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Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated photothermal ablation with checkpoint inhibitor immunotherapy. Our previous studies have demonstrated that SYMPHONY photoimmunotherapy not only treats the primary tumor but also dramatically amplifies anticancer immune responses in synergy with checkpoint blockade immunotherapy to treat remote and unresectable cancer metastasis. The SYMPHONY treatment also induces a ‘cancer vaccine’ effect leading to immunologic memory and prevents cancer recurrence in murine animal models. This manuscript provides an overview of our research activities on the SYMPHONY therapy with plasmonic GNS for cancer treatment.

Abstract Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44 °C, significantly enhance radiotherapy and chemotherapy effectiveness [1]. Driven by the developments in computational techniques and computing power, personalised hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimising treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical set-ups are now being performed to achieve patient-specific treatment optimisation. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from 'model' to 'clinic'. In addition, we illustrate the major techniques employed for validation and optimisation. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer.

This paper presents a complete thermal analysis of a novel conformal surface thermometer design with directional sensitivity for real-time temperature monitoring during hyperthermia treatments of large superficial cancer. The thermal monitoring sheet (TMS) discussed in this paper consists of a 2-D array of fiberoptic sensors embedded between two layers of flexible, low-loss, and thermally conductive printed circuit board (PCB) film. Heat transfer across all interfaces from the tissue surface through multiple layers of insulating dielectrics surrounding the small buried temperature sensor and into an adjacent temperature-regulated water coupling bolus was studied using 3-D thermal simulation software. Theoretical analyses were carried out to identify the most effective differential TMS probe configuration possible with commercially available flexible PCB materials and to compare their thermal responses with omnidirectional probes commonly used in clinical hyperthermia. A TMS sensor design that employs 0.0508-mm Kapton MTB and 0.2032-mm Kapton HN flexible polyimide films is proposed for tissue surface thermometry with low influence from the adjacent waterbolus. Comparison of the thermal simulations with clinical probes indicates the new differential TMS probe design to outperform in terms of both transient response and steady-state accuracy in selectively reading the tissue surface temperature, while decreasing the overall thermal barrier of the probe between the coupling waterbolus and tissue surface. Index Terms--Heat transfer, hyperthermia, noninvasive thermometry, surface thermal modeling, temperature distribution measurement, thermal monitoring sheet.

This paper concerns the optimization and performance analysis of an automatic control algorithm for managing power output of large multielement array hyperthermia applicators. Simulation and corresponding measurement of controller performance in a solid tissue equivalent phantom model is utilized for analysis of controller response to dynamically varying thermal load conditions that simulate clinical treatments. The analysis leads to an optimum controller which demonstrates the ability to achieve a uniform and stable temperature profile over a large surface area regardless of surrounding thermal load. This paper presents several advancements to the performance of a previously published control routine, including: 1) simplified simulation techniques for thorough characterization of controller performance; 2) an optimization procedure leading to an improved hybrid control algorithm for maintaining optimal performance during periods of both 'rising' and 'steady-state' temperature; 3) performance analysis of a control algorithm tailored for large area hyperthermia treatments with a multielement array applicator. The optimized hybrid controller is applied to the conformal microwave array (CMA) hyperthermia system previously developed for heating large area surface disease such as diffuse chestwall recurrence of breast carcinoma, and shown to produce stable, uniform temperatures under the multielement array applicator for all thermal load conditions. Index Terms--Control systems, hyperthermia, microwave antenna arrays, temperature control.

The behavior of arrays of coupled oscillators has been previously studied by computational solution of a set of nonlinear differential equations describing the time dependence of each oscillator in the presence of signals coupled from neighboring oscillators. The equations are sufficiently complicated in that intuitive understanding of the phenomena which arise is exceedingly difficult. We propose a simplified theory of such arrays in which the relative phases of the oscillator signals are represented by a continuous function defined over the array. This function satisfies a linear partial differential equation of diffusion type, which may be solved via the Laplace transform. This theory is used to study the dynamic behavior of a linear array of oscillators, which results when the end oscillators are detuned to achieve the phase distribution required for steering a beam radiated by such an array. Index Terms - Beam steering, coupled oscillators, injection locked, phased array.

Background: Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. Objective: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). Methods: Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. Results: The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120mg dose. Conclusions: Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs. [ABSTRACT FROM AUTHOR]