were suprasellar (12/27; 44.4%), closely followed by the pineal (10/27; 37%). All multifocal tumors affected suprasellar compartment, being bifocal with pineal in four cases. A male gender predilection was noted among pineal region (9/10;90%) and multifocal tumors (5/7;71%). Germinoma was the commonest subtype (21/34; 61.8%) with male gender predilection (17/21; 81%) (M: F =4.3:1), with female predilection seen among mixed GCTs (MGCTs) (8/10; 80%) (M: F =1:4) and suprasellar location (M: F =1:2). Serum tumor markers (25 cases) and CSF markers (7 cases) were concordant with histology in all, except two cases. Though histology and immunohistochemistry were diagnostic, correlation between serum and/or CSF marker was essential to rule out GCT component(s) that may be missed on biopsy due to sampling error.

PAEDIATRIC-07 IMAGING OF PINEAL REGION TUMOURS IN CHILDREN

Abstract Pineal tumors comprise between 3% and 8% of all pediatric brain tumors. Pineal region tumors can be divided into four categories: Germ cell tumors, pineal cysts, pineal parenchymal tumors, and tumors of the supporting tissues of the pineal gland or adjacent structures (such as pineal gliomas, dermoids, and epidermoids). The most common pineal region tumors are germ cell tumors, most are pure germinomas. Other variants such as nongerminomatous germ cell tumors, mixed germ cell tumors, teratomas, embryonal cell carcinoma, yolk sac tumor, and choriocarcinoma constitute the remainder. Germinomas are hyperdense on CT and enhance homogenously. The typical appearance on CT is a calcified pineal gland surrounded by noncalcified tumor. On MRI, these lesions have homogenous signal isointense to gray matter on all sequences with intense contrast enhancement. These tumors may infiltrate the thalami and midbrain. Spinal dissemination is seen in up to 36% of cases. Pineocytomas are well-differentiated tumors that retain morphologic features of the pineal parenchymal cells. They are slow-growing, circumscribed, but noncapsulated tumors. They are more commonly solid tumors, although cystic variants have been described. Solid tumors are either hypointense or isointense to gray matter and T2-hyperintense. Enhancement is homogenous and calcification is common. Cystic variants are often indistinguishable from pineal cysts. Pineoblastomas are malignant, unencapsulated tumors that resemble embryonal tumors NOS, but are distinct from such tumors in other locations due to their photosensory differentiation. On MRI, these lesions are hypointense to isointense on T1-weighted images and variable low, high, or mixed signal on T2-weighted images. They have lobulated contours and enhance homogenously. They calcify less often than pineocytomas. The “exploded pattern” of calcification with peripheral displacement of pineal gland calcification is considered more typical of pineal parenchymal tumors, differentiating them from germ cell tumors.

Pineal cysts in children: a paediatric series treated over the last twenty years in Lyon.

Pineal cysts are a rare lesion of the pineal gland. Pineal cysts are benign lesions, generally asymptomatic, and are usually an incidental discovery on MRI performed for other problems. The management of pineal cysts in children remains a matter for debate. Here, we report our own retrospective paediatric cases that have been surgically treated and review the paediatric literature on this topic. This is a retrospective monocentric study. All patients operated by the senior author (CM) for a benign pineal cyst from 2000 to 2021 were included. All other pineal region cystic lesions were excluded. Medical and surgical data were extracted from the hospital medical database. Twelve patients were included. The clinical symptomatology was characterized by headaches in seven patients, visual troubles in two patients, precocious puberty in one patient, signs of intracranial hypertension in two patients, seizures associated with headache in one patient, and headaches associated with behavioural troubles in another patient. No major post-operative complications were observed in this series. It is to noted that surgery was performed because a suspicion of a true pineal parenchymal tumour has been made. Histopathological study came back with the diagnosis of pineal cyst. Pineal cyst is rare. If the radiological diagnosis is clear, no surgery is advocated except in cases associated with hydrocephalus and rapid growth. In case of a suspicion of a true pineal parenchymal tumour, a surgery may be needed to confirm the diagnosis. Lastly, we stress that only cystic lesions of the pineal gland itself should be considered as pineal cyst.

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.

The Paramedian Supracerebellar Infratentorial Approach: 2-Dimensional Operative Video.

The supracerebellar-infratentorial approach uses the plane between the tentorium and the superior surface of the cerebellum to expose the pineal region. The bone opening is just underneath the level of the transverse sinus, and so its position must be noted preoperatively. The anatomy of the internal cerebral veins and the veins of Galen and Rosenthal should be examined as well. The sitting position allows gravity-assisted expansion of the supracerebellar corridor, and a paramedian approach provides the biggest working space in the TIGER triangle, delineated by the tentorial surface of the cerebellum, the internal cerebral vein/Galen complex, and the vein of Rosenthal. The veil of arachnoid beyond the triangle must be carefully opened to expose the pineal region. For the sitting position, the operative team must be careful about air emboli. A patent foramen ovale is a contraindication for the position. The deep veins must be handled delicately to avoid complications. Several variations are shown in this video. For visualization, augmented reality is helpful, but since current augmented reality technology is microscope-based, its use can be ergonomically challenging if the tentorium is steep.1 Our current preference is to use the exoscope for the major portion of the procedure until most of the tumor is out and then switch to hand-held endoscopes with various angles to finish the operation.The patients consented to the surgery, and all relevant participants consented to publication of their images.

Simulation of the occipital transtentorial approach incorporating visualization of the cerebellar tentorium using three-dimensional computed tomography angiography and gadolinium-enhanced T1-weighted magnetic resonance imaging: technical note

The occipital transtentorial approach (OTA) is one of the useful approaches to the lesions of the pineal region, dorsal brainstem, and supracerebellar region. However, a wide operative field is sometimes difficult to obtain due to the tentorial sinus and bridging veins. This study evaluated the usefulness of preoperative simulation of OTA, specifically including the cerebellar tentorium in 9 patients. All patients underwent computed tomography angiography and venography and gadolinium-enhanced three-dimensional T1-weighted magnetic resonance images (Gd-3D-T1WI). The images were fused, and the cerebellar tentorium, vessels, and tumor were manually extracted from Gd-3D-T1WI to obtain the simulation images. Visualization of the cerebellar tentorium could discriminate between bridging veins from the occipital lobe and cerebellum, and recognize the site of bridging to the tentorial sinus and variants which may interfere with the tentorial incision. Simulation of the tentorial incision was also possible based on the relationships between the tumor, tentorial sinus, bridging vein, and cerebellar tentorium. The simulation suggested that safe tentorial incision was difficult in two sides because of the crossed tentorial sinus draining the left basal vein and draining veins from the glioblastoma. The OTA was performed in eight cases, and no difficulty was experienced in the tentorial incision in all cases. The simulation findings of the bridging vein and tentorial sinus were consistent with the intraoperative findings. Preoperative simulation including the cerebellar tentorium is useful for determining the optimum and safe side and required extent of the tentorial incision necessary for tumor resection with the OTA.

Neurosurgical application of pineal region tumor resection with 3D 4K exoscopy via infratentorial approach: a retrospective cohort study.

The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus. In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center. The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome. The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.

The sub-occipital transtentorial approach for pineal region tumors: how I do it.

Two major approaches exist for the surgical removal of pineal region tumors: the supracebellar infratentorial and the sub-occipital transtentorial. We present the Lyon's technique of the sub-occipital transtentorial approach for pineal region tumors and our tricks to avoid complications. The principle is to expose the pineal region under the occipital lobe and not through the interhemispheric fissure. The sub-occipital transtentorial approach is a direct, extra cerebral, safe, and effective way to access tumors of the pineal region.

Sudden death in patients with pineal cyst: Evidence from autopsy studies.

Pineal cysts are usually benign, fluid-filled sacs and most pineal cysts are asymptomatic. Sudden death specifically related to pineal cysts is extremely uncommon. A literature review of the pertinent databases, including PubMed, Google Scholar, Scopus, and Web of Science, was carried out to review the existing literature describing sudden death in patients with pineal cysts. In the evaluation of 49 articles, it was found that four reports discussed the unexpected death of patients who had pineal cysts. A total of four cases of sudden death and a pineal cyst were reported. There were 75% females and a mean age of 29 (range: 20-45). Cyst size on average was 1.3 cm (1.2-1.5). In each case, the cause of death and the involvement of important brain structures were confirmed by autopsy results. A pathological analysis of the pineal region and the surrounding brain tissue revealed a variety of lesions. Vascular malformation was found in one case, adding another layer of complexity to the study of sudden death syndrome. In this research, the authors highlight the fact that patients with pineal cysts can experience serious, even fatal, complications. Increased vigilance and early detection through neuroimaging and neurological assessments are required due to the wide variety of clinical manifestations and underlying mechanisms. To explain the mechanism and enhance the management and prevention of sudden deaths associated with pineal cysts, additional research with larger sample sizes is required.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-yearOS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-yearprogression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

P20.15.A DESCRIPTIVE ANALYSIS OF A SERIES OF H3 K27-ALTERED DIFFUSE MIDLINE GLIOMAS IN CHILDREN AND ADULT POPULATION

Abstract BACKGROUND Molecular biomarkers have gained importance in providing diagnostic information for brain and spinal cord tumors. Diffuse midline gliomas (DMG) are now defined as H3 K27-altered. H3 K27M mutations were first described in pediatric diffuse pontine gliomas but can also be encountered in adult gliomas. The H3 K27M mutation often co-occurs with mutations in TP53, PDGFR, or ACVR1 and is mutually exclusive to IDH1/2 mutations and 1p/19q co-deletion. Surgical resection is often not feasible for its localization and the benefit of temozolomide (TMZ) is not clear as they are MGMT unmethylated; all of it conferring a poor prognosis. It has been suggested that pediatric patients (pts) have worse outcomes. Our aim was to describe pts with H3 K27-altered gliomas to better understand the characteristics of this population. MATERIAL AND METHODS We analyzed clinical, histological and molecular features of 6 adults and 10 pediatric pts diagnosed with H3 K27M-mutant gliomas between May 2016 and January 2021 in a tertiary hospital in Barcelona. RESULTS For adults, mean age at diagnosis was 34.6 years (range = 20 - 55 years). For children, mean age was 11.2 years (range = 4 - 17 years). Male-to-female ratio was 1:1. Tumors involved thalamus (adult = 3; pediatric = 3), pons (adult = 1; pediatric = 6), and pineal region (n = 1). Ki67 range was 2-60% (pediatric mean 32%, adult mean 20%). A molecular panel was analyzed in 8 pediatric pts and 1 adult. No EGFR amplifications were detected.Three of them had TP53 mutations and 2 had PDGFRA amplification. Only 2 pediatric pts had MGMT methylation. Regarding treatment, 9 pediatric and 4 adult pts underwent radiotherapy and TMZ as first-line, with a mean time to intervention of 5.6 months. One child went through palliative care. As a second-line treatment, re-irradiation was used in 3 pediatric pts and irinotecan-bevacizumab was used in 2 adults. One adult received up to 4 different treatments (TMZ chemoradiotherapy followed by adjuvant TMZ, irinotecan-bevacizumab, lomustine and metronomic TMZ).All 9 pediatric pts died, with a mean OS of 12.0 months. Among adults, 2 pts died, 10.5 and 31.2 months after diagnosis, 1 has progressed to first-line and is receiving PCV as second-line treatment, and 1 has completed Stupp regimen with stable disease as best response. CONCLUSION Although the sample size is limited, our cohort data resembles what has been previously reported in terms of clinical and molecular characteristics: diagnosed in young adults and pediatric pts, characterized by a midline location, a low rate of MGMT promoter methylation, frequent TP53 and PDGFR alterations, and poor prognosis. There is currently no consensus on optimal treatment sequence or best treatment for these pts. Collaborative effort and participation in clinical trials are needed to keep advancing in this poor prognosis disease.

Considerations on surgical strategies and associated risk profiles for endoscopic tumor biopsies within the third ventricle and periaqueductal region

IntroductionNeuroendoscopic techniques have proven to be a successful and minimally-invasive technique for tumor biopsies within the third ventricle in pediatric patients. However, a comprehensive assessment of associated surgical strategies, techniques, and morbidity is essential to optimize patient outcomes.MethodsThis retrospective study analyzed full endoscopic tumor biopsies in pediatric patients with tumors in the third ventricle and periaqueductal region. Data from 1995 to 2022 were collected from medical records, imaging, and intraoperative video documentation.ResultsIn this study, 16 shear endoscopic tumor biopsies were performed using the transventricular transforaminal approach. Tumors were located in the anterior or mid part of the third ventricle (50%) or in the periaqueductal and pineal recess region (50%). Preoperative hydrocephalus was seen in 81.25%. Tumor biopsies were harvested successfully in all cases. Simultaneous ETV was performed in 12 (75%) cases and additional septostomy in 3 (18.75%). Significant intraoperative bleeding occurred in 3 cases (18.75%). All bleeding situations could be successfully managed with continuous irrigation. Histopathology revealed astrocytoma as the predominant diagnosis (75%). No new neurologic deficits were observed, except for one case of transient oculomotor nerve paralysis after ETV. Hydrocephalus persisted in 18.6% of all cases with the need of urgent ventriculoperitoneal shunting in two patients.ConclusionIn conclusion, neuroendoscopy emerges as an effective technique for tumor biopsies within the third ventricle in pediatric patients, offering the added advantage of simultaneous treatment of obstructive hydrocephalus. However, it is essential to acknowledge the specific intra- and postoperative risks associated with various surgical strategies. The safe management and achievement of favorable clinical results demand extensive experience and expertise.

P03.05.B PRIMARY GAMMA KNIFE RADIOSURGERY FOR PINEAL REGION TUMORS, A SYSTEMATIC REVIEW AND POOLED ANALYSIS OF AVAILABLE LITERATURE WITH HISTOLOGICAL STRATIFICATION

Abstract BACKGROUND Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality following surgery or as a salvage treatment at recurrence. We aimed to gather the existing evidence on the topic and analyze single-patient level data to address the efficacy and safety of primary GKSR when only a biopsy was attempted or biochemical or neuroimaging diagnosis was available. MATERIAL AND METHODS This is a systematic review of literature (Pubmed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers in our final analysis comprising 64 patients. Additional 12 patients were included from the authors’ original series. RESULTS A total of 76 patients reached the final analysis. Presumptive diagnoses included intrinsic pineal low-grade (46%), glial low-grade (LGG, 5%), pineoblastoma (4%), germ cell tumors (GCTs, 4%), pineal tumors of intermediate differentiation (3%), other pineal tumors (3%), glial high-grade (HGG, 2%) and meningioma (1%). In 32% of cases, the diagnosis was unclear. Only 57% of cases received histological confirmation. The mean age at treatment was 38.7y and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose (50% isodose) of 14.7 ± 2.1 Gy. At a median 36mo follow-up, local control was achieved in 84% of cases. Ten patients showed progression within a mean time of 24.2mo. Progression was more common in HGG and GCTs (p=0.03) compared to intrinsic pineal tumors. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3y-OS was 100% for LGG, 90% for the intrinsic pineal, 60% for GCTs, 50% for HHG, and 82% for undetermined tumors. The 3y-PFS was 100% for LGG, 90% for the intrinsic pineal, 32% for GCTs, and 0% for HHG. Median PFS was 5mo for HHG and 34mo for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as presenting symptom strongly predicted mortality (OR 104, p=0.02), while GCTs and HHG histology well predicted PD (OR: 13, p=0.04). CONCLUSION These results support the efficacy and safety of primary GKSR treatment of pineal region tumors. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

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.

Clinical characteristics of malignant germ cell tumors in adolescents: A multicenter 10-year retrospective study in Beijing.

The aim of this study was to review clinical features of adolescent malignant germ cell tumors (MGCTs) in Beijing and analyze the peculiar characteristics of this age group. Clinical characteristics, pathological presentations, and survival outcomes of 34 patients were analyzed retrospectively. Of 34 patients, 12 girls and 22 boys, 18 (52.9%) had an extra-cranial tumor, including one testicular tumor, five ovarian tumors, one sacrococcygeal tumor, and 11 mediastinal tumors. Histologically, we found immature teratomas (n = 6), yolk sac tumors (n = 5), mixed malignant tumors (n = 5), an embryonic carcinoma (n = 1), and seminoma (n = 1). Three-year event-free survival (EFS) and overall survival (OS) were 48.8% and 62.9%, respectively. Another 16 (47.1%) patients had an intracranial tumor, including nine in the pineal region, five in the suprasellar region, one in basal ganglia, and one in cerebellopontine. All patients had localized disease and an excellent outcome with 3-year EFS and OS of 93.7% and 100%, respectively. Adolescent MGCTs are rare with a strong dependence on gender, and the mediastina and pineal region are the most common tumor locations. The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups. MGCTs in mediastina have a tendency to companion with other hematological malignancies, and the prognosis is extremely poor in these patients.