BIOM-05. CASE SERIES OF MULTI-INSTITUTIONAL UTILITY OF CNSide TO MANAGE LEPTOMENINGEAL DISEASE IN PATIENTS WITH METASTATIC BREAST CANCER

INTRODUCTION Leptomeningeal Disease (LMD) occurs in 5% of breast cancer patients. Diagnosing LMD remains challenging. Current standard of care has limited sensitivity and is inadequate for monitoring treatment response. Biocept’s CNSide™ is a proprietary assay utilizing a 10-antibody capture cocktail with microfluidic chamber that quantitatively detects tumor cells in the cerebrospinal fluid (CSF). We present a case series using CNSide to manage LMD of 4 unique breast cancer patients treated at three different institutions and demonstrate its impact on clinical management. METHODS Patients were treated at Smilow Cancer Hospital at Yale-New Haven (1 patient), Northwestern Medicine Lou and Jean Malnati Brain Tumor Institute (1 patient) and Barrow Neurological Institute (2 patients). All patients received intrathecal treatment (IT) via an Ommaya Reservoir. CSF tumor cells were detected via cytology and CNSide at diagnosis (3 patients) and throughout treatment (4 patients). RESULTS At diagnosis, CNSide detected tumor cells in 3/3 patients, vs 2/3 patients for cytology. The fourth patient was diagnosed with LMD before CNSide was available. CNSide detected CSF tumor cells in 9/9 (100%) of measurements, vs 4/9 (44%) for cytology for samples analyzed in parallel. Throughout treatment, CNSide was able to track the quantitative LMD response and showed a decrease in CSF tumor cells in all four patients, ranging from 99.7% (from 773 to 2 cells, 1 patient) to 100% (from 4447 to 0 cells; and from 33 to 0 cells, 2 patients). CONCLUSION Intrathecal treatment of LMD via Ommaya reservoir is not widely adopted across the US. Our experience suggests that using CNSide for quantitative CSF tumor cell detection may aid in diagnosing LMD, as well as in quantifying response to treatment particularly in the setting of intrathecal therapy. However, larger prospective clinical trials are needed to establish the role of CNSide in the diagnosis and management of LMD.

P14.26 Leptomeningeal Disease Secondary to Melanoma: Diagnosis, Treatment, and Outcomes at a Single Institution between 2013 and 2019

BACKGROUND Leptomeningeal disease (LMD) is devastating with a median survival of only 8–10 weeks. LMD affects approximately 5% to 25% of melanoma patients. Its pathophysiology remains unknown and effective treatments are virtually non-existent. The aim was to evaluate demographics, validity of Veridex CellSearch® System (VCS) compared to Gold Standard test (i.e., CSF cytology), risk factors for LMD, and treatment outcomes. MATERIALS AND METHODS A retrospective chart review was performed of subjects with suspected LMD from melanoma enrolled in the MCC 19332/19648 studies between 2013 and 2019 at Moffitt Cancer Center. The patients underwent standard of care with different treatments as deemed appropriate by treating physician. CSF samples were obtained from lumbar punctures, surgeries, and Ommaya reservoir, and sent for analysis. Peripheral blood and CSF were evaluated for detection and quantification of CSF circulating tumor cells (CTCs) with the Veridex CellSearch® System, which is adapted to enumerate CTCs from CSF. RESULTS More than 100 patient charts were reviewed. Only patients with melanoma as primary tumor (N=48) were included in the analysis, with ages 29–80. N=28 (58%) met criteria for LMD (median age 59, M:F ratio of 3:1). Within the LMD group, n=26 patients had cutaneous melanoma as primary tumor; BRAF mutant n=17 (V600E n=14; G469E n=1). At the time of diagnosis, median KPS score was 70, with most prevalent symptoms of headaches, encephalopathy, focal weakness, and nausea/vomiting. N=20 (71%) patients were diagnosed radiographically and n=5 (18%) with CSF cytology; n=14 (52%) had positive cytology on first LP, n=18 (67%) on first two LPs. From 25 patients with LMD who underwent CellSearch® to quantify CTCs, n=22 (88%) patients had positive CSF CTCs; n=18 (72%) on first sample sent for analysis, n=20 (80%) on first two samples. The sensitivity and specificity of the Veridex CellSearch® System compared to the Gold Standard CSF cytology were analyzed. Survival in months plotted against the percentage of CSF-CTCs showed a significant value of p=0.0377. CSF analysis i.e., inflammatory markers, and treatments pre-/post-LMD diagnosis will be described. Most patient were managed with Ommaya reservoir placement, radiation therapy, immunotherapy, BRAF +/- MEK inhibitors, IT thiotepa, or IT topotecan. The median survival of those with LMD was 3.15 months. Two patients outlived their counterparts by 21.1 and 39.0 months after the LMD diagnosis, one of them is still alive but with a very poor functional status. CONCLUSION These results indicate the potential value of the VCS as an additional tool to the gold standard in the diagnosis of LMD in patients with high suspicion of the disease. Future directions involve doing prospective studies to further validate this method, and to better understand this patient population to enhance diagnostic tools and management of LMD.

Intrathecal methotrexate combination with systemic chemotherapy in glioblastoma patients with leptomeningeal metastases

Purpose Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a bad outcome. Leptomeningeal disease (LMD) is a severe complication of GBM, with a worse outcome and have no effective treatment. A combination chemotherapy was conducted to evaluated the effective of GBM patients with LMD. Methods A retrospective analysis was conducted of GBM patients diagnosed with LMD between January 2012 and December 2019 in our institution. All these patients accepted at least one cycle of combination therapy combination intrathecal methotrexate(MTX) with systemic chemotherapy. Clinical and pathological data were analyzed to explore the effective treatment and the outcome of GBM patients with LMD. Results Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 months (range 2–59 months). The median overall survival of LMD patients from diagnosis after accepted systemic chemotherapy combination with intrathecal methotrexate was 10.5 months (range 2–59 months). In the Cox univariate analysis, gross resection of tumor (p = 0.022), KPS༞60 (p = 0.002) and Ommaya reservoir implantation (p༜0.001) were correlated with survival. Multivariate analysis showed that KPS༞60 (p = 0.037) and Ommaya reservoir implantation (p = 0.014) were positive factors correlated with survival. The common toxicities of combination therapy were myelotoxicity and gastrointestinal reactions. According to Common Terminology Criteria of Adverse Events 4.03, most of the toxicities were less than grade 3. Conclusion Intrathecal methotrexate combined with systemic chemotherapy is an effective treatment for GBM patients with LMD and has mild treatment-related side effects.

Intraoperative Chemotherapy for Leptomeningeal Metastases After Ommaya Placement

IntroductionThere is a wide variety in the timing of the first intraventricular chemotherapy dose after Ommaya reservoir placement. Given the rapid nature of leptomeningeal metastasis, it is important to avoid any delays in treatment in order to have the optimal therapeutic benefit. We present the first series of immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement.MethodsA single-institution, retrospective review of twenty patients who underwent surgical placement of an Ommaya reservoir from 2012 to 2020 and had intraoperative infusion of chemotherapy was conducted. Inclusion criteria consisted of patients 18 years and older with a diagnosis of leptomeningeal metastases, central nervous system lymphoma or leukemia. Outcomes such as leukoencephalopathy, wound healing, intracranial hemorrhage, catheter malfunction, Ommaya days, mortality, and other complications were reviewed.ResultsThe mean patient age was 55.1 years and the most common diagnosis was breast cancer (40%). All catheters were placed into the ventricular system, and there were no wound healing complications, infections or symptomatic leukoencephalopathy. Intraventricular chemotherapy was administered for a total of 201 cycles and a mean of 10 times per patient. The number of Ommaya days ranged from 7 to 2177, with a mean of 326.5 days, and 30-day mortality was 10%.Conclusions Ommaya reservoirs are effective intraventricular delivery mechanism for chemotherapy in patients with leptomeningeal metastases. Endoscopy-assisted placement of Ommaya catheters provides a real-time, visual confirmation of adequate placement. Immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement is safe, effective, and may increase efficiency in time to treatment for patients.

Clinical Application of a Neurosurgical Robot in Intracranial Ommaya Reservoir Implantation

Background: The Ommaya reservoir implantation technique allows for bypass of the blood-brain barrier. It can be continuously administered locally and be used to repeatedly flush the intracranial cavity to achieve the purpose of treatment. Accurate, fast, and minimally invasive placement of the drainage tube is essential during the Ommaya reservoir implantation technique, which can be achieved with the assistance of robots.Methods: We retrospectively analyzed a total of 100 patients undergoing Ommaya reservoir implantation, of which 50 were implanted using a robot, and the remaining 50 were implanted using conventional surgical methods. We then compared the data related to surgery between the two groups and calculated the accuracy of the drainage tube of the robot-assisted group.Results: The average operation time of robot-assisted surgery groups was 41.17 ± 11.09 min, the bone hole diameter was 4.1 ± 0.5 mm, the intraoperative blood loss was 11.1 ± 3.08 ml, and the average hospitalization time was 3.9 ± 1.2 days. All of the Ommaya reservoirs were successful in one pass, and there were no complications such as infection or incorrect placement of the tube. In the conventional Ommaya reservoir implantation group, the average operation time was 65 ± 14.32 min, the bone hole diameter was 11.3 ± 0.3 mm, the intraoperative blood loss was 19.9 ± 3.98 ml, and the average hospitalization time was 4.1 ± 0.5 days. In the robot-assisted surgery group, the radial error was 2.14 ± 0.99 mm and the axial error was 1.69 ± 1.24 mm.Conclusions: Robot-assisted stereotactic Ommaya reservoir implantation is quick, effective, and minimally invasive. The technique effectively negates the inefficiencies of craniotomy and provides a novel treatment for intracranial lesions.

Interferon-alfa in the management of cystic craniopharyngioma in children under 5 years of age

Introduction: the best therapeutic option for the management of craniopharyngioma in younger children remains controversial, ranging from complete surgical resection, partial surgical resection associated with radiotherapy and application of chemotherapeutic agents such as bleomycin and interferon-alfa. Objective: to verify the response to treatment with interferon-alfa via Ommaya reservoir in a group of children under 5 years of age with diagnosis of cystic craniopharyngioma. Methods: description of a case series through consecutive review of medical records of children under 5 years of age diagnosed with cystic adamantinomatous craniopharyngioma who had an Ommaya reservoir catheter surgically implanted for intratumoral application of interferon-?. Results: seven children aged 18 to 60 months (median 46 months) with the abovementioned diagnosis and treated with interferon-alfa between 2010 and 2019, according to a pre-established protocol, were identified. A reduction in tumor volume, ranging from 88 to 100%, one year after the end of treatment was observed in the study sample. There were no complications that justified the interruption or modification of the established therapy. Conclusion: in all the cases evaluated of children less than 5 years of age with predominantly cystic adamantinomatous craniopharyngioma we observed a reduction of tumor volume on magnetic resonance imaging one year after the end of treatment with interferon-alfa.