Microwave hyperthermia for cancer treatment

Start date 01/02/2005
This is a project on the development of systems for hyperthermia treatment of deep-seated cancerous tumors, based on the microwave technique. The Chalmers research team concentrates especially on tumors in the neck area, and brain tumors in children.
 
Hyperthermia means repeated heating of the tumor to just over 40°C. This treatment is toxic for the tumor itself, whilst also making the tumor more sensitive to traditional chemo and radiation therapies. This in turn leads to the possibility of reducing treatment side effects by reducing radiation doses and cytostatic drugs with unchanged treatment results. Clinical studies have also shown doubled cure rates when combining hyperthermia with traditional cancer treatment.
 
The microwave technique also enables heat treatment of tumors which are deep-seated and/or relatively hard to access in the body. The microwaves are transmitted from a number of antennas enclosing the relevant body part. The heat effect is developed in the tumor by the transmission of microwaves which are adjusted in time, frequency and strength in order to work together to form a focus in the desired location. This places high demands on the precision of the system, in order for the heating to be concentrated on just the tumor, without heating surrounding healthy tissue.
 
It presents a great challenge to calculate exactly how each antenna should transmit signals to reach the desired focus on the right spot. The research group is therefore developing algorithms based on the so called “time reversal” technique. The heavy mathematical computations must for instance take into account the shape of the body tissue and the electric material qualities of the relevant body part. This requires a computer model which is completely unique for each patient and each time of treatment. The research group is investigating the possibility of using microwave tomography to develop this model (see the research project Patient specific modeling). 


 

Background
Cancer is a leading cause of death in the western countries, preceded only by cardiovascular diseases.  An improved treatment of cancer would lead to an improved life expectancy of the population.  However, the degree of success and progress in cancer treatment does not correspond to the large resources invested. It is increasingly clear that in order to improve the cancer cure-rates, the conventional oncological methods need to be combined with new treatment modalities.

Why hyperthermia can make a difference

Above all, today's cancer care often fails in the treatment of locally advanced cancer diseases (tumors of 3 cm or larger) and/or cancer recurrences. Regions that have already been treated with radiation are particularly difficult to cure since the radiation dose, which can additionally be given to the normal tissue in the treated region, is strictly limited. Moreover, oxygen supply, which is an important accessory for the effect of radiation, is insufficient in pre-irradiated tissues impaired, additionally limiting the effect of the radiation curable effect.
 
Adding heat to irradiation and/or chemotherapy has shown a highly beneficial effect in treatment of above mentioned cancer types. Significant improvements were achieved on metastatic lymph nodes of head and neck tumors, chest wall recurrences, malignant melanoma, cervical cancer, rectal and bladder cancer. Moreover, treatment outcomes for previously irradiated patients treated with hyperthermia were remarkably better.

Hyperthermia in cancer treatment

Hyperthermia is a type of cancer treatment, in which the tumor is exposed to elevated temperatures for a sufficiently long period of time. Hyperthermia sensitizes cells (tumor cells more than normal tissue cells) to radiation as well as to chemotherapy, without any additional long-term side effect. The cytotoxic effect of hyperthermia increases significantly with higher therapeutic temperatures.
 
The objective of hyperthermia treatment is to raise the temperature in the tumors to 40 - 44°C for one hour to achieve cell death or render the cells more sensitive to ionizing radiation or chemotherapy. To achieve the prescribed elevated temperatures of the protocols, three heating techniques are traditionally used: electromagnetic heating (EM), thermal conduction and ultrasound. EM heating is, due to its versatility, the most developed technique as well as the most frequently used. Presently, it is clinically available for treatment of most tumor sites. The major problem with this technique is, due to the large wavelengths and high absorption rates in tissues, the limited energy focus on small, deep-seated tumors.
 
The most widely used method for treatment of deep-seated tumors is the annular phased array. It is based on an array of radiators placed circumferentially around a patient, relying on a constructive wave interference to selectively heat the tumor. The wave interference can be driven inside the hyperthermia applicator by changing the amplitude and phase at the feed-points of the antennas. These can be obtained by optimization techniques during the treatment planning phase.
More information

​The Head and Neck challenge

There are two closely related objectives of this project; the technical development and the clinical application. The main aim of the clinical part is to establish hyperthermia treatment in Gothenburg.  The objective of the technical part is to develop a new applicator for treatment of Head and Neck (H&N) tumors. The methods and approaches are however viable for other tumor sites.
 
There is a clinical need for system enabling treatments of deep-seated tumors in H&N region. Tumors in the head and neck region are often discovered late because of the accompanying behavior of the typical patients (smoking and over-consumption of alcohol).
 
Locally advanced tumors are often inoperable and will be treated by a high dose radio-chemotherapy.  This is especially true for big size tumors, which show a high amount of necrotic parts or parts, which are not adequately perfused and lead to unpleasant outcomes or recurrences after radio-chemotherapy. In these patients, the addition of hyperthermia can significantly improve the treatment outcome. Heating of the head and neck is however challenging, since it contains complicated structures with areas requiring heat protection. 

The Children Brain Tumor challenge

Information to follow.

The Chalmers approach; Microwave hyperthermia for deep-seated tumors

The main challenge of current hyperthermia treatment is to adequately heat whole volumes of deep-seated tumors without overheating surrounding healthy tissues. The clinically achievable temperatures are 40-41°C compared to the goal temperature of 43°C. To resolve this problem, the Chalmers research group has developed an applicator capable of modifying the focus size according to the tumor position and volume.
 
The motivation for the foci-spot size adjustments lies in restraining hot spots near the tumor, which are difficult to suppress and limits reaching of higher tumor temperatures. Adaptation of heating pattern can be realized by varying the operating frequency of the antennas and potentially by using UWB pulse sequences instead of pure harmonic signals used in the present heating equipment.
 
The ambition of this project is to employ a large number of independent antennas, placed in multiple rings around the patient, which allows working with high frequencies and consequently shrinking the foci spot in the target area. Using low frequencies, on the other hand, is advantageous for heating of large or deep-seated tumors.
 
 A new generation of hyperthermia systems should therefore provide the possibility of a wide range of frequency variations. Moreover, combined design of traditional single frequency system with a UWB pulse regime has a potential to further improve the energy distribution in the treated area and thus open up new possibilities in DHT treatment.

Computations using Time Reversal (TR)

Chalmers researchers have developed a novel focusing technique for treatment planning based on time reversal (TR). The main idea of the time reversal method is that an event can be reversed in time and played back. The experiments typically consist of two steps. First, a wave field is generated and measured at different fixed positions as a function of time and stored. Next, the measurements at each position are reversed in time, which results in the time reversed signals.
 
In the second step, the measurement positions are used as sources where the time reversed signals are applied simultaneously. The resulting waves propagate back through the medium and interfere constructively at the position of the original source.

Time Reversal in action

The advantage of using this method comes from the fact that it can be easily used for treatment planning with both sinusoidal and UWB pulse regimes. Moreover, the speed of the method is independent on the number of antennas, which makes the whole approach attractive for clinical use. In order to validate the feasibility of the proposed approach, Chalmers has developed a laboratory prototype consisting of an antenna applicator and a wide band multi-channel system to steer it. The achieved experimental results have shown great promise and encourage the development of a clinical prototype of the TR hyperthermia system.
Future/challenges

​The clinical system is under development and several issues remain to be solved before moving to the clinics.  The antenna elements need to be re-designed for full UWB operation and the system has to be tested on an anthropomorphic phantom.  There is also a need for a positioning device and an optimal water bolus for coupling and surface cooling. The water bolus is an important part of the antenna applicator as it affects the heating pattern. This effect is however difficult to predict since the shape of the water bolus varies substantially from treatment to treatment. 

Another challenging task is controllable and reproducible positioning of the patient. Incorrect patient positioning inside the applicator can diminish the advantage of using the treatment planning tool and cause patient burns.  Last but not least, the antenna applicator must be comfortable for the patient. A comfortable system will help patients to better accept hyperthermia treatment lasting more than one hour.

Parallel to that, the treatment planning for the TR method will be further improved and the integration with microwave tomography used for a low cost 3D noninvasive temperature control and quality assurance during the treatment. This will allow for safer and more effective application of the hyperthermia treatment. In the future, the 3D temperature information from MW tomography will be used to automatically adjust the heating pattern during treatment. 

​Chase Hyperthermia project 2012-01-01 – 2014-12-31

Barncancerfonden 2012-01-01

KG Eliasson supplementary fund

Published: Mon 28 Oct 2013.