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. Particularly, the treatment of locally advanced cancer diseases, without any detectable metastasis, can be improved by addition of hyperthermia to radiation or chemotherapy (or both).
UNDERLYING PROBLEM
This is incredibly important for treatment of cancer recurrences, which have already been treated with radiation before. The radiation dose, which can additionally be given to the normal tissue in the treated region, is often strictly limited. Moreover, supply with oxygen in pre irradiated tissues is impaired due to the sparse number of small vessels, in pre irradiated tissues, while oxygen is an important accessory for the effect of radiation. Therefore, it is highly recommended to enhance the effect of radiation dose by other treatment modalities. Unfortunately, addition of chemotherapy is due to insufficient perfusion in the pre-irradiated tissues, not enough in this case.
Hyperthermia can sensitize 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 markedly with higher therapeutically temperatures. A number of clinical trials have shown a highly beneficial effect of adding heat to irradiation and/or chemotherapy. 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, the treatment outcomes for previously irradiated patients were remarkable.
The main research focus of this project is on treatment of head and neck tumors, although the method is viable for other tumor sites. There is a clinical need for system enabling treatments of deep seated tumors in this region. Hyperthermia in this area is achieved most often by superficial techniques not optimal for deep-seated tumors. Tumors in the head and neck region are often lately discovered because of the accompanying behavior of the typical patients (smoking and over-consumption of alcohol). Locally advanced tumors are often no more operable and will be treated by a high dose radio-chemotherapy. In particular big tumor sizes show a high amount of necrotic parts or parts, which are not adequate perfused and lead to unpleasant outcome or recurrences after radio-chemotherapy. In these patients, the addition of hyperthermia can significantly improve the treatment outcome.
CLINICAL BENEFITS WITH CONCEPT
Deep HT systems development has shown a clear progress from one ring antenna applicators with limited control of radiation pattern, through multiple-ring multiple-element systems based on patient-specific modeling, to site-specific applicators. With our approach we continue this trend by developing a flexible applicator, but one that is tumor-volume-specific rather than site-specific. In other words, an applicator that is capable of modifying the focus size depending of the tumor position and volume. The motivation for the foci-spot size adjustments lies in restraining hot spots near the tumor. These are difficult to suppress, because at the same time a high tumor temperature should be maintained. Adaptation of a heating pattern can now be realized by varying the operating frequency of the antennas and potentially by use of 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, which allow us to work with high frequencies, and consequently, to shrink 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 system should therefore provide the possibility of a wide range of frequency variations. Moreover, a 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 treatment of deep seated tumors.
The advantage of using our TR-focusing technique 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 of the number of antennas, which makes the whole approach attractive for clinical use. In order to validate the feasibility of the proposed approach, we have developed a laboratory prototype consisting of an antenna applicator with a wide band multi-channel system to steer it.
MEDICAL DEVICE CONCEPT
The objective of hyperthermia treatment is to raise the temperature in the tumors to 40 - 44°C for a sufficient period of time 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 as well as 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 focusing of energy to 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.
Application of local hyperthermia, used for treatment of superficial tumors, is more straightforward (simple).
PROJECT DESCRIPTION AND OBJECTIVES
There are two, closely related, objectives of the project, the technical development and the clinical application. The main aim of the clinical part is to establish hyperthermia treatment in Gothenburg. We will start with treatment of locally advanced superficial tumors and recurrences (for example chest wall recurrences of breast cancer, malignant melanomas). Since a development of superficial applicator is not a direct part of the Chalmers hyperthermia project, we will use Duke's applicator of 3th generation called Jacket applicator. The goal of this part is to establish collaboration with the Oncology department at SU and gain experience from this, quite straightforward hyperthermia application.
The objective of the technical part is to develop a new applicator for treatment of Head and Neck (H&N) tumors. The reason for choosing the H&N region is twofold. Firstly, this region is smaller in comparison with, for example, the pelvic area but still contains complicated structures with areas requiring protection from heat. Secondly, there is a clinical need for such applicators since there is only one, recently introduced, clinical system intended for the treatment of deep tumors in H&N, which can be used without a general anesthesia. Most often hyperthermia treatment in this area is achieved by superficial techniques, which are not optimal for deep-seated tumors. In very few cases, interstitial hyperthermia is used for deep seated tumors, but this requires an operation as well as an general anaesthesia.
Project leader: Dr. Hana Dobšíček Trefná, Chalmers, Dep. of Signals & Systems
Co-researchers:
Johanna Gellermann, Chalmers
Dep. of Oncology, Sahgrenska University hospital
