Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients.

INTRODUCTION: Despite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging. Traditionally, invasive strategies such as open or stereotactic biopsies have been used to confirm the etiology of clinical and imaging changes. Liquid biopsies can enable physicians to noninvasively analyze the evolution of a tumor and a patient's response to specific treatments. However, as a consequence of biology and the current limitations in detection methods, no blood or cerebrospinal fluid (CSF) brain tumor-derived biomarkers are used in routine clinical practice. Enhancing the presence of tumor biomarkers in blood and CSF via brain-blood barrier (BBB) disruption with MRI-guided focused ultrasound (MRgFUS) is a very compelling strategy for future management of brain tumor patients. METHODS: A literature review on MRgFUS-enabled brain tumor liquid biopsy was performed using Medline/Pubmed databases and clinical trial registries. RESULTS: The therapeutic applications of MRgFUS to target brain tumors have been under intense investigation. At high-intensity, MRgFUS can ablate brain tumors and target tissues, which needs to be balanced with the increased risk for damage to surrounding normal structures. At lower-intensity and pulsed-frequency, MRgFUS may be able to disrupt the BBB transiently. Thus, while facilitating intratumoral or parenchymal access to standard or novel therapeutics, BBB disruption with MRgFUS has opened the possibility of enhanced detection of brain tumor-derived biomarkers. CONCLUSIONS: In this review, we describe the concept of MRgFUS-enabled brain tumor liquid biopsy and present the available preclinical evidence, ongoing clinical trials, limitations, and future directions of this application.

Comparison of adult and pediatric pilocytic astrocytomas using competing risk analysis: A population-based study.

BACKGROUND: Pilocytic astrocytoma(PA) is a relatively benign tumor occurring primarily in the pediatric population. Comparison of characteristics and survival of this tumor between adult and pediatric patients in a single, population-based study is yet to be performed. OBJECTIVE: We aimed to directly compare the characteristics and survival of pilocytic astrocytoma between pediatric and adult patients in a single, population-based study. METHODS: We utilized the SEER database using data from 1983 to 2016. All patients with histologically confirmed, intracranial pilocytic astrocytoma were included and divided into a pediatric(age<18 years) or adult group. Due to lower risk of tumor-specific-mortality, we utilized a competing risk analysis to account for mortality from other causes. Univariable and multivariable competing risk analysis(CRA) was performed, and sub-distribution hazard ratio(SHR) or adjusted SHR(aSHR) was reported. RESULTS: A total of 4357 patients comprised the final cohort, with 3014(69.2%) pediatric patients. As compared to the pediatric group, adult patients were predominantly White(p < 0.01), with PA less likely fully resected(p = 0.01), smaller tumor size(p < 0.01), and were less often located in the cerebellum(p < 0.01). Multivariable CRA revealed a worse prognosis for the adult group(p < 0.01), regional or distal extension(p < 0.01), and non-cerebellar locations including frontal(p < 0.01), parietal(p < 0.01), ventricular(p < 0.01) or brainstem(p < 0.01). Improved prognosis was seen with more recent year-of-diagnosis(2003-2016, p = 0.03), gross-total/total resection(p < 0.01), and biopsy only patients(p = 0.02). CONCLUSIONS: Pilocytic astrocytomas in adult patients have a worse prognosis than pediatric patients. Cumulative incidence of cancer-specific-mortality is higher in adults when adjusted for other factors. PAs with regional or distal extension and non-cerebellar locations carry worse outcomes. Surgery remains an effective treatment and GTR/TR should be achieved when possible.

Clinical features and surgical outcomes of intracranial and spinal cord subependymomas.

OBJECTIVE: Subependymomas are low-grade ependymal tumors whose clinical characteristics, radiographic features, and postsurgical outcomes are incompletely characterized due to their rarity. The authors present an institutional case series and a systematic literature review to achieve a better understanding of subependymomas. METHODS: Adult patients with histologically confirmed subependymoma or mixed subependymoma-ependymoma surgically treated at a tertiary hospital between 1992 and 2020 were identified. A systematic literature review of the PubMed, Embase, Web of Science, and Google Scholar databases from inception until December 4, 2020, was conducted according to PRISMA guidelines. Data extracted from both groups included demographics, radiographic features, tumor characteristics, management, and follow-up variables. RESULTS: Forty-eight unique patients with subependymoma were identified by chart review; of these patients, 8 (16.7%) had mixed subependymoma-ependymoma tumors. The median age at diagnosis was 49 years (IQR 19.8 years), and 26 patients (54.2%) were male. Forty-two patients (87.5%) had intracranial subependymomas, and 6 (12.5%) had spinal tumors. The most common presentation was headache (n = 20, 41.7%), although a significant number of tumors were diagnosed incidentally (n = 16, 33.3%). Among the 42 patients with intracranial tumors, 15 (35.7%) had hydrocephalus, and the most common surgical strategy was a suboccipital approach with or without C1 laminectomy (n = 26, 61.9%). Gross-total resection (GTR) was achieved in 33 cases (68.7%), and 2 patients underwent adjuvant radiotherapy. Most patients had no major postsurgical complications (n = 34, 70.8%), and only 1 (2.1%) had recurrence after GTR. Of 2036 reports initially identified in the systematic review, 39 were eligible for inclusion, comprising 477 patients. Of 462 patients for whom tumor location was reported, 406 (87.9%) were intracranial, with the lateral ventricle as the most common location (n = 214, 46.3%). Spinal subependymomas occurred in 53 patients (11.5%), with 3 cases (0.6%) in multiple locations. Similar to the case series at the authors' institution, headache was the most common presenting symptom (n = 231, 54.0%) among the 428 patients whose presentation was reported. Twenty-seven patients (6.3%) were diagnosed incidentally, and 36 cases (8.4%) were found at autopsy. Extent of resection was reported for 350 patients, and GTR was achieved in 250 (71.4%). Fifteen of 337 patients (4.5%) had recurrence or progression. CONCLUSIONS: The authors' case series and literature review demonstrate that patients with subependymoma are well managed with resection and generally have a favorable prognosis.