Emeritus Faculty, Acad Council, Radiation Oncology
View details for Web of Science ID 000229274300023
Radiobiological measurements have been made under various conditions of muliport pion irradiation using the Stanford Medical Pion Generator (SMPG). Chinese hamster cells (HA-1) were suspended in a tissue-equivalent 25% gelatin/medium solution. Hypoxic and aerobic HA-1 cells were irradiated simultaneously in a cylindrical water tank at either 4 or 16 degrees C. Irradiation at the focus of 60 converging pion beams, at a peak dose rate of 6 rads/min, gave relative biological effectiveness (RBEs) of 2.8, 1.8 and 1.4 at 50, 20 and 5% survival, respectively, and an oxygen enhancement ratio (OER) of 1.7. Plateau irradiation with crossing pion beams, at a peak dose-rate of 3 rads/min, resulted in survival values very close to those obtained with similar doses of 85 kV X-rays. Preliminary studies with large irradiation volumes in broadened pion stopping regions indicate RBEs significantly > 1 for survival > 50%. Supporting microdosimetric data with the SMPG are consistent with the radiobiological results.
View details for Web of Science ID A1994NP47600008
View details for PubMedID 7930802
Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study.From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures.Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively.From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.
View details for Web of Science ID A1994MP35300020
View details for PubMedID 8270436
An adaptive temperature control system has been developed for the microstrip antenna array applicators used for large area superficial hyperthermia. A recursive algorithm which allows rapid power updating even for large antenna arrays and accounts for coupling between neighbouring antennas has been developed, based on a first-order difference equation model. Surface temperatures from the centre of each antenna element are the primary feedback information. Also used are temperatures from additional surface probes placed within the treatment field to protect locations vulnerable to excessive temperatures. In addition, temperatures at depth are observed by mappers and utilized to restrain power to reduce treatment-related complications. Experiments on a tissue-equivalent phantom capable of dynamic differential cooling have successfully verified this temperature control system. The results with the 25 (5 x 5) antenna array have demonstrated that during dynamic water cooling changes and other experimentally simulated disturbances, the controlled temperatures converge to desired temperature patterns with a precision close to the resolution of the thermometry system (0.1 degree C).
View details for Web of Science ID A1993LB46600013
View details for PubMedID 8515149
The optimal treatment with hyperthermia of superficially located tumors which involve large surface areas requires applicators which can physically conform to body contours, and locally alter their power deposition patterns to adjust for nonuniform temperature caused by tissue inhomogeneities and blood flow variations. A series of 915 MHz microstrip array applicators satisfying these criteria have been developed and clinically tested. Clinical and engineering design tradeoffs for practical devices are discussed. Measurements taken in tissue equivalent phantoms and a summary of our clinical experiences with these microstrip arrays are presented.
View details for Web of Science ID A1992HR46100006
View details for PubMedID 1526638
Pretreatment and treatment related factors were reviewed for 996 hyperthermia sessions involving 268 separate treatment fields in 131 patients managed with hyperthermia for biopsy confirmed local-regionally advanced or recurrent malignancies to ascertain parameters associated with the development of complications. A subset of 249 fields were identified in which multipoint or mapped temperature data were available for at least one treatment session per field. A total of 198 fields involved superficially located tumors (less than or equal to 3 cm from the surface), whereas 51 fields involved more deeply located tumors. Most of these patients had received extensive prior therapy: 77% had surgery, 75% chemotherapy, 65% radiation therapy and 28% hormonal therapy. They were treated with hyperthermia in conjunction with radiation therapy (244 fields) or hyperthermia alone (5 fields). The hyperthermia treatment objectives were to elevate intratumoral temperatures to a minimum of 43.0 degrees C for 45 minutes while maintaining maximum normal tissue temperatures to less than or equal to 43 degrees C and maximum intratumoral temperatures to less than or equal to 50 degrees C. The hyperthermia was given within 30 to 60 minutes following radiation therapy without the administration of additional analgesics. Hyperthermia treatment regimens using radiative electromagnetic, ultrasound, or radiofrequency interstitial techniques were individualized, with 3 to 4 days between hyperthermia treatments and an average of 3.6 treatments (range 1-14; standard deviation 2.2) utilized per field. A total of 38 complications in 33 treatment fields were noted; an incidence of 27/198 (13.6%) for fields with superficially located tumors, and 6/51 (11.8%) in fields with more deeply located tumors. Univariate analyses demonstrated statistically significant correlations between the maximum tumor temperature (p = 0.0005), average of the maximum tumor temperatures (p = 0.0006), the average of the % tumor temperatures greater than 43.5 degrees C (p = 0.0071), and the average number of hyperthermia treatments (p = 0.033), with the development of complications. The average of the maximum measured tumor temperature for fields without complications was 44.6 degrees C compared with 45.9 degrees C for fields with complications. The complication rate increased from 7.5% (9/120) in fields that received one or two hyperthermia treatments to 18.6% (24/129) in fields that received greater than two hyperthermia treatments. Multivariate logistic regression analyses revealed the best bivariate model predictive of the development of complications included average of the maximum tumor temperature and the number of treatments per field (p = 0.00012 for the bivariate model).(ABSTRACT TRUNCATED AT 400 WORDS)
View details for Web of Science ID A1992HN40700024
View details for PubMedID 1555992
From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia-radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.
View details for Web of Science ID A1990EQ58000021
View details for PubMedID 2262371
Total-Skin Electron Therapy (TSET) modalities have been developed at two energies on a Varian Clinac 1800. The physical criteria for the beams were determined mainly from the requirement of continuing the Stanford treatment technique, which was 12 Total-Skin Electron Therapy portals combined in six pairs. The penetration of the lower energy mode matches that previously obtained at Stanford on the Varian Clinac 10, (about 4 mm for the 80% isodose contour in the 12-field treatment). The penetration of the higher energy mode is about 8 mm at the 80% contour. The Total-Skin Electron Therapy modes necessarily use electrons produced by the two standard electron-beam modes of lowest energy, nominally 6 and 9 MeV. Measurements to verify the beam specifications were carried out with diodes, a variety of ionization chambers, and a specially constructed circular phantom for film dosimetry. Initially, the penetration of the Total-Skin Electron Therapy beams was too large to match our criteria, so two methods of reducing it were explored: (a) the energies of the electron beams produced by the machine were reduced (which also reduced the energies of the corresponding standard electron modes) and (b) a large polymethylmethacrylate degrader (2.4 m X 1.2 m) 1 cm thick was placed just in front of the patient plane. Acceptable Total-Skin Electron Therapy beams could be produced by either method and the latter was finally used. The use of the standard dose monitoring system for the Total-Skin Electron Therapy modes considerably simplifies the daily treatment delivery as well as the implementation. However, the need for reasonable dose rates at the treatment plane (3.5 meters beyond the isocenter) requires dose rates of 24 Gy/min at the isocenter. Nevertheless, it is possible to use the internal dose monitor provided the problems associated with high dose rates (recombination and amplifier saturation) are addressed. Solutions to these problems involved switching the primary and back-up dose monitors, increasing the collecting voltage on the ion chambers, and calibrating the dose monitor so that 1 unit = 1 cGy at the patient rather than at the isocenter.
View details for Web of Science ID A1990CZ51100024
View details for PubMedID 2318700
Spiral microstrip microwave (MW) antennas have been developed and adapted for use as clinical hyperthermia applicators. The design has been configured in a variety of forms including single fixed antenna applicators, multi-element arrays, and mechanically scanned single or paired antennas. The latter three configurations have been used to allow an expansion of the effective heating area. Specific absorption rate (SAR) distributions measured in phantom have been used to estimate the depth and volume of effective heating. The estimates are made using the bioheat equation assuming uniformly perfused tissue. In excess of 500 treatments of patients with advanced or recurrent localized superficial tumors have been performed using this applicator technology. Data from clinical treatments have been analyzed to quantify the heating performance and verify the suitability of these applicators for clinical use. Good microwave coupling efficiency together with the compact applicator size have proved to be valuable clinical assets.
View details for Web of Science ID A1990CK39500029
View details for PubMedID 2298626
The smearing effects due to thermal conduction along various, nonenergized, interstitial devices were quantified in a flow cell-thermal step gradient. An insulated cylindrical flow cell with a high (ca 45 degrees C, 1.12 cm i.d., 1.6 cm o.d.) temperature region surrounded by a low (ca 37 degrees C) temperature region was used to compare temperature profiles measured with a thermocouple sensor inside a Stanford radiofrequency (RF) hyperthermia/brachytherapy catheter, a BSD instrumented microwave (MW) antenna (i.e., thermistor integrated into a dipole antenna) and a Dartmouth MW antenna with a juxtaposed optical sensor. Two parameters were used to quantify the thermal smearing of each interstitial device in the flow cell: (a) the maximum temperature difference (MTD) and (b) the full- width- half-maximum (FWHM) of the high temperature region. The "true" temperature maximum (45.4 degrees C) and distribution (FWHM = 1.65 +/- 0.06 cm) were measured with an optical sensor. These data indicate that the BSD instrumented MW antenna significantly smeared the true temperature profile (MTD = 2.7 degrees C, FWHM = 2.1 cm), as did the Dartmouth MW antenna (MTD = 1.5 degrees C, FWHM = 1.7 cm). The Stanford RF catheter, when insulated, resulted in minimal smearing (MTD = 0.3 degrees C, FWHM = 1.9 cm). Moreover, when the insulation was removed so the RF electrode was exposed to the thermal step gradient, smearing was again minimal (MTD = 0.3 degrees C, FWHM = 1.9 cm).
View details for Web of Science ID A1989AA87300029
View details for PubMedID 2722595
A mathematical model for heating and cooling during hyperthermia has been developed from an appropriate solution of a bioheat transfer equation. Predicted cooling rates obtained from the model have been compared with cooling rates obtained from experiments performed on both perfused and non-perfused normal canine brain tissue. The agreement between the predicted and observed cooling rates in non-perfused tissue is satisfactory (within 6-11 per cent) and provides confidence that the conduction process is being accurately represented. The model is then used to estimate the relative contribution of conductive and convective (blood flow) heat loss during cooling for the in vivo experiments. Estimates of blood flow dynamics are made from cooling data taken early and late in a heating course using the model to correct for conductive heat loss. Simplified forms of the bioheat transfer equation are examined. An adequate model for the observed cooling data is one that treats heat loss (both conduction and blood flow) as a heat sink (i.e. an effective perfusion model) rather than an effective thermal conductivity model.
View details for Web of Science ID A1989T145300010
View details for PubMedID 2926188
The effects of blood flow and thermal conduction during microwave hyperthermia were investigated in normal canine brain. Heating was accomplished with an external microstrip spiral antenna and temperature measurements were made using a multichannel fluoroptic thermometry system. In order to determine cooling rates, temperature measurements made during cooling were fitted with a model consisting of a constant value and an exponential term. Data from experiments in both perfused and non-perfused brains could be fitted with this simple model. The resulting cooling rates indicated that heat loss by conduction is comparable to that by blood flow. In another series of experiments, temperature measurements were made during several 1 min cooling intervals in which the power was shut off intermittently during a 35 min heating episode. Results were consistent with a 2-3-fold increase in blood flow rate which occurred gradually throughout the course of heating. Parameters that affect the determination of cooling rates are discussed in terms of the bioheat transfer equation. These investigations demonstrate that a simple heat sink model provides a good representation of the cooling data for the thermal distributions obtained.
View details for Web of Science ID A1989T145300009
View details for PubMedID 2926187
View details for Web of Science ID A1988M032300001
From September 16, 1981, through April 4, 1986, a total of 21 radiative electromagnetic (microwave and radiofrequency), ultrasound and interstitial radio-frequency hyperthermia applicators and three types of thermometry systems underwent extensive phantom and clinical testing at Stanford University. A total of 996 treatment sessions involving 268 separate treatment fields in 131 patients was performed. Thermal profiles were obtained in 847 of these treatment sessions by multipoint and/or mapping techniques involving mechanical translation. The ability of these devices to heat superficial, eccentrically located and deep-seated tumours at the major anatomical locations is evaluated and the temperature distributions, acute and subacute toxicities, and chronic complications compared. Average measured tumour temperatures between 42 degrees C and 43 degrees C were obtained with many of the devices used for superficial heating; average tumour temperatures of 39.6 degrees C to 42.1 degrees C were achieved with the three deep-heating devices. When compared to the goal of obtaining minimum tumour temperatures of 43.0 degrees C, all devices performed poorly. Only 14 per cent (118/847) of treatments with measured thermal profiles achieved minimum intratumoural temperatures of 41 degrees C. Fifty-six per cent of all treatments had associated acute toxicity; 14 per cent of all treatments necessitated power reduction resulting in maximum steady-state temperatures of less than 42.5 degrees C. Direct comparisons between two or more devices utilized to treat the same field were made in 67 instances, including 19 treatment fields in which two or more devices were compared at the same treatment session. The analyses from direct comparisons consistently showed that the static spiral and larger area scanning spiral applicators resulted in more favourable temperature distributions. Three fibreoptic thermometry systems (Luxtron single channel, four channel and eight channel multiple [four] probe array), the BSD Bowman thermistor system and a thermocouple system were evaluated with respect to accuracy, stability and artifacts. The clinical reliability, durability, and patient tolerance of the thermometry systems were investigated. The BSD Bowman and third generation Luxtron systems were found clinically useful, with the former meeting all of our established criteria.
View details for Web of Science ID A1988M032300006
View details for PubMedID 3346585
The rates of cooling ("thermal washout") in selected sites in tumor and adjacent normal tissues following the completion of clinical hyperthermia sessions were analyzed in ten patients treated with combined radiation and hyperthermia for deep seated recurrent or metastatic tumors. The temperatures were recorded at 10 second intervals for at least 2 minutes after the cessation of microwave power at the end of the 30-60 minute duration hyperthermia treatments. These thermal washouts were characterized by the slope of a log-linear relation between temperature elevation above the oral baseline temperature and time. Washout rates (expressed as a perfusion rate in ml/100g-min) significantly correlated with tissue categories as noted on CAT scan (i.e., tumor, normal tissue, tumor/normal tissue interface, hypodense tumor areas). Relationships between thermal washout rate and steady-state temperature elevation were tested and also showed significant correlations in general and for some specific tissue categories. The implications of these findings in explaining inhomogeneities in heating patterns, and in hyperthermia treatment modeling will be presented.
View details for Web of Science ID A1987H568400015
View details for PubMedID 3583862
Regional heating administered with an annular array to 12 patients with deep-seated advanced malignant disease eccentrically located in the lower abdomen and pelvis is compared based on the annular array operating configuration. One configuration (4 quadrants active) delivers radiofrequency power with relative uniformity throughout the patient cross-section. The other (2 quadrants active) allows the radiofrequency power deposition to be shifted preferentially into the eccentrically located treatment volume. Phantom measurements have been made to demonstrate the redistribution of radiofrequency power that results when the annular array is operated in these respective configurations. Systemic responses (i.e. oral temperature rise, changes in blood pressure, and heart rate) to these regional hyperthermia applications are compared and are not significantly different with respect to these heating configurations. Temperature data obtained during treatment sessions using these two annular array operating configurations are analyzed based on the fraction of measured tumor and normal tissue temperatures exceeding or equal to a given index temperature. Although the two quadrant configuration is more efficient in delivering power to the treatment volume, this analysis does not indicate a significant gain in therapeutic heating as a result of this preferential power deposition. Treatment tolerance and heterogeneity with respect to tissue type and blood flow remained the dominant limiting factors with regard to temperatures achieved.
View details for Web of Science ID A1987F971200013
View details for PubMedID 3804820
The clinical application of hyperthermia in the treatment of deep-seated tumors remains an empirical science. The pleomorphic nature of the neoplasms and the great diversity in the anatomy and physiology of the individual tumor locations make the treatment of nearly every neoplasm a unique challenge. A wide variety of devices is required, both for the administration of hyperthermia and for the measurement of the temperatures achieved. At Stanford University, these include the BSD Medical Corp. annular phased array system, an isospherical ultrasound device, and interstitial radiofrequency for deep heating. Ultrasound transducers and a variety of microwave applicators are used for superficial hyperthermia. Six illustrative case studies, selected from the 91 patients treated in our program since October 1981, are presented, with discussion and comparison of treatment devices. Difficulties in deep heating were encountered in several instances, believed secondary to the thickness of the s.c. fat, the relatively high heat-induced tumor blood flow, and the presence of adjacent bone. It is suggested that ultimate improvement in clinical results will be possible once a better understanding is achieved of such anatomical and physiological factors.
View details for PubMedID 6467237
View details for Web of Science ID A1984TQ25600017
View details for Web of Science ID A1984TQ25600024
The PIOTRON is a large solid angle superconducting channel built for the use of negative pi-mesons in radiotherapy. The pions are produced by protons of 590 MeV striking a target of molybdenum or beryllium. The pions are divided into 60 channels and deflected twice to enter the treatment volume radially. The momentum and the momentum band for all 60 channels can be chosen and the beam spot of Bragg peak pions at the isocenter of the applicator is a few centimeters in each direction. Dynamic scanning can thus achieve 3-dimensionally shaped treatment volumes. Two different methods are available: the ring scan, using changes of pion range; and the spot scan, involving translation of the patient through the fixed beam spot. Dose distributions of individual and multiple beams were plotted in a cylindrical water phantom. Radiobiological experiments with mammalian cells in gel and with mouse feet were performed. A special beam geometry using a sector of 15 beams was selected for the first treatments of patients with metastatic skin nodules. Six patients were treated. Acute skin reactions were scored and compared with those from orthovoltage therapy with comparable beam geometry. The RBE for 10 fractions is between 1.4 and 1.5. The next step involved treatment of patients inside water-bolus rings in preparation for dynamic therapy. Patients were then treated with the spot scan dynamic mode in the water bolus. The initial responses and reactions are favorable and confirm the feasibility and accuracy of dynamic pion therapy.
View details for Web of Science ID A1982PH01400004
View details for PubMedID 6815138
View details for Web of Science ID A1981LG57500002
The skin-sparing effect of megavoltage photons is lost to a varying extent when tangential beams are used to irradiate the chest wall. The skin dose for this technique, with and without a bolus, was investigated for 4- and 6-MV photons using film, thermoluminescent dosimeters, and an ionization chamber. Metal/tissue interface effects were observed when a flexible brass fabric material was used as a bolus.
View details for Web of Science ID A1978FH28200040
View details for PubMedID 96492