Cranial Transposition and Revascularization of Autologous Omentum: A Novel Surgical Technique for Bypassing the Blood Brain Barrier after Resection of Recurrent Glioblastoma Multiforme

Background: Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system .Objective: Assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM.Methods: Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study.Results: Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Conclusion: Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

PurposeImmunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS.Patients and methodsOne hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity.ResultsSixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02).ConclusionsPostoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.

Preliminary Report: Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope

Objective: The surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain–tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence–guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we have developed an intraoperative rapid fluorescence cytology system, and exploratorily evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: A total of 25 selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A “weak fluorescence” indicated a reduction in the tumor cell density, whereas “no fluorescence” did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence. Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was probably useful to evaluate the presence of tumor cells in the resection cavity walls, and could provide surgical implications for the more complete resection of malignant gliomas.

Predicting the Extent of Resection of Motor-Eloquent Gliomas Based on TMS-Guided Fiber Tracking

Background: Surgical planning with nTMS-based tractography is proven to increase safety during surgery. A preoperative risk stratification model has been published based on the M1 infiltration, RMT ratio, and tumor to corticospinal tract distance (TTD). The correlation of TTD with corticospinal tract to resection cavity distance (TRD) and outcome is needed to further evaluate the validity of the model. Aim of the study: To use the postop MRI-derived resection cavity to measure how closely the resection cavity approximated the preoperatively calculated corticospinal tract (CST) and how this correlates with the risk model and the outcome. Methods: We included 183 patients who underwent nTMS-based DTI and surgical resection for presumed motor-eloquent gliomas. TTD, TRD, and motor outcome were recorded and tested for correlations. The intraoperative monitoring documentation was available for a subgroup of 48 patients, whose responses were correlated to TTD and TRD. Results: As expected, TTD and TRD showed a good correlation (Spearman’s ρ = 0.67, p < 0.001). Both the TTD and the TRD correlated significantly with the motor outcome at three months (Kendall’s Tau-b 0.24 for TTD, 0.31 for TRD, p < 0.001). Interestingly, the TTD and TRD correlated only slightly with residual tumor volume, and only after correction for outliers related to termination of resection due to intraoperative monitoring events or the proximity of other eloquent structures (TTD ρ = 0.32, p < 0.001; TRD ρ = 0.19, p = 0.01). This reflects the fact that intraoperative monitoring (IOM) phenomena do not always correlate with preoperative structural analysis, and that additional factors influence the intraoperative decision to abort resection, such as the adjacency of other vulnerable structures. The TTD was also significantly correlated with variations in motor evoked potential (MEP) responses (no/reversible decrease vs. irreversible decrease; p = 0.03). Conclusions: The TTD approximates the TRD well, confirming the best predictive parameter and giving strength to the nTMS-based risk stratification model. Our analysis of TRD supports the use of the nTMS-based TTD measurement to estimate the resection preoperatively, also confirming the 8 mm cutoff. Nevertheless, the TRD proved to have a slightly stronger correlation with the outcome as the surgeon’s experience, anatomofunctional knowledge, and MEP observations influence the expected EOR.

EXTH-35. INCREASING THERAPEUTIC INDUCED NEURAL STEM CELL PERSISTENCE IN THE GLIOBLASTOMA TUMOR RESECTION CAVITY

BACKGROUND Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for anti-tumor payloads. However, iNSC persist for only two weeks in the murine GBM tumor resection cavity. We hypothesized that by encapsulating iNSCs in a scaffold matrix, we could increase both the persistence of the cells the therapeutic durability. METHODS iNSCs expressing TRAIL were encapsulated in a gelatin-thrombin matrix; fibrinogen was used to polymerize the matrix. SEM was used to explore interactions between iNSCs and the scaffold matrix. To evaluate persistence, iNSCs encapsulated in the matrix were implanted into mock resection cavities of athymic nude mice and followed via BLI. To study the impacts of encapsulation on iNSC efficacy, athymic nude mice were implanted with U87 or GBM8 tumors. Tumors were then resected, and iNSCs encapsulated in the matrix were implanted; tumor volume was monitored via BLI. RESULTS SEM images showed homogeneous distribution of iNSCs throughout the matrix; iNSCs were completed encased in the fibrin clot component of the matrix and did not adhere to gelatin. In vivo, encapsulated iNSCs persisted for nearly 100 days whereas iNSCs directly injected into the brain parenchyma persisted &lt; 20 days. Using mice bearing GBM8 tumors, animals treated with a high dose of therapeutic encapsulated iNSCs survived ~60 days longer than animals treated with non-therapeutic cells. A similar trend was observed in animals inoculated with U87 tumors. While not statistically significant, 25% of mice treated with iNSCs encapsulated in the gelatin-thrombin matrix survived longer than those treated with iNSCs encapsulated in a fibrin-only matrix, suggesting additional benefit due to the gelatin component. FUTURE DIRECTIONS: Prospective experiments will explore the impact of the scaffold on iNSC phenotype, including proliferation, differentiation, and migration markers.

Revisiting Intraoperative 2D USG with Saline–Air Mixture as Contrast for Resection of Eloquent Area Glioma in Resource-Deficient Countries

Background Advanced ultrasound, intraoperative magnetic resonance imaging (MRI), neuromonitoring, and aminolevulenic acid have improved the resection and safety of eloquent area gliomas. However, availability of these modern gadgets is a major concern in resource-deficient countries. A two-dimensional ultrasonography 2D USG is cheaper, provides real-time imaging, and is already established but underutilized instrument. Objective Here, we revisited the principles of 2D USG and used it for eloquent-area glioma surgery. Materials and Methods Fifty-eight patients with eloquent area gliomas were operated in last 2 years with the aid of 2D USG with 6-13 MHz curvilinear probe. Preoperative diagnosis was high-grade glioma in 38 and low-grade glioma (LGG) in 20 patients. Tumors were categorized as predominantly hyperechoic (27), uniformly hyperechoic (7), mixed echogenicity (21), and cystic (3). Results Intraoperatively, 2D USG could define the tumor margins in 46 cases. Of these, USG suggested gross total excision in 38 patients and subtotal in 8 patients. The findings matched with follow-up MRI in 34 patients who showed hyperechogenicity (predominant/uniform). Injecting saline with air in to the resection cavity and insinuating through adjacent brain parenchyma helped in detecting residual lesion in three cystic gliomas and in two LGG where the tumor cavity collapsed. Conclusion 2D USG is a helpful tool in eloquent area glioma surgery, especially in resource-limited countries. Visualization through adjacent parenchyma and injection of saline–air mixture in to the resection cavity helped in delineating residual lesion. Extent of resection is best monitored by 2D USG when tumor appeared hyperechoic (predominant/uniform).

Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope

Objective: Surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain-tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence-guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we developed an intraoperative rapid fluorescence cytology system, and evaluated its clinical feasibility for the management of malignant glioma. Materials and methods: Twenty-five selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. Results: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A &ldquo;weak fluorescence&rdquo; indicated a reduction in the tumor cell density, whereas &ldquo;no fluorescence&rdquo; did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence.Conclusion: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was a useful to evaluate the presence of tumor cells in the resection cavity walls, and provides surgical implications for the more complete resection of malignant gliomas.

A-158 Case Study: Cognitive Deficits Associated with Postoperative Intracranial Hemorrhage Following Meningioma Resection

Objective Postoperative intracranial hemorrhages (PIH) are an infrequent complication following cranial tumor resection and associated with prolonged hospitalization as well as long-term neurologic deficits. There is limited research examining the neuropsychological deficits resulting from PIH following meningioma resection, especially with neuropsychological data. Here, we present the neurocognitive profile of a patient who underwent a meningioma resection surgery and subsequently suffered a PIH within the resection cavity. Method Mr. Doe is a bilingual male in his late 40s who developed right-side vision loss and an isolated incidence of disorientation, resulting in discovery of a left anterior clinoid meningioma. He underwent a left frontotemporal craniotomy for gross total resection of the mass a month after discovery. Postoperative neuroimaging the following day revealed the appearance of a hematoma and intracranial hemorrhage within the resection cavity, resulting in right hemiplegia, aphasia, and ophthalmoplegia. He underwent neuropsychological evaluation 15 months post-resection, to assess residual cognitive deficits following his hospitalization and subsequent inpatient rehabilitation. Results In the context of average premorbid intellectual functioning, Mr. Doe’s neurocognitive profile was notable for deficits in processing speed, receptive and expressive language, and executive functioning associated with speed/verbally mediated tasks. Testing revealed lateralized deficits indicative of left (language-dominant) hemisphere dysfunction secondary to meningioma resection and subsequent PIH within the resection cavity. Conclusion The current poster aims to contribute to the limited body of literature examining residual neuropsychological deficits resulting from PIH following intracranial resection of meningioma. This is especially crucial given that long-term cognitive deficits can negatively impact patients’ quality of life over time.

Intraoperative radiotherapy with low-energy x-rays after neurosurgical resection of brain metastases—an Augsburg University Medical Center experience

Purpose External-beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50-kV x‑rays is an alternative way to focally irradiate the resection cavity after BM surgery, with the option of shortening the overall treatment time and limiting normal tissue irradiation. Methods We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50-kV x‑ray IORT between 2013 and 2020 at Augsburg University Medical Center. Results We identified 40 patients with 44 resected BM treated with 50-kV x‑ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5–5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3‑monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for alive patients of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1‑year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1‑year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1‑year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%. Conclusion IORT with 50-kV x‑rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM, with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.