Pineal Tumors Research Articles

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.

​Occult extracranial malignancy after complete remission of pineal mixed germ cell tumors: a rare case report and literature review

Background​Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors (NGGCTs) is often accompanied by elevated tumor markers. ​Occult extracranial metastases or recurrences with negative markers are often difficult to detect in time, resulting in a very poor prognosis.Case presentationA 12-year-old boy was admitted to our institution with dizziness, headache, vomiting, and sleepiness. Magnetic resonance imaging (MRI) showed a pineal mass, accompanied by a significant increase in serum alpha-fetoprotein (AFP). The patient subsequently underwent total removal of the tumor. Pathology revealed that the tumor was a mixed GCT, consisting of mature teratoma, germinoma, and yolk sac tumor. Intracranial GCT achieved complete remission after intensive adjuvant chemotherapy and radiotherapy. Regular follow-up MRI revealed no recurrence of the intracranial tumor and continued monitoring of tumor markers revealed no abnormalities. ​Eight months later, the patient was readmitted due to progressive abdominal pain. Imaging and physical examination revealed abdominal occupation and lymphatic mass in the neck. He received salvage chemotherapy, anti-PD-1 immunotherapy, and palliative chemotherapy, but still developed multiple organ dysfunction syndromes (MODS) due to tumor progression and eventually died after one month.Conclusions​This profound case suggests that intracranial NGGCTs may develop occult extracranial malignancy, which can be very severe at the time of clinical symptoms and has an extremely poor prognosis. Therefore, in addition to tumor marker monitoring, regular follow-up with extracranial imaging may be warranted to detect extracranial tumors as early as possible, although perhaps not as frequently as with neuroimaging.

A rare and challenging case of pineal gland tumor – A case report

Pineal gland tumors are of rare occurrence and may arise from pineal parenchymal cells, the neighboring glia or residual stem cells. Due to its rarity pineal gland tumors are often misdiagnosed. The World Health Organsation (WHO) classifies and grades pineal parenchymal tumors from grade I to grade IV. We present a case report of a rare pineal parenchymal tumor (PPT) in an adult female which was diagnosed mainly on histopathology and aided by immunohistochemistry. The case report includes review of histopathological features and grading of pineal region tumors of intermediate malignancy which is necessary for further management of such cases.

The surgical intervention for pineal region tumors.

Histological and molecular characterization is essential for the diagnosis of pediatric brain tumors. In the pineal region tumors, it is necessary to remove a sufficient tumor volume to make a diagnosis. However, surgery in this region is challenging due to its deep anatomical location and surrounded by critical structures and complex venous system. Knowledge of the anatomy and function of the pineal region and tumor histological types is imperative for the successful management of pineal region tumors. This article describes surgical approaches to pineal tumors, focusing on the occipital transtentorial approach and adding the author's experience to what has been known in the literature. Recent innovations have made this approach more popular and can be applied to occipital fossa lesions.

“A tumour registry initiative”

BackgroundPublished literature on epidemiological profile of paediatric brain tumours in India is limited. Aim: To present a retrospective analysis of the histological spectrum of 158 paediatric age group central nervous system tumours operated in a single tertiary care hospital in Coastal South India between January 2015 and December 2021. Material and methodsRetrospective analysis of the data regarding frequencies of various primary brain tumours among 158 paediatric patients (<18 years of age). The tumours were categorised according to the revised 4th edition of World Health Organization (WHO) classification of tumours of the Central Nervous system. ResultsPaediatric CNS constituted 8.5% of total intracranial tumours (158/1860) operated in the study period. The mean age of the patients was 10.2 years and a definite male predominance was noted (1.54:1) Astrocytomas, glioneuronal tumours, and neuronal tumours constituted the majority (72/158; 45.6%) followed by embryonal tumours (31/158; 19.6%) and craniopharyngiomas(24/158; 15.4%).Of the glial neoplasms majority were pilocytic and other astrocytic tumours(41.6%), followed by mixed neuroglial tumours (19.4%), diffuse high grade astrocytomas (Grade III/IV) (11.1%), diffuse low -grade astrocytomas (Grade II) (9.7%) and ependymomas (13.8%). Our series also included six meningiomas (3.8%), five germ cell tumours (3.16%), four nerve sheath tumours (2.53%), two choroid plexus tumours (1.26%), two pineal parenchymal tumours (1.26%) and one metastasis from a soft tissue sarcoma from the thigh. Supratentorial tumours (58.2%) were more common than posterior fossa (34.6%) and spinal tumours (7.6%) and visual pathway gliomas accounted for 5.6% of all our tumours. ConclusionsPaediatric central nervous system tumours are more common in boys and in the second decade of life. Astrocytomas are the most common paediatric brain tumours followed by medulloblastomas and craniopharyngiomas. Pediatric tumours affect the supratentorial compartment more often than the infratentorial compartment. The profile of paediatric brain tumours in our series is similar to that reported from other Indian centres as well as most western literature.

Machine learning-based classification of pineal germinoma from magnetic resonance imaging

IntroductionSurgical approaches for tissue diagnosis of pineal tumors have been associated with morbidity and mortality. The classification of images by machine learning (ML) may assist physicians in determining the extent of resection and treatment plans for a specific patient. Therefore, the present study aimed to evaluate the diagnostic performances of the ML-based models for distinguishing between pure and non-germinoma of the pineal area. In addition, the secondary objective was to compare diagnostic performances among feature extraction methods. MethodsThis is a retrospective cohort study of patients diagnosed with pineal tumors. We used the RGB feature extraction, histogram of oriented gradients (HOG), and local binary pattern methods from magnetic resonance imaging (MRI) scans; therefore, we trained an ML model from various algorithms to classify pineal germinoma. Diagnostic performances were calculated from a test dataset with several diagnostic indices. ResultsMRI scans from 38 patients with pineal tumors were collected and extracted features. As a result, the k-nearest neighbors (KNN) algorithm with HOG had the highest sensitivity of 0.81 (95% CI 0.78–0.84), while the random forest (RF) algorithm with HOG had the highest sensitivity of 0.82 (95% CI 0.79–0.85). Moreover, the KNN model with HOG had the highest AUC, at 0.845. Additionally, the AUCs of the artificial neural network and RF algorithms with HOG were 0.770 and 0.713, respectively. ConclusionsThe classification of images using ML is a viable way for developing a diagnostic tool to differentiate between germinoma and non-germinoma that will aid neurosurgeons in treatment planning in the future.

Papillary Tumor of Pineal Region: A Case Report

Pineal region tumors constitute about 0.4%-1% of intracranial tumors in adults. These tumors may arise from pineal gland itself or structures around it which are all termed as pineal region tumor. Papillary tumor of the pineal region is a non-parenchymal tumor of the pineal region. First described in 2003, it is an extremely rare tumor. We have presented a case of 27-year-old female patient presented as a pineal tumor. After successful excision, the tumor proved to be Papillary tumor of Pineal region (PTPR) both histomorphologically and immunohistochemical study.&#x0D; Pulse Volume 12-14 2020-2022 p.13-15

ATRT-02. AN INFANTILE PINEAL EMBRYONAL TUMOR SHOWING PATHOLOGICAL FEATURES OF A CNS GANGLIONEUROBLASTOMA IN ADDITION TO SMARCA4 MUTATIONS AND THE METHYLATION PROFILING OF AN ATYPICAL TERATOID/RHABDOID TUMOR

Abstract Embryonal central nervous system tumors require genetic and epigenetic molecular analyses for further classification owing to the pathological, clinical, and molecular heterogeneity among these tumors. Here, we report a case of an infantile pineal tumor showing the pathological features of a CNS ganglioneuroblastoma; however, the specimen also contained SMARCA4 mutations and a methylation signature that is close to an atypical teratoid/rhabdoid tumor. A 2-year-old girl was referred to our hospital because of headache and dizziness presented with a pineal tumor and obstructive hydrocephalus. Radiologically, a large calcification was observed in the mass on head CT. The patient underwent tumor resection, and the pathological diagnosis was CNS ganglioneuroblastoma at that time. The specimen contained a variety of tumor cells, including undifferentiated embryonal cells, neurocytic cells, and ganglion cells embedded in a fibrillary matrix. The patient has been well for 5 years since they received multiagent chemotherapy and local proton irradiation. Subsequent genome-wide DNA methylation analysis revealed that the tumor was molecularly close to a sonic-hedgehog pathway-activated atypical teratoid/rhabdoid tumor. Genetic analysis also revealed SMARCA4 alterations in the splicing region of exons 10 and 34. This report indicates that genetic and epigenetic molecular approaches may facilitate elucidation of the clinical heterogeneity of CNS embryonal tumors, particularly the pathological appearance of CNS ganglioneuroblastomas.

OTHR-09. A RETROSPECTIVE COHORT STUDY EXAMINING RADIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN AND ADOLESCENTS WITH ATYPICAL/COMPLEX PINEAL CYSTS

Abstract INTRODUCTION The significance of atypical or complex pineal cysts (CPC) on magnetic resonance imaging (MRI) is often unclear, and the appropriate management has not been well defined. We conducted a retrospective cohort study of children and adolescents (0-18 years of age) with complex pineal cysts noted on brain MRIs obtained at Children’s Hospital Los Angeles (CHLA) prior to 05/31/2022. METHODS We retrospectively reviewed electronic medical records at CHLA to identify patients &amp;lt;18 years of age who were diagnosed with CPC upon MRI between January 1, 2010 and May 31, 2022. CPC were defined as cysts that are multi-cystic, enhancing, ≥1 cm in size, have a solid component, or exhibit restricted diffusion. Patients were identified by an automated Boolean search of a radiology report database; individual reports were then reviewed for eligibility. Patients with normal pineal glands or simple (&amp;lt;1 cm) pineal cysts were excluded. Electronic medical records were evaluated for patient chief complaint, initial clinical and radiographic symptoms, tumor markers (beta-human chorionic gonadotropin and alpha-fetoprotein), and final diagnosis. RESULTS We identified a cohort of 175 patients; 106 (61%) were female. Mean age at initial MRI was 8.36 years of age (SD 5.36). Tumor markers were measured in 52 patients (30%). The most common presenting symptoms for patients were headache (34%), seizures (26%), nausea/vomiting (19%), weakness/fatigue (17%), and dizziness (12%). Additional presenting symptoms included ataxia, sensory changes, and anxiety. Pineal malignancies were identified in 4 patients (2.2%), which consisted of a pituitary pure germinoma, a pineal region parenchymal tumor, and two pineoblastomas. The remaining 98% of patients (171 patients) either had a benign pineal cyst or were categorized as unknown. CONCLUSION Most CPC are not associated with malignant neoplasms and represent incidental findings with scant clinical significance.

Not a usual sight: A rare case of pineal gland tumor associated with Down syndrome presenting with absence of ophthalmologic signs: A case report

We describe a 24-year old man diagnosed with Down syndrome who developed intracranial germinona located at the pineal region who presented with no ophthalmologic signs on neurologic examination on admission. However, after external ventricular device (EVD) insertion, the patient developed upward gaze palsy and convergence retraction nystagmus.

An infantile pineal embryonal tumor showing pathological features of a CNS ganglioneuroblastoma and the methylation profiling of an atypical teratoid/rhabdoid tumor and SMARCA4 mutation.

An infantile pineal embryonal tumor showing pathological features of a CNS ganglioneuroblastoma and the methylation profiling of an atypical teratoid/rhabdoid tumor and SMARCA4 mutation.

Abstract 3521: CCND2 promotes proliferation in Drosha and DICER1 driven tumors

Abstract Mutations in microRNA processing genes such as DROSHA and DICER1 consist of 1.5-2% of pediatric cancers including a brain tumor called pineoblastoma. We developed a genetically engineered mouse model of Drosha- and Dicer1- driven pineal tumors. These tumors develop without microRNAs and express early pineal developmental markers. Gene set enrichment analysis revealed E2F target genes to be highly expressed in these tumors. One of the most upregulated genes in these tumors is cyclin D2 (Ccnd2). Additionally, these tumors stain positively for Rb phosphorylation. In a Wilms tumor cell line (WiT49) with Drosha knocked down, RNA sequencing revealed that CCND2 was the most upregulated gene. Similarly, in patient-derived xenografts (PDXs) of DICER1-related tumors such as pleuropulmonary blastoma (PPB), we observed high expression of CCND2 and positive staining for Rb phosphorylation. To test the dependence of Rb phosphorylation in Drosha and Dicer tumors, we next treated a Drosha pineal tumor allograft with a CDK4/6 inhibitor, palbociclib, and observed tumor growth suppression. Additionally, treatment of DICER1 mutant PPB PDXs with palbociclib had similar results. These experiments suggest that CDK4/6 is important for tumor proliferation in Drosha and DICER1 driven cancers. Citation Format: Claudette R. Fraire, Uma Obalapuram, Patricia D. Tiburcio, Kavita Desai, Kenneth S. Chen. CCND2 promotes proliferation in Drosha and DICER1 driven tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3521.

Surgical Treatment of Pineal Region Tumors: An 18year-Experience at a Single Institution.

The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy. The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy. The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7months to 10years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes. The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy.

Evaluation of Publications on Pineal Tumor from a Bibliometric Perspective

There are still many unknowns about the classification, diagnosis, and treatment of pineal tumors. The aim of this study was to review the accumulated knowledge of pineal tumors to guide future research. Web of Science (WoS) Core Collection was used to access the articles, and the Vosviewer package program was used for visualizations. The results showed that, between 1970 and December 2022, the WoS database indexed 1103 publications and 668 articles on pineal tumors. 92,365% of the articles were published in journals within the scope of the Science Citation Index Expanded. 798 institutions and 2,841 authors contributed to the pineal tumors literature. The most important contributions to the literature on pineal tumors were made by institutions in France and the United States. The majority of the articles were from the USA (n=190, 28.443%), Japan (n=111, 16.617%), and France (n=62, 9.281%). The number of articles were irregular in each per year. However, more citations have been made, especially since 2010. In this study, the studies on pineal tumors in the world were examined and the main underlied issues were tried to be emphasized. In addition, it has been observed that the scientific and industrial sectors should cooperate in order to increase the allocated resources for multidisciplinary researches.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Accuracy of apparent diffusion coefficient values for distinguishing between pineal germ cell tumour and pineoblastoma

To differentiate between pineal germ cell tumour and pineoblastoma using apparent diffusion coefficient (ADC) values due to their overlapping imaging findings on magnetic resonance imaging (MRI). This retrospective study was conducted on 33 patients with pineal germ cell tumours and eight patients with pineoblastoma who underwent pretreatment MRI. Twenty-seven patients (21 with pineal germ cell tumour and six with pineoblastoma) were included for ADC measurement. The minimum and mean ADC values of the tumours were measured, with normalized tumour to control ADC ratios generated. The MRI characteristics of the tumours were evaluated. The mean and minimum ADC values, normalized mean and minimum ADC ratios of pineal germ cell tumours were significantly higher than those of pineoblastomas (all p<0.005). A cut-off value of 0.92 for the normalized mean ADC ratio was used to distinguish between pineal germ cell tumour and pineoblastoma and achieved an area under the curve of 0.95, sensitivity of 90.5%, specificity of 83.3%, and accuracy of 92.6%. An equal degree of contrast enhancement to the adjacent venous sinus was the only MRI characteristic that suggested the diagnosis of pineal germ cell tumour. The ADC values could help differentiate between pineal germ cell tumour and pineoblastoma, specifically when conventional MRI findings are indeterminate.

Papillary Tumor of the Pineal Region: A Case Report and Literature Review

Pineal tumors of the pineal region (PTPR) are rare neuroepithelial tumors of the central nervous system, and their clinical features often lack specificity, so it is always difficult to make a definite diagnosis before surgery, and the treatment is mainly based on complete surgical resection. We report the case of a 21-year-old male who presented with intermittent dizziness and headache with vomiting for more than 2 months. The imaging revealed a mass in the region of the pineal region with obstructive hydrocephalus. After the hospitalization, the patient underwent a microscopic excision of the pineal mass, and the tissue was sent for histopathological examination and available immunohistochemical tests, which resulted in a definitive diagnosis of a papillary tumor of the pineal region. He had undergone several radiation treatments during his hospitalization and remained recurrence-free until the latest follow-up visit. This article highlights the similarities between this case and the PTPR described in WHO 2021 in terms of clinical presentation, imaging, and histopathological features. Therefore, this case report completes the sample database of PTPRs. By reviewing the literature related to PTPRs, we hope that this report will be helpful to improve the understanding of clinicians and pathologists about this rare tumor. However, more relevant studies are needed to clarify the pathogenesis, prognosis, and optimal treatment options to achieve early diagnosis, early treatment, and improved prognosis.

Radiation therapy for pineal parenchymal tumor of intermediate differentiation: A case series and literature review.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare, primary tumor of the pineal gland. Due to its rarity, there is no consensus on optimal therapeutic strategies or standard characterization of the tumor's behavior. Here, we report 2 new cases of PPTID and an extensive review of the literature involving the use and extent of radiation therapy. Patient 1 is a 54-year-old male who presented with PPTID and drop metastases in the spinal cord, received cranial spinal irradiation (CSI), and experienced recurrence 3.5 years after treatment. Stereotactic body radiation therapy (SBRT) helped the patient into remission for 9months. Patient 2 is a 32-year-old male with a local PPTID at presentation who went on to receive surgical resection followed by focused adjuvant radiation therapy to the pineal tumor bed. He then presented 6years after treatment with extensive disseminated recurrence and died due to leptomeningeal disease (LMD) about 4years after recurrence. The available literature on PPTID is limited and reported cases of LMD with ongoing follow-up in PPTID are scarce. Our report adds to the current known PPTID cases, contributing to the information available regarding prognosis and treatment response. Although an optimal therapeutic strategy for PPTID still cannot be determined, data from the literature suggest that utilizing radiation therapy in patients with low-risk disease and gross total resections as well as the use of upfront CSI have the potential to improve patient progression and survival outcomes.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/β ratio of 2 for late normal tissue toxicity and 10 for the tumor. A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Dorsal Midbrain Syndrome from Thalamocapsuloganglionic Hemorrhage: A Case Report

Dorsal midbrain syndrome (DMS) is a supranuclear palsy of vertical gaze characterized by conjugate upgaze palsy, light-near dissociation, convergence-retraction nystagmus, lid retraction, and skew deviation. Majority of cases are due to primary midbrain lesions such as strokes or neoplasms, or due to pineal gland tumors compressing the said area. Presented here is the case of a 57-year-old male who came in with a chief complaint of diplopia and the typical signs of DMS. Cranial tomography scan revealed a parenchymal hemorrhage at the left thalamocapsuloganglionic region, a rarely reported site of a primary lesion causing DMS. In this case, the syndrome may have been a consequence of the mass effects and perilesional edema associated with the thalamocapsuloganglionic hemorrhage, or may have been due to disruption of supranuclear inputs to the dorsal mibdrain. This case provides further evidence that DMS may arise from lesions without obvious involvement of the said region. This case also highlights the importance of a thorough physical examination to elicit the findings associated with DMS, and the need to correlate these with a keen analysis of diagnostic test results.