Project Funding Details

Purpose:

Background: Hyperthermia (HT), the application of elevated temperatures (41-45°,C) to tumor tissue, is a powerful radio and chemo sensitizer. Randomised trials have demonstrated a significant improvement in tumor control and patient survival for cervical and other cancer sites by combining radiotherapy and HT. The results of clinical trials were positive in spite of the fact that goal temperatures rarely achieved in the tumor due to the incidence of unwanted hot spots in normal tissue. Clinical results can improve further when these treatment limiting hot spots could be suppressed as treatment outcome is strongly correlated to the achieved tumor temperatures. The 3-D power control of the latest generation phased array antenna systems for locoregional HT is in principle capable of preventing hot spots. However, manual optimization of system settings is very difficult due to the large number of degrees of freedom of these systems, and pre treatment planning is presently not yet sufficiently reliable due to uncertainty in input data. Instead, treatment planning guided active hot spot suppression can potentially improve tumor temperatures.

The aim of this project is therefore to develop methods for active hot spot suppression that can be applied in a practical way to all locoregional HT patients.

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Plan of investigation:

Development and implementation of active hot spot suppression involves three steps: development of algorithms, pre-clinical tests and clinical tests.
i. , , , , , , , , , , , Development of algorithms: Step one is the development of algorithms capable of adapting phase and amplitude settings to suppress hot spots occurring at any possible location. To facilitate clinical use for the individual patient all potential hot spot locations are determined prior to treatment using a planning tool developed earlier at the AMC. Subsequently a set of phase and amplitude shifts is computed for suppression of each of these potential hot spots. ,Online application of this method is helpful for hot spots at locations not covered by the precomputed hot spots, this requires implementing fast graphics card computations.
ii. , , , , , , , , , , , Pre-clinical tests: Computer simulations will be used to test the performance of the developed algorithms under realistic clinical conditions, with emphasis on performance with limited temperature and E-field data, and uncertainty in tissue properties. In addition a series of tests will be performed in tissue equivalent phantoms using E-field and temperature probes at clinical locations. These pre-clinical tests will reveal the most reliable algorithm.
iii. , , , , , , , , , , , Clinical validation: The performance of the algorithm will be validated in 20 cervical cancer patients treated with hyperthermia using the 70 MHz AMC-8 regional HT system. Each patient will receive five HT sessions, and each HT session will start with standard experience based phase and amplitude settings. Hot spots are recorded subjectively by ,patient complaints. When a hot spot occurs these settings will be corrected using the phase and amplitude shifts computed by the algorithm for that location, without inducing new hot spots at other locations. The latter may require alternating different phase/amplitude settings to balance power deposition in different potential hot spot locations. Temperature, E-field and SAR measurements will be performed in the tumor and at other locations before and after correcting the settings. This correction procedure will be repeated whenever a hot spot occurs.
Two criteria will be used to evaluate the gain achieved by active hot spot suppression: (1) gain in tumor temperature, where a gain exceeding 0.5°,C will be considered clinically relevant, and (2) without increase in incidence of hot spot complaints.

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Possible results:

Good treatment control becomes possible for non-experienced staff. Active hot spot suppression will help to reduce the incidence of hot spots in normal tissue, and thus result in a higher thermal dose in the tumor, which is associated with a better local control and improved clinical outcome. A 0.5°,C gain in tumour temperature is equivalent to doubling the thermal dose and >,10% increase in Tumor Control Probability.

Relevance for other cancer research:

The active hot spot suppression algorithm developed during this project will be generally applicable for all forms of locoregional HT using phased array antenna systems.