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Future Oncology (London, England) May 2022We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Glioma patients...
We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12 and 24 months. We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n = 68, 52.3%), long-term memory (n = 46, 35.3%) and short-term memory (n = 39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.
Topics: Brain Neoplasms; Cognition; Glioma; Humans; Neuropsychological Tests
PubMed: 35196869
DOI: 10.2217/fon-2021-0963 -
Turkish Neurosurgery 2017Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can... (Meta-Analysis)
Meta-Analysis Review
AIM
Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can be challenging. To compare the efficacy of common therapies, we performed network meta-analysis to estimate the efficacy and safety among procarbazine, lomustine, vincristine, temozolomide, bevacizumab plus temozolomide, and placebo for patients with malignant glioma.
MATERIAL AND METHODS
Relevant studies (as of March, 2014) were identified by searching PubMed, Embase, and Central databases. The primary endpoint of the analysis was the overall survival (OS) and progression-free survival (PFS) of glioma patients.
RESULTS
Nine trials with a total of 3472 patients were included in our network meta-analyses. Compared with placebo, bevacizumab plus temozolomide was associated with the highest estimates of OS and PFS for 12 and 24 months (12 month OS odds ratio [OR]: 2.44; 95% credibility interval [CrIs]: 0.76-9.69; 24 month OS OR: 2.56; 95% CrIs: 1.12?5.24; 12 month PFS OR: 6.76; 95% CrIs: 2.80?17.34; 24 month PFS OR: 3.69; 95% CrIs: 0.62?28.63). However, bevacizumab plus temozolomide did not significantly improve OS or PFS compared to temozolomide alone.
CONCLUSION
Bevacizumab plus temozolomide combination therapy is not significantly more effective than temozolomide alone in improving survival of glioma patients. Moreover, bevacizumab was associated with higher hematologic toxicities. Bevacizumab should be used with caution in glioma patients. Additional randomized controlled trials are required to confirm this finding.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Disease-Free Survival; Glioma; Humans; Network Meta-Analysis
PubMed: 27337236
DOI: 10.5137/1019-5149.JTN.15462-15.0 -
Seminars in Cancer Biology Jan 2021Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases... (Review)
Review
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Discovery; Drug Repositioning; Glioma; Humans
PubMed: 31734137
DOI: 10.1016/j.semcancer.2019.10.018 -
International Journal of Molecular... Nov 2021Despite extensive preclinical research on immunotherapeutic approaches, malignant glioma remains a devastating disease of the central nervous system for which standard... (Review)
Review
Despite extensive preclinical research on immunotherapeutic approaches, malignant glioma remains a devastating disease of the central nervous system for which standard of care treatment is still confined to resection and radiochemotherapy. For peripheral solid tumors, immune checkpoint inhibition has shown substantial clinical benefit, while promising preclinical results have yet failed to translate into clinical efficacy for brain tumor patients. With the advent of high-throughput sequencing technologies, tumor antigens and corresponding T cell receptors (TCR) and antibodies have been identified, leading to the development of chimeric antigen receptors (CAR), which are comprised of an extracellular antibody part and an intracellular T cell receptor signaling part, to genetically engineer T cells for antigen recognition. Due to efficacy in other tumor entities, a plethora of CARs has been designed and tested for glioma, with promising signs of biological activity. In this review, we describe glioma antigens that have been targeted using CAR T cells preclinically and clinically, review their drawbacks and benefits, and illustrate how the emerging field of transgenic TCR therapy can be used as a potent alternative for cell therapy of glioma overcoming antigenic limitations.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen
PubMed: 34884607
DOI: 10.3390/ijms222312810 -
Oncogene Jun 2023The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its...
The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its benefits to more patients. Alleviating various modes of immune suppression has so far failed to achieve such expansion, but exploiting endogenous immune enhancers among mutated cancer genes could represent a more direct approach to immunotherapy improvement. We found that Isocitrate Dehydrogenase-1 (IDH1), which is commonly mutated in gliomas, enhances glioma vaccine efficacy in mice and discerns long from short survivors after vaccine therapy in GBM patients. Extracellular IDH1 directly enhanced T cell responses to multiple tumor antigens, and prolonged experimental glioma cell lysis. Moreover, IDH1 specifically bound to and exhibited sialidase activity against CD8. By contrast, mutant IDH1R132H lacked sialidase activity, delayed killing in glioma cells, and decreased host survival after immunotherapy. Overall, our findings identify IDH1 as an immunotherapeutic enhancer that mediates the known T cell-enhancing reaction of CD8 desialylation. This uncovers a new axis for immunotherapeutic improvement in GBM and other cancers, reveals novel physiological and molecular functions of IDH1, and hints at an unexpectedly direct link between lytic T cell function and metabolic activity in target cells.
Topics: Mice; Animals; Isocitrate Dehydrogenase; N-Acetylneuraminic Acid; Brain Neoplasms; Neuraminidase; Glioma; Glioblastoma; CD8-Positive T-Lymphocytes; Immunotherapy; Mutation
PubMed: 37161052
DOI: 10.1038/s41388-023-02713-7 -
Viruses Jul 2021Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic... (Review)
Review
Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood-brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood-brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Glioblastoma; Glioma; Humans; Immunotherapy; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 34372501
DOI: 10.3390/v13071294 -
Trends in Pharmacological Sciences Feb 2020Glioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in... (Review)
Review
Glioma is the most common intracranial primary malignancy, with limited treatment options and a poor overall survival (OS). Immunotherapy has been used successfully in various cancers, leading to the development of similar therapies that activate the patient's immune system to eliminate glioma. In this review, we introduce the diverse immunotherapeutic approaches available for treating glioma, highlighting the successes and challenges resulting from current clinical trials. Additionally, we emphasize the effect of multiple clinical factors on immunotherapy to help optimize individualized treatment regimens. Finally, we also highlight several novel concepts and technologies that could be used to design new and/or improve existing immunotherapies. Such approaches will delineate a new blueprint for glioma treatment.
Topics: Brain Neoplasms; Glioma; Humans; Immunologic Factors; Immunotherapy
PubMed: 31973881
DOI: 10.1016/j.tips.2019.12.003 -
ACS Nano Jul 2023Glioblastoma (GBM) is one of the most challenging malignant brain tumors to treat. Herein, we describe a nanoenzyme hemostatic matrix strategy with the tumor cavity...
Glioblastoma (GBM) is one of the most challenging malignant brain tumors to treat. Herein, we describe a nanoenzyme hemostatic matrix strategy with the tumor cavity application that simultaneously serves as photothermal agent and induces immunogenic cell death after GBM surgical resection to enhance the antitumor immunity and delay tumor recurrence. The hemostatic matrix system (Surgiflo@PCN) contains Surgiflo, a multispace structure that can be used to penetrate different shapes of tumor cavities to prevent postoperative tumor cavity hemorrhage. As well, porous palladium-copper nanoclusters (PCNs) have adjustable enzyme-like activities (oxidase, peroxidase, and catalase) responsible for formation of reactive oxygen species (ROS) under near-infrared (808 nm) laser irradiation. When the Surgiflo@PCN entered the resected tumor cavity, the first action was the direct killing of glioma cells via ROS and photothermal therapy (PTT). The second action was the induction of immunogenic cell death by PCN-enhanced oxidative stress and PTT, which reversed the immunosuppressive tumor microenvironment and enhanced the antitumor immune response. This eradicated residual glioma cells and prevented recurrence. The collective findings demonstrate that Surgiflo@PCN kills glioma cells directly through ROS and PTT and enhances antiglioma immunity and kills glioma cells indirectly. The "one-stone, two-birds" strategy could become an effective photothermal immunotherapy in GBM patients.
Topics: Humans; Reactive Oxygen Species; Glioma; Glioblastoma; Immunomodulation; Hemostatics; Cell Line, Tumor; Tumor Microenvironment; Neoplasms
PubMed: 37399132
DOI: 10.1021/acsnano.3c03696 -
Lasers in Surgery and Medicine Jul 2018Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. (Review)
Review
BACKGROUND
Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard.
AIMS
This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients.
MATERIALS AND METHODS
From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience.
RESULTS AND DISCUSSION
The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT).
CONCLUSION
5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Topics: Aminolevulinic Acid; Brain Neoplasms; Glioma; Humans; Photochemotherapy; Photosensitizing Agents
PubMed: 29737540
DOI: 10.1002/lsm.22933 -
JPMA. the Journal of the Pakistan... Jun 2018The average rate of gross total resection (GTR) for malignant gliomas (MGs) is reported to be around 36%. One of the major challenges to GTR is the recognition of tumour... (Review)
Review
The average rate of gross total resection (GTR) for malignant gliomas (MGs) is reported to be around 36%. One of the major challenges to GTR is the recognition of tumour margins. Sodium fluorescein is a freely available fluorophore used to recognize the boundaries of MGs. It accumulates in tumour areas with disrupted blood brain barrier that can then be visualized under a microscope with dedicated filters. No randomized controlled trial or meta-analysis is available that reports the impact of fluorescein use on the extent of tumour resection. Several prospective studies and a phase II trial prove it to be safe and helpful in achieving GTR rates of 68.42-100%. At higher doses i.e., 15-20 mg/Kg, sodium fluorescein can even be used under white illumination. The dye is safe even at high doses and has helped achieve GTR rates of 80-84.4.
Topics: Brain Neoplasms; Fluorescein; Fluorescent Dyes; Glioma; Humans; Neurosurgical Procedures
PubMed: 30323373
DOI: No ID Found