Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial

Guthkelch, A. N.; Carter, L. P.; Cassady, J. Robert; Hynynen, Kullervo; Iacono, Robert P.; Johnson, P. C.; Obbens, Eugenie A.M.T.; Roemer, R. B.; Seeger, Joachim F.; Shimm, David S.; Steal, B.

doi:10.1007/bf00177540

Cited by 160 publications

(100 citation statements)

References 16 publications

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“…Thus, water bath, infrared radiation, focused ultrasound, and micro-or radiowaves are some examples of heat sources placed outside the body (external heating sources). 4,5 Additionally, the progress of nanotechnology has brought a minimally-invasive approach based on the use of biocompatible 6 iron oxide magnetic nanoparticles (MNPs) as heating mediators when subjected to alternating magnetic fields (AMFs). Under these conditions, heat dissipation occurs due to magnetization reversal processes of MNP magnetic moments.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

Ludwig¹,

Terán²,

Teichgraeber³

et al. 2017

IJN

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So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.9 kA/m; f=410 kHz) was always superior to that of EH. The thermal effects were confirmed by the following observations: 1) decreased number of vital cells, 2) altered expression of pro-caspases, and 3) production of reactive oxygen species, and 4) altered mRNA expression of Ki-67, TOP2A, and TPX2. The MH treatment of tumor xenografts significantly ( P ≤0.05) reduced tumor volumes. This means that different therapeutic outcomes of hyperthermia are related to the different responses cells exert to thermal stress. In particular, intratumoral MH is a valuable tool for the treatment of pancreatic cancers.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

Ludwig¹,

Terán²,

Teichgraeber³

et al. 2017

IJN

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“…Beyond thermal ablation, HIFU has notably been shown to allow safe, nondestructive, and transient focal blood-brain barrier disruption to facilitate drug delivery [24,25] and is being evaluated as a tool to induce hyperthermia to enhance the therapeutic effect of radiotherapy and chemotherapy [26][27][28]. Transcranial noninvasive HIFU has also been used to modulate cortex activity in a study with human volunteers [29] and to stimulate deep brain nuclei [30].…”

Section: Discussionmentioning

confidence: 99%

First Non-invasive Thermal Ablation of a Brain Tumor with MR Guided Focused Ultrasound

Coluccia¹,

Fandiño²,

Schwyzer³

et al. 2014

J Neurol Surg A Cent Eur Neurosurg

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Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue.

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“…In 1991, Guthkelch et al described FUS-mediated tumor ablation via craniotomy in 15 patients with primary high-grade gliomas, but the authors noted inconsistent heating throughout the tumor bed. 21 In the early 2000s, once MR guidance of FUS procedures was available, investigators revisited MRgFUS as a tool for tumor ablation, using MRgFUS via a craniotomy to ablate glioblastoma lesions in 3 separate patients. 57 Progression-free survival was 4 and 9 months for 2 of the patients, and the third still had no progression by time of reporting at 39 months after MRgFUS treatment.…”

Section: Direct Tumor Ablationmentioning

confidence: 99%

Focused ultrasound in neurosurgery: a historical perspective

Harary

Segar

Huang

et al. 2018

Neurosurgical Focus

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Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

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Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial

Cited by 160 publications

References 16 publications

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

First Non-invasive Thermal Ablation of a Brain Tumor with MR Guided Focused Ultrasound

Focused ultrasound in neurosurgery: a historical perspective

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