Medicine and Health Sciences Commons^™

Hyperthermic Extracorporeal Applied Tumor Therapy (Heatt®) In Advanced Unresponsive Cancer, Joseph B. Zwischenberger, Peyton Skaggs, Katherine Breetz, Jan Winetz, Roger Vertrees

Journal of Shock and Hemodynamics

Hyperthermia has been utilized for cancer therapy, including metastatic cancer, for decades with isolated success. Previous research has indicated that the elevated temperature of 42°C induces cell death, apoptosis, or senescence of responsive cancers, providing a mechanism for tumor destruction and management. Veno-venous perfusion-induced systemic hyperthermia (V-V PISH) may be the key to improving advanced tumor responsiveness to previously failed chemotherapy and/or radiation as combination therapy. The most recent iteration of V-V PISH, Hyperthermic Extracorporeal Applied Tumor Therapy (HEATT®), provides homogeneous heating of all tissues with electrolyte and pH control and continues to prove safe and effective. The utilization of …

Magnetic Resonance-Guided High Intensity Focused Ultrasound (Mrghifu) Induced Hyperthermia (Ht) For Treatment Of Cervical Cancer, Lifei Zhu

McKelvey School of Engineering Theses & Dissertations

Hyperthermia (HT), which refers to increasing the temperature of the tumor tissue to 40–45°C for an extended period of time, has been reported to be one of the most effective sensitizers for radiation therapy (RT) and/or chemotherapy. High intensity focused ultrasound (HIFU) has been developed as a non-invasive and non-ionizing tool to induce localized HT. Magnetic resonance thermometry (MR thermometry) is one of the most reliable methods for non-invasively and precisely measuring the in vivo volumetric temperature in real time. The integration of MR thermometry with HIFU has been implemented in commercially available magnetic resonance guided high intensity focused ultrasound …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations & Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Feasibility Of Removable Balloon Implant For Simultaneous Magnetic Nanoparticle Heating And Hdr Brachytherapy Of Brain Tumor Resection Cavities., Paul R. Stauffer, Dario B. Rodrigues, Robert Goldstein, Thinh Nguyen, Yan Yu, Shuying Wan, Richard Woodward, Michael Gibbs, Ilya L. Vasilchenko, Alexey M. Osintsev, Voichita Bar-Ad, Dennis B. Leeper, Wenyin Shi, Kevin D. Judy, Mark D. Hurwitz

Department of Radiation Oncology Faculty Papers

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant.

METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency …

Hyperthermia And Immunotherapy: Clinical Opportunities., Mark D Hurwitz

Department of Radiation Oncology Faculty Papers

Hyperthermia holds great promise to advance immunotherapy in the treatment of cancer. Multiple trials have demonstrated benefit with the addition of hyperthermia to radiation or chemotherapy in the treatment of wide-ranging malignancies. Similarly, pre-clinical studies have demonstrated the ability of hyperthermia to enhance each of the 8 steps in the cancer-immunotherapy cycle including stimulation of tumor-specific immunity. While there has been an extensive recent focus on augmenting immunotherapy with radiation, surprisingly to date, there have been no clinical trials assessing the combination of hyperthermia with immunotherapy. The study of hyperthermia with immunotherapy is particularly compelling when considered in the context …

Quality Assurance Guidelines For Interstitial Hyperthermia., H. Dobšíček Trefná, M. Schmidt, G. C. Van Rhoon, H. P. Kok, S. S. Gordeyev, U. Lamprecht, D. Marder, J. Nadobny, P. Ghadjar, S Abdel-Rahman, A. M. Kukiełka, V. Strnad, M. D. Hurwitz, Z. Vujaskovic, C. J. Diederich, P. R. Stauffer, J. Crezee

Department of Radiation Oncology Faculty Papers

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment …

It's Getting Hot In Here: A Rare Case Of Heat Stroke In A Young Male., Oriana Ramirez, Yury Malyshev, Sonu Sahni

Touro College of Osteopathic Medicine (New York) Publications and Research

Heat stroke is a severe acute illness characterized by a core temperature greater than 40°C (104°F) and central nervous system manifestations, such as delirium, convulsions, or coma, resulting from exposure to environmental heat or strenuous physical activity. Early recognition and treatment including aggressive cooling and management of life-threatening systemic complications, such as cardiac arrest, rhabdomyolysis and acute renal failure, are essential to reduce morbidity and mortality. Herein we describe a case of heat stroke in a 23-year-old male who suffered cardiac arrest in which prompt initiation of cooling measures prevented permanent neurological sequelae, provided swift neurological recovery and resolution of …

Analysis Of Clinical Data To Determine The Minimum Number Of Sensors Required For Adequate Skin Temperature Monitoring Of Superficial Hyperthermia Treatments., Akke Bakker, Rebecca Holman, Dario B. Rodrigues, Hana Dobšíček Trefná, Paul R. Stauffer, Geertjan Van Tienhoven, Coen R.N. Rasch, Hans Crezee

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients.

METHODS: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm²). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset …

Temperature Induces Significant Changes In Both Glycolytic Reserve And Mitochondrial Spare Respiratory Capacity In Colorectal Cancer Cell Lines, Mihail I. Mitov, Jennifer W. Harris, Michael Alstott, Yekaterina Y. Zaytseva, B. Mark Evers, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach.

This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32°C, 37°C and 42°C using assay …

Quality Assurance Guidelines For Superficial Hyperthermia Clinical Trials : Ii. Technical Requirements For Heating Devices., Hana Dobšíček Trefná, Johannes Crezee, Manfred Schmidt, Dietmar Marder, Ulf Lamprecht, Michael Ehmann, Jacek Nadobny, Josefin Hartmann, Nicolleta Lomax, Sultan Abdel-Rahman, Sergio Curto, Akke Bakker, Mark D. Hurwitz, Chris J. Diederich, Paul R. Stauffer, Gerard C. Van Rhoon

Department of Radiation Oncology Faculty Papers

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this …

Compact Heat Exchanger For Veno-Venous Perfusion-Induced Systemic Hyperthermia Systems, Dongfang Wang, Joseph B. Zwischenberger

Surgery Faculty Patents

A compact heat exchanger for vena-venous perfusion-induced hyperthermia includes an integral pneumatic pump and a hollow tubule heat exchange array. A vena-venous perfusion-induced hyperthermia system incorporating the compact heat exchanger is described. The heat exchanger provides a compact, efficient design allowing a lesser heat exchanging surface area and lesser required pumping power compared to conventional systems. In turn, the system provides a shorter blood circuit compared to conventional systems, allowing maintaining a lower blood temperature than such conventional systems while supplying sufficiently heated blood to patient visceral organs to provide a therapeutic effect, such as in supplementing chemotherapy drugs.

Overview Of Bladder Heating Technology: Matching Capabilities With Clinical Requirements., Paul R. Stauffer, Gerard C. Van Rhoon

Department of Radiation Oncology Faculty Papers

Moderate temperature hyperthermia (40-45°C for 1 h) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle-invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle-invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for …

Optimization Of Chest Wall Hyperthermia Treatment Using A Virtual Human Chest Model, Dario B. Rodrigues, Mark D. Hurwitz, Paolo F. Maccarini, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

This work explores different coupling configurations (direct contact, air and water coupling) between a single 915 MHz waveguide applicator and human tissue in the setting of chest wall recurrence (CWR) of breast cancer. The objective is to treat chest wall tumours with microwave hyperthermia, while avoiding hot spots in critical areas such as scars and ribs. The best coupling configuration was a customized 24×29 cm water bolus developed by our team. It helps the applicator deliver an effective field size of 268 cm2 at 1 cm depth and a penetration depth of 2-3 cm. Water bolus thickness can be adjusted …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Salvage Brachytherapy In Combination With Interstitial Hyperthermia For Locally Recurrent Prostate Carcinoma Following External Beam Radiation Therapy: A Prospective Phase Ii Study., Andrzej M Kukiełka, Vratislav Strnad, Paul R. Stauffer, Tomasz Dąbrowski, Marcin Hetnał, Damian Nahajowski, Tomasz Walasek, Piotr Brandys, Robert Matys

Department of Radiation Oncology Faculty Papers

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear …

Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care., Mark Hurwitz, Md, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

The compelling biologic basis for combining hyperthermia with modern cancer therapies including radiation and chemotherapy was first appreciated nearly half a century ago. Hyperthermia complements radiation as conditions contributing to radio-resistance generally enhance sensitivity to heat and sensitizing effects occur through increased perfusion/tumor oxygenation and alteration of cellular death pathways. Chemosensitization with hyperthermia is dependent on the particular mechanism of effect for each agent with synergistic effects noted for several commonly used agents. Clinically, randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in treatment of a wide range of malignancies. Improvements in …

Thermal Dosimetry Characteristics Of Deep Regional Heating Of Non-Muscle Invasive Bladder Cancer., Titania Juang, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Yu Yuan, Shiva K Das, Mark W Dewhirst, Brant A Inman, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue.

MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used …

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

Alpcs(2a)-Mediated Photochemical Internalization Of Bleomycin And Concurrent Hyperthermia Of Multicellular Tumor Spheroids, Aaron Andersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Treatments for glioblastoma multiforme and invasive ductal carcinoma involve surgical resection and adjuvant or concurrent targeted therapies. The goal of the secondary treatment is to reduce the cancer cells in the resection margin and other areas of suspected involvement. Photochemical internalization is a targeted therapy using light to activate photosensitizers embedded in cellular structures to improve the delivery of macromolecules within the cell.

In a previous study, optimized treatment parameters including radiant exposure, and irradiance, concentration of AlPcS(2a), temperature, and the concentration of bleomycin were determined for human ACBT glioma multicell spheroids. The current study investigates the effectiveness of the …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations & Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …