scholarly journals Development of a Standardized Semantic Feature-Based Reporting Proforma for Intraoperative Ultrasound Findings in Brain Tumors and Application in High-Grade Gliomas – A Preliminary Study

2021 ◽  
Vol 07 (02) ◽  
pp. E55-E63
Author(s):  
Prakash Shetty ◽  
Vikas Kumar Singh ◽  
Amit Choudhari ◽  
Aliasgar V Moiyadi
Keyword(s):  
Brain Tumors ◽  
Intraoperative Ultrasound ◽  
Labelling Index ◽  
Semantic Feature ◽  
High Grade ◽  
Histological Features ◽  
Ultrasound Findings ◽  
Feature Based ◽  
High Grade Gliomas ◽  
Grade 3

Abstract Purpose A semantic feature-based reporting proforma for intraoperative ultrasound findings in brain tumors was devised to standardize reporting. It was applied as a pilot study on a cohort of histologically confirmed high-grade supratentorial gliomas (Grade 3 and 4) for internal validation. Materials and Methods This intraoperative semantic ultrasound proforma was used to evaluate 3D ultrasound volumes using Radiant DICOM software by 3 surgeons. The ultrasound semantic features were correlated with histological features like tumor grade, IDH status, and MIB index. Results 68 patients were analyzed using the semantic proforma. Irregular crenated was the most common margin (63.2%) and lesions were heterogeneously hyperechoic (95.6%). Necrosis was commonly seen and noted as single (67.6%) or multiple (13.2%) in over 80% cases. A separate perilesional zone, which was predominantly hyperechoic in 41.8% and both hypo and hyperechoic in 12.7%, could be identified in 54.5% of cases. Grade 4 tumors were more likely to have an irregular crenated margin (71.2%) with a single large area of necrosis, while Grade 3 tumors were likely to have smooth (31.3%) or non-characterizable margins (31.2%) with no or multiple areas of necrosis. IDH-negative tumors were more likely to have a single large focus of necrosis. Among the GBMs (52 cases), MIB labelling index of>15% was associated with poorly delineated, uncharacterizable margins, when compared with MIB labelling index<15% (23.5 vs. 0%), (p=0.046). Conclusion A detailed semantic proforma was developed for brain tumors and was internally validated. A few ultrasound sematic features were identified correlating with histological features in high-grade gliomas. It will require further external validation for refinement and acceptability.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

scholarly journals Hypofractionated Stereotactic Re-Irradiation with Pembrolizumab and Bevacizumab in Patients with Recurrent High Grade Gliomas: Results from a Phase 1 Study

2020 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Peter A Forsyth ◽  
Nam D Tran ◽  
John A Arrington ◽  
Robert Macaulay ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
High Grade ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Abstract Background Radiotherapy may synergize with programmed death 1 (PD-1)/PD-1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended Phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high grade gliomas (HGGs). Methods Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. Results Thirty two patients were enrolled (bevacizumab naïve, n = 24; bevacizumab resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab naïve cohort, twenty patients (83%) had a complete response (CR) or partial response (PR). The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (20/26 pts; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression &lt;1%. Conclusions The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Differences in the distribution of methotrexate into high grade gliomas following intravenous administration, as monitored by microdialysis, are associated with blood brain barrier integrity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1548-1548 ◽  
Author(s):  
J. J. Olson ◽  
J. O. Blakeley ◽  
S. A. Grossman ◽  
J. Weingart ◽  
A. Rashid ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Half Life ◽  
Extracellular Fluid ◽  
Brain Barrier ◽  
Published Data ◽  
High Grade ◽  
Blood Brain ◽  
Drug Concentrations ◽  
High Grade Gliomas

1548 Background: Microdialysis (MD) is an accepted technique to monitor neurochemicals in pts with traumatic brain injury. This study was conducted to evaluate the use of MD to define the time course of intratumoral drug concentrations in pts with high grade gliomas (HGG) receiving systemic chemotherapy. Methods: MD catheters were placed in residual HGG following tumor debulking and infused with Ringer’s solution at 1 μL/min. MD probe location and integrity of the blood brain barrier (BBB) in adjacent tissue were determined by fused MRI/CT. Highdose (12g/m2) methotrexate (MTX), was given as a 4 h iv infusion the next day. MTX was measured in plasma and dialysate samples, collected at 30 min intervals from 1 h before to 24 h after dosing, with an LC/MS assay. Results: Six pts have been enrolled without any adverse events attributed to the MD catheter. Adequate pharmacokinetics (PK) were obtained in 4/6pts. MTX plasma pharmacokinetics (PK) were very consistent between the 4 evaluable pts and similar to published data. Time courses of the uncorrected MTX concentration in extracellular fluid (CECF) exhibited two distinctly different kinetic profiles. For 2pts in whom the MD probe resided within contrast enhancing tumor, CECF increased and decreased in parallel with drug levels in plasma, with a peak CECF of 189 ± 6 μM, an apparent elimination half-life in ECF of 4.44 ± 0.07 h, and an ECF/plasma AUCratio of 0.13 ± 0.01. The other 2pts had a much lower peak CECF (10.4 ± 0.4 μM) and AUC ratio (0.028 ± 0.020), with a more prolonged ECF half-life (11.4 ± 4.5 h). Fused images from 2 of these pts showed that the MD probe was located in nonenhancing tissue. Conclusions: MD is a clinically practical technique to monitor the distribution of systemically administered drugs to brain tumors in pts. It has the capability to elucidate variations in kinetic behavior that are consistent with regional differences in BBB integrity. Appropriate interpretation of data from MD studies to evaluate the distribution of investigational new drugs into brain tumors necessarily requires radiographic determination of the region of the tumor into which the probe has been placed. No significant financial relationships to disclose.

Age and Bromodeoxyuridine Labelling Index as Prognostic Factors in High-grade Gliomas Treated with Surgery and Radiotherapy

2006 ◽  
Vol 18 (6) ◽  
pp. 459-465 ◽  
Author(s):  
A. Gasinska ◽  
J. Skolyszewski ◽  
B. Glinski ◽  
J. Niemiec ◽  
A. Adamczyk ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Labelling Index ◽  
High Grade ◽  
High Grade Gliomas

scholarly journals Differentiation between high-grade gliomas and metastatic brain tumors using Diffusion Tensor Imaging metrics

2015 ◽  
Vol 46 (4) ◽  
pp. 1099-1104 ◽  
Author(s):  
Lamiaa Galal El-Serougy ◽  
Ahmed Abdel Khalek Abdel Razek ◽  
Amani Ezzat Mousa ◽  
Hany A. Fikry Eldawoody ◽  
Ahmad El-Morsy Ebraheem El-Morsy
Keyword(s):  
Diffusion Tensor Imaging ◽  
Brain Tumors ◽  
Diffusion Tensor ◽  
High Grade ◽  
Metastatic Brain Tumors ◽  
High Grade Gliomas

Post-operative concomitant radiochemotherapy in the treatment of primitive CNS high grade gliomas. A retrospective analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 11528-11528
Author(s):  
P. Costa ◽  
F. Braga ◽  
C. Sottomayor ◽  
M. Honavar ◽  
M. Resende ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Haematological Toxicity ◽  
Small Sample ◽  
Routine Practice ◽  
High Grade ◽  
Tumour Control ◽  
Concomitant Radiochemotherapy ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
The Impact

11528 Background: The authors analyse retrospectively the impact on tumour control and toxicity of concomitant radiotherapy (RT) and Temozolomide (TMZ) in high grade gliomas (HGG) of the CNS, in patients treated in the Clínica de Radioterapia do Porto - Portugal. Methods: This cohort represents all patients with HGG treated between January 2002 and January 2006, with concomitant RT a median total dose of 60 Gy, 2 Gy per treatment given once daily 5-days/week and TMZ 75mg/m2 for 42 days, followed by adjuvant treatment with TMZ 5-days schedule every 28 days (150 mg/m2 for the first cycle increased to 200mg/m2). The cohort was retrospectively analyzed for gender distribution, age, extent of surgical resection, initial KPS, median overall survival (OS) and haematological toxicity. Results: 23 with HGG (6 females, 17 males) were treated with concomitant RT (44–72 Gy) and TMZ followed by adjuvant TMZ; median age was 58 (ranging from 17–72); median KPS was 80 (ranging from 40–90); 3 patients had complete resection, 17 partial resection and 3 biopsy. All patients except one, who had treatment interruption for thrombocytopenia, completed the concomitant phase of treatment; 19 patients continued to received adjuvant treatment with TMZ (median number of cycles was 5 (ranging from 1–20). Median OS (measured from the date of diagnosis to the date of death) was 20.4 month and 1 yr OS was 54%. During concomitant phase, one patient had grade 3–4 thrombocytopenia. During the adjuvant TMZ therapy 4 patients had grade 3–4 haematological toxicity (anaemia: 1; thrombocytopenia: 1; leucopoenia and thrombocytopenia: 2). Conclusions: The results of concomitant RT+TMZ followed by TMZ in these patients with HGG showed values in accordance with the latest data published on literature for this association. Differences observed might be due to the small sample size.RT+TMZ followed by adjuvant TMZ is a well tolerated treatment with better results in median OS comparatively with previous results of RT only treatment in HGG. Treatment related toxicity was within acceptable levels, and this approach became routine practice in this set of patients. No significant financial relationships to disclose.

Phase I study of erlotinib administered concurrently with and after irradiation (RT) in the treatment of children, adolescents, and young adults with newly diagnosed intracerebral high-grade glioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9553-9553
Author(s):  
A. Broniscer ◽  
S. J. Baker ◽  
T. E. Merchant ◽  
F. H. Laningham ◽  
M. Kocak ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
High Grade Glioma ◽  
Maximum Tolerated Dose ◽  
Exclusion Criterion ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3

9553 Background: High-grade gliomas are uncommon neoplasms in childhood that portend a poor prognosis. Because of the promising activity of erlotinib in adults with high-grade glioma, we conducted this Phase I study to determine the maximum tolerated dose and dose limiting toxicity (DLT) of erlotinib administered concurrently with and after RT. Methods: Patients between 3 and 25 years of age with newly diagnosed high-grade glioma received erlotinib continuously once daily during and after RT for a maximum of 52 weeks. Pharmacokinetic studies of erlotinib and its metabolite OSI-420, and genotyping were performed during course 1 in consenting patients. Use of enzyme-inducing anticonvulsants was an exclusion criterion. Dose escalation followed a typical Phase I design (dosage levels of 70, 90, and 120 mg/m2 per day). The DLT-evaluation period comprised the first 8 weeks of erlotinib. Results: Seventeen patients (median age 10.4 yrs; 10 males) were enrolled. Diagnoses consisted of glioblastoma (n=9), anaplastic astrocytoma (n=4), and other high-grade gliomas (n=4). Two of seven patients experienced reversible grade 3 hypokalemia / hypophosphatemia at the 70 mg/m2 level. Once electrolyte abnormalities were excluded as DLT, only one of seven patients at the 120 mg/m2 level has experienced grade 3 diarrhea so far. Pharmacokinetic studies were obtained in 14/17 patients. At the 70 mg/m2 dosage level, the median (range) erlotinib and OSI-420 Cmax and Tmax were 1,405 ng/ml (937–2,180) and 4.1 hr (2.2–8.2) and 158.5 ng/ml (45–203) and 4.1 hr (2.2–7.9), respectively. Three patients have received erlotinib for more than 1 year with disease stabilization. Six patients have already experienced disease progression. Conclusions: Erlotinib administered concurrently with RT on this schedule has been well tolerated. Preliminary pharmacokinetic results are comparable to those observed in adults. Rather than continue to escalate erlotinib dosages, we plan to complete this study and open a phase II study of erlotinib and RT for this same patient population. No significant financial relationships to disclose.

Current strategies for the treatment of malignant gliomas – experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw

2020 ◽  
Vol 92 (4) ◽  
pp. 1-5
Author(s):  
Grzegorz Turek ◽  
Tomasz Pasterski ◽  
Krzysztof Bankiewicz ◽  
Sebastian Dzierzęcki ◽  
Mirosław Ząbek
Keyword(s):  
Brain Tumors ◽  
San Francisco ◽  
Malignant Gliomas ◽  
High Grade ◽  
Current Standard ◽  
Convection Enhanced Delivery ◽  
Surgical Methods ◽  
High Grade Gliomas ◽  
Standard Medical Treatment ◽  
Intraoperative Electrical Stimulation

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. Material and methods: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management – from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. Results: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. Discussion: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

scholarly journals Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

2014 ◽  
Vol 36 (2) ◽  
pp. E10 ◽  
Author(s):  
Serge Marbacher ◽  
Elisabeth Klinger ◽  
Lucia Schwyzer ◽  
Ingeborg Fischer ◽  
Edin Nevzati ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Low Grade ◽  
High Grade ◽  
Open Resection ◽  
Who Grade ◽  
Primary Brain Tumors ◽  
High Grade Gliomas ◽  
Surgical Adjunct

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

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