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Introduction
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack
This is not a textbook covering every aspect of the science and practice of pediatric neuro-oncology as that would need to encompass the whole of developmental neuroscience, cancer biology, and the application of multidisciplinary clinical care for children in hospital, in the community, in their education, and ultimately, in their adult life. Rather, this book is a series of authoritative statements written by international experts working as multidisciplinary collaborative groups, who have first-hand experience with how treatments have been influenced by science and delivered to children and how the scientific processes will influence the approaches in the future. The aim of the editors has been to establish an appropriate balance of authors from North America and Europe.
Quantitative imaging using MRI
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
David A. Hormuth, John Virostko, Ashley Stokes, Adrienne Dula, Anna G. Sorace, Jennifer G. Whisenant, Jared A. Weis, C. Chad Quarles, Michael I. Miga, Thomas E. Yankeelov
The most successful clinical application of MT-MRI has occurred in neurology, owing to the sensitivity of MT to myelin and its use in interrogated demyelinating disease [39]. Correspondingly, MT-MRI has been applied clinically in neuro-oncology. Studies of tumor grading have indicated that MTR is higher in high grade astrocytomas [40] and gliomas [41] versus low grade tumors. In these studies, the MTR correlated with the collagen content of meningiomas [40], suggesting that magnetization transfer may probe the tumor extracellular matrix. Given the recent interest in the role of the extracellular matrix in tumor progression and its identification as a druggable target [42], MT-MRI may prove useful in future oncological studies assessing therapeutic response. MT-MRI has also been performed in breast cancer with initial preliminary indications that MTR may be useful in differentiated benign and malignant lesions [43,44] (Figure 5.3).
FUS-Mediated Image-Guided Neuromodulation of the Brain
Published in Yu Chen, Babak Kateb, Neurophotonics and Brain Mapping, 2017
Seung-Schik Yoo, Wonhye Lee, Ferenc A. Jolesz
Clinical applications can have transformative potential. In neurosurgery and radiation oncology, the thermal and/or nonthermal ablation of brain tumors (McDannold et al. 2010) can replace some brain tumor surgeries and radiation surgeries. In neuro-oncology, targeted drug delivery may be used through the transiently opened BBB for chemotherapy to treat brain metastases (Hynynen et al. 2001, 2006, Kinoshita et al. 2006, McDannold et al. 2012, Treat et al. 2007). In functional neuromodulation, the direct acoustic effect or targeted delivery of neurotransmitters through the BBB can be used (Gavrilov et al. 1996, McDannold et al. 2014, Tufail et al. 2010, Yoo et al. 2011a). This chapter describes the intriguing new potential of functional neuromodulation in the brain.
Gene Therapy for High Grade Glioma: The Clinical Experience
Published in Expert Opinion on Biological Therapy, 2023
Maria Luisa Varela, Andrea Comba, Syed M Faisal, Anna Argento, Andrea Franson, Marcus N Barissi, Sean Sachdev, Maria G Castro, Pedro R Lowenstein
Gene therapy is a versatile and promising technique to be employed in neuro-oncology. Viral vectors used for gene therapy can be administered locally during initial surgery and reach infiltrating cells that cannot be resected, therefore overcoming therapeutic resistance and reducing recurrence. The high infection efficiency of viral vectors has made them widely popular for gene therapy in HGG clinical trials. Furthermore, several different vectors employing a variety of genome editing strategies have been proven to be safe. Histopathological analyses of pre- and post-treatment tissue have demonstrated not only virus activity in vivo but also lysis of tumor cells and an increase in immune cell infiltration and activation. Despite these promising data, several Phase III clinical trials have been conducted with suicide gene therapy, targeted therapy, and immunotherapy without achieving an increase in survival for patients suffering from HGG.
In vitro evidence for glioblastoma cell death in temperatures found in the penumbra of laser-ablated tumors
Published in International Journal of Hyperthermia, 2020
Joshua D. Frenster, Shivang Desai, Dimitris G. Placantonakis
Brain tumors have always been considered a challenge in the field of oncology due to limited efficacy of conventional chemoradiotherapeutic approaches. Our biggest challenge in neuro-oncology remains the treatment of malignant primary brain tumors. The most common primary brain malignancy, glioma, is in dire need of new treatments. In glioblastoma (GBM) in particular, the most aggressive form of glioma, median survival remains only ∼16 months after surgery, and chemoradiotherapy [1]. The high propensity of GBM tumor cells to infiltrate brain tissue eliminates a curative role for the surgery. Instead, surgery is used as a key cytoreductive step in therapy, which is almost always followed by chemoradiotherapy. However, GBM utilizes tumor-intrinsic and microenvironment-mediated mechanisms to resist conventional cytotoxic chemotherapy and high doses of radiotherapy. In addition, recent large-scale randomized trials testing anti-angiogenic therapy, gene therapy and antibody-drug conjugates targeting the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase commonly amplified in GBM, have shown minimal efficacy [2–6]. There is therefore a critical need to identify novel therapies or potentiate current treatments.
The effect of thermal therapy on the blood-brain barrier and blood-tumor barrier
Published in International Journal of Hyperthermia, 2020
Bhuvic Patel, Peter H. Yang, Albert H. Kim
Energy from photons emitted by lasers applied intracranially has a variety of effects depending on the way in which it is applied. For example, using two-photon laser techniques, lesions as small as 15 µm have been created in the parenchyma to study the microglial response to intracranial injury and in the wall of CNS microvasculature to study hemorrhagic and ischemic stroke [71,72]. LITT is a clinical application of laser energy to create thermal lesions as large as 3 cm through conduction of heat to tissues distant from the laser probe. LITT is widely utilized in neuro-oncology due to its ability to effectively kill tumor cells. Photons emitted by the laser are absorbed by tumor cell chromophores, resulting in chromophore excitation followed by release of thermal energy and heating of surrounding tissue [65,73]. In order to achieve cell death, a minimum temperature must be maintained for a certain duration of time. Although heat capacity may vary between cell types and target organs, a specific thermal dose results in cellular necrosis and tissue coagulation. Thermal treatment of tumors takes advantage of the fact that tumor cells are more sensitive to thermal injury than normal cells. However, this therapeutic window is narrow, and accurate targeting and temperature measurement is therefore critical. In the case of CNS tumors, antineoplastic effects become apparent at 42 °C, while normal neurons become damaged at 43 °C [74].