Medicine and Health Sciences Commons^™

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma, Christopher Cultrara, Christopher Uhl, Kenneth Kirby, Essam Abed Elrazaq, Amelia Zellander, David W. Andrews, Charles B. Scott, Lorenzo Galluzzi, Mark A. Exley, Jenny Zilberberg

Department of Neurosurgery Faculty Papers

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

Methods Mouse (m) or human (h) variants of IGV-001 …

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival Of Patients With Recurrent Glioblastoma In A Randomized Trial, Tulika Ranjan, Soma Sengupta, Michael J. Glantz, Richard M. Green, Alexander Yu, Dawit Aregawi, Rekha Chaudhary, Ricky Chen, Mario Zuccarello, Christine Lu-Emerson, Hugh D. Moulding, Neil Belman, Jon Glass, Aaron Mammoser, Mark Anderson, Jagan Valluri, Nicholas Marko, Jason Schroeder, Steven Jubelirer, Frances Chow, Pier Paolo Claudio, Anthony M. Alberico, Seth T. Lirette, Krista L. Denning, Candace M. Howard

Department of Neurosurgery Faculty Papers

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.

In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = …

Temozolomide Rechallenge In Patients With Recurrent High-Grade Glioma Treated With Re-Irradiation, Mustafa Basree, Ayesha Ali, Shivank Garg, Jonathan Glass, Lyndon Kim, Christopher J Farrell, James J. Evans, Kevin Judy, David W. Andrews, Wenyin Shi, Maria Werner-Wasik, Joshua Palmer

Department of Neurosurgery Faculty Papers

PURPOSE/OBJECTIVE(S): To evaluate the clinical role of temozolomide rechallenge (TMZ) in patients with recurrent high-grade glioma (HGG) treated with re-irradiation (re-RT) regardless of surgical status. MATERIALS/METHODS: Single-center retrospective review of patients with a primary diagnosis of World Health Organization (WHO) Grade III anaplastic astrocytoma or Grade IV GBM treated from 2008 to 2016 for disease recurrence with re-RT (35 Gy in 10 fractions) with and without temozolomide rechallenge. Baseline characteristics were analyzed with pairwise tests. OS/PFS were assessed with the Kaplan-Meier method and multivariable cox regression models for OS. RESULTS: Two hundred and thirty patients were treated with re-irradiation (n …

Post-Operative Seizure Control In Patients With Glioblastoma, Ummey Hani, Muhammad Ammar Haider, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

While the median survival in patients with glioblastoma has not improved significantly over the past decade, aggressive attempts have been made on palliation and improving quality of life in these patients. A confluence of two debilitating pathologies which massively distorts the normal day-to-day functioning of the patients who experience it, seizures in glioblastoma patients portends a poor prognosis. There exists a paucity of reported seizure outcomes after glioblastoma treatment in neurosurgical literature. Herein we present a review examining post-operative seizure control in patients with glioblastoma.

Glioma Stem Cells As Immunotherapeutic Targets: Advancements And Challenges, Keenan Piper, Lisa Depledge, Michael Karsy, Charles Cobbs

Department of Neurosurgery Faculty Papers

Glioblastoma is the most common and lethal primary brain malignancy. Despite major investments in research into glioblastoma biology and drug development, treatment remains limited and survival has not substantially improved beyond 1–2 years. Cancer stem cells (CSC) or glioma stem cells (GSC) refer to a population of tumor originating cells capable of self-renewal and differentiation. While controversial and challenging to study, evidence suggests that GCSs may result in glioblastoma tumor recurrence and resistance to treatment. Multiple treatment strategies have been suggested at targeting GCSs, including immunotherapy, posttranscriptional regulation, modulation of the tumor microenvironment, and epigenetic modulation. In this review, we …

Polio To The Rescue; New Frontiers In Glioblastoma Treatment, Syed Sarmad Bukhari, Aneela Darbar, Muhammad Shahzad Shamim

Section of Neurosurgery

Lack of substantial progress in effective treatment of glioblastomamultiforme has led investigators to explore unconventional treatment options including the use of tumour treating fields and oncolyticvirotherapy. Herein the authors have reviewed some of the recent literature on oncolyticvirotherapy for the treatment of glioblastomamultiforme.

Progression-Free But No Overall Survival Benefit For Adult Patients With Bevacizumab Therapy For The Treatment Of Newly Diagnosed Glioblastoma: A Systematic Review And Meta-Analysis., Nagham Kaka, Karim Hafazalla, Haider Samawi, Andrew Simpkin, James Perry, Arjun Sahgal, Sunit Das

Department of Neurosurgery Faculty Papers

Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment …

Timing Of Postoperative Magnetic Resonance Imaging (Mri) Following Glioma Resection: Shattering The 72 Hour Window, Syed Sarmad Bukhari, Muhammad Shahzad Shamim, Fatima Mubarak

Section of Neurosurgery

Extent of enhancing tumour resection is correlated with progression free survival following glioma surgery. Historically, a contrast enhanced MRI has been recommended within 72 hours following surgery to evaluate for residual disease. This theoretical window was established amidst conflicting evidence to avoid reactive enhancement. Recent studies with better designs and better imaging quality have sought to challenge this window with a more pragmatic method of evaluating residual disease.

Tumour Treating Fields (Ttfs) For Recurrent And Newly Diagnosed Glioblastoma Multiforme, Farhan Ahmed, Muhammad Shahzad Shamim

Section of Neurosurgery

In the last decade, significant advances have been made in Glioblastoma Multiforme treatment with the novel use of alternating electrical fields, also termed as tumour treating fields (TTFs). This modality has shown promising results in recurrent and newly diagnosed GBM patients, and according to some, may soon be considered an addition to the previously known 'trifecta' of GBM standard of care, i.e., surgery, chemo and radiation therapy.Here we review the existing data on TTF for both recurrent and newly diagnosed GBM. This review does not discuss the limitations of TTF, especially from compliance and cost point of view.

Radiomic Features From Muti-Institutional Glioblastoma Mri Offers Additive Prognostic Value To Clinical And Genomic Markers, Spencer Liem, Bs, Gaurav Shukla, Md, Phd, Spyridon Bakas, Phd, Sung Min Ha, Ms, Saima Rathore, Phd, Christos Davatzikos, Phd

Sigma Xi Student Research Day

Objective

Synergies between clinical, genomic, and radiomic features should improve the predictive value of each group of features and their combinations through a prognostic classifier based on machine learning in patients with glioblastoma.

Role Of Extent Of Resection On Quality Of Life In Patients With Newly Diagnosed Gbm, Usama Khalid Choudry, Huzaifa Ismail Shaikh, Areeba Nisar, Saad Akhtar Khan, Muhammad Shahzad Shamim

Section of Orthopaedic Surgery

Glioblastomas known for their adverse outcomes are most reportedly managed by surgical resection. Studies on the impact of (Extent of Resection) EOR against Quality of Life (QOL) are very limited. We have collected data from recent studies in this review to extract a general consensus among the neurosurgeons regarding the EOR. Key parameters like functional independence, neurocognitive improvements and global health status have been explored in the context of QOL. The currently available data suggests that an increased EOR may help improve QOL in GBM patients. With the help of recent advancements it may be possible to attain a better …

Role Of 5-Ala In Improving Extent Of Tumour Resection In Patients With Glioblastoma Multiforme, Muhammad Waqas, Inamullah Khan, Muhammad Shahzad Shamim

Section of Neurosurgery

Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use …