Advances in Treatment Options for High-grade Glioma—Current Status and Future Perspectives

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 55 ◽  
Author(s):  
Ryan T Merrell ◽  
Eudocia C Quant ◽  
Patrick Y Wen ◽  
◽  
◽  
...  
Keyword(s):  
Brain Tumors ◽  
Anaplastic Astrocytoma ◽  
Treatment Options ◽  
High Grade Glioma ◽  
Multimodality Therapy ◽  
Current Status ◽  
High Grade ◽  
Novel Therapies ◽  
Targeted Agents ◽  
Future Perspectives

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma, and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumors diagnosed in adults. The prognosis for these tumors is poor despite multimodality therapy with surgery, radiation, and/or chemotherapy. This article summarizes treatment options for high-grade glioma, including standard regimens, targeted agents, and novel therapies.

Advances in Treatment Options for High-grade Glioma - Current Status and Future Perspectives

2010 ◽  
Vol 5 (1) ◽  
pp. 49 ◽  
Author(s):  
Ryan T Merrell ◽  
Eudocia C Quant ◽  
Patrick Y Wen ◽  
◽  
◽  
...  
Keyword(s):  
Anaplastic Astrocytoma ◽  
Brain Tumours ◽  
Treatment Options ◽  
High Grade Glioma ◽  
Current Status ◽  
High Grade ◽  
Novel Therapies ◽  
Targeted Agents ◽  
Future Perspectives ◽  
Primary Brain Tumours

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumours diagnosed in adults. The prognosis for these tumours is poor despite multimodality therapy with surgery, radiation and/or chemotherapy. This review summarises treatment options for high-grade glioma, including standard regimens, targeted agents and novel therapies.

Phase I dose escalation of temozolomide with thiotepa and carboplatin with autologous hematopoietic cell reinfusion in patients with recurrent/refractory malignant brain tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2060-2060 ◽  
Author(s):  
S. Gardner ◽  
M. Fisher ◽  
J. Belasco ◽  
P. Phillips ◽  
J. Finlay
Keyword(s):  
Brain Tumors ◽  
Dose Level ◽  
Dose Escalation ◽  
Standard Dose ◽  
Treatment Options ◽  
High Grade Glioma ◽  
High Dose ◽  
High Grade ◽  
Malignant Brain Tumors ◽  
Dose Limiting Toxicity

2060 Background: The prognosis for most patients with recurrent malignant brain tumors is dismal. Treatment options are limited especially for patients who have already received irradiation. TMZ is an oral alkylating agent which is approved for use in patients with high grade glioma and has also been shown to have activity in patients with recurrent medulloblastoma. It’s primary dose-limiting toxicity is non- cumulative bone marrow suppression. In the present study, TMZ is given in a dose escalation fashion with fixed doses of high dose thiotepa and carboplatin with AHCR in the treatment of patients with recurrent or refractory malignant brain tumors. Methods: Treatment consisted of TMZ twice daily on days -10 to -6 followed by thiotepa 300 mg/m2/day and carboplatin AUC=7/day on days -5 to -3 with AHCR on day 0. Filgrastim was given day +1 and continued until engraftment. Results: 27 patients (18M; 9F) ages 3–46 years were treated from 11/00 until 10/04. Diagnoses included high grade glioma (n=12); medulloblastoma/PNET (n=9); CNS germ cell tumor (GCT) (n=4); and 1 each ependymoma and spinal cord PNET. TMZ doses ranged from 50 mg/m2 twice daily (100 mg/m2/day) to 200 mg/m2 twice daily (400 mg/m2/day) for 5 days. One patient had dose limiting toxicity consisting of reversible veno-occlusive disease at dose level 3 (TMZ 100 mg/m2 twice daily). Two patients had dose limiting toxicity at dose level 7 (TMZ 200 mg/m2 twice daily) consisting of transient encephalopathy (n=1) and severe mucositis (n=1). Additional toxicities included bacteremia (n=11), C. difficile enteritis (n=6) and grade 4 elevation of bilirubin and/or liver transaminases (n=2). There were no toxic deaths. Survival included 3 patients with glioma (38–48 months); two of whom had relapsed following standard dose TMZ; 3 patients with PNET/MB (48–72 months) and 3 patients with CNS GCT (26–71 months). Conclusions: Increased doses of TMZ are feasible when given with AHCR. There is presently a phase II study underway through the Pediatric Blood and Marrow Transplant Consortium evaluating the efficacy of TMZ at a dose of 175 mg/m2/day twice daily for 5 days with high dose thiotepa and carboplatin and AHCR. No significant financial relationships to disclose.

scholarly journals High-Grade Glioma/Glioblastoma Multiforme: Is There a Role for Photodynamic Therapy?

2012 ◽  
Vol 10 (Suppl_2) ◽  
pp. S-31-S-34 ◽  
Author(s):  
Harry T. Whelan
Keyword(s):  
Photodynamic Therapy ◽  
Brain Tumors ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
The United States ◽  
Primary Treatment ◽  
High Grade ◽  
Clinical Use ◽  
Potential Alternative

In the United States, the 5-year survival rate for patients of all ages with all types of brain tumors is approximately 20%, with the scale skewed toward even poorer survival in patients with gliomas. Although surgery and radiotherapy are primary treatment options, surgery is rarely curative and radiotherapy has had little impact on overall survival. Predominantly studied in adults with advanced high-grade gliomas, photodynamic therapy (PDT) represents a paradigmatic shift in the treatment of brain tumors. With no clear standard of care for brain tumors, PDT may emerge as a potential alternative, although challenges regarding its clinical use remain and studies confirming its promise are necessary.

scholarly journals Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

2021 ◽  
Vol 11 (3) ◽  
pp. 386
Author(s):  
Alice Giotta Lucifero ◽  
Sabino Luzzi
Keyword(s):  
Monoclonal Antibodies ◽  
Natural Killer ◽  
Immune Escape ◽  
Meta Analysis ◽  
Treatment Options ◽  
High Grade Glioma ◽  
High Grade ◽  
Future Challenges ◽  
Genetic Landscape ◽  
High Grade Gliomas

The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

scholarly journals Assessing Biological Response to Bevacizumab Using 18F-Fluoromisonidazole PET/MR Imaging in a Patient with Recurrent Anaplastic Astrocytoma

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Ramon F. Barajas ◽  
Miguel H. Pampaloni ◽  
Jennifer L. Clarke ◽  
Youngho Seo ◽  
Dragana Savic ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Anaplastic Astrocytoma ◽  
Biological Effects ◽  
Biological Response ◽  
High Grade Glioma ◽  
Index Patient ◽  
High Grade ◽  
Initial Experience ◽  
Vascular Normalization ◽  
Single Modality

We present our initial experience in using single modality fluoromisonidazole (FMISO) PET/MR imaging to noninvasively evaluate the biological effects induced by bevacizumab therapy in a patient treated for recurrent high grade glioma. In this index patient, bevacizumab therapy resulted in the development of nonenhancing tumor characterized by reduced diffusion and markedly decreased FMISO uptake in the setting of maintained CBF and CBV. These observations suggest that the dynamic biological interplay between tissue hypoxia and vascular normalization occurring within treated recurrent high grade glioma can be captured utilizing FMISO PET/MR imaging.

scholarly journals Parents’ experiences of postmortem tumor donation for high-grade gliomas: benefits and suggested improvements

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Eden G Robertson ◽  
Claire E Wakefield ◽  
Maria Tsoli ◽  
Stewart J Kellie ◽  
Frank Alvaro ◽  
...  
Keyword(s):  
Qualitative Data ◽  
High Grade Glioma ◽  
Research Progress ◽  
High Grade ◽  
Novel Therapies ◽  
Knowing That ◽  
Bereaved Parents ◽  
Improve Access ◽  
Pediatric High Grade Glioma ◽  
Parents Experiences

Abstract Background Pediatric high-grade glioma is a devastating diagnosis. There has been no improvement in outcomes for several decades, with few children surviving 2 years postdiagnosis. Research progress has been hampered by a lack of tumor samples, which can be used to develop and test novel therapies. Postmortem tumor donations are therefore a valuable opportunity to collect tissue. In this study, we explored Australian parents’ experiences of donating their child’s tumor for research after their child had died. Methods We collected qualitative data from 11 bereaved parents who consented to donate samples of their child’s high-grade glioma for research postmortem. We asked parents about their perceived benefits/burdens of the autopsy, recommendations for improving consent discussions, and decision regret. Results Parents hoped that their donation would help to find a cure for future children with high-grade glioma. They described feeling comforted knowing that their child’s suffering may help others. Some parents also felt that the donation would help them better understand their child’s tumor. Although some parents described discomfort about procedures leading up to the autopsy, parents reported minimal regret regarding their decision to donate their child’s tumor. Parents provided recommendations to improve consent discussions, such as providing more information about the autopsy logistics and why the donation was needed. Conclusion Parents consented to autopsy for altruistic reasons, although donation may also assist parents in their grieving. There is a strong need to improve access to tumor donations for any family who wishes to donate.

Phase II study of extended schedule temozolomide in refractory gliomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1516-1516 ◽  
Author(s):  
A. Berrocal ◽  
P. Perez-Segura ◽  
M. Gil ◽  
C. Balaña ◽  
R. Yaya-Tur ◽  
...  
Keyword(s):  
Anaplastic Astrocytoma ◽  
Drug Withdrawal ◽  
Haematological Toxicity ◽  
High Grade Glioma ◽  
Primary Objective ◽  
Response To Treatment ◽  
High Grade ◽  
Time To Progression ◽  
Unacceptable Toxicity ◽  
Grade Iii

1516 Background: Temozolomide resistance is mainly mediated by the enzyme AGT that repair DNA damage in a suicide way. Inhibition of this enzyme is greater when temozolomide is administered in a extended schedule that also obtains higher exposure to the drug. Methods: Primary objective is to assess is extended schedule temozolomide can revert resistance. Patients with bidimensionally measurable high grade glioma refractory to temozolomide defined as either progression during treatment or in the following tree months of drug withdrawal were included. Temozolomide was administered at a dose of 85 mg/m2 daily for 21 consecutive days every 28 days until unacceptable toxicity or progression. Results: Up to now we have included 41 patients, 29 of them available for the first analysis. Mean age is 51.3 (23–77), male 22 (76%), ECOG 0/1/2 7 (24%)/13 (45%)/9 (31%), histology is glioblastoma 18 (61%), anaplastic astrocytoma 9 (31%), anaplastic oligodendroglioma 1 (3.4%) other high grade glioma 1. Fourteen patients received more than one line of chemotherapy before study entrance. 65% were on anticonvulsant therapy mainly with phenytoin 56% or valproic acid 42%. Response to treatment was partial in 2 (6.7%), stable in 9 (31%) progression in 13% (45%) and not assessed in 5. Response only in assessable patients was PR/SD/P 2 (8.3%)/9 (37.5%)/13 (54%). Responses were seen in oligodendroglioma and anaplastic astrocytoma. Median survival has been 5.9 months and time to progression 2 months. 80 courses have been administered with a mean per patient of 2 (1–7). Toxicity has been very mild mainly haematological and grade I and II. 7% of the patients experienced platelet toxicity grade III and 3.5% neutropenia grade III. Non haematological toxicity was mainly transaminase elevation grade I to II in 24% of patients and nausea and vomiting grade I to II in 31%. Conclusions: Extended schedule temozolomide is an active regimen in resistant patients with moderate toxicity. Resistance to temozolomide may be reverted by extended schedule of administration [Table: see text]

scholarly journals The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review

Cancer ◽  
2016 ◽  
Vol 122 (16) ◽  
pp. 2469-2478 ◽  
Author(s):  
Alireza Mansouri ◽  
Sheila Mansouri ◽  
Laureen D. Hachem ◽  
George Klironomos ◽  
Michael A. Vogelbaum ◽  
...  
Keyword(s):  
Systematic Review ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
High Grade ◽  
Future Perspectives

scholarly journals High-grade glioma management and response assessment—recent advances and current challenges

2016 ◽  
Vol 23 (4) ◽  
pp. 383 ◽  
Author(s):  
M.N. Khan ◽  
A.M. Sharma ◽  
M. Pitz ◽  
S.K. Loewen ◽  
H. Quon ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Tumour Progression ◽  
Performance Status ◽  
Treatment Options ◽  
High Grade Glioma ◽  
Tumour Resection ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Dynamic Susceptibility Contrast ◽  
Recent Advances

The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques—including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging— can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology.

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