CTNI-59. A MULTICENTER OBSERVATIONAL STUDY OF CS-131 SEEDS EMBEDDED IN A COLLAGEN CARRIER TILE FOR NEWLY DIAGNOSED AND RECURRENT OPERABLE INTRACRANIAL NEOPLASMS – TRIAL IN PROGRESS

BACKGROUND For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy has been limited by uneven dose distributions, complicated workflows, extended procedural times, cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and efficacy in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the GammaTile. METHODS Patients undergoing resection (R) of brain tumors with intra-operative GammaTile placement are eligible for enrollment. Planned sample size is 600 at up to 50 enrolling sites. First subject was enrolled 10/14/2020. Tumor pathology, overall survival, radiation- and surgery-related adverse events, patient- and provider-reported quality of life, serial MRIs, and timing of surgical bed and/or distant recurrence are collected. Powered primary endpoints for recurrent brain metastases, recurrent glioblastoma, and recurrent meningioma (surgical bed-progression free survival (PFS), overall survival, and PFS, respectively), compare STaRT to standard-of-care benchmarks. Results will be used to improve awareness and access to this treatment, benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, facilitate the design of future clinical trials, and contribute to the optimal sequencing of treatments for intracranial neoplasms.

TRLS-05. A multicenter observational study of Cs-131 seeds embedded in a collagen carrier tile for newly diagnosed and recurrent operable intracranial neoplasms –Trial in progress

Background For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy (EBRT),. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy methods have been limited by uneven dose distributions, complicated workflows, extended procedural times, the cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, including brain metastases, and has demonstrated excellent safety and local control in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study [NCT04427384] are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the device. Methods Subjects (N=600) at up to 50 enrolling sites undergoing resection of brain tumors of any pathology with intra-operative GammaTile placement are eligible for enrollment. We project 40% of enrollees to have brain metastasis. Tumor pathology, overall survival, radiation- and surgery-related adverse events, quality of life, serial MRIs, and timing of surgical bed recurrence and/or distant recurrence will be collected. The powered primary endpoint for recurrent brain metastases, surgical bed-progression free survival, will compare STaRT to standard-of-care benchmarks. This study will be the first observational study of resection plus GammaTile. Results will be used to benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, and facilitate the design of future clinical trials.

Selective Dysarthria due to Clival Chordoma

Chordoma is a rare, slow-growing malignant bone tumor originating from the remains of the notochord and predominantly affecting the axial skeleton (especially the sacrum and occipital region). Clival chordomas represent 1-4% of intracranial neoplasms and only 0.2% of central nervous system tumors, so their prevalence is very low (1 case per 2 million inhabitants). The mean age of onset is in the 4th decade of life and its usual symptoms are diplopia due to involvement of the ocular pairs, dysphagia and headache (1,2). More rarely, it affects phonetics in isolation due to the involvement of the lower cranial nerves (hypoglossal or glossopharyngeal) (3-5).

Headache related to an intracranial neoplasm

Patients presenting for headache often worry about having a brain tumour. Specific tumours may induce headache by varied mechanisms, producing different phenotypes. Virtually all headache and facial pain phenotypes can be secondary to a brain tumour, but clinical clues to a secondary aetiology are often present. Headaches may also be related to the treatment of intracranial neoplasms such as intrathecal chemotherapy, radiotherapy, and craniotomy. The ICHD-3 therefore includes several codes related to brain tumours, illustrating this diversity. Although not specifically represented in the classification, the association of trigeminal autonomic cephalalgias with pituitary tumours is now supported by the literature and is discussed in a specific section.

Epigenetic dysregulation in pituitary tumors

Pituitary tumors are common intracranial neoplasms associated with significant morbidity due to hormonal dysregulation and neurologic symptoms. Somatic mutations are uncommon in sporadic pituitary adenomas, and only few monogenic conditions are associated with pituitary tumors. However, increasing evidence suggests that aberrant epigenetic modifications are found in pituitary tumors. In this review, we describe these mechanisms, including DNA methylation, histone modification and microRNA expression, and the evidence supporting their dysregulation in pituitary tumors, as well as their regulation of pro-tumorigenic genes. In addition, we provide an overview of findings from preclinical studies investigating the use of histone deacetylase inhibitors to treat pituitary adenomas and the need for further studies involving epigenetic drugs and functional characterization of epigenetic dysregulation.

The Histopathologic Patterns of Intracranial Neoplasms in the Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos, Nigeria: A 10-Year Retrospective Study, January 2008 to December 2017

Objectives Intracranial neoplasms have distinct diagnostic histologic features and some are common in certain gender and age groups. The most common intracranial neoplasm worldwide is meningioma, followed by gliomas, most especially astrocytic tumors, and then pituitary adenomas. There are geographical differences in the pattern of occurrence of intracranial neoplasms. Few studies have been done in Nigeria to demonstrate the pattern of occurrence, age, and sex distributions of these neoplasms. The aim for this study is to establish the pattern of occurrence with age and sex distribution of different histologic types of intracranial neoplasm in our environment. This study may help portray the health burden of these tumors and aid in epidemiological studies. Methods A total of 296 patients (165 females, 131 males) diagnosed with intracranial neoplasms between January 2008 and December 2017 at Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos, Nigeria, were retrospectively analyzed. Patients’ data were retrieved from the archives of the Department of Anatomic and Molecular Pathology, LUTH, Idi-Araba, Lagos. Histologic patterns with age and gender distribution were noted. The data obtained were analyzed with SPSS version 23. Results Majority of the patients diagnosed with intracranial neoplasm were between 41 and 50 years of age. The most frequently diagnosed intracranial neoplasm at LUTH within the study period was meningioma (105 cases, median age of 42 years, male to female ratio of 3:7), followed by pituitary adenoma (78 cases, median age of 47 years, male to female ratio of 3:2), and then gliomas (66 case), most especially the astrocytic and oligodendroglial tumors (median age of 37 years, male to female ratio of 2:3). Conclusion The result of the study shows that the pattern of occurrence of primary intracranial neoplasms in our environment is different from that in Caucasians, with meningiomas being the most common, followed by pituitary adenomas and then gliomas.

Ependymoma with Intraorbital Extracerebral Recurrence: Case Report

Ependymomas are rare neuroepithelial tumors that originate from a type of glial cell called ependymal cell. In general, they correspond to ∼ 1.2 to 7.8% of all intracranial neoplasms, and to ∼ 2 to 6% of all gliomas. Although it corresponds only to ∼2 to 3% of all primary brain tumors, ependymoma is the fourth most common cerebral neoplasm in children, especially in children younger than 3 years of age.1 2 In patients younger than 20 years of age, the majority (90%) of ependymomas are infratentorial, more precisely from the IV ventricle. In spite of this, in adults, medullary ependymomas are more frequent (60%). In this context, supratentorial and extraventricular ependymomas, as in the case reported in the present article, are infrequent in both adults and children.1 2 Both sexes are equally affected.3 Recurrence of intracranial ependymomas occurs in almost 50% of the cases, and the follow-up outcome is not favorable.4 In another perspective, the recurrence of extracerebral ependymomas is extremely rare, and even more unusual in the intraorbital site, as it occurred in the case in question.