RU2324509C2 - Shf emitter for heating human body tissues - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: emitter of superhigh frequency electromagnetic waves for hyperthermia includes the quarter-wave resonator based on non-symmetrical microstrip transmission line, which consists of dielectric base, screen conductor, emitting conductor and input coaxial plug. The input coaxial plug is installed outside the thermo emission zone of electromagnetic emission from the emitting conductor and radiation field of the source of γ-irradiation, and plugged to the emitting conductor and screen conductor of the microstrip transmission line via L-shaped filter, which includes the strip powering line in power point of the quarter-wave resonator and container.

EFFECT: efficiency of radiation effect on tumor is increased.

2 dwg, 1 tbl

Description

The invention relates to medical equipment, namely to hyperthermia of malignant neoplasms.

High mortality rates from malignant neoplasms and the associated significant socio-economic losses make it possible to justifiably consider the fight against malignant neoplasms as a global problem of paramount importance.

Despite the fact that in recent years, certain progress has been achieved in the detection of malignant tumors at an early stage of their development, and the therapeutic capabilities of modern antitumor effects are steadily improving, the results of treatment of cancer patients are still far from desired.

Methods of radical and palliative treatment of malignant tumors can be conditionally divided into 3 main groups:

1) antitumor effects of local-regional type - surgical treatment, radiation therapy, perfusion of antitumor drugs can also be attributed here;

2) antitumor effects of the general type - systemic chemotherapy, hormone therapy;

3) auxiliary or indirect antitumor effects - immunotherapy, metabolic and metabolic rehabilitation, the use of modifying (i.e., increasing the effectiveness of the main active agent) factors.

Until now, none of the methods of treating cancer patients, despite their continuous improvement, can satisfy the requirements of clinical practice. Each method has its own advantages and disadvantages. Therefore, complex treatment is increasingly being used to treat many malignant tumors, i.e. sequential or simultaneous application of several methods in the calculation of the synergistic effect of increasing the results of antitumor activity.

Of particular interest in this regard is the combination of radio and chemotherapy with a modifying factor - hyperthermia (heating the tumor to temperatures up to 44 ° C and above).

Hyperthermia, on the one hand, significantly increases the sensitivity of cancer cells to ionizing radiation and a number of anticancer drugs, and on the other hand, at temperatures above 43 ° C, the actual thermal irreversible damage to cancer cells occurs [1, 2, 3]. Due to the combination of these two factors among the various methods of increasing the effectiveness of radio and chemotherapy, developed to date and used in medicine, hyperthermia is one of the most promising modifiers, especially in the treatment of radioresistant tumors [1, 2, 3, 4].

The most effective and therefore, mainly used in clinical practice, method of heating tumor tissues is their irradiation with electromagnetic oscillations of the RF and microwave frequencies.

Electromagnetic (EM) vibrations are preferable, in comparison with other physical methods of creating elevated temperature in a certain volume of the body, due to the direct absorption of electromagnetic energy not only in surface but also in deeply located biological tissues. Therefore, an increase in temperature at the depth of tissues occurs not only due to heat transfer from the surface inward due to thermal conductivity, but also mainly due to the conversion of the energy of EM waves into heat directly at each point of the irradiated volume. This allows you to remove the problem of thermal overload (burns) of the skin by cooling it and at the same time ensure the creation of a hyperthermic regime in tumor tissues at a level of 42-44 ° C.

For the treatment of cancer with the method of hyperthermia, special hyperthermic units are used, including domestic ones - Yacht-3, Yacht-4, Yacht-5. All these installations differ from each other in operating frequency, generator output power and emitter design. In domestic installations, original emitters are used (US Pat. SU 1804793, 1993).

It was found that with a sequential combination of hyperthermia and radiation therapy, the effectiveness of the latter increases by an average of 1.5 times. This effect is confirmed in numerous international randomized trials conducted in Belarus, Russia, the USA, Germany, Italy, England, the Netherlands, France, etc. [4, 5, 6, 7].

The results are achieved using the currently existing techniques and methods for carrying out hyperthermia and radiation therapy, allowing only consistent application of radiation and heating procedures. At the same time, there is information obtained in the experiment that, while conducting them simultaneously, the effectiveness of radiation therapy increases by an additional 2.5–4 times [8].

The latest radiobiology data also confirms that with the simultaneous effects of radiation and heating (OVRN) in clinical practice, a significant increase in the effectiveness of radiotherapy can be obtained. This statement is based on the fact that with moderate hyperthermia (about 40 ° C), blood flow in the tumor accelerates, which, in turn, is accompanied by an increase in oxygen concentration in tumor cells [14] and, accordingly, an increase in the sensitivity of cancer cells to the damaging effects of ionizing radiation. This effect disappears when the heating ceases and the pO ₂ level returns to its original value [13]. Accordingly, the intensity of radiation damage to cells due to the oxygen effect is maximum when exposed to radiation and heat [2, 3, 13].

It is significant that, in combination with OVRN, a hyperthermia regimen of 42.5–44 ° C can be used, leading to thermal fatal damage to tumor cells and inhibition of repair of sublethal radiation injuries [2, 3]. In particular, this may be additional (after OVRN) hyperthermia, but already under the usual conditions (outside the source of ionizing radiation) and in a higher temperature regime - up to 44 ° С. Such a new combined regimen of thermoradiotherapy will allow to achieve the maximum antitumor effect and significantly reduce the time of the entire procedure.

In the clinic, the method of simultaneous exposure to radiation and heating has been tested in equipment only for the treatment of oncological diseases of the rectum and in gynecology with many hours of exposure to hyperthermia under conditions of brachytherapy - continuous contact low-intensity ionizing radiation [9, 10]. However, the features of this equipment, tested in the clinic, limit the scope of its application, allowing you to irradiate only vaginal and rectal malignant neoplasms.

Attempts are being made to disseminate this successful experience of using radiation under conditions of tumor hyperthermia in the most widely used remote radiotherapy, using high-intensity fluxes of ionizing radiation of tens of Gy [11, 12]. However, the duration of the hyperthermic stage of the simultaneous thermoradiation procedure in these works is 60-70 min, which is unacceptable for the clinic due to the high cost of the operating time of the radiation equipment. In addition, the hyperthermic equipment used in these experiments, including emitters, on the one hand, due to its extreme complexity, is unacceptable in wide clinical practice, and on the other hand, the equipment used significantly reduces (by more than 25%) the radiation intensity due to due to radiation losses introduced by emitters emitting EM energy and compensating devices [ibid]. In addition, the radiation losses introduced by these emitters are not uniform over the irradiated field. It is essential that the type of emitters used cannot fundamentally be improved in terms of introduced radiation losses and their uniformity.

The closest in technical essence and the achieved result to the claimed object relates to a microwave electromagnetic wave emitter for hyperthermia, which is a quarter-wave resonator based on an asymmetric microstrip transmission line, consisting of a dielectric substrate, a screen conductor, a radiating conductor and an input coaxial connector, the internal contact of which is connected to radiating conductor, and the outer contact to the screen conductor of the microstrip line (ed. St. No. 1246452). However, despite the positive results, the known device does not allow conducting electromagnetic hyperthermia of the tumor with this type of emitter and at the same time conducting remote γ-therapy of the tumor through it.

The objective of the present invention is to provide an emitter of microwave energy, allowing you to simultaneously affect the tumor with γ-rays and electromagnetic fields in various temperature, time and dose modes.

This goal can be achieved by using a microwave transmitter for hyperthermia for hyperthermia, including a quarter-wave resonator based on an asymmetric microstrip transmission line, consisting of a dielectric substrate, a screen conductor, a radiating conductor and an input coaxial connector, while the input coaxial connector is located outside heat-release zones of electromagnetic radiation of the radiating conductor and the radiation field of the γ-ray source Ia and connected to the radiating conductor and shield conductor of the microstrip line through a T-shaped filter comprising a strip line powering at powering quarter-wave resonator and capacity.

The emitter consists (see FIGS. 1 and 2) of a quarter-wave resonator based on an asymmetric microstrip transmission line, including a dielectric substrate - 1, a screen conductor - 2, equal to the size of the substrate, a radiating conductor - 3, connected to the screen conductor with a short circuit - 4; L-shaped filter, including a strip line of power supply 9 of the resonator at point 8, capacity 5; input coaxial connector - 6; conductor - 7, providing symmetry of the emitter, aligning spatial resistance. Moreover, the small thickness of the conductors of the emitter provides a small absorption of γ-radiation.

The microwave energy supplied to the emitter through connector 6 and the L-shaped filter, which serves to match the resistances of the input input transmission line with the input impedance of the quarter-wave resonator, excites vibrations in the substrate of the quarter-wave resonator formed by conductors 2, 3, and 4. In this case, the emitter can be presented in the form of a planar dipole above the conductive volume of the heated body. At the open end of conductor 3, an edge field of the standing resonator wave arises, which excites electromagnetic waves in equivalent transmission lines between 3 and biological tissue and between 7 and biological tissue (Fig. 2), propagating in the direction of the ends of conductors 3 and 7, after reflection from the edges of which standing waves are formed that form the required electromagnetic field profile in biological tissue.

The emitter is in contact with a heated area of biological tissue through a dielectric silicone bolus filled with running distilled water to cool the surface layers of tissues. The length of the radiating conductor 3 is equal to a quarter of the length of the electromagnetic wave in the dielectric substrate 1. The width of the radiating conductor 3 is determined by the required angle of the biological object. The dimensions of the screen conductor 2 and the dielectric substrate 1 are determined from the conditions of matching the emitter with a microwave energy source. The input coaxial connector 6 is located outside the zone of heat generation (electromagnetic radiation) and radiation field. The L-shaped filter is designed to match the resistances of the input input transmission line with the impedance at the power point (8) of the quarter-wave resonator and allows you to expand the frequency band and ensure matching of the antenna with different types of tissues having different values of dielectric constant.

Thus, the proposed emitter, introducing a small and uniform absorption of γ-radiation throughout the aperture, can improve the efficiency of treatment of patients with malignant neoplasms, using the method of simultaneous exposure to radiotherapy and heating in clinical practice.

The result of using the inventive device.

A technique was applied using the inventive emitter for simultaneous radiation exposure and electromagnetic local hyperthermia (HT) of 434 MHz of the tumor. For this, rats with Guerin's carcinoma were used (rat mass 150-175 g, tumor volume 0.8-1.0 cm ³ ). The duration of the CT is 45 minutes (43 ° C under the bed of the tumor), irradiation began at the time the tumor temperature reached the plateau - 43 ° C (in the vast majority of cases - 15 minutes after the start of heating). A single dose was applied - 5 Gy or 10 Gy, the absorbed dose - 1.23 Gy / min.

The effectiveness of thermoradiotherapy (TRT) was determined according to the following scheme: GT (43 ° C, 45 min) + radiation (5 Gy or 10 Gy, one fraction, 8 and 14 rats in subgroups, respectively). The following TRT regimen served as a control: irradiation (5 Gy and 10 Gy, one fraction, 5 and 7 rats in subgroups, respectively) and after 1.5 hours of hypertension (43 ° C, 45 min). The results are presented in the Table.

Table
The results of thermoradiotherapy of rats with Guerin's carcinoma Exposure (single) Inhibition of tumor growth (%) The number of rats with complete tumor regression (%) The number of cured rats (%) GT, 43 ° C, 45 min + simultaneous irradiation, 5 Gy 60 35 Observation Irradiation, 5 Gy, after 1.5 hours
GT, 43 ° C, 45 min fifty 25 Observation GT, 43 ° C, 45 min + simultaneous irradiation, 10 Gy 80 45 thirty Irradiation, 10 Gy, after 1.5 hours
GT, 43 ° C, 45 min 60 thirty twenty Conclusions: the results indicate a more pronounced antitumor effect of simultaneous irradiation and heating of the tumor.

Literature

1. Alexandrov N.N., Savchenko N.E., Fradkin S.Z., Zhavrid E.A., 1980, The use of hyperthermia and hyperglycemia in the treatment of malignant tumors, "Medicine", M.

2. Overgaard. Y., 1989, The current and potential role of HT in radiotherapy. Int. J. Rad. Oncol. Biology. Physics, V.16, 538-549.

3. Field, S.B., & Hand J.W., editors, 1990, An Introduction to the Practical Aspects of Clinical Hyperthermia, Taylor & Francis, London-New-York.

4. Vemon, C., J. Hand, S. Field et al., 1996, Radiotherapy with and without hyperthermia in the treat ment of superficial localized breast cancer: results from five randomized control trials, Int. J. Radiation Oncology, Biology, Physics, v. 35, No.4, 731-744.

5. Sherar M., F. F. Liu, M. Pintilie et al., 1997, Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial. Int. J. Radiation Oncology, Biology, Physics, v. 39, No.2, 371-380.

6. Proceeding of the Int. Congress on Hyperthermia Oncology, 1996, v. 1, 2. Tor Vergata University of Roma, Roma, Italy.

7. Mavrichev AS, 1996, Renal cell carcinoma, Bel. TsNMI, Minsk.

8. Horsmann MR, Overgaard J., 1995, The influence of nicotinamid and hyperthermia on the radiation responce of tumor and normal tissues. Book of Abstracts, 15 ^{th Annual Meeting of ESHO, Wadham College} , Oxford, UK. 3-6 September 1995, p. 12.

9. Vinogradov L.I. et al. RF patent RU 2029575 04/15/93 priority

10. Diederich C.J., Stauffer P.R., Khalil J.S. et al., 1996. Direct-coupled interstitial ultrasound applicators for simultaneous thermobrachytherapy: a feasibility Study, Int. J. Hyperthermia, v. 12, No.3, p. 401-410.

11. Moros E.G., W.L. Straube, E.E. Klein et al., 1995, Clinical system for simultaneous external superficial microwave hyperthermia and Co-60 radiation. Int. J. of Hyperthermia, v. 11, No.1, 11-12.

12. Straube W.L., E.G. Moros et al., 1996, A US (ultrasound) System for Simultaneous US Hyperthermia and Photon Beam Irradiation, Int. Joum. Radiation Oncology, Biology, Physics, v. 36, No.5, 1189-1200.

13. Horsmann, M. R., and Overgaard, J., 1997, Can mild hyperthermia improve tumor oxygenation? International Journal of Hyperthermia, 13, No.2, p. P. 141-148.

14. Vaupel P., 1994 Blood Flow, Oxigenation and Bioenergetic Status of Tumours, Ernst Schering Research Foundation, Berlin.

Claims (1)

A microwave radiator for hyperthermia, comprising a quarter-wave resonator based on an asymmetric microstrip transmission line, consisting of a dielectric substrate, a screen conductor, a radiating conductor and an input coaxial connector, characterized in that the input coaxial connector is located outside the heat emission zone of the electromagnetic radiation of the radiating conductor and the radiation field of the γ-radiation source and is connected to the radiating conductor and the screen conductor microstrip line through the L-shaped filter comprising a strip line powering point powering the quarter-wave resonator and capacity.

Images