Margarethus M Paulides

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights a b s t r a c t Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45 °C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio-and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or ther-moradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyper-thermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

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 setups 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.

Clinical studies have established a strong benefit from adjuvant mild hyperthermia (HT) to radio- and chemotherapy for many tumor sites, including the head and neck (H&N). The recently developed HYPERcollar allows the application of local radiofrequency HT to tumors in the entire H&N. Treatment quality is optimized using electromagnetic and thermal
simulators and, whenever placement risk is tolerable, assessed using invasively placed thermometers. To replace the current invasive procedure, we are investigating whether magnetic resonance (MR) thermometry can be exploited for continuous and 3D thermal dose assessment. In this work, we used our
simulation tools to design an MR compatible laboratory prototype applicator. By simulations and measurements, we showed that the redesigned patch antennas are well matched to 50  (S11<−10 dB). Simulations also show that, using 300 W input power, a maximum specific absorption rate (SAR) of 100 W kg−1 and a temperature increase of 4.5 ◦C in 6 min is feasible at the center of a cylindrical fat/muscle phantom. Temperature measurements using the MR scanner confirmed the focused heating capabilities and MR compatibility of the setup.We conclude that the laboratory applicator provides
the possibility for experimental assessment of the feasibility of hybrid MR-HT in the H&N region. This versatile design allows rigorous analysis of MR thermometry accuracy in increasingly complex phantoms that mimic patients’ anatomies and thermodynamic characteristics.

To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR₁₀g) in the brains of 16 select...

ABSTRACT Investigations have been carried out to determine the limitations of currently used technology in the field of hyperthermia cancer treatment. A novel hyperthermia treatment planning tool and a new head&amp;amp;neck applicator have been developed. The treatment planning tool is optimized for high quality, accurate, realistic simulations of highly detailed models. The applicator offers superior steerability and online control.

Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyperthermia treatment planning. Hyperthermia treatment planning is based on tissue segmentation for 3D patient model generation. We present here an automatic atlas-based segmentation algorithm for the organs at risk from CT images of the head and neck. To overcome the large anatomical variability, atlas registration and intensity-based classification were combined. A cost function composed of an intensity energy term, a spatial prior energy term based on the atlas registration and a regularization term is globally minimized using graph cut. The method was evaluated by measuring Dice similarity coefficient, mean and Hausdorff surface distances with respect to manual delineation. Overall a high correspondence was found with Dice similarity coefficient higher than 0.86 and a mean distance lower than the voxel resolution.

Purpose: Definition of all features and the potential of the novel HYPERcollar applicator system for hyperthermia treatments in the head and neck (H&N) region. Methods and Materials: The HYPERcollar applicator consists of 1) an antenna ring, 2) a waterbolus system and 3) a positioning system. The specific absorption rate (SAR) profile of this applicator is investigated by performing infra-red

The objective of this theoretical study is to design an ultrasound (US) cylindrical phased array that can be used for hyperthermia (40-44 degrees C) treatment of tumours in the intact breast. Simultaneously, we characterize the influence of acoustic and thermal heterogeneities on the specific absorption rate (SAR) and temperature patterns to determine the necessity of using heterogeneous models for a US applicator design and treatment planning. Cylindrical configurations of monopole transducers are studied on their ability to generate interference patterns that can be steered electronically to the location of the target region. Hereto, design parameters such as frequency, number of transducers per ring, ring distance and number of rings are optimized to obtain a small primary focus, while suppressing secondary foci. The models account for local heterogeneities in both acoustic (wave velocity and absorption) and thermal (blood perfusion rate, heat capacity and conductivity) tissue properties. We used breast models with a central tumour (30x20x38 mm3) and an artificial thorax tumour (sphere with a radius of 25 mm) to test the design. Simulations predict that a US cylindrical phased array, consisting of six rings with 32 transducers per ring, a radius of 75 mm and 66 mm distance between the first and sixth transducer ring, operating at a frequency of 100 kHz, can be used to obtain 44 degrees C in the centre of tumours located anywhere in the intact breast. The dimensions of the volumes enclosed by the 41 degrees C iso-temperature are 19x19x21 mm3 and 21x21x32 mm3 for the central and the thorax tumours, respectively. It is demonstrated that acoustic and thermal heterogeneities do not disturb the SAR and temperature patterns.

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment deliv...