Z. Rijnen

The clinical feasibility of deep hyperthermia treatment in the head and neck: new challenges for positioning and temperature measurement.

To apply high-quality hyperthermia treatment to tumours at deep locations in the head and neck (H&N), we have designed and built a site-specific phased-array applicator. Earlier, we demonstrated its features in parameter studies, validated those by phantom measurements and clinically introduced the system. In this paper we will critically review our first clinical experiences and demonstrate the pivotal role of hyperthermia treatment planning (HTP). Three representative patient cases (thyroid, oropharynx and nasal cavity) are selected and discussed. Treatment planning, the treatment, interstitially measured temperatures and their interrelation are analysed from a physics point of view. Treatments lasting 1 h were feasible and well tolerated and no acute treatment-related toxicity has been observed. Maximum temperatures measured are in the range of those obtained during deep hyperthermia treatments in the pelvic region but mean temperatures are still to be improved. Further, we found that simulated power absorption correlated well with measured temperatures illustrating the validity of our treatment approach of using energy profile optimizations to arrive at higher temperatures. This is the first data proving that focussed heating of tumours in the H&N is feasible. Further, HTP proved a valuable tool in treatment optimization. Items to improve are (1) the transfer of HTP settings into the clinic and (2) the registration of the thermal dose, i.e. dosimetry.

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck.

Abstract Background and purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment. Materials and methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SARtarget) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients’ CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SARtarget. Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar. These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SARtarget from 96 to 178 W/kg (case 1); or show that the first SAR distribution was already optimum (case 2). Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.

Accurate 3D temperature dosimetry during hyperthermia therapy by combining invasive measurements and patient-specific simulations

Abstract Purpose: Dosimetry during deep local hyperthermia treatments in the head and neck currently relies on a limited number of invasively placed temperature sensors. The purpose of this study was to assess the feasibility of 3D dosimetry based on patient-specific temperature simulations and sensory feedback. Materials and methods: The study includes 10 patients with invasive thermometry applied in at least two treatments. Based on their invasive thermometry, we optimised patient-group thermal conductivity and perfusion values for muscle, fat and tumour using a ‘leave-one-out’ approach. Next, we compared the accuracy of the predicted temperature (ΔT) and the hyperthermia treatment quality (ΔT50) of the optimisations based on the patient-group properties to those based on patient-specific properties, which were optimised using previous treatment measurements. As a robustness check, and to enable comparisons with previous studies, we optimised the parameters not only for an applicator efficiency factor of 40%, but also for 100% efficiency. Results: The accuracy of the predicted temperature (ΔT) improved significantly using patient-specific tissue properties, i.e. 1.0 °C (inter-quartile range (IQR) 0.8 °C) compared to 1.3 °C (IQR 0.7 °C) for patient-group averaged tissue properties for 100% applicator efficiency. A similar accuracy was found for optimisations using an applicator efficiency factor of 40%, indicating the robustness of the optimisation method. Moreover, in eight patients with repeated measurements in the target region, ΔT50 significantly improved, i.e. ΔT50 reduced from 0.9 °C (IQR 0.8 °C) to 0.4 °C (IQR 0.5 °C) using an applicator efficiency factor of 40%. Conclusion: This study shows that patient-specific temperature simulations combined with tissue property reconstruction from sensory data provides accurate minimally invasive 3D dosimetry during hyperthermia treatments: T50 in sessions without invasive measurements can be predicted with a median accuracy of 0.4 °C.

Quality and comfort in head and neck hyperthermia: A redesign according to clinical experience and simulation studies.

Abstract Purpose: Clinical phase III trials have shown the benefit of adding hyperthermia to radiotherapy and chemotherapy for head and neck cancer (H&N). The HYPERcollar, a functional prototype capable of applying hyperthermia to the entire H&N region was developed. Specific absorption rate-based hyperthermia treatment planning (HTP) is used to optimise HYPERcollar treatments. Hence, besides treatment quality, reproduction and reproducibility of the HTP are also pivotal. In the current work we analysed the impact of key parameters on treatment quality and completely redesigned the mechanical layout of the HYPERcollar for improved treatment quality and patient comfort. Material and methods: The requirements regarding patient position and the water bolus shape were quantified by simulation studies. The complete mechanical redesign was based on these requirements and non-modellable improvements were experimentally validated. Results: From simulation studies we imposed the required positioning accuracy to be within ±5 mm. Simulation studies also showed that the water bolus shape has an important impact on treatment quality. Solutions to meet the requirements were 1) a redesign of the applicator, 2) a redesign of the water bolus, and 3) a renewed positioning strategy. Experiments were used to demonstrate whether the solutions meet the requirements. Conclusions: The HYPERcollar redesign improves water bolus shape, stability and skin contact. The renewed positioning strategy allows for positioning of the patient within the required precision of ±5 mm. By clinically introducing the new design, we aim at improving not only treatment quality and reproducibility, but also patient comfort and operator handling, which are all important for a better hyperthermia treatment quality.

Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

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 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR₁₀g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma – a feasibility study

Abstract Purpose: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patients comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC. Methods and materials: 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39–43 °C in the target area, up to patients’ tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed. Results: Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007 W (median 543 W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3 months were 46% (complete) and 7% (partial). Conclusion: Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.

OC-0335: Feasibility of deep head and neck hyperthermia

necrosis – 74,5% in 6 months observation time for each: HDRBT and PDR-BT method in h/n. Serious late side-effects were seen in two patients (9%) l/t and PDR-BT group. Conclusions: 1. HDR and PDR both had similar percentages of side effects. 2. Early complications due to the total radiation dose are frequent and needs to be treated by intensive pharmacology. 3. HDR or PDR are effective tools in tumor recurrence radiation treatment, when surgical procedure is impossible and using another EBRT schedule very dangerous for the patient. 4. Future studies should aim to determine the maximum tolerated dose and appropriate patient selection.

PD-0524: Visualization tool for Electromagnetic Dosimetry and Optimization (VEDO) during deep hyperthermia

Results: The maximum doses (in EQD2) for different critical organs in the H&N case are presented in Table 1, along with doses calculated without deformable registration or compensation for biological dose effects. For medulla, deformable EQD2 values are approximately 10% less than for the rigid raw sum; for other organs the difference varies from 0 to 8%. Conclusions: Considerations of dose to organs at risk may be a limiting factor for treatment planning of secondary malignancies at the same site. This work has shown a complete framework to examine re-treatment planning accounting for different patient positions, dose sizes and fractionation schemes of new and previous treatments. This accurate summed EQD2 distribution is helpful in seeing which dose tolerances are reached, and where the treatment plan could be modified further.

PO-0647: Target-selective radio-sensitization in head and neck tumors by the novel HYPERcollar3D hyperthermia applicator

Purpose/Objective: Current treatment of advanced cancer of the head and neck is unsatisfactory in terms of outcome and the toxicity of current treatments are severe. Phase III clinical trials have shown that hyperthermia (heating in the range of 40-44°C for one hour) is a potent sensitizing agent of radiotherapy, which is achieved without additional toxicity [1-3]. To enable heat-sensitization also in target regions at deep locations, we developed the HYPERcollar and showed in 45 patients that inducing hyperthermia in tumors located deeply and laterally in the head and neck region is feasible and has potential. Over the years, we further introduced an adaptive hyperthermia strategy based on electromagnetic field simulations. In this study, we analyze the HYPERcollar3D that is a redesigned version of the HYPERcollar aimed at improving heating quality, heating reproducibility and patient comfort. Materials and Methods: In the HYPERcollar3D, patient comfort and treatment accuracy/stability are improved by splitting the waterbolus functions into a stable outer part and a patient conformal inner part. Patient positioning according to the CT resembles that of radiotherapy and is obtained by immobilization and a laser alignment procedure. Based on a mechanical redesign, we performed parameter studies using electromagnetic simulator SEMCAD-X (v. 14.8.6) to investigate further improvement by increasing the number of antennas and their locations.