EP0632708A4 - Appareil de traitement local de tumeurs. - Google Patents
Appareil de traitement local de tumeurs.Info
- Publication number
- EP0632708A4 EP0632708A4 EP93900762A EP93900762A EP0632708A4 EP 0632708 A4 EP0632708 A4 EP 0632708A4 EP 93900762 A EP93900762 A EP 93900762A EP 93900762 A EP93900762 A EP 93900762A EP 0632708 A4 EP0632708 A4 EP 0632708A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- coil
- thermoseeds
- tumor
- magnetic field
- hyperthermia
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
- A61N1/403—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia
- A61N1/406—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia using implantable thermoseeds or injected particles for localized hyperthermia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N2/00—Magnetotherapy
Definitions
- the present invention relates to medical treatment and more particularly to local treatment of tumors either cancerous or benign on an out patient basis.
- the present invention contemplates equipment for treatment of various localized tumors such as prostate, rectal, cervical or uterine.
- tumor refers to any abnormal tissue growth.
- the invention may be used for any temperature sensitive tumor.
- the present invention will be described with regard to a typical type of tumor suitable for treatment with the equipment of the present invention, namely, prostate cancer.
- Prostate cancer is the second most common cancer in males in the United States, and the third most common cause of male cancer death. In 1986, an estimated 90,000 men in the US were diagnosed with prostate cancer, and 26,100 death from the disease were estimated to have occurred.
- the disease is uncommon in men younger than age 50, but the incidence increases sharply to more than 1,000 per 100,000 man-years for American males age 85 and over.
- the average age of prostate cancer patients at the time of diagnosis is 73 years.
- mortality due to prostate cancer is exceeded only by lung cancer. Relative to other forms of malignancy, this disease accounts for 21 percent of newly diagnosed cancers in males and 11 percent of cancer deaths.
- the cost, including physician fees, of perineal prostatectomy is substantial with typically 8.0 hospitalization days required.
- the delivery of external radiation therapy for localized prostate cancer according to the present invention may be a 6-weeks- course on an outpatient basis. Treating patients with the method of the present invention, e.g. hyperthermia delivered on an outpatient basis, would lead to a reduction of hospital days associated with surgery.
- effective hyperthermia can enhance the effect of radiation and result in a higher local cure rate.
- radical prostatectomy has been widely employed on otherwise healthy men with clinical Stage A or B and occasionally small Stage C lesions. Limitations in success in treatment stem from inaccurate clinical staging which fails to predict extraprostatic carcino atous spread prior to surgery.
- Interstitial radiation therapy with iodine isotope (1-125) has been reported to carry a 16% incidence of local failure in patients with stage C disease followed five years. Scardino et al., however, observed an incidence of positive postradiation biopsy of 50%. Local tumor recurrence using a combination of radical surgery and interstitial gold isotope (AU-198) has been reported in the range of 4% to 8%.
- Hyperthermia can be achieved through an induced temperature of more than 41.4°C, within living organism or a part of it, where the physiological temperature regulation of the body is partially overcome with the aim of achieving a therapeutic effect.
- thermotolerance is a complication in the clinical use of hyperthermia. Riabowol suggests that synthesis of a small group of highly conserved proteins in response to the first thermal shock causes significantly higher survival rates to a second, otherwise lethal damage. A correlation exists between the expression and decay of thermotolerance and the induction, accumulation, and degradation of heat shock protein. Those referred to as the hsp70 family are the most conserved and the best characterized.
- hsp70 In most mammalian cells there are two prominent forms of hsp70, an abundant constitutive member, hsp73, and a highly stress-inducible member, hsp72. In response to heat shock, these proteins are rapidly sequestered in the nucleolus involved in the assembly of small ribonucleoproteins and preribosomes. During recovery from heat shock, the 70k hsp accumulates in the cytoplasm where a portion colocalizes with ribosomes and polysomies. At lower temperature of around 42°C, thermotolerance is induced during the heating period after an exposure of around 2 or 3 hours.
- thermotolerance cannot be produced during the heating, and it is delayed by 8 hours or so after the heating period.
- the time taken for cells that have become ther otolerant to revert to their normal sensitivity may take as long as 100 hours.
- the faster the increase of temperature, the higher the temperature, and the longer the time of exposure the smaller are the number of thermotolerant cells found within cultured cell lines.
- Hyperthermia generally decreases blood flow in tumors, frequently irreversibly, however, blood flow is sometimes restored 1-3 days after application of heat, depending on the tumor model.
- the intratu or environment Upon heating, the intratu or environment becomes acidic, hypoxic and nutritionally deprived due probably to vascular damage.
- Such a suboptimal environment in the heated tumors potentiates the response of tumor cells to hyperthermia, inhibits the repair of thermal damage, and also interferes with the development of thermal tolerance. Heating and damage of tumor cells can be expected only if heat is preferentially delivered to the tumor or if heat dissipation by blood flow is slower in the tumor than in the surrounding normal tissue.
- Tumor vasculature is less able to dissipate heat and more likely to be damaged when treated with hyperthermia.
- Systemic temperature elevation during regional hyperthermia results from the dissipation of large quantities of thermal energy through circulation. This is generally an undesirable by-product of regional hyperthermia, which may seriously compromise adequate delivery of thermal treatment.
- Electromagnetic (microwave) and ultrasonic methods can be used to heat tissue locally. At high temperature, e.g. above 45°C, heat begins to indiscriminately damage both normal and cancer cells. This limits temperature rise in tissue to a narrow therapeutic range, to avoid both enhancement of the active growing tumor edge and damage to normal cells. Using this method it is difficult to selectively act on the desired tissue, e.g.
- Electromagnetic field focusing is capable of producing intense heat at a given point in tissue. If biological tissue is placed in an electromagnetic field, eddy currents are induced to flow within the tissue. The tissue is not heated until it is grounded by a conductor, eg. needle electrode, at which time a sharp and intense convergence of the eddy currents, at the point of contact of the electrode to tissue, produces heat.
- a conductor eg. needle electrode
- thermoseeds are implanted and then may be inductively heated by a magnetic field.
- a needle is used to implant thermoseeds.
- the biocompatable thermoseeds after insertion, remain in place over an extended period of time.
- the seeds are heated by induced current flow without electrical connection such as that needed in the EFF-method.
- As the magnetic field strength needed to heat the implanted seeds is low (less than 100 Oersteds) , there is no adverse short term or long term tissue effect.
- Thermoseeds are very small and less invasive than other techniques. Thermoseeds once inserted have no connection with the outside world.
- Thermoseeds can be made from materials having a ferromagnetic to paramagnetic transition (Curie point) at the desired temperature. As the Curie point is approached, the implants begin to lose their ferromagnetism, and thereby their rate of heat production is decreased and temperature becomes static. The automatic regulation offered by this technique leads to better temperature homogeneity. These are the so called self-regulating thermoseeds.
- the rate at which heat is produced by a cylindrical thermoseed depends on its radius, length, magnetic permeability, and on the intensity and frequency of the applied induction field. The rate of heat production goes up if any of these parameters are increased.
- the heating power depends on the orientation of the implants with respect to the magnetic induction field. Thermoseeds must be oriented properly, e.g. with the direction of the magnetic field in order to function properly. Although deviations of up to 45 degrees are acceptable, larger angles of misalignment lead to a substantial drop in heating power.
- thermoseeds have theoretical advantages in localized and accessible tumor systems.
- the prostate fulfills these criteria, and has immense clinical importance, because of benign enlargement and malignant potential.
- thermoseed consisting of 70.4% nickel and 29.6% copper gave consistent temperatures of 50.1 ⁇ C, although other seeds have also been used, e.g. palladium - copper, nickel - silicon, iron oxide, and manganese oxide. Suitable seeds would also include coated seeds, e.g. TeflonTM PTFE fluorocarbon coated seeds.
- the thermoseed may be of a radioactive material such as a coating of radioactive gold on nickel/copper. This would provide a dual function treatment.
- seeds are about 3 or 4 centimeters in length. Seeds tend to migrate if they are 5cm or larger in length. Calorimetric measurements of seeds of 0.9mm diameter showed that they should not be shorter than 7mm in length. The spacing of seeds should not exceed 1cm to effect uniform heating.
- hyperthermia is a potent modifier of the response of tumors to radiation and can be tumoricidal per se; 2) hyperthermia enhances the killing of tumor cells by selected chemotherapy agents; 3) hypoxia does not protect cells against the effects of hyperthermia as it does against x-rays, and; 4) when subjected to local hyperthermia, solid tumors act as a heat reservoir because of their poor blood flow. Since tumors are unable to augment blood flow in response to thermal stress, they are more vulnerable to heat damage than the surrounding normal tissue with its efficient vascular cooling system, which rapidly adjusts to local heating burden. Using the annular phased array system, toxicity to hyperthermia has been observed in 30% of patients treated. The so-called post-hyperthermia stress syndrome consisted of sudden rise in systemic temperature and pulse rate, and chills within a short time of hyperthermia with all the symptoms subsiding in less than 24 hours.
- an array of ferromagnetic seeds are implanted in the tumor.
- the patient is placed in a magnetic induction field which produces heat within the seeds.
- the absence of any electrical connecting wires between the implant* and the power source makes this heating method very practical.
- Human patients tolerated hyperthermia with mild sedation. While the present invention is disclosed with respect to prostate cancer, it may be used with various other tumors.
- Clinical studies have demonstrated the efficacy of hyperthermia with radiotherapy in the treatment of adenocarcinoma of the breasts. About half of the lesions treated with radiotherapy alone were controlled, while all of the lesions treated with the combination were controlled at one year.
- Some researchers are using an electromagnetic hyperthermia system with rectal cooling to treat patients with BPH and prostatic cancer. Intraprostatic temperatures of 43 to 43.5°C are achieved 10 to 15 minutes after initiation of therapy. Patients received 6-10 treatments during the study. Hyperthermia was applied three times a week. In patients with prostatic cancer, radiation preceding hyperthermia was the preferred treatment combination. Local control of prostate cancer was achieved within the reported follow- up period. All patients treated with hyperthermia for BPH had resolution of their voiding problems. Patients were evaluated during hyperthermia treatment and at 3 and 6 month intervals. Each case was evaluated by transrectal ultrasonography, residual urine, uroflowmetry, rectoscopy and blood/urine analysis.
- the rats were divided into two equal groups and washed according to tumor size. Each group was anesthetized with intraperitoneal Nembutal (50mg/kg) . All tumors were treated with topical iodine solution and the hyperthermia needles were disinfected with 70% ethanol. The treated group was prepared and the tungsten needle with the attached thermocouple was inserted into the tumor and heated. Hyperthermia was created by the resistive heating of a 22 gauge, 1.5 cm long tungsten needle by a DC power supply. The thermocouple, placed at the center of the needle, monitored the temperature and a specially constructed closed loop feed back circuit held the temperature constant (+/-0.5°C) . The hyperthermia treatment continued for two hours after the needle temperature reached 46.5°C.
- the mean volume of tumor in the treated group was significantly less than that in the control group. No other areas of injury were identified and no immediate mortality occurred, but two rats died from lung metastases of the prostatic carcinoma on day 22. In the treated group, no lung metastases were found and no rats died before day 29.
- Microscopic evaluation of the tumors included determination of the amount of solid or stratified pattern versus simple nonstratified glandular pattern, the mitotic rate, and the size of the tumor made up by stroma and observed injuries, e.g. infarct ⁇ , vascular thrombosis, and hemorrhage. The hyperthermia treated tumors exhibited increased areas of solid or stratified morphology.
- the mitotic rate and the relative amount of stroma did not vary significantly from group to group. Infarcts, vascular thrombosis, stromal sclerosis, necrosis and organizing foci were typically present in the hyperthermia treated group. Hyperthermia treated tumors characteristically showed also increased areas of piled up cells with no lumen formation.
- thermotolerance with the development of heat resistant proteins may represent a clinical problem, especially in tumors treated at lower temperatures.
- a temperature of 46.5°C was used by an interstitial technique, which has the possibility to raise temperatures to a degree overcoming these problems, without associated surrounding tissue damage.
- Other effects, as previously discussed, are related to blood flow and systemic temperature elevations.
- thermoseeds In order to create the necessary magnetic field strength to inductively heat thermoseeds, a commercially available power supply is utilized to power a specially designed coil. Both supply and coil may be watercooled if needed to control equipment temperature. In some instances, water cooling will be unnecessary.
- the power supply in one preferred embodiment is 7.1 kw and utilizes a frequency of 115 kHz.
- the frequency may be in the range of 50 to 200 kHz, preferably between 80 and 120 kHz. In any event, the frequency must be below 500 kHz.
- the coil is 42 cm in diameter, 20 cm in length and consist of 10 turns of copper tubing. The coil may have, for example, an impedance of approximately 60 ohms at the operating frequency.
- the power supply and coil produce a maximum magnetic field strength of from approximately 5 to 150 oersteds, preferably 10 to 100 oersteds on the axis at the edge of the coil.
- the axis of the coil is mounted vertically, with a plexiglass work table (e.g. seat or chair) covering the entire diameter.
- This field intensity creates a working volume 20 cm to 65 cm in diameter and 15 cm to 45 cm in height, centered about the coil axis and 4 cm above the uppermost coil winding. In the working volume the field is of sufficient intensity to inductively heat the thermoseeds to the desired temperature.
- a reflector may be provided around the periphery and beneath the coil as a shield protection with the only exposed field being in an upward direction.
- the present invention may include a control panel with the necessary controls, switches, indicators and monitoring devices.
- the seeds may be of any suitable metal or alloy that provides the previously described properties.
- Typical alloys include nickel/copper, platinum/copper, nickel/silicon, iron/manganese, and manganese/ferrite.
- seeds of 70% nickel and 30% copper with a diameter of 1 mm are used.
- This alloy has a Curie point temperature of 50°C.
- the Curie point of each wire is determined by placing it in a small vial of approximately 5 cc of water.
- the vials are placed in the working space of the magnetic field and their temperature is measured by thermocouple every 5 minutes.
- the field is turned off during the temperature measurement to avoid interfering induced currents on the thermocouple leads. Seeds which attain 50 +/- o.5°c within-15 minutes of field activation are desirable.
- the heat produced by the alloy thermoseeds is proportional to the magnetic field intensity times the operating frequency, HF; this value for our system is 1.2 x 10 8 A/ms.
- Figure 1 is a front view of one embodiment of the present invention
- Figure 2 is a side sectional view of the device of Figure 1;
- Figure 3 shows a cylindrical coil of the present invention
- Figure 4 shows a pancake coil of the present invention
- Figure 5 is a perspective view of an embodiment of the present invention including a seat coil and an articulated arm coil;
- Figure 6 is a perspective view of an embodiment of the present invention comprising an articulated arm coil. Preferred equipment for carrying out the present invention is shown in Figures 1 and 2. Figure
- FIG. 1 shows a support 10 of the present invention including a platform 11 and a coil 12 disposed beneath the platform 11.
- the coil 12 may be constructed of copper tubing having a tube diameter of about 1 inch.
- the copper tubing may be connected to a self-contained water circulating system to control the temperature of the tubing.
- the platform 11 is contoured to require positioning of the patient to assure positioning of the tumor with the thermoseeds within the field of the coil during treatment.
- the coil as shown in Figures l and
- the 2 is a cylindrically shaped coil; however, other types of coils may be used such as a pancake coil ( Figure 4) .
- Such coils may have from 5 to 15 turns.
- the cylindrical coil may typically be 40 cm in diameter and 30 cm in length.
- the pancake coil may typically be 30 cm in diameter and 15 cm in length.
- the coil may be a small portable coil and may be tightly wound coil with very little spacing between the turns. In this case, the coil may have from 50 to several hundred turns of fine conductor.
- the coil will usually be disposed in the seat or chair as shown in Figures l and 2.
- a smaller coil may be mounted on an arm which is moveable to center the coils' field on a given area of the body where a tumor is to be treated.
- all parts in the vicinity of the coil will be of a nonconducting material to avoid heating of such parts.
- Device 110 includes a control housing 111 which may contain the electrical components and controls as described.
- the device 110 includes a seat 112 which may be constructed similar to seat 10 of Figure l.
- Seat 112 has a seat housing 113, a coil 114 and a support platform 116.
- the coil 114 is in electrical contact with the components of housing 111.
- the device 110 has an articulated arm 117 which carries a coil 118.
- the coil 118 is suitable for treating tumors in any of various parts of the body.
- a device 210 of the present invention is shown in Figure 6.
- the device 210 includes a housing 211, an articulated arm 212 and a coil 213.
- the articulated arm 212 may be of any desired form such that it is capable of supporting the coil 213 in position adjacent a patient's body for treatment of a tumor.
- the coil 213 may be moved to the desired location for treatment of a tumor.
- the housing 211 is portable and may be moved on its supporting wheels to a position adjacent to a patient's hospital bed for use.
- the housing 211 may carry the power supply of a type as previously described.
- the power supply may provide current at a frequency of from 50 to 200 kHz to produce a magnetic field of between 50 and 150 oersteds.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Thermotherapy And Cooling Therapy Devices (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/471,498 US5197940A (en) | 1990-01-29 | 1990-01-29 | Local application tumor treatment apparatus |
CA002132730A CA2132730C (fr) | 1990-01-29 | 1992-11-30 | Appareil de traitement des tumeurs par application locale |
PCT/US1992/010321 WO1994012101A1 (fr) | 1990-01-29 | 1992-11-30 | Appareil de traitement local de tumeurs |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0632708A1 EP0632708A1 (fr) | 1995-01-11 |
EP0632708A4 true EP0632708A4 (fr) | 1996-03-13 |
Family
ID=25677518
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP93900762A Ceased EP0632708A4 (fr) | 1990-01-29 | 1992-11-30 | Appareil de traitement local de tumeurs. |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0632708A4 (fr) |
AU (1) | AU3230593A (fr) |
CA (1) | CA2132730C (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7510577B2 (en) | 2004-06-29 | 2009-03-31 | Micardia Corporation | Adjustable cardiac valve implant with ferromagnetic material |
US7536228B2 (en) | 2006-03-24 | 2009-05-19 | Micardia Corporation | Activation device for dynamic ring manipulation |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH103335A (fr) * | 1922-10-03 | 1924-02-16 | Luthi Robert | Appareil thérapeutique électro-magnétique à triple effet. |
FR2362640A1 (fr) * | 1976-08-23 | 1978-03-24 | Fellus Marcel | Appareil de basse frequence a usage medical |
US4574782A (en) * | 1981-11-16 | 1986-03-11 | Corning Glass Works | Radio frequency-induced hyperthermia for tumor therapy |
EP0244784A2 (fr) * | 1986-05-09 | 1987-11-11 | Moshe Dr. Rosenthal | Dispositif électrothérapeutique |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3306391A1 (de) * | 1983-02-24 | 1984-08-30 | Forschungsinstitut Manfred von Ardenne, DDR 8051 Dresden | Einrichtung zur hyperthermie des menschlichen koerpers |
-
1992
- 1992-11-30 AU AU32305/93A patent/AU3230593A/en not_active Abandoned
- 1992-11-30 CA CA002132730A patent/CA2132730C/fr not_active Expired - Fee Related
- 1992-11-30 EP EP93900762A patent/EP0632708A4/fr not_active Ceased
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH103335A (fr) * | 1922-10-03 | 1924-02-16 | Luthi Robert | Appareil thérapeutique électro-magnétique à triple effet. |
FR2362640A1 (fr) * | 1976-08-23 | 1978-03-24 | Fellus Marcel | Appareil de basse frequence a usage medical |
US4574782A (en) * | 1981-11-16 | 1986-03-11 | Corning Glass Works | Radio frequency-induced hyperthermia for tumor therapy |
EP0244784A2 (fr) * | 1986-05-09 | 1987-11-11 | Moshe Dr. Rosenthal | Dispositif électrothérapeutique |
Non-Patent Citations (1)
Title |
---|
See also references of WO9412101A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP0632708A1 (fr) | 1995-01-11 |
CA2132730A1 (fr) | 1994-06-09 |
CA2132730C (fr) | 2001-07-03 |
AU3230593A (en) | 1994-06-22 |
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