Neurosurgical Clinical Trials for Glioblastoma: Current and Future Directions

Shah, Ashish H.; Heiss, John D.

doi:10.3390/brainsci12060787

Cited by 5 publications

(3 citation statements)

References 68 publications

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“…After surgery, the smallest amount of residual tumor correlates with higher survivals [ 287 , 288 ]. However, radical surgical resection is limited by the highly invasive nature of GB cells [ 289 ].…”

Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…Since the development of CED in the 1990s, there have been many advancements over the years. Although CED in its current state has limited anti-tumor effects for astrocytomas, it may show promise in the near future with many current clinical trials seeking to improve the technique [197,198]. Another method to cross the BBB employed by Gregory et al [196] is nanoparticle technology.…”

Section: Future Treatmentmentioning

confidence: 99%

Update for astrocytomas: medical and surgical management considerations

Willman

Figg

et al. 2023

Explor Neurosci

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Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.

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“…Nevertheless, manual labeling of brain tumor lesions by physicians alone is time-consuming and requires a high level of diagnostic experience, and the accuracy of labeling tumor lesions still needs to be considered. In contrast, the utilization of computer-aided medical technology for tumor diagnosis is not only convenient and fast, but also less dependent on cumulative experience, which has broad development prospects and practical significance [ 1 , 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

RMTF-Net: Residual Mix Transformer Fusion Net for 2D Brain Tumor Segmentation

et al. 2022

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Due to the complexity of medical imaging techniques and the high heterogeneity of glioma surfaces, image segmentation of human gliomas is one of the most challenging tasks in medical image analysis. Current methods based on convolutional neural networks concentrate on feature extraction while ignoring the correlation between local and global. In this paper, we propose a residual mix transformer fusion net, namely RMTF-Net, for brain tumor segmentation. In the feature encoder, a residual mix transformer encoder including a mix transformer and a residual convolutional neural network (RCNN) is proposed. The mix transformer gives an overlapping patch embedding mechanism to cope with the loss of patch boundary information. Moreover, a parallel fusion strategy based on RCNN is utilized to obtain local–global balanced information. In the feature decoder, a global feature integration (GFI) module is applied, which can enrich the context with the global attention feature. Extensive experiments on brain tumor segmentation from LGG, BraTS2019 and BraTS2020 demonstrated that our proposed RMTF-Net is superior to existing state-of-art methods in subjective visual performance and objective evaluation.

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Neurosurgical Clinical Trials for Glioblastoma: Current and Future Directions

Cited by 5 publications

References 68 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

Update for astrocytomas: medical and surgical management considerations

RMTF-Net: Residual Mix Transformer Fusion Net for 2D Brain Tumor Segmentation

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