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Interstitial microwave-induced hyperthermia in combination with brachytherapy
Proceedings
1295
of the 23rd Annual ASTR Meeting
AlCE is produced in significant quantities by endothelial cells. Treatment with ionizing radiation can lead to the development of long-term normal lung tissue damage. Similarly, Bleomycin (BLM), an antitumor antibiotic, has been shown to produce damage in lung endothelial cells, resulting in the doselimiting toxicity of pulmonary fibrosis. The development of this pulmonary fibrosis is often irreversible and progressive even after cessation of the treatment. Commonly, pulmonary fibrosis is determined radiographicallyand by pulmonary function studies; thus, it is detectable only after the damage has been expressed. In the hope of predicting lung toxicity at an earlier and pqssible reversible stage, a study was undertaken utilizing a rat lung model system to determine if serum AlCE levels could be correlated with the damage produced in the lung by BLM and/or ionizing radiation. BLM (10.0 mg/kg body weight) was administered intraperitoneally. Irradiation (12 Gy of 25 MV X-rays to the thoracic region) was performed either one day before or after BLM administration. At present, the levels of AlCE is serum at short (0 - 1.5 months) intervals after treatment have been assayed. BLM alone reduced the levels of serum AlCE below that of controls within 3 days of treatment. Treatment with X-rays alone produced a further reduction in the levels of serum AlCE that was progressive until day 7, whereupon a recovery to the level of the BLM-treated animals was seen at day 14. The combined treatment of BLM and radiation produced the greatest reduction in levels of serum AlCE at 3 days. However, there was an indication of recovery as early as 7 days (although the mean value was still below that of the individual treatments); and, at 14 days, was essentially at the level of the individual treatments. These early biochemical changes will be correlated with the later expression of histologic and radiographic evidence of normal tissue damage in the lung. Such an evaluation will not only increase our understanding of the time-course for the development of long-term normal tissue damage in lung following BLM and/or radiation treatment, but hopefully will provide a predictive assay for these changes that can be applied to the clinical situation.
INTERSTITIAL
MICROWAVE-INDUCED
HYPERTHERMIA
IN COMBINATION
WITH BRACHYTHERAt'Y
Evan B. Douple,' John W. Strohbehn,2 Christopher T. Coughlin,' Walter L. Eaton, Jr., l B. Stuart Trembly' and Terence Z. Wang' INorris 2Thayer
Cotton School
Cancer Center, Dartmouth-Hitchcock of Engineering, Dartmouth College,
Medical Center, and Hanover, NH 03755
A system for delivering local microwave-induced hyperthermia has been developed in our institution and is currently undergoing clinical trial. Flexible, gold-braid coaxial cables with outer diameters of less than 1 mm have been modified so as to serve as microwave antennas operating in the l-2 GHz frequency range. These antennas are inserted into nylon afterloading tubes which have been implanted into tumors using conventional interstitial implantation techniques for iridium-192 seed brachytherapy. The individual antennas were designed using a combination of analytical calculations and experimental measurements in tissue-equivalent phantom. Antenna arrays were tested in the tissue phantom to determine the number of antennas required, their length, and their spacing prior to insertion into patients. Planar arrays of 4 antennas for planar implants up to 6 cm x 6 cm x 2 cm or rectangular arrays of 4 antennas for volume implants up to 4 cm x 6 cm x 3 cm were used to heat a variety of tumors. The nylon afterloading tubing was implanted in the operating room under general anesthesia in a geometry prescribed for the appropriate radiation dosimetry, but antenna insertion and heating was performed in the radiation therapy department in alert patients Since the iridium-192 brachytherapy required more nylon tubes than the micro\Iraveantenna arrays, flexible thermistors (Bailey and Yellow Springs) were inserted into some of the extra tubes for thermometry. In addition, needle thermistors (Yellow Springs) were inserted directly into the tumor. Power was applied with the intent to heat the tumor volume to 42-45oC within 15 minutes and heating continued to a total of 1 hour for each treatment. Antennas were withdrawn and iridium-192 seeds were afterloaded for brachytherapy. The tumors were heated in a second treatment (1 hr) following brachytheraDy and Prior to removal of the nylon tubing. This interstitial technique of delivering local hyperthermia should be compatible for any brachytherapy technique including the suture technique and the one-side technique. Temperature distributions obtained in the tumors will be described, and alterations in power requirements resulting from blood flow changes during the heat treatment will be discussed. Responses of the tumors following the clinical trials will be summarized.
Radiation Oncology 0 Biology 0 Physics
12%
September1981, Volume’7, Number9
(This investigation was supported in part by a grant from the Whitaker Foundation and by PHS grants CA 23108 and CA 23594 awarded by the National Cancer Institute, DHHS.)
LOCALIZEDHYPERTHERMIA FOR CANCERTHERAPY WHATTREARIENTDATASHOULDBE COLLECTED? Charles F. Cottlieb.
Ph.D.,
Young H. Kim. M.D., and Juan V. Fayos, M.D.
Radiation Therapy Division CD311 University of Miami School of Medicine P.O. Box 016960. Mfrmi. Florida 33101 The last decade has witnessed an explosion in hyperthermic research. The thrust of this work has been to fill the therapeutic void which exists after failure of treatments by surgery, radiation, and chemotherapy. Unfortunately, the published reports lack precise technical lnfonnaticn. and the reporting is restricted to the presentation of temperature given to the tumor over a certain period of time. The assunption is that the tumor receives precisely the stated temperature without variation over the treatment period, an event which does not occur in clinical applications, since, in reality, the temperature fluctuates during treatment. The controlled production of localized hyperthermia is a complex problem, composed of the primary physical processes of heat production (e.g. microwave, ultrasound) and transfer in tissue, and the resulting rise in tissue temperature. The physics of these processes, involving penetration, reflection and refraction at tissue interfaces, etc. makes prediction of the result in any given instance dubious, at best. In addition, the eventual three dimensional pattern of temperature actually achieved in tissue Is secondarily dependent on physiological phenanena. principally vascularity and blood flow alterations consequent to the temperature rise. Therefore, we are forced to make careful measurements in each &nd every instance to be confident
of the temperature actually achieved in the patient. The minimum physical data required for recording and further objective evaluation of hyperthermic therapy include: 1) an accurate picture of the heating pattern produced in tissue by the hyperthermia applicator, 2) the actual temperature achieved in the tumor and surrounding tissues, 3) the heat input necessary to achieve and maintain the therapeutic temperature. and 4) The temperature and heat input must the length of the hyperthermic treatment. be sampled at sufficiently frequent intervals to detect any significant peaks or valleys which may occur during treatment. We have developed a computerized data gathering system which collects, and displays the above data. Hanual collection of information, stores, is subject to error due to the tedious and monotonous al though adequate, Our hyperthermia system automatically nature of hyperthermia treatment. collects data for the heat input to the hyperthermia applicator, and data from four temperature channels, as a finction of time, and stores the information on floppy diskette for later analysis. The stored data permits CCWPLETE reconstruction of a treatment. Our analysis includes calculation of the minimum, maximum, and mean (and standard deviation) power (heat) input to the hyperthermia applicator: the minimum, maximum, and mean (and standard deviation) temperatures for each of the four channels, and the decay of hyperthermic temperature for
AN INVESTIGATION OF HYPERTHERMIC EFFECTS ON CELL SURVIVAL REPAIR OF DNA DAMAGED BY IONIZING RAOIATION Frank Krasin,
Ph.D.
Department Tufts-New
and Edward
S. Sternick,
AND
Ph.D.
of Therapeutic Radiology England Medical Center Boston, MA 02111
These studies were carried out to establish a basis for understanding the mechanism of hyperthermia effects leading to the killing of cells also It is generally accepted that unrepaired exposed to ionizing radiation. Normally, cellular processes radiation damage in DNA leads to cell death.
1295
of the 23rd Annual ASTR Meeting
AlCE is produced in significant quantities by endothelial cells. Treatment with ionizing radiation can lead to the development of long-term normal lung tissue damage. Similarly, Bleomycin (BLM), an antitumor antibiotic, has been shown to produce damage in lung endothelial cells, resulting in the doselimiting toxicity of pulmonary fibrosis. The development of this pulmonary fibrosis is often irreversible and progressive even after cessation of the treatment. Commonly, pulmonary fibrosis is determined radiographicallyand by pulmonary function studies; thus, it is detectable only after the damage has been expressed. In the hope of predicting lung toxicity at an earlier and pqssible reversible stage, a study was undertaken utilizing a rat lung model system to determine if serum AlCE levels could be correlated with the damage produced in the lung by BLM and/or ionizing radiation. BLM (10.0 mg/kg body weight) was administered intraperitoneally. Irradiation (12 Gy of 25 MV X-rays to the thoracic region) was performed either one day before or after BLM administration. At present, the levels of AlCE is serum at short (0 - 1.5 months) intervals after treatment have been assayed. BLM alone reduced the levels of serum AlCE below that of controls within 3 days of treatment. Treatment with X-rays alone produced a further reduction in the levels of serum AlCE that was progressive until day 7, whereupon a recovery to the level of the BLM-treated animals was seen at day 14. The combined treatment of BLM and radiation produced the greatest reduction in levels of serum AlCE at 3 days. However, there was an indication of recovery as early as 7 days (although the mean value was still below that of the individual treatments); and, at 14 days, was essentially at the level of the individual treatments. These early biochemical changes will be correlated with the later expression of histologic and radiographic evidence of normal tissue damage in the lung. Such an evaluation will not only increase our understanding of the time-course for the development of long-term normal tissue damage in lung following BLM and/or radiation treatment, but hopefully will provide a predictive assay for these changes that can be applied to the clinical situation.
INTERSTITIAL
MICROWAVE-INDUCED
HYPERTHERMIA
IN COMBINATION
WITH BRACHYTHERAt'Y
Evan B. Douple,' John W. Strohbehn,2 Christopher T. Coughlin,' Walter L. Eaton, Jr., l B. Stuart Trembly' and Terence Z. Wang' INorris 2Thayer
Cotton School
Cancer Center, Dartmouth-Hitchcock of Engineering, Dartmouth College,
Medical Center, and Hanover, NH 03755
A system for delivering local microwave-induced hyperthermia has been developed in our institution and is currently undergoing clinical trial. Flexible, gold-braid coaxial cables with outer diameters of less than 1 mm have been modified so as to serve as microwave antennas operating in the l-2 GHz frequency range. These antennas are inserted into nylon afterloading tubes which have been implanted into tumors using conventional interstitial implantation techniques for iridium-192 seed brachytherapy. The individual antennas were designed using a combination of analytical calculations and experimental measurements in tissue-equivalent phantom. Antenna arrays were tested in the tissue phantom to determine the number of antennas required, their length, and their spacing prior to insertion into patients. Planar arrays of 4 antennas for planar implants up to 6 cm x 6 cm x 2 cm or rectangular arrays of 4 antennas for volume implants up to 4 cm x 6 cm x 3 cm were used to heat a variety of tumors. The nylon afterloading tubing was implanted in the operating room under general anesthesia in a geometry prescribed for the appropriate radiation dosimetry, but antenna insertion and heating was performed in the radiation therapy department in alert patients Since the iridium-192 brachytherapy required more nylon tubes than the micro\Iraveantenna arrays, flexible thermistors (Bailey and Yellow Springs) were inserted into some of the extra tubes for thermometry. In addition, needle thermistors (Yellow Springs) were inserted directly into the tumor. Power was applied with the intent to heat the tumor volume to 42-45oC within 15 minutes and heating continued to a total of 1 hour for each treatment. Antennas were withdrawn and iridium-192 seeds were afterloaded for brachytherapy. The tumors were heated in a second treatment (1 hr) following brachytheraDy and Prior to removal of the nylon tubing. This interstitial technique of delivering local hyperthermia should be compatible for any brachytherapy technique including the suture technique and the one-side technique. Temperature distributions obtained in the tumors will be described, and alterations in power requirements resulting from blood flow changes during the heat treatment will be discussed. Responses of the tumors following the clinical trials will be summarized.
Radiation Oncology 0 Biology 0 Physics
12%
September1981, Volume’7, Number9
(This investigation was supported in part by a grant from the Whitaker Foundation and by PHS grants CA 23108 and CA 23594 awarded by the National Cancer Institute, DHHS.)
LOCALIZEDHYPERTHERMIA FOR CANCERTHERAPY WHATTREARIENTDATASHOULDBE COLLECTED? Charles F. Cottlieb.
Ph.D.,
Young H. Kim. M.D., and Juan V. Fayos, M.D.
Radiation Therapy Division CD311 University of Miami School of Medicine P.O. Box 016960. Mfrmi. Florida 33101 The last decade has witnessed an explosion in hyperthermic research. The thrust of this work has been to fill the therapeutic void which exists after failure of treatments by surgery, radiation, and chemotherapy. Unfortunately, the published reports lack precise technical lnfonnaticn. and the reporting is restricted to the presentation of temperature given to the tumor over a certain period of time. The assunption is that the tumor receives precisely the stated temperature without variation over the treatment period, an event which does not occur in clinical applications, since, in reality, the temperature fluctuates during treatment. The controlled production of localized hyperthermia is a complex problem, composed of the primary physical processes of heat production (e.g. microwave, ultrasound) and transfer in tissue, and the resulting rise in tissue temperature. The physics of these processes, involving penetration, reflection and refraction at tissue interfaces, etc. makes prediction of the result in any given instance dubious, at best. In addition, the eventual three dimensional pattern of temperature actually achieved in tissue Is secondarily dependent on physiological phenanena. principally vascularity and blood flow alterations consequent to the temperature rise. Therefore, we are forced to make careful measurements in each &nd every instance to be confident
of the temperature actually achieved in the patient. The minimum physical data required for recording and further objective evaluation of hyperthermic therapy include: 1) an accurate picture of the heating pattern produced in tissue by the hyperthermia applicator, 2) the actual temperature achieved in the tumor and surrounding tissues, 3) the heat input necessary to achieve and maintain the therapeutic temperature. and 4) The temperature and heat input must the length of the hyperthermic treatment. be sampled at sufficiently frequent intervals to detect any significant peaks or valleys which may occur during treatment. We have developed a computerized data gathering system which collects, and displays the above data. Hanual collection of information, stores, is subject to error due to the tedious and monotonous al though adequate, Our hyperthermia system automatically nature of hyperthermia treatment. collects data for the heat input to the hyperthermia applicator, and data from four temperature channels, as a finction of time, and stores the information on floppy diskette for later analysis. The stored data permits CCWPLETE reconstruction of a treatment. Our analysis includes calculation of the minimum, maximum, and mean (and standard deviation) power (heat) input to the hyperthermia applicator: the minimum, maximum, and mean (and standard deviation) temperatures for each of the four channels, and the decay of hyperthermic temperature for
AN INVESTIGATION OF HYPERTHERMIC EFFECTS ON CELL SURVIVAL REPAIR OF DNA DAMAGED BY IONIZING RAOIATION Frank Krasin,
Ph.D.
Department Tufts-New
and Edward
S. Sternick,
AND
Ph.D.
of Therapeutic Radiology England Medical Center Boston, MA 02111
These studies were carried out to establish a basis for understanding the mechanism of hyperthermia effects leading to the killing of cells also It is generally accepted that unrepaired exposed to ionizing radiation. Normally, cellular processes radiation damage in DNA leads to cell death.