CA1072186A - Diathermy apparatus - Google Patents

Abstract

A METHOD FOR TREATING BENIGN AND
MALIGNANT TUMORS UTILIZING RADIO
FREQUENCY, ELECTROMAGNETIC RADIATION

Abstract of the Disclosure A method of treating tumors, both benign and malignant, such as carcinoma, sarcoma, cysts and avascular lesions, in animals, such as humans, by radio frequency heating at the location of the tumor in the host with intensity and duration sufficient to cause necrosis of the tumor tissue but insufficient to damage the surrounding normal tissue substantially.

Description

`- I ~ 107Z186 1 ¦ S P E C I F I C ~ T I O N

2 I
S I
¦ This invention relates to the treatment of tumors 5 ¦in animal hosts, such as human beings, and in particular 6 ¦provides a technique for destroying the tumor without injury 7 ¦to adjacent normal tissue. The tumors can be either benign ¦or malignant and include carcinomas, sarcomas, cysts and 9 ¦avascular lesions.
10 ¦ It has been noted that tumors can be affected by 11 ¦hyperthermia ~Brit. of Cancer 25:771, 1971; Cancer Research 12¦ 32:1916, 1972). This observation was coupled with the 13 ¦statement that the tumors were heat sensitive. Experiments 14 ¦with external surface heating do not produce deep heating 15 land in some cases, using hyperthermia, the whole animal was 16 Iheated as much as the tumor. Others have felt that a slight 17 ¦raise in temperatures produced by metabolic changes in the 18 ¦cancer interfered with cell growth (Europ. J`. Cancer '9 ¦9:103, 1973). Others have heated tumors for a few degrees 20 ¦by diathermy to observe the effect on the tumor which was 21 ¦inhibitory but not obstructive (Zelt. fur Naturforschung 22 8,~-26:359, 1971). ;
23 Anatomical studies suggest that the blood flow 24 through carcinomas and other neoplasms is sluggish (Acta athalogica Microbiologica Scand, 22:625, 1945; Advances in 26 Biology of the Skin 21:123, 1961). Tumors possess an 27 angiogenetic factor which initiates the formation of new blood 28 vessels. These bood vessels, however, are capillaries which 29 ecause of their sm~ll diameter offer great resistance to ~lood flow. e c~pi1laries make Conne~tioD6 ~i h tDe normal ,' , . .. .
: ..... . , ' . ` ` ` ` ` ' ` ` ` . :, ~ . . `" ' :

1¦ capillaries on the periphery of the tumor and are tortuous ¦~ollowing haphazard pathways before emptying into some small

3 Ivein at the periphery of the tumor. Frequently there is

4 ¦marked venous obstruction within the tumor caused by com-¦pression of the peripheral veins due to enlargement of the 6 ¦tumor and sometimes due to ingrowth of tumor cells into the Iblood vessels obstructing them.
8 ¦ Anatomical studies also demonstrate the presence 9 ¦of arterio-venous fistulae at the periphery of tumors which 10 ¦can cause the tumors to appear vascular on angiography 11 ¦because of the rapid appearance of contrast media, but which 12 actually deprive the tumor of-the blood supply. The arterio-3 ¦venous fistulae at the periphery of the tumor tend to create 14 la low resistance pathway at the surface of the tumor which ¦lowers the arterial pressure and diverts blood from entering 16 ¦the tumor.
17 ¦ Aithough anatomical studies suggest that the tumor18 ¦blood flow is diminished and slow, only angiographic studies 19 ¦have functi~nally confirmed that blood flow, through tumors 20 ¦is actually sluggish giving rise to an appe,arance of non-21 ¦filling on angiography. Residual constrast medium remains 22 ¦in the tumor after it has been swept out of- the~adjacent=~ -23 ¦normal tissùe by normal blood flow. This remaining residual 24 contrast medium has been called a "Tumor Stain". The tumors 25 which have ~een studied radiographically have been brain 26 tumors and kidney tumors.
27 This has been confirmed by the applicant by the 28 indicator dilution technique measuring the actual flow of 29 blood through normal tissue and through tumors. The 30 indicator dilution technique is more reliable,than the visual , l ¦method as seen on angiography. Such studies were done 2 ¦in vivo usinq X-ray contrast medium dilution and in vitro ¦on excised specimens. In the excised specimens blood flow was measured by indicator dilution technique using radio-

5 iodinated serum albumin. The albumin molecule was tagged

6 with I and the isotope dilution was measured in the tumor

7 and in normal tissue by a columnated scintillation counter.
These studies indicated that the magnitude of flow through -9 the adjacent normal tissue is-such that the tumor tissue is 10 differentially heated when the area of the body containing ~1 th~ tumor is trea~e~ ~y ~iatherny~
12 Thus, in accordance with this invention, tumors are¦
dest~ye~ hum~ns ~nd otl~er animal~ ~y ~.eati~g ~if~eren-~4 tially, such that the temperature of the tumor is raised to ~5 a point at ~hich the tumor is necrosed, i.e., at or above -16 about 50C. In some instances necrosis of the tumor is ~7 achieved at temperatures as low as 46C. Such temperatures, 18 of course, also destroy or severely damage normal tissue and 19 the present invention is based on the discovery that when a 20 portion of the body is heated by applied radio frequency, 21 electromagnetic radiation the tumor is heated differentially 22 to`~a greater extent, such that the temperature-of the normal--- .
23 tissue adjacent the tumor can be kept below 40C.
24 This is caused primarily by the normal blood flow 25 in the adjacent normal non-cancerous tissue. Thus the 26 temperature at which tissue is heated by induction or direct 27 passage of alternating current depends upon the blood supply 28 to the tissue. Although the blood itself is heated, it 29 serves to carry heat away from the part being heated. As a 30 result, tissues which are poorly perfused with blood become ., - _4_ -' ' : ' 1 heated more rapidly and to a higher temperature than tissues

8 which have a normal rate of blood flow. As polnted out 3 above, cancerous and other mal ignant and benign growths develop outside a preformed blood vessel distribution network and derive their blood supply from the periphery of the tumor 6 where it meets the adjacent normal blood supply. As a con-7 sequence, the slow rate and volume of blood flow through the tumor provides a lesser cooling rate in the tumor than the flow of blood through the normal tissue adjacent the tumor.
lQ Thus, when diathermy is applied to tissue contain-11 ing a tumor, the tumor is heated more than the adjacent i2 normal tissue. If the applied radiation is of sufficient 15 intensity and for a sufficient duration of time the differ-14 ential heating of the tumor can necrose the tumor without 15 significant thermal injury to the adjacent normal tissue.
16 In accordance with this invention diathermy is used 17 to produce differential heating in the body by using 18 insulated conductive metal plates, i.e., applicators, which

9 are connected to the output of an R.F. generator ana wnlch 20 are placed in intimate contact with the body adjacent the 21 llocation of the tumor such that the applicators are located 221 on opposite sides of the tumor to produce localized heating 23 in the tumor differentially higher than the remaining normal 24 ¦tissue, adjacent to the tumor, which is in the path of the 26 IR.F. radiation, i.e., generally between the applicators.
26jiHeatillg the tissue between the applicators is continued for a 27 duration of time and at an intensity sufficient to cause 28 necrosis of the tumor by heating the tumor to about 50C or 29 above. In some cases tumor necrosis can be caused be heating 30 to temperatures as low as 46C. In any event heating is 1 ¦insufficient to raise the temperature of the surrounding 2 ¦normal e4~o to cause slgni~lcant damage to that tissue.
5 ¦ This effect of,destroying tumors by differential ¦heating has been confirmed in both human cancers and cancers 5 ¦in animals by simultaneous measurement of the temperature in I the tumor and ip the adjacent normal tissue. Differential 7 ¦thermometry between the tumor and normal tissue is performed 8 ¦ with non-metallic thermometers having non-electrolyte fluids, 9l such as liquid alcohol filled thermometers. Normal tissue ~0~ is irreversibly damaged at temperatures above 50C. (Chic.
11¦ Med. Sch. Q 17:49, 1956). Temperatures as high as 60C can ; 121 easily be achieved in the tumor while the adjacent normal ~31 tissue is heated only to the vicinlty of 40C using about 14¦ 500 watts of energy at 13.56 MHz.
15¦ Genera~ly, the radio frequencies employed should be 16¦ as low as permissable in order to enhance the absorption of 171 the energy by the tissue. Consequently, the lower frequen-18 ¦ cies permitted by the F.C.C. are preferable. The results of 19¦ this invention generally are achieved with energies ranging 20¦ between 200 and 500 watts and for periods of times typically 21¦ of 10 to 20 minutes, although lower and higher power levels -. l ~, .
22 ¦and longer and shorter periods of time can be used depending 23 ¦on the size and location of the tumor. The conventional 24 ¦diathermy machine cannot provide the necessary heat and has 25 ¦the disadvantage that the distribution of heat in the tissues 26 ¦is apt to be non-uniform and cannot àlways be predicted.
27 ¦A1SO a considerable amount of the energy on the standard 28 ¦diathermy machine is often reflected back into the diathermy ¦machine without entering the tissue. Thus it is difficult to 30 ¦determine the dosage. Utilizing the energies required in . . 107Z186 l ¦a~cordance with this invention, the conventional machine a 1itself ~d ~1~e cabies become very overheated.
3 ¦ In accordance with this invention it has been found 4 ¦that a device known as the Marzoli applicator can be utilized 5 ¦to supply the necessary energy input and distribution.
6 1 The ~larzoli applicator basically is in the form of 7 la pair of spiral discs, i.e., applicators, which are placed 8 ¦spaced apart confronting each other with the object to which ¦the radio requency energy is to be applied betwen them. The ¦spirals of the electrodes are the reverse of each other in ll ¦this position, such that when they are adjacent each other 12 Ithe inductive effects of current flowing through them cancels.
13 ¦As they are moved apart the inductance (L) increases, but the 14 ¦capacitance (C) between them decreases correspondingly.
It is preferred, however, in present usage to 16 employ applicator generally having the shape of a paddle, 17 i.e., having a handle and a round plate more or less coplanar 18 with the end of the handle. The plate itself is a conductive l9 metal disc which is coated with an insulating film, such as a 20 coating of polyurethane resin, and is connected to the power 21 source through a small coil contained in the handle of the 22 applicator. Suitable applicators which have been used have 23 copper plates 2 inches and 4 inches in diameter. The leads 24 to the applicators from the power amplifier, of course, are 25 necessarily insulated and preferably are shielded cables, 26 such as coaxial cables, with the outer shield grounded, as 27 peak voltages on the order of 300 volts are developed in the 28 utput circuit of the R.F. amplifier.
29 The app~icators are connected across the radio 30 fre~uency output in the present usage of an amplifier capable ````` 1072186 of up to 1000 watt output. `
For a more complete understanding of the practical application of this invention reference is made to the appended drawings in which:
FIG. 1 is a block diagram indicating one appratus set-up for carrying out the process of this invention;
FIG. 2 is a plan view of an applicator suitable for carrying out the process of this invention;
FIG~ 3 is an enlarged, fragmentary section taken

- 10 at line 3-3 in FIG. 2;
FIG. 4 is a schematic diagram of a control circuit useful in stabilizing the power level of the apparatus shown ; in FIG. l; and FIG. 5 is a block diagram of a safety circuit in order to insure fail-safe operation of the apparatus shown in FIG. 1 in the event of a breakdown in the control circuit or the like.
Referring to FIG. 1 a simple arrangement of appa-ratus for carrying out the process of this invention involves an exciter 10, a power amplifier 20, and a pair of applica-tors 30~ Both the exciter 10 and power amplifier 20 are conventional. Exciter 10 has a crystal controlled oscillator, in the illustrated case operating on 13.56 MHz. Exciter 10 has an output of between 2 watts and 110 watts dependent on the bias of the oscillator; the less negative the bias the -- higher the output of exciter 10.
Power amplifier 20 is designed to amplify the ~ 107Z186 . I ~ .
1 ¦ output of exciter 10, and to this end the output circuit o ~ ¦ exciter 10 is con~ected to the input circuit of power 5 ¦ amplifier 20 as denoted by the reference numeral 11. Power ¦ amplifier 20 is designed for an output 30 watts to 1,0~0 5 ¦watts dependent upon the output of exciter 10 and of course, 6 ¦is tuned to the same frequency of 13.56 MHz.
¦ The output circuit of power amplifier 20 is 8 ¦connected to energize applicators 30 by means of coaxial ¦cables 21. Cables 21 have their inner conductors connected .0 ¦across the tank circuit of the output of power amplifier 20 1 ¦and lead to applicators 30, as more fully described with i2 ¦respect to FIG.'s 2 and 3. As shown in FIG. 2, each coaxial 13 ¦cable 21 includes a central conductor 22 which is provided 14 ¦with insulation 23 over which there is a braided shield 24 ~5 ¦and an ou-'er jac~et 25. The two conductors 22 are connected 16 ¦across the tank coil in the output circuit of power amplifier 17 ¦20, or optionally one can be grounded. In either case the ¦two shields 24 are grounded at the power amplifier, and, as 19 ¦shown in FIG. 1, are preferably also provided with an inter-20 ¦connection 26 between shields 24 adjacent the handle 31 of 21 ¦each..applicator.30.
22 ¦ Generally applicators 30, as c~n be seen best in 23 ¦FIG. 2, are in the shape of a paddle having a handle 31 and 24 an applicator portion 32.
Each handle 31 is made of insulating material, such 26 as a phenol~c resin, and, as can be seen best in FIG. 3, is 27 hollow such that, as coaxial cable 21 is brought into the 28 end of handle 31, the central conduc`tor 22 is electrically 2 connected to a coil 33 positioned in handle 31. The applica-tor portion 32 is secured to handle 31 at the end of handle g ` ~

107Z186 1 .
1 ¦ 31 opposite that to which conductor 22 is connected and is2 ¦ ln the ~ n of a flat, clrcular copper disc 34 which is 3 ¦ electrically connected at its periphery adjacent the end of 4 ¦ handle 31 to the end of coil 33 remote from connection with 5 ¦ conductor 22.
¦ As illustrated in FIG. 3 copper plate 34 is pro-7 ¦ vided with an insulating coating 35, for example of a poly--8 ¦ urethane resin, such that electrical contact with plate 34 9 ¦ can only be made through coil 33.
10 l Two sizes of applicators 30 have presently been ~1¦ constructed. In one copper plate 34 is 4 inches in diameter, 12 ¦and in the other copper plate 34 is 2 inches in diameter. In 13 ¦each case copper plate 34 is about 1/8 inch thickness. In - ~4 ¦ the instance of the 4 inch plate coil 33 is 6 turns with an 15 ¦ outside diameter-of 1/2 inch (wound about a pencil) and is 16 ¦ 1/2 inch in length. Coil 33 is positioned in the center of 17 ¦ insulated handle 31 and potted using a silicone rubber 18 ¦ conlposition. In the case of the two inch copper plate 34 19 ¦coil 33 is again wound about a pencil and is 18 turns having 20 ¦ an outside diameter of 1/2 inch and is 1 inch in length.
21 ¦ Again coil 33 is potted in the handle using silicone rubber 22 composition. In each case, coil 33 is a copper wire about 23 ~ AWG. In each case coaxial cable 21 is of a type 24 known RG 58-U and is approximately 3 feet in length from 25 power amplifier 20 to the associated applicator 30. In each 26 case the thickness of insulated coating 35 is approximately 27 4 mils and is a polyurethane resin which is clear, containing 28 no oxides.
29 FIG. 4 illustrates a servo control generally desig-30 nated by the reference numeral 40 in FIG. 1 in which the -~ ........ , . l 1 ¦ power output of power amplifier 20 is sensed and the ampli-¦ flca~on ln exciter 10 is controlled to hold the power output 5 ¦ of amplifier 20 at any desired constant level which can be 4 ¦ pre-selected by manual control.
S ¦ In the arrangement shown in FIG. 4 the reference 6 ¦ numeral 27 indicates the tank circuit in the output stage of 7 ¦power amplifier 20 which includes a tank coil 41 and tuning 8 I capacitor 42 which are adjusted to resonance at 13.56 MHz 9 ¦ and are connected through a coupling condenser 43 to the lO ¦plates of a pair of parallel output tubes indicated schemat-

11 ¦ically as a single tube 44. In the illustra*ed case these ;2 ¦are a pair of 3-500 Z triodes, connected as grounded-grid 13 ¦amplifiers, having a plate supply of approximately 2400 volts 14 ~DC.
15 ¦ Coupling capacitor 43 is .001 uf and tuning capa-16¦ citor 42 is a variable capacitor having 10-250 pf. Tank 171 coil 41 has 5 turns and is grounded 1-1/2 turns above its 18¦ end remote from triodes 44 and is tapped at such end and 191 1-1/2 turns above the ground tap for connection to conductors 20¦ 22 through a double pole switch 45 in one mode of connection 21¦ of such switch. The other mode of connection of such switch-22¦ is utilized when only one applicator 30 is to be used and 23¦ the other side is grounded.
241 Also approximately 2 turns from the high voltage 251 end, coil 41 is tapped to withdraw the servo (sensing) signal 26¦ through a voltage divider comprising a pair of . serially 271 connected capacitors 46 and 47 of 200 pf each and a third 28¦ serially connected variable capacitor 48 of 50-900 pf which 291 is in turn connected to ground.
301 The common connection 49 of capacitors 48 and 47 l leads to a rectifier voltage doubler 50 which is a dual 2 dlo~e 6ALS. Connectlon 49 ~s thus to the plate of one and 3 the cathode of the other diode, while the cathode of the 4 first is grounded and the plate of the other leads to a filter circuit consisting of a 2.2 K ohm resistor 51 having 6 its end adjacent the plate by-passed the ground through a : 7 115 pf capacitor 52 and its end remote from the plate by-passed to ground through a .02 uf resistor 53. .-. The common junction 54 of resistor 51 and capacitor : l.O 53 thus has on it a negative DC voltage which is a function l.l of the RF voltage at junction 49 in the voltage divider 1.2 comprising capacitors 46 and 47 and capacitor 48, rectified - 1.3 and amplified by voltage doubler 50, Junction;.54 is connected 14 through a blocking diode 55 to crystal 56 and to the grid of 15 an oscillator tube 12 in exciter lO, which in the illustrated .
16 case is a 6Y6G. ¦
.~ 1 Oscillator tube 12 is also biased at the common 18 ¦junction 57 of diode 55 and crystal 56 by means of a voltage l9 ¦divider consisting of a pair serially connected resistors 20 158 and 59 which are connected, respectively, between -llO
21 ¦volts DC and jun-ction 57 and between junction 57 and ground.
. 22 ¦Resistor 58 is 75 K ohm and resistor 59 is lO K ohm. An RF
. 23 ¦by-pass capacitor 60 having .005 uf is also connected from 24 ¦common junction 57 to ground. .
25 ¦ It will be apparent that variable capacitor 48 ~ 26 ¦functions to control the amount of RF voltage impressed on : 27 ¦voltage doubler and rectifier 50 and consequently to control 28 ¦the negative bias at terminal 54. Diode 55 prevents the 29 ¦flow of current from terminal 57 to terminal 54 when the ¦negative bias at terminal 54 is less negative.than the fixed negative bias supplied by the voltage divider formed of resistors 58 and 59 and thus limits the maximum power output of amplifier 20. When, however, the negative bias at terminal 54 goes below that at terminal 57 current flows from terminal 54 through resistor 59 to make the bias on tube 12 more negative, and hence decreases the amplification in exciter 10.
This, of course, is a function of the capacitance of capacitor 48. Since the power output of amplifier 20 is a function of the bias on oscillator tube 12, servo loop 40 thus, under the control of the manual setting of capacitor 48, functions to control and hold stable the power output of amplifier 20 by controlling the voltage output of exciter 10 through control of the amplification in oscillator tube 12.
It will be apparent, however, that should there be a breakdown in the servo system oscillator 12 will be driven to full amplification as determined by the fixed bias supplied by resistors 58 and 59. As a consequence, a fail-safe circuit is supplied, as shown diagramatically in FIG. 5. In this fail-safe circuit the connection of AC supply 13 to the high-voltage DC
supply 14 for exciter 10 is made through a relay operated switch 15 which is normally closed. Switch 15 is operated to open position by a relay coil 16 connected in series in the DC high voltage lead 17 to the anodes of the amplifier tubes in exciter 10. Coil 16 is shunted by an adjustable resistor 18 which functions to control the sensitivity of relay coil 16 and which is set such that, when the current flowing in line 17 exceeds a predetermined maximum, relay coil 16 will operate switches 15 to open them and break the high voltage supply.

Thus, if for any reason servo circuit 40 should fail - or if for any other reason amplification in exciter 10 should suddenly increase to an undesired value, the high voltage supply 14 will be shut off and exciter 10 rendered inoperative, thereby preventing the use of power amplifier 20 until the difficulty has been located and switch 15 manually reset.
Tissue temperatures during therapy can be determined by inserting into the tissue being heated non-metallic thermometers - having non-electrolyte indicator fluids, such as glass alcohol thermometers. It is essential that during therapy the adjacent normal tissue temperature be raised only to 40C, as higher temperatures can cause its destruction as well. With increased --skill a surgeon can avoid the necessity of using thermometers, as he can sense the temperature of the normal tissue by palpation when the diathermy is turned off. In order to destroy the tumor it is usually essential that its temperature be raised above 50C. In some instances the tumor tissue can be necrosed at temperatures as ~ow as 46C. Destruction of the tumor can be observed either by thermometric means, by X-ray techniques used to sense the presence of the tumor, biopsy or the like.
In some instances, for example, cancer in some human organs, such as the liver, is treated by surgically exposing the organ to place the applicators directly in contact with the organ at the location of the cancer.
In the case of human lung carcinoma, both metastatic and primary, the applicators can be applied to the external chest wall. Massive necrosis of the lung tumor can induce complications of pulmonary abscess or hemorrhage, but these can be dealt with surgically after all the tumor has been destroyed.
~ Similarly it may be necessary to divert the fecal ; stream with a proximal defunctionalizing colostomy, when rectal and colon tumors are treated to avoid the danger of necrosis with performation.
Other avascular lesions occurring in otherwise normal tissue will response equally to this therapy. Similarly polycystic kidneys can be treated, since the cysts have no blood supply they will be heated while the vascular kidney substance will remain cool. Thus the therapy will destroy the lining of the cyst wall which secretes fluid and causes compression atrophy of the normal kidney.
Example I

A 67 year old white male had an unresectable carcinoma of the left lung which proved on biopsy to be a squamous cell He had mild dyspenea and dull pain on the left side of his chest and a brachial neuralgia.
-~ The four inch applicators 30 described above, were positioned one flat against the anterior and the other flat against the posterior of his chest to position the tumor between them. He was given general anesthesia and the applicators 30 were energized at a power level of 200 watts for 20 minutes at 13.56 MHz. The voltage (R.M.S.) across applicators 30 at this level was 100 volts. No measures were taken to insure intimate contact with the skin and the applicators 30. Conse-quently, a skin burn resulted.
Three days later a thoracotomy was done to biopsy the lesion. The entire tumor was incised and a large biopsy taken. This biopsy was reported as inflammatory reaction ~;~

only although the surgeon was sure he had incised the tumor.
Subsequently the patient's course has shown gradual improve-ment. His brachial neuralgia has cleared and his chest X-rays are improved. The treatment resulted in considerable necrosis of the chest wall. This has now healed completely.

Example II

In this example the patient was a 57 year old white male who had undergone total laryngectomy for carcinoma of the vocal cord approximately two years before treatment.
Approximately four months before treatment, the patient developed a large mass the size of an orange (3" in diameter) over the manubrium of the sternum (breastplate bone). Biopsy showed it to be a squamous cell carcinoma.
The tumor was irradiated (cobalt) but there was no . substantial improvement and no reduction in the size of the mass. He was deemed inoperable by thoracic surgery. The tumor - mass was stoney hard; the skin overlying the mass was stetched and shiny; and the tumor had pushed the tracheotomy to the right.
There was also invasion of the underlying bone. The patient was having respiratory difficulty because the tumor compressed the trachea and his situation was desperate.
This patient was given four treatments utilizing generally the apparatus shown in Fig. 1 with the four inch applicators 30 described above. Prior to positioning the applicators, the skin of the patient was moistened with EKG
jelly to decrease skin resistance, and a bronze wool sponge was placed over the location of the tumor on each side to main-tain even electrical contact. One applicator 30 was then placed flat against the bronze sponge over the tumor with the second applicator 30 placed flat against the ~ ` I 107Z186 ~ .

} midaxilla, Thus in effect the patient's bod~ was positioned betwee~ ~h~ ~wo applicators 30 such that the tumor was 3 located between them.
Power was initially raised gradually to 300 watts (about 120 volts R.M.S. at 13.56 MHz) and maintained for 20 6 minutes between 275-300 watts.

7 One week later, the hard mass had become softer 8 and fluctuant in parts. Ten days after the treatment the 9 mass was aspirated and semi-liquid, necrotic material was withdrawn. In order to further liquify the necrotic material 11 Bovine fibrinolysin and desoxyribonuclease were injected into

12 the tumor. Two days later, the tumor was again aspirated.

13 Nineteen days after the first treatment, the pat- -

14 ient was given a second treatment with the 4" applicators 30

15 again placed in the same manner except that the second

16 applicator was placed on the back of the chest to the right

17 of the midline. Treatment was for 20 minutes. Again the

18 power was gr~dually increased this time to 385 watts (135 .9 volts ~.M.S. at 13.56 M~z) and then varied between 350 to 410 20 watts during the ramainder of the therapy. -21 Two wèeks later, the tumor was aspirated again.
22 Liquid~material was obtainèd and t~e tumor-had decreased-23 considerably in size. No viable tumor cells were shown.
24 There were some autolyzed cells. The third treatment immedi-ately followed such aspiration and was similar to the first 26 treatment except that initial power was 135 watts which was 27 increased to 235 watts (108 volts R.M.S. at 13.56 M~z) and 28 continued for a total of 11 minutes.
29 Although ~urther therapy was considered super-30 fluous, since the tumor had already been destroyed, a fourth : 107Z186 l ~ ., 1¦ treatment was given ten days later. In this instance, 2¦ applicators 30 were placed one on the ml~axllla, as descri~ed above, and the other first to the right and then to the left 4¦ of the tumor. In each case, the skin was moistened with EKG
51 jelly and bronze wool sponge is placed against the skin 6¦ beneath the applicator 30 to maintain even electrical contac~t.
q ¦ The treatment was at 475 watts (150 volts R.M.S. ~t 13.56 .~ 81 MHz) on the left side for 20 minutes and at 375 to 400 watts 91 (138 volts R.M.S. at 13.56 MHz) on the right side for 20 lO¦ minutes.
11¦ The final pathological diagnosis indicated no 12¦ malignancy. The mass has almostlcompletely disappeared 13¦ although there is some inflammation and an ulcer under *he 14¦ site of the necrotic tumor.
~51 Before treatment in accordance with this invention -16¦ the patient was having severe respiratory difficulty because 17 ¦the tumor was closing off his trachea just below the site of 18 ¦the tracheotomy. Since the treatment, the patient can "~ ¦breathe freely and has had no respiratory difficulty. Ther-20 lapy in accordance with this invention resulted in minimal 21 ¦necrosis of the stretched skin over the lesion which will 22 require-future--grafting.- -23 ¦ Example III
24 ¦ In this case the patient had what was considered 2~ ¦to be a large, inoperable carcinoma of the lung which filled 26 the entire right upper chest. The tumor mass was larger 27 than the 4 inch applicators 30 which were available. One 28 applicator 30 was put on the anterior portion of the chest 29 wall after moistening the skin with conductive paste, and 3 the other applicator 30 was similarly positioned on the ~ -18-` ` 1072186 posterior of the chest wall, such that the tumor mass was largely positioned between them. Fluoroscopy was utilized `- to define the location of the tumor mass. The patient was not anesthesized.
The apparatus was turned on to apply 50 watts and then increased to 256 watts (112 volts R.M.S. at 13.56 MHz) over a three minute interval. Power was then gradually decreased to 175 watts (90 volts) for the remainder of the period of 20 minutes.
Four days later a second treatment was given to the patient with the same positioning of applicators 30 in which power was gradually increased over a 9 minute period to 215 watts (105 volts) and then slowly lowered to 185 watts for 1 minute. The power level was then increased to 375 watts and kept for a four minute interval and thereafter between 300 and 350 watts for the rest of the 20 minutes. Because of the size of the applicators, the treatment was considered spacially inadequate to reach the entire tumor.

Five days later a right upper lobectomy was done.
The entire right upper lobe was necrotic with severe inflam-matory reaction. The entire lobe was fixed and cut on alarge microtone. Ninety-nine percent of the tumor was necrosed but a small rim of tumor was still present where the applicators had not completely covered the tumor. All of the treated area was entirely free of tumor, as the ~umor in the treated area was dead and undergoing autolysis.
In this case the inoperable carcinoma was consid-ered to have been made operable since the tumor tissue adherent to the pleura and chest wall was completely necrotic and the lesion could be removed without leaving live tumor.

` -'" 107Z186 The structure of the two applicators and energy feed cables from the power source are structurally unique. Each applicator 30 and its shielded coaxial cable 21 are designed and constructed for use repeatedly in the operatingroom both inside and outside the body cavity with necessary exposure to contamination so as to require sterilization between uses. The entire applicator-cable unit are one detachable unit entirely encased in a continuous film of insulating resin such as polyurethane of a thickness of about 14 mils. The unit hence has a low dissipation factor for radiant energy passing through ` and are waterproof. During most uses a sleeve of bronze wool or austenitic steel (18% nickel content) is placed over the insulated disc applicators. This sleeve is about 1/2 to 1 inch thick and compressible against the skin surface to reduce skin and deep tissue reflectance and reduce scattering of the input radiation. Since the metal sleeve is of a magnetic permeability equal to the subadjacent tissue it does not itself absorb energy - -- and heat up but serves to direct the wave deep into the body cavity.
In the several preceding examples the frequency referred to is preferably 13.56 megaHertz which is selected as a convenient point within a broad band of from 100 kiloHertz to about 200 megaHertz at which frequencies the wavelength is long enough to control and penetrate with our particular apparatus.
The bronze wool control sleeve also eliminates "hot spotting" in the tumor where parts of the tumor do not receive a uniform dose of heat because of irregular contour on the skin surface caused by ribs protruding etc. The non glossy coat of polyurethane insulation is also critical to avoid eddy currents and skin burn in cases where the skin may have residual salt thereon.
With an input of 500 watts for 30 minutes and long wave length this factor of skin burn becomes of significance. In some cases of tumors in difficult positions it is possible to move the applicators a short distance back from the tissue surface to treat.

-2~-'.

~07Z186 The insulating coating 35 should in any event be formed of a dielectric material having a low dissipation factor, ie., below about 0.01. By dissipation factor reference is made to the reciprocal of Q which is sometimes denoted by the expression "tan" and is further defined as follows:

tan ~= " = Q

I = dielectric constant ~"= loss factor .
Generally insulating materials suitable are glass and mica which have dissipation factors of the order of 0.001 to 0.002, polyethylene which has a dissipation factor 0.0002, polytetra-fluoroethylene which has dissipation factors of the order of 0.002 to 0.006, polystyrene which has dissipation factors below 0.0002 and polyurethane which has a factor below 0.007 and of the order of 0.005. The above noted dissipation factors are of course frequency dependent and the values noted above are for frequencies on the order of 107 Hertz. All of this relates to the need to have low-loss insulating surfaces on tumor treating applicators working in the 13-14 megaHertz range with high wattage input required to give effective treatment to destroy the tumor tissue. The polyurethane is of the thermosetting type not the thermoplastic type which does not have the proper dissipation factor.

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. In a system for applying radio frequency electrical power of selectable level to a load which includes:
a radio frequency electrical signal source having an input circuit and an output circuit for generating a radio frequency electrical signal in said output circuit, the amplitude of said signal in said output circuit being a function of the amplitude of a control signal applied to said input circuit, radio frequency power amplifier means having an input circuit and an output circuit for generating a radio frequency electric signal in said output circuit of said amplifier means having a power level which is a function of the amplitude of a radio frequency signal applied to said input circuit of said amplifier means, and said output circuit of said signal source being coupled to said input circuit of said amplifier means, the improvement in which said output circuit of said amplifier means is coupled to said input circuit of said signal source through a negative feedback servo loop including sensing means connected to said output circuit of said amplifier means for sensing the radio frequency power level in said output circuit of said amplifier means, said sensing means including manually operated control means and being connected to said input circuit of said signal source for connecting a portion of the sensed output level as a control signal for said signal source, said portion being controlled by said control means, and a high voltage supply connected to an external power source, means connecting said high voltage supply to said signal source, current sensitive means in said connecting means responsive to an increase therein above a preselected maximum to interrupt the connection between said external power source and said high voltage supply to disable said high voltage supply.