Phase I study of safety and immunogenicity of ADU-623, a live-attenuated Listeria monocytogenes vaccine (ΔactA/ΔinlB) expressing EGFRvIII and NY-ESO-1, in patients with WHO grade III/IV astrocytomas.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS3106-TPS3106
Author(s):  
Marka Crittenden ◽  
Keith S. Bahjat ◽  
Rui Li ◽  
Pankaj A. Gore ◽  
Chris Fountain ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Phase I ◽  
Phase I Study ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Nivolumab combined with hypofractionated stereotactic irradiation (HFSRT) for patients with recurrent high grade gliomas: A phase I trial (NCT02829931).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2084-TPS2084 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Peter A. J. Forsyth ◽  
John Arrington ◽  
Nam D. Tran ◽  
Michael Vishal Jaglal ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Maximum Diameter ◽  
Imaging Biomarkers ◽  
High Grade ◽  
Who Grade ◽  
Flat Dose ◽  
High Grade Gliomas ◽  
Who Grade Iii ◽  
Grade Iii

TPS2084 Background: Nivolumab is an IgG4 monoclonal antibody that targets the PD-1 immune checkpoint pathway and prevents binding of PD-1 with PD-L1 and PD-L2. Expression of PD-1 and PD-L1 is found in the microenvironment of high grade gliomas and correlates with worse outcome providing a rationale for investigating nivolumab in this group of patients (pts) with very limited treatment options. Nivolumab monotherapy is well tolerated in recurrent glioblastoma pts. Preclinical studies have demonstrated that radiotherapy synergizes with anti PD-1/PD-L1 blockade and produces tumor regression and long-term survival in orthotopic murine models of glioma. This report describes an ongoing phase I trial of nivolumab in combination with HFSRT in pts with recurrent WHO grade III or IV gliomas. Methods: This phase I study includes a safety cohort of 6 pts followed by dose expansion cohort of 20 pts (NCT02829931). Pts with bevacizumab naïve recurrent WHO grade III or IV gliomas (maximum diameter of enhancing brain lesion ≤ 4 cm) are eligible. An interval of at least 6 months after the end of prior radiation therapy is required unless there is a new recurrence outside of the previous radiotherapy treatment field. Eligible patients will be treated with HFSRT to the recurrent tumor (30 Gy delivered in 5 fractions). Nivolumab will be started 5 days after HFSRT. It will be administered intravenously every 2 weeks (at 240 mg flat dose) for 4 months. After 4 months, nivolumab will be administered every 4 weeks at 480 mg flat dose. The primary study objectives are to determine safety and tolerability of nivolumab administered in combination with HFSRT to recurrent high grade gliomas. Secondary endpoints include determination of the preliminary antitumor activity (response rate, 6-months survival and 9-months survival rates), and exploring tissue and imaging biomarkers. Study Progress: At deadline for abstract submission, 5 patients have been treated on this study. Clinical trial information: NCT02829931.

CTNI-47. INTERIM RESULTS OF NCT03011671: A MULTI-INSTITUTIONAL PHASE I STUDY OF ACETAZOLAMIDE WITH TEMOZOLOMIDE IN ADULTS WITH NEWLY DIAGNOSED MGMT-METHYLATED MALIGNANT GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi70-vi70
Author(s):  
Bakhtiar Yamini ◽  
Seán Lyne ◽  
Riley Driscoll ◽  
Giovanna Bernal ◽  
Longtao Wu ◽  
...  
Keyword(s):  
Phase I ◽  
Malignant Glioma ◽  
Phase I Study ◽  
Objective Response ◽  
Controlled Study ◽  
Current Phase ◽  
Newly Diagnosed ◽  
Biomarker Analysis ◽  
Secondary Endpoints ◽  
Grade Iii

Abstract Preclinical studies indicate that up-regulation of carbonic anhydrase (CA) by temozolomide (TMZ), via a mechanism requiring the proto-oncogene BCL-3, promotes resistance to therapy in glioblastoma (GBM) cells. Moreover, the CA inhibitor, acetazolamide (ACZ), sensitizes patient-derived GBM cells and xenografts to TMZ. These findings led to the current Phase I study investigating the safety and efficacy of adding ACZ to adjuvant TMZ in patients with newly diagnosed, MGMT-methylated malignant glioma. 24 patients were enrolled (23 GBM and one Grade III IDH-mutant astrocytoma), median age was 53.5 and mean KPS 91. ACZ was given on days 1-21 of each adjuvant TMZ cycle (250 mg BID days 1-7, increased to 500 mg BID days 8-21). No patient experienced the primary outcome of regimen limiting toxicity (RLT) and there were only three grade III adverse events deemed likely unrelated to ACZ. For the secondary endpoints of overall and progression free survival (OS and PFS, respectively), only the 23 GBM patients were included (22 IDH-wildtype and 1 IDH-mutant). From diagnosis, median PFS was 18.8 months (95% CI: 10.4-23.0) and median OS was 25.0 months (95% CI: 19.9-28.4). Median time from diagnosis to consent was 2.9 months. As of April 2021, only 7 of 23 deaths had occurred. 2-year OS% was 68.2%. Further analysis of secondary endpoints including 6-month objective response rate (ORR) and biomarker analysis of BCL-3 by IHC will be available in the coming months. In sum, the data indicate that addition of ACZ to TMZ is safe and does not lead to reduced TMZ dosing. Also, compared to historical data, interim outcomes suggest that addition of ACZ may substantially improve PFS and 2-year overall survival. These findings support the hypothesis that ACZ acts as a chemosensitizer of alkylating chemotherapy in GBM and support examination of this regimen in a randomized, placebo-controlled study.

Radiotherapy with Concomitant Temozolomide in WHO Grade III Glial Tumors

2008 ◽  
Vol 72 (1) ◽  
pp. S235
Author(s):  
F. Zorlu ◽  
M. Gurkaynak ◽  
U. Selek ◽  
S. Ulger ◽  
A. Turker ◽  
...  
Keyword(s):  
Who Grade ◽  
Glial Tumors ◽  
Who Grade Iii ◽  
Grade Iii

scholarly journals High-grade glioma with anterior skull base erosion and intranasal extension: case report

2017 ◽  
Vol 126 (5) ◽  
pp. 1484-1487 ◽  
Author(s):  
Matthew T. Stib ◽  
Michael Johnson ◽  
Alan Siu ◽  
M. Isabel Almira-Suarez ◽  
Zachary Litvack ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Skull Base ◽  
Radiation Treatment ◽  
High Grade Glioma ◽  
Brain Parenchyma ◽  
Anterior Skull Base ◽  
High Grade ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment.

scholarly journals The Expression of Progesterone Receptors in Meningiomas of Different Grades

2019 ◽  
Vol 8 (2) ◽  
pp. 65-69
Author(s):  
Mohammad Tahir ◽  
Tehreem Atif ◽  
Summaya Sohail ◽  
Arfa Nawazish ◽  
Huma Mushtaq
Keyword(s):  
Progesterone Receptor ◽  
Treatment Options ◽  
Progesterone Receptors ◽  
Lower Grade ◽  
Immunoperoxidase Method ◽  
Nuclear Staining ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Background: Meningiomas are slow growing intracranial and intraspinal neoplasms with a tendency to recur locally. WHO grades them as I (benign), II (atypical) and III (anaplastic) in order of their increasing aggressiveness, based on histological parameters and brain parenchymal invasion. Progesterone receptors (PR) are more prevalent amongst the lower grade meningiomas. The objective of this study was to determine the immunohistochemical expression of progesterone receptors in meningiomas of different grades.Material and Methods: A total of 100 cases were selected over a period of 2.5 years. Three to five microns’ thick sections stained with Hematoxylin and Eosin were examined microscopically by a team of two Histopathologists and graded into grades I, II and III, according to 2016 WHO classification criteria. Another section of the original tumor was stained with progesterone receptor antibody using the conventional immunoperoxidase method. Stained slides were than examined by the same team of Histopathologists and declared positive (if nuclear staining was observed in more than 10% of tumor cells) or negative. Statistical analysis was done using SPSS version 21.Results: Out of a total of 100 cases of meningioma, there were 79 cases of benign/typical WHO grade I, 15 cases of atypical/ WHO grade II and 6 cases of anaplastic/ WHO grade III tumor. PR status was positive in 89.8 % (71/79) of grade I meningiomas and 46.6 % (7/15) of grade II/Atypical meningiomas. The 06 cases of Anaplastic/WHO grade III tumors were negative for PR. There was a higher prevalence of Progesterone receptors in female patients (89.8%; 53/59) as compared to male meningioma patients (60.9%; 25/41).Conclusion: We observed a decreased expression of progesterone receptor in higher grades of meningioma in this study. It is an effort to explore conservative treatment options for inoperable lesions, as anti-progesterone therapy may hold a promise as a new treatment option in the near future.

High-grade gliomas and molecular biology of neurosurgical oncology

2019 ◽  
pp. 89-106
Author(s):  
Stephen J Price ◽  
Harry Bulstrode ◽  
Richard Mair
Keyword(s):  
Molecular Markers ◽  
Who Classification ◽  
High Grade Glioma ◽  
High Grade ◽  
Optimal Management ◽  
Who Grade ◽  
Normal Human ◽  
Who Grade Iii ◽  
Grade Iii

The term high-grade glioma (HGG) encompasses a number of histological entities that are considered by the WHO Classification as WHO Grade III and IV tumours. They have traditionally been considered as having similar behaviour and had been treated in a similar manner but recent advances in our understanding of tumour biology have led to the identification of molecular markers that are now central to the classification of these tumours. Normal human cells develop into cancer cells through a stepwise accumulation of genomic and epigenomic alterations and this chapter considers the molecular markers of gliomas and explains their significance before going on to discuss the optimal management.

scholarly journals Treatment of Glioma Using neuroArm Surgical System

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yaser Maddahi ◽  
Kourosh Zareinia ◽  
Liu Shi Gan ◽  
Christina Sutherland ◽  
Sanju Lama ◽  
...  
Keyword(s):  
Anaplastic Astrocytoma ◽  
Glioma Surgery ◽  
Who Grade ◽  
Interaction Forces ◽  
Mean Values ◽  
Tissue Interaction ◽  
Oligodendroglial Component ◽  
Size Type ◽  
Who Grade Iii ◽  
Grade Iii

The use of robotic technology in the surgical treatment of brain tumour promises increased precision and accuracy in the performance of surgery. Robotic manipulators may allow superior access to narrow surgical corridors compared to freehand or conventional neurosurgery. This paper reports values and ranges of tool-tissue interaction forces during the performance of glioma surgery using an MR compatible, image-guided neurosurgical robot called neuroArm. The system, capable of microsurgery and stereotaxy, was used in the surgical resection of glioma in seven cases. neuroArm is equipped with force sensors at the end-effector allowing quantification of tool-tissue interaction forces and transmits force of dissection to the surgeon sited at a remote workstation that includes a haptic interface. Interaction forces between the tool tips and the brain tissue were measured for each procedure, and the peak forces were quantified. Results showed maximum and minimum peak force values of 2.89 N (anaplastic astrocytoma, WHO grade III) and 0.50 N (anaplastic oligodendroglioma, WHO grade III), respectively, with the mean of peak forces varying from case to case, depending on type of the glioma. Mean values of the peak forces varied in range of 1.27 N (anaplastic astrocytoma, WHO grade III) to 1.89 N (glioblastoma with oligodendroglial component, WHO grade IV). In some cases, ANOVA test failed to reject the null hypothesis of equality in means of the peak forces measured. However, we could not find a relationship between forces exerted to the pathological tissue and its size, type, or location.

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