scholarly journals STMO-16 The usability of Detailed pre-operative 3D simulation image for Tumor Resection of High grade glioma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi13-vi14
Author(s):  
Yoshihiro Tsukamoto ◽  
Manabu Natsumeda ◽  
Makoto Oishi ◽  
Yukihiko Fujii
Keyword(s):  
3D Visualization ◽  
Cerebral Arteries ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
3D Simulation ◽  
Average Score ◽  
Cerebral Veins ◽  
High Grade ◽  
Clinical Images ◽  
Anatomical Structures

Abstract Introduction Understanding micro structures is important for the safety and reliable tumor resection for high grade glioma(HGG). The high-resolution 3-demension pre-operative simulation image (3D simulation imege) provides the useful information to the operators. We will report the outcome and the device of 3D simulation image at our single institute. Material and Method From April 2019 to July 2021, 56 cases of HGG (grade III: 18 cases, grade IV: 38 cases, initial cases: 49 cases, recurrent cases: 7) were included retrospectively. Zedview, Horos, and Freeform were used to create 3D simulation image from conventional clinical images as CT, MRI, and angiography. The evaluations of anatomical structures were 9 items: cerebral arteries (A), cerebral veins (V), perforators (Per), passing arteries (Pass), feeders (F), drainers (D), sylvian fissure vessels (SV), brain structures (B), and ventricles (Vent). After determining the necessity of 3D visualization for operative planning and evaluating whether it was possible to create the 3D image, the consistency with the anatomical structure and the usefulness for surgery were scored (Excellent 3 points / Good 2 points / Poor 1 point) respectively. Result A: 56 out of 56 cases (100%) was judged as necessary, and the average score was 2.73 points. V: 56/56 cases (100%), 2.70 points. Per: 7/7 cases (100%), 1.80 points. Pass: 7/7 cases (100%), 2.86 points. F: 34/36 cases (94.5%), 2.56 points. D: 22/22 cases (100%), 2.36 points. SA: 7/7 cases (100%), 2.43 points. B: 53/54 (98.1%), 2.70 points. Vent: 27/28 cases (96.5%), 2.50 points. The average score of all structures was 2.59 points. Discussion and Conclusion 3D imaging of the required anatomical structures was possible in almost all cases, and consistency and usefulness in most items were highly scored. Although the evaluation of the perforators was low, the 3D simulation image seemed to be useful for surgical planning.

CTNI-41. INITIAL RESULTS OF A PHASE I WINDOW OF OPPORTUNITY TRIAL EVALUATING A FIRST-IN-CLASS CD29 INHIBITOR, OS2966, IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi69-vi69
Author(s):  
James Liu ◽  
Chibueze D Nwagwu ◽  
Amanda V Immidisetti ◽  
Gabriela Bukanowska ◽  
Anne-Marie Carbonell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Underlying Disease ◽  
Tissue Level ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Tumor Biopsy ◽  
Safety Issues

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

scholarly journals Effect of Anesthesia on The Outcome of High-Grade Glioma Patients Undergoing Supratentorial Resection: Study Protocol for A Randomized Controlled Trial 

2021 ◽  
Author(s):  
Dexiang Wang ◽  
Jia Dong ◽  
Min Zeng ◽  
Xiaoyuan Liu ◽  
Xiang Yan ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Controlled Trial ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
High Grade ◽  
Intravenous Anesthesia ◽  
Inhalation Anesthesia ◽  
Randomized Controlled

Abstract Background High-grade glioma (HGG) is the most malignant brain tumor with poor outcome. Whether anesthetic methods have impact on the outcome of these patients is still unknown. Retrospective study has found that there is no difference between two anesthesia methods on the overall survival (OS), however, intravenous anesthesia with propofol might be beneficial in subgroup patients of KPS<80. Further prospective studies are needed to evaluate the results.Methods This is a single-centered, randomized controlled, parallel group trial. 196 patients with primary HGG for tumor resection will be randomly assigned to receive either the intravenous anesthesia with propofol or inhalation anesthesia with sevoflurane. The primary outcome is the OS within 18 months. Secondary outcomes include progression-free survival (PFS), the numerical rating scale (NRS) of pain intensity and sleep quality, the postoperative encephaloedema volume, complications, the length and cost effectiveness of hospital stay of the patients.Discussion This is a randomized controlled trial to compare the effect of intravenous or inhalation anesthesia maintenance on the outcome of supratentorial HGG patients.The results will help to optimizing the anesthesia methods in these patients.Trial registration: ClinicalTrials.gov (ID: NCT02756312). Registered on 27 April 2020 https://register.clinicaltrials.gov/

scholarly journals Fluorescence-Guided Surgery and Biopsy in Gliomas with an Exoscope System

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
José Piquer ◽  
Jose L. Llácer ◽  
Vicente Rovira ◽  
Pedro Riesgo ◽  
Ruben Rodriguez ◽  
...  
Keyword(s):  
Tumor Resection ◽  
Brain Biopsy ◽  
High Grade Glioma ◽  
Radical Resection ◽  
Histopathological Diagnosis ◽  
High Grade ◽  
Tumor Surgery ◽  
High Definition ◽  
Stereotactic Brain Biopsy ◽  
High Grade Astrocytoma

Background. The introduction of fluorescence-guided resection allows a better identification of tumor tissue and its more radical resection. We describe our experience with a modified exoscope to detect 5 ALA-induced fluorescence in neuronavigation-guided brain surgery or biopsy of malignant brain tumors.Methods. Thirty-eight patients with a suspected preoperative diagnosis of high-grade astrocytoma were included. We used a neuronavigation device and a high-definition exoscope system with a built-in filter to detect 5-ALA fluorescence in all cases. Thirty patients underwent craniotomy with tumor resection and 8 underwent frameless stereotactic brain biopsy.Results. Histopathological diagnosis confirmed the presence of high-grade gliomas in 34 patients. Total resection was achieved in 23 cases and subtotal in 7. No relevant complications related to the administration of 5-ALA were detected.Conclusions. The use of the exoscope in 5-ALA fluorescence-guided tumor surgery has twofold implications: during brain tumor surgery it can be considered a valuable tool to achieve a more radical resection of the lesion, and when applied to a biopsy of a suspected brain high-grade glioma, it decreases the possibility of a negative biopsy.

scholarly journals Pediatric Non–Brain Stem High-Grade Glioma: A Single-Center Experience

2020 ◽  
Vol 9 (03) ◽  
pp. 162-169
Author(s):  
Ehsan Alimohammadi ◽  
Seyed Reza Bagheri ◽  
Nasrin Delfani ◽  
Roya Safari-Faramani ◽  
Maryam Janatolmakan
Keyword(s):  
Brain Stem ◽  
Poor Prognosis ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Tumor Location ◽  
High Grade ◽  
Related Factors ◽  
Single Center Experience ◽  
The Impact

Abstract Background Pediatric high-grade gliomas (PHGGs) consist of a heterogeneous class of central nervous system (CNS) neoplasms with a poor prognosis. We aimed to present our 10-year experience in the management of children with high-grade glioma focusing on patients’ survival and related factors. Methods All pediatric patients with high- grade glioma (HGG) who were admitted to our center between May 2009 and May 2018 were investigated. Overall survival (OS) was calculated from the time of diagnosis until the day of death. The impact of suggested variables on survival was evaluated using the univariate and multivariate analyses. Results There were 41 children with non–brain stem high-grade glioma (NBSHGG). The mean OS of patients was 21.24 ± 10.16 months. The extent of resection (p = 0.002, hazard ratio [HR] = 4.84), the grade of the tumor (p = 0.017, HR = 4.36), and temozolomide (TMZ) therapy (p = 0.038, HR = 3.57) were the independent predictors of OS in children with NBSHGG. Age, gender, tumor location, and size of tumor were not associated with the survival of these patients. Conclusion HGGs are uncommon pediatric tumors with an aggressive nature and a poor prognosis. Our results revealed that in NBSHGG cases, children with maximal safe tumor resection and children that received temozolomide therapy as well as children with grade III of the tumor had higher survival.

scholarly journals Recurrent high-grade glioma surgery: a multimodal intraoperative protocol to safely increase extent of tumor resection and analysis of its impact on patient outcome

2021 ◽  
Vol 50 (1) ◽  
pp. E20
Author(s):  
Giuseppe Maria Vincenzo Barbagallo ◽  
Francesco Certo ◽  
Stefania Di Gregorio ◽  
Massimiliano Maione ◽  
Marco Garozzo ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
High Grade ◽  
Functional Grade ◽  
Second Surgery ◽  
Eloquent Area ◽  
The Mean ◽  
Met Pet

OBJECTIVENo consensus exists on the best treatment for recurrent high-grade glioma (HGG), particularly in terms of surgical indications, and scant data are available on the integrated use of multiple technologies to overcome intraoperative limits and pitfalls related to artifacts secondary to previous surgery and radiotherapy. Here, the authors report on their experience with the integration of multiple intraoperative tools in recurrent HGG surgery, analyzing their pros and cons as well as their effectiveness in increasing the extent of tumor resection. In addition, they present a review of the relevant literature on this topic.METHODSThe authors reviewed all cases in which recurrent HGG had been histologically diagnosed after a first surgery and the patient had undergone a second surgery involving neuronavigation with MRI, intraoperative CT (iCT), 11C-methionine–positron emission tomography (11C-MET-PET), 5-aminolevulinic acid (5-ALA) fluorescence, intraoperative neurophysiological monitoring (IONM), and intraoperative navigated ultrasound (iUS). All cases were classified according to tumor functional grade (1, noneloquent area; 2, near an eloquent area; 3, eloquent area).RESULTSTwenty patients with recurrent HGG were operated on using a multimodal protocol. The recurrent tumor functional grade was 1 in 4 patients, 2 in 8 patients, and 3 in the remaining 8 patients. In all patients but 2, 100% EOTR was obtained. Intraoperative 5-ALA fluorescence and navigated iUS showed low specificity and sensitivity. iCT detected tumor remnants in 3 cases. Postoperatively, 6 patients (30%) had worsening neurological conditions: 4 recovered within 90 days, 1 partially recovered, and 1 experienced a permanent deficit. The median Karnofsky Performance Status remained substantially unchanged over the follow-up period. The mean progression-free survival after the second surgery was 7.7 months (range 2–11 months). The mean overall survival was 25.4 months (range 10–52 months), excluding 2 long survivors. Two patients died within 60 days after surgery, and 3 patients were still under follow-up at the end of this study.CONCLUSIONSThis is the first study reporting the integration of neuronavigation, 5-ALA fluorescence, iUS, iCT, 11C-MET-PET, and IOM during microsurgical resection of recurrent glioma. The authors believe that the proposed multimodal protocol is useful to increase the safety, effectiveness, and EOTR in patients with recurrent HGG and brain alterations secondary to radio- and chemotherapy.

OS05.8.A A Phase 0/1 ‘Trigger’ Trial of Ribociclib Plus Everolimus in Recurrent High-Grade Glioma

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
N Sanai ◽  
A Tien ◽  
J Jiang ◽  
Y Chang ◽  
C Pennington-Krygier ◽  
...  
Keyword(s):  
Tumor Resection ◽  
High Grade Glioma ◽  
High Grade ◽  
Mtor Inhibition ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Drug Concentrations ◽  
Limit Of Quantitation ◽  
Unbound Concentration ◽  
Dose Levels

Abstract BACKGROUND The RB-CDK4/6 and mTOR signaling pathways are deregulated in high-grade glioma (HGG) and mTOR activation is a potential mechanism of resistance to CDK4/6 inhibition. This study evaluates the tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of combined CDK4/6 and mTOR inhibition in recurrent HGG patients. MATERIAL AND METHODS Eligible patients had recurrent HGG with (1) intact RB expression, (2) CDKN2A/B deletion or CDK4/6 amplification, and (3) PTEN loss or PIK3CA mutations. Six patients received five days of presurgical ribociclib (400mg QD) plus everolimus (2.5mg QD) and then underwent tumor resection at 2, 8 or 24 hours following the last dose. Five subsequent dose-escalation cohorts each enrolled three additional patients, reaching a maximum dose-level of ribociclib (600mg QD) plus everolimus (60mg QW). Tumor tissue (gadolinium [Gd]-enhancing and nonenhancing regions), CSF, and plasma were collected. Total and unbound drug concentrations were determined using validated LC-MS/MS methods. Tumor PD effects, including RB and S6 phosphorylation, were compared to matched archival tissue. A PK ‘trigger’ (i.e., unbound concentration &gt; 5-fold biochemical IC50) and a PD ‘trigger’ (&gt;30% decrease in both pRB and pS6) were set for each drug. Gd-nonenhancing tissue exhibiting both PK and PD effects in excess of these thresholds qualified patients for postoperative combination therapy. RESULTS 21 patients with WHO Grade III (n=2) and WHO Grade IV (n=19) gliomas were enrolled. No dose-limiting toxicities were observed. Following presurgical drug, all patients demonstrated marked decrease in Gd-enhancement on preoperative MRI. In Gd-nonenhancing tumor regions, the median unbound concentration of ribociclib was 719 nM (i.e., &gt; 5-fold biochemical IC50 for CDK4/6 inhibition), whereas the unbound everolimus tumor concentrations in all patients were below the lower limit of quantitation (i.e., &lt; 0.2 nM). The median total concentrations of everolimus in tumors at dose-levels 0 to 5 were 2.9, 8.8, 10.3, 5.0, 15.7, and 13.7 nM, respectively. Across all dose-levels, 62% (13/21) and 22% (5/21) of tumors demonstrated decreased tumor RB and S6 phosphorylation, respectively. Tumor proliferation (MIB-1) was decreased in 67% (14/21) of all patients. CONCLUSION In adult HGG, ribociclib achieves pharmacologically-relevant concentrations in Gd-nonenhancing tumor, consistent with the observed tumor PD effects. Everolimus exhibits very limited penetration into human glioma tissue. Our study supports further development of ribociclib, but not everolimus, for the treatment of glioma patients.

A first-in-human study of neural stem cells (NSCs) expressing cytosine deaminase (CD) in combination with 5-fluorocytosine (5-FC) in patients with recurrent high-grade glioma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2018-2018 ◽  
Author(s):  
Jana Portnow ◽  
Behnam Badie ◽  
Timothy W. Synold ◽  
Alexander Annala ◽  
Bihong Chen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Human Study ◽  
Tumor Resection ◽  
Cytosine Deaminase ◽  
High Grade Glioma ◽  
Intracerebral Microdialysis ◽  
High Grade ◽  
Drug Concentrations ◽  
Average Maximum ◽  
The Brain

2018 Background: Human NSCs are inherently tumor-tropic, making them attractive drug delivery vehicles. This pilot-feasibility study assessed the safety of using genetically-modified NSCs for tumor selective enzyme/prodrug therapy. An immortalized, clonal NSC line was retrovirally-transduced to stably express CD, which converts the prodrug 5-FC to 5-fluorouracil (5-FU), producing chemotherapy locally at sites of tumor in the brain. Methods: Patients 18 years or older with recurrent high-grade glioma underwent intracranial administration of NSCs during tumor resection or biopsy. Four days later, 5-FC was administered orally every 6 hours for 7 days. Study treatment was given only once. A standard 3+3 dose escalation schema was used to increase doses of NSCs from 1 x 107 to 5 x 107 and 5-FC from 75 to 150 mg/kg/day. Intracerebral microdialysis was performed to measure brain levels of 5-FC and 5-FU; serial blood samples were obtained to assess systemic drug concentrations. Three patients received iron-labeled NSCs for MRI tracking. Brain autopsies were done on 2 patients. Results: Fifteen patients received study treatment. Three were inevaluable for toxicity and replaced. All patients tolerated the NSCs well. There was 1 dose-limiting toxicity (grade 3 transaminitis) possibly related to 5-FC. At the highest dose level of NSCs, the average steady-state concentration of 5-FU in the brain was 63.9±7.9 nM. The average maximum 5-FU level in brain was 104±88 nM compared to 24±36 nM in plasma, indicating local production of 5-FU in the brain by the NSCs. MR imaging of iron-labeled NSCs showed preliminary evidence of NSC migration. Autopsy data documented (by IHC, FISH, and PCR) NSCs at distant sites of tumor in the brain and no development of secondary tumors. Conclusions: This first-in-human study has demonstrated safety and proof-of-concept regarding NSC-mediated conversion of 5-FC to 5-FU and NSC tumor-tropism. NSCs have the potential to overcome obstacles of drug delivery that limit current gene therapy strategies. Results of this pilot study will serve as the foundation for future NSC studies. (Supported by NCI 1R21 CA137639-01A1, CIRM DR-01421). Clinical trial information: NCT01172964.

scholarly journals SURG-18. 5-AMINOLEVULINIC ACID FLUORESCENCE (5-ALA) GUIDED RESECTION OF GLIOBLASTOMA, LESSON LEARNED FROM 19 CASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi243-vi243
Author(s):  
Jinmo Cho
Keyword(s):  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Grade ◽  
Total Resection ◽  
Glioma Surgery ◽  
Term Survival ◽  
Tumor Bed ◽  
Key Factor

Abstract BACKGROUND 5-ALA is known as useful tool for high grade glioma resection and the accumulation extent of 5-ALA is known as far beyond gadolinium enhancement. Extent of resection is key factor for favorable outcome and long-term survival for high grade glioma patients and 5-ALA might increase extent of resection. We present our experience of 5-ALA guided glioma surgeries METHODS Total 19 patients were performed 5-ALA guided surgery. They ingested 20mg/kg, four hours before craniotomy. We tried to perform supra-total resection rather than gross total resection according to the tumor consistency and if the tumor located relatively non-eloquent area, we tried to perform lobectomy rather than lesionectomy. After tumor resection, we inspect the tumor bed under 5-ALA fluorescence, and we confirmed the complete loss of fluorescence on the tumor resected bed. We check the MRI within 48 hour after operation and assess the extent of resection RESULTS Among the 19 patients, 15 patients were confirmed glioblastoma and 3 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. We confirmed all enhancing lesion was completely removed, however, 2 patients show residual non-enhancing lesion in post-operative MRI. Two patients suffered temporary hemiparesis and 2 patients show permanent visual field defect. CONCLUSION 5-ALA is useful tool for glioma surgery. Resection extent could be increased, however, non-enhancing lesion in the high grade gliomas, might be missed under 5-ALA guidance.

scholarly journals Combined Awake Craniotomy with Endoscopic Port Surgery for Resection of a Deep-Seated Temporal Lobe Glioma: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Lance Bodily ◽  
Arlan H. Mintz ◽  
Johnathan Engh
Keyword(s):  
Minimally Invasive ◽  
Temporal Lobe ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Awake Craniotomy ◽  
High Grade ◽  
Technical Aspects ◽  
Case Outcome ◽  
Invasive Techniques ◽  
The Brain

The authors describe the combination of awake craniotomy and minimally invasive endoscopic port surgery to resect a high-grade glioma located near eloquent structures of the temporal lobe. Combined minimally invasive techniques such as these may facilitate deep tumor resection within eloquent regions of the brain, allowing minimum white matter dissection. Technical aspects of this procedure, a case outcome involving this technique, and the direction of further investigations for the utility of these techniques are discussed.

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