A Single-institution Study of So-called “non-secreting” Intracranial Germinomas: Neurological Characteristics, Treatment Procedures, and Clinical Outcomes

Background and ObjectiveIntracranial germinomas are rare brain tumors. In the present study, we collected data of patients with histology-proven germinomas, and analyzed their neurological characteristics, treatment procedures, and clinical outcomes.MethodsWe reviewed the data of patients with “non-secreting” intracranial germinomas, and analyzed the neurological characteristics, treatment procedures, and clinical outcomes.ResultsThere were 162 (69.8%) male patients and 70 (30.2%) female patients. Pineal germinomas were mainly found in male patients (98.3%), and germinomas in sellar/suprasellar region were often observed in female patients (67.5%). The most common clinical presentations were polyuria/polydipsia (42.7%), headache (40.5%), visual disturbance (37.5%), and motor impairment (28.4%). Patients in the pure germinoma group had a higher serum beta-human chorionic gonadotropin (β-HCG) level than in the germinoma plus syncytiotrophoblastic giant cells (STGCs) group (P=0.001), and no significant difference was noted in serum alpha-fetoprotein (AFP) level between the two groups (P=0.540). Bifocal or multifocal tumors had a higher tendency to intracranial dissemination and spinal seeding (P<0.001 and P<0.001, respectively). The mean duration of open craniotomy was 268.8 min with an average volume of blood loss of 316.9 mL, compared with 27.0 min and 6.2 mL in cases who received stereotactic biopsy (P<0.001 and P<0.001). The most common complication in both groups was postoperative hemorrhage (7.0% and 8.5%). Patients who received biopsy had higher KPS scores after surgery and at hospital discharge than on admission in contrast to open craniotomy (P<0.001 and P=0.047, respectively). Deterioration of KPS at hospital discharge than on admission was observed in 4, 7, 18, and 1 cases who received partial resection, subtotal resection, gross total resection, and biopsy (P<0.001).ConclusionsBifocal and multifocal germinomas have a higher tendency of dissemination, and additional attention should be paid to the imaging findings. Patients may not necessarily benefit from the surgical resection because of the surgical trauma and the postoperative complications, and stereotactic biopsy is highly significant in clinical practice.

CTNI-20. FEASIBILITY OF SINGLE-PASS STEREOTACTIC NEEDLE BIOPSY IN RECURRENT GLIOBLASTOMA PATIENTS TO SUPPORT CLIA-CERTIFIED TUMOR PHARMACODYNAMICS FOR A PHASE 0/2 CLINICAL TRIAL

BACKGROUND In neuro-oncology clinical trials, pharmacodynamic (PD) analysis of tumor tissue before and after experimental therapy is challenging. Today, Phase 0 studies in brain tumor patients typically employ archival tissue from a prior resection as the baseline PD comparator. However, the time-interval between tissue acquisitions can be months to years and often includes confounding exposure to other therapies. Here, we demonstrate the feasibility of a pre-treatment, single-pass stereotactic needle biopsy to support CLIA-certified genetic screening and tumor PD analysis in a Phase 0/2 clinical trial. METHODS In support of an ongoing Phase 0/2 ‘trigger’ trial testing CDK4/6 plus ERK1/2 inhibition in recurrent glioblastoma (GBM), a single-pass stereotactic biopsy was completed in select patients prior to enrollment. Each biopsy yields six tissue cores for immunohistochemistry (IHC) and genetic characterization. Using CLIA-certified protocols, genomic DNA (gDNA) was extracted from two cores, followed by library preparation and next-generation sequencing of a customized panel of 37 genes (IvySeq). In the four remaining cores, IHC staining was performed for RB, pRB, pERK, pS6, CDKN2A, MIB-1, ClCas-3 and pH2AX. RESULTS Single-pass stereotactic needle biopsies were collected from five recurrent GBM patients. No intraoperative, perioperative, or radiographic evidence of morbidity was observed. 800-2400ng of gDNA was isolated from each stereotactic biopsy. IvySeq analysis detected CDKN2A deletion, ATRX loss, and mutations in IDH, PTEN and TP53 genes. Based on IHC and genetic analyses of the biopsied samples, three patients were enrolled into the Phase 0/2 clinical trial and baseline value were used for PD analysis. CONCLUSION Single-pass stereotactic needle biopsy is a feasible and safe strategy to collect pre-treatment tissue in support of a Phase 0 clinical trial, enabling CLIA-certified genetic analysis for trial screening and tumor PD analysis.

Pilocytic Astrocytoma-Derived Cells in Peripheral Blood: A Case Report

Imaging limitations, invasive tissue biopsies and poor information over the course of treatment to evaluate ‘real-time’ tumor dynamics justify the emerging use of liquid biopsies in the field of brain tumors. Circulating tumor cells (CTCs) from high-grade astrocytomas might reach the circulation by crossing the blood–brain barrier. Here, for the first time, CTCs cytology in a case of pylocitic astrocytoma is described. An obstructive hydrocephalous due to a lateral mesencephalic tectum mass occluding the Silvio Aqueduct was diagnosed in a young, 18 years old, male. Considering the location of the tumor and the rapid deterioration of the neurological status, it has been decided to urgency treat the patient with ventriculoperitoneal shunting. Magnetic resonance imaging showed a nodular shaped lesion localized within the left lateral mesencephalic tectum. Stereotactic biopsy was not approachable due significant risk of neurological consequences. The diagnosis was performed by blood sampling, a non-invasive procedure for the patient, in order to provide tumor information. Cytopathological features on detected circulating atypical GFAP positive cells led to pilocytic diagnosis confirmed by the patient’s 68 months outcome.

Versatile Use of Intraoperative Ultrasound Guidance for Brain Puncture

BACKGROUND Intraoperative ultrasound (iUS) is an effective guidance and imaging system commonly used in neuro-oncological surgery. Despite the versatility of iUS, its utility for single burr hole puncture guidance remains fairly underappreciated. OBJECTIVE To highlight the simplicity, versatility, and effectiveness of iUS guidance in brain puncture by presenting the current case series and technical note collection. METHODS We present 4 novel uses of iUS guidance for single burr hole brain puncture: cannulation of normal-sized ventricles, endoscopic third ventriculostomy (ETV) guidance, evacuation of interhemispheric empyema, and stereotactic biopsy assistance. RESULTS All techniques were performed successfully in a total of 16 patients. Normal-sized ventricles were cannulated in 7 patients, among whom 5 underwent Ommaya reservoir placement and 2 underwent ventriculoperitoneal shunt placement for idiopathic intracranial hypertension. No more than 1 attempt was needed for cannulation. All ventricular tip positions were optimal as shown by postoperative imaging. iUS guidance was used in 5 ETV procedures. The working cannula was successfully introduced to the lateral ventricle, providing the optimal trajectory to the third ventricular floor in these cases. Interhemispheric subdural empyema was aspirated with iUS guidance in 1 patient. Volume reduction was clearly visible, allowing near-total evacuation of the empyema. iUS guidance was used for assistive purposes during stereotactic biopsy in 3 patients. No major perioperative complications were observed throughout this series. CONCLUSION iUS is an effective and versatile guidance system that allows for real-time imaging and can be easily and safely employed for various brain puncture procedures.

Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report

BackgroundSolitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported.MethodTwenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed.ResultsThe male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%).ConclusionEither surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders

Risk of tract recurrence with stereotactic biopsy of brain metastases: an 18-year cancer center experience

OBJECTIVE Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate. METHODS In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria. RESULTS In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3–17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy. CONCLUSIONS In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.