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Biomedical subjects

J R Oleson

Publications and source records attributed to J R Oleson.

At least 19 recordsLinked to original sources
PubMed1992

Use of nitroprusside to increase tissue temperature during local hyperthermia in normal and tumor-bearing dogs.

The present study investigates the effects of nitroprusside, a potent vasodilating agent, on tissue temperature during local hyperthermia in five normal and five tumor-bearing dogs. Caudal thigh muscles were heated in normal dogs and muscle temperatures were recorded during hyperthermia. Tumor-bearing dogs received two hyperthermia treatments during a course of radiation therapy. Temperatures were recorded in tumor and surrounding normal tissues. Mean arterial pressure was decreased by approximately 40-45% during nitroprusside infusion and was associated with a compensatory increase in heart rate and increases in tissue temperature. In normal dogs, muscle temperatures increased an average of 1.7 degrees C with nitroprusside administration. When nitroprusside was administered at the beginning of local hyperthermia to induce step-down heating, approximately 48% of the measured positions in caudal thigh muscle achieved a temperature greater than or equal to 43 degrees C, sufficient to induce step-down heating, during the hyperthermia episode. In tumor-bearing dogs, there was a significant increase in tumor and normal tissue temperatures during nitroprusside administration. Estimated T90 and T50 descriptors increased by 0.9 degrees C and 1.6 degrees C, respectively, for tumor tissue and by 0.4 degrees C and 1.2 degrees C, respectively, for normal tissue. Despite the increase in normal tissue temperatures no toxicity was observed in these dogs. Nitroprusside may be a useful agent for manipulation of tumor temperatures during the entire hyperthermia treatment or for a short time period at the initiation of treatment to induce step-down heating.

Animals↗
PubMed1992

Phase I/II study of external radio frequency phased array hyperthermia and external beam radiotherapy in the treatment of prostate cancer: technique and results of intraprostatic temperature measurements.

As part of an ongoing Phase I/II study at Duke University Medical Center investigating the toxicity and efficacy of external beam radiotherapy plus hyperthermia for deep-seated, locally advanced or recurrent solid tumors, 12 patients with prostate malignancies (adenocarcinoma--11, leiomyosarcoma--1) were treated with radiotherapy plus hyperthermia. Hyperthermia was given after radiotherapy using a Radio Frequency Phase/Amplitude Control Sigma 60 annular phased array device. All patients had simultaneous temperature measurements made in the rectal lumen and within the prostate during at least one hyperthermia session. Intraprostate thermometers were placed via a unique method described herein using both computerized tomography scan and a rigid sigmoidoscope for guidance. We were able to achieve the desired tumor temperature of > or = 42.5 degrees C in only 1/28 (3.5%) of hyperthermia treatments. Subjective symptoms of pain and/or pressure limited power deposition in 79% of hyperthermia treatments. Higher temperatures were achieved in the distal rectum than in the prostate in all treatments, although the differences were not statistically significant. This temperature differential could not be compensated by using phase and amplitude steering. Rectal temperatures adjacent to the prostate were predictive of prostate temperatures. We conclude that using this regional heating technique we were unable to demonstrate an ability to get an advantageous temperature differential between the prostate and normal tissue. This technique is not useful as an adjuvant to radiation therapy for prostate cancer. The usefulness of other regional heating techniques and devices should be explored.

Adenocarcinoma↗
PubMed1991

Heating patterns generated by phase modulation of a hexagonal array of interstitial antennas.

In this paper, we investigate an array of six interstitial microwave antennas used for hyperthermia cancer treatment. The purpose is to generate both uniform and controlled nonuniform heating patterns in biological tissue by phase modulating the signals applied to each antenna. The array consists of six antennas positioned on the corners of a hexagon. The distance between two diagonal antennas is 4 cm. The distributions of absorbed power per unit mass within the array are computed, and then converted into temperature distributions through a thermal conduction simulation. The SAR and temperature patterns are presented in both the lateral plane (perpendicular to the antennas) and the axial plane (parallel with the antennas). By proper phase modulation of microwave signals applied to each antenna, a uniform heating pattern can be produced within the entire array volume. Also, a peripheral heating pattern may be generated around the array; again, by using the proper phase modulation. The modulation schemes for generating both types of heating patterns are discussed.

Animals↗
PubMed1990

Effects of hyperthermia and irradiation on the growth of mouse melanoma tumors following immunotherapy.

Recent investigations suggest that adjuvant hyperthermia enhances the response of human malignant melanoma to ionizing radiation. A study was undertaken to explore the effect of radiation and hyperthermia on the responsiveness of melanoma following active immunization with lethally irradiated B16 melanoma cells in C57 BL 6 mice. Two groups of mice were treated: group 1 received immunotherapy on days 2-5 following tumor inoculation, and group 2 received immunotherapy on days 15-18 following tumor inoculation. The mice in each group were subsequently randomized into one of three subgroups: 1) no further treatment; 2) radiation therapy alone (6 Gy in a single fraction); 3) radiation therapy and regional hyperthermia (43 degrees C x 1 hour). Tumor sizes were measured regularly, and between day 52 and 63 the animals were sacrificed and the lungs sectioned for counting of metastatic tumors. Results from this study show that the immunomodulated B16 murine melanoma is responsive to radiation therapy alone and that this responsiveness is enhanced by the addition of adjuvant regional hyperthermia. There did not appear to be any significant effect of radiation therapy or radiation therapy plus hyperthermia on the development of lung metastases in this tumor model system.

Animals↗
PubMed1990

Interstitial thermoradiotherapy: thermal dosimetry and clinical results.

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.

Brachytherapy↗
PubMed1990

Transperineal templates for brachytherapy treatment of pelvic malignancies--a comparison of standard and customized templates.

A technique is described for the design and construction of customized templates for transperineal implants and interstitial hyperthermia of pelvic malignancies. The design of the template and the distribution of the transperineal Iridium-192 seed ribbons are based on prior optimization of the dose distribution. The target volume is defined by means of pelvic examination and pertinent radiographic studies including a CT. The pelvic CT study is obtained with a plastic obturator in the rectum or the vagina. The obturator is used as a reference structure for aligning the target contour from each image plane to form a composite 2-dimensional contour of maximum tumor extent in a plane perpendicular to the obturator. Dose distributions are calculated to determine the placement of the Iridium-192 seed ribbons in the template. Laparoscopic guidance is used for actual placement of brachytherapy source needles together with a rectal or vaginal obturator to stabilize the template and to assure that the needle placement conforms with the planned geometry. Dose distributions for 10 consecutive patients calculated for customized templates as well as for five commercially available standard templates show that the customized templates are superior to standard templates in that the planned dose distribution matches the configuration of the target volume and is more uniform than with standard templates.

Adult↗
PubMed1990

Soft-tissue sarcomas: MR imaging and MR spectroscopy for prognosis and therapy monitoring. Work in progress.

The authors studied the usefulness of hydrogen-1 T2 measurements and phosphorus-31 magnetic resonance (MR) spectroscopy as indicators of prognosis and monitors of response to therapy in a group of patients with soft-tissue sarcomas. All eight patients were treated with combined local hyperthermia and fractionated radiation therapy, followed by surgical resection of the tumor. Each patient underwent T2 measurements and five patients underwent MR spectroscopy (phase encoded in one dimension) before treatment, after the first hyperthermia treatment, at the end of the therapy course, and just before surgery. Catheter thermometry was performed at each hyperthermia treatment. The T2 and MR spectroscopic variables were compared with thermometric data and the histologic findings from the complete surgical specimen. Changes in T2 correlated with histologic grade of tumor and thermometric data. The pretherapy tumor pH correlated positively, and changes during therapy in pH, ratio of phosphocreatine to inorganic phosphate (Pi), ratio of nucleoside triphosphate to Pi, and the phosphomonoester signal-to-noise ratio correlated negatively, with the percentage of tumor necrosis on the surgical specimen. These preliminary data suggest MR imaging and MR spectroscopy may be useful in the evaluation of such patients before and during therapy.

Adult↗
PubMed1989

Preoperative hyperthermia and radiation for soft tissue sarcomas: advantage of two vs one hyperthermia treatments per week.

As part of an ongoing Phase II trial at Duke University Medical Center (DUMC), patients with Stage IIB-IVA soft tissue sarcomas (STS) potentially amenable to wide local excision were treated with preoperative hyperthermia (HT) plus radiation therapy (RT), with HT randomized to one versus two treatments per week, stratified with respect to tumor volume. 17 patients were treated and analyzed. HT was given 30-60 minutes after RT, with heating maintained for 1 hour after 42.0 degrees C was reached. In patients treated with 2 HT per week, treatments were separated by 48 hrs. Concurrent RT was given with 180-200 cGy fractions, five treatments per week, to a nominal tumor dose of 5000-5040 cGy. Surgical extirpation was performed 4 weeks after completion of HT/RT. Treatment effect was evaluated by histopathologic examination of the resected lesions, according to a previously reported system. The mean number of HT given in the 1 and 2/wk groups was 4.4 and 7.3, respectively (p less than 0.01). Tmax for the 1 and 2 HT/wk groups was 42.4 +/- 2.1 degrees C and 43.5 +/- 1.8 degrees C, and T min was 38.1 +/- 0.8 degrees C and 38.6 +/- 0.5 degrees C, respectively. The increase in T min from first to last treatment was 0.5 +/- 1.2 degrees C and 1.0 +/- 0.8 degrees C, respectively. The T min from the best treatment was 39.1 +/- 1.2 degrees C and 40.0 +/- 1.0 degrees C, and the Tmax from the best treatment was 44.5 +/- 3.4 degrees C and 45.4 +/- 2.5 degrees C for the 1 and 2 HT/wk groups, respectively. There were no statistically significant differences between the 2 treatment groups for any of the above temperature parameters. Severe histopathologic changes were found in 71% (12 of 17) of the lesions. T min and Tmax and highest T min and Tmax were between 0.4-1.1 degrees C higher in patients with severe changes (p = NS). All 9 patients in the 2 HT/wk group had extensive changes, versus only 3 of the 8 patients in the 1 HT/wk group. This difference was highly statistically significant (p = 0.009, two-tailed Fisher's exact test). These findings suggest an advantage to twice weekly, as opposed to weekly, HT in the setting of this study. Whether there is a corresponding therapeutic gain, or whether these results can be extrapolated to other settings requires further investigational efforts. It is recommended that treatment parameters, particularly temperature parameters, continue to be examined in Phase II trials.

Adult↗
PubMed1989

Tumor temperature distributions predict hyperthermia effect.

Review of clinical hyperthermia (HT) trial results shows that there previously has not been a robust model relating efficacy of HT treatments to characteristics of the temperature distribution. Lack of a model has been an impediment in Phase II trials; these trials must include defining the prescription for HT treatment, optimizing the schedule of HT treatments, and defining quality assurance procedures. We propose a model that is based upon noting that the majority of a tumor volume is contained in the outermost "shell" of a solid tumor, across which shell the radial temperature distribution is assumed to be linear. Any linear distribution can be defined by coordinates of a point and a slope, and we choose the temperature at the radiographically defined edge of a tumor and the slope (dT/dr) across the outer shell as these determinants of the linear radial temperature distribution. A discriminant analysis of success or failure of treatment can then be based upon these two descriptors (Tedge, dT/dr). We have tested this model using data from patients with soft tissue sarcoma (Stage IIB or greater) that have entered an ongoing prospective trial of conventional preoperative radiotherapy (5000 cGy/25 Fx/5 wk) together with HT, the latter randomized to be given once or twice weekly during the 5 week course. Wide local excision of the primary tumor is done 1 month after completion of radiotherapy, and the extent of histologic change in the resected specimen is scored. Our model has an 86% predictive value for lack of complete or nearly complete necrosis in the resected specimen according to whether the time-averaged Tedge and slope during each HT treatment satisfy the equation Tedge + 1.2 (slope in degree C/cm) less than or equal to 40.6 degrees C in all but one treatment at most. Conversely, in 85% of cases with complete or nearly complete tumor necrosis, temperature distributions satisfied Tedge + 1.2 (slope in degree C/cm) greater than 40.6 degrees C during at least one HT treatment. Requiring greater than or equal to one third of treatments of a patient to satisfy the preceeding discriminant equation resulted in 80% of patients being correctly classified as a responder or nonresponder, with only one false positive prediction (patient incorrectly classified as a responder). The model can reveal systematic changes in the edge temperature distribution during the treatment course that are consistent with tumor perfusion changes inferred and measured by independent means.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Temperature↗
PubMed1989

Improved coupling of ultrasound hyperthermia applicators to patients.

Coupling ultrasound (US) hyperthermia (HT) applicators to patients requires an acoustical medium conforming to both applicator and patient that allows for rapid, reproducible set-up for each treatment and prevents drift or misalignment of the applicator during treatments. We describe a technique that uses a commercially available immobilization foam to create a rigid, conforming foam block that kinematically positions the US applicator over the tumor area. The central volume of the foam block is removed and filled with a plastic bag of degassed water or with US gel during treatments. We also describe a technique for positioning surface and interstitial thermometry sensors in alignment with individual elements of a multi-element US applicator. Using these techniques, relative movement between patient and applicator is minimized, correct thermometry sensor location relative to each US element is confirmed, and efficient transmission of the acoustical power into the target volume is assured. These techniques are particularly important when using multi-element applicators with complex temperature-power control algorithms.

Humans↗
PubMed1989

Deep regional hyperthermia of the liver. A clinical study of 49 patients.

From 1981 to 1986, six medical centers participated in feasibility studies of radiofrequency deep regional hyperthermia (HT) in the treatment of hepatic metastases. A total of 49 patients, 32 men and 17 women, were treated with an annular phased array. Colon was the primary site in 74% of the patients, and adenocarcinoma was the diagnosis in 80%. More than one half of the patients had been treated previously. This included chemotherapy (CT) in 17 patients and radiotherapy (RT) in 10 patients, with a mean RT dose of 24 Gy. Upper abdominal pain was the dominant presenting symptom in 53% of patients. In the study, treatment was administered as follows: 14 (28%) patients received HT alone, 17 (35%) received HT + RT, 14 (28%) received HT + CT, and 4 (8%) received HT + RT + CT. A total of 157 HT treatments was administered at a mean frequency of 55 MHz and a mean power of 780 watts. The number of HT sessions ranged from 1 to 8, with a mean of 3.2 treatments per patient. Temperature was monitored continuously throughout each treatment session. The treatment aim was to reach and maintain a temperature of 42.5 degrees C for 30 min. In practice, owing to the difficulty in reaching this temperature, an equivalent (lower) temperature from 40 to 42 degrees C was used, extending the duration of treatment sessions to 45-60 min. Thermal dose was defined as the number of minutes at 42.5 degrees C or its equivalent. In 21 (43%) patients, a temperature less than 40 degrees C was obtained and thermal dose = 0. Thermal dose was less than or equal to 50 in 17 (35%) patients, greater than 50 less than or equal to 100 in 7 (14%), and greater than 100 in 4 (8%). RT was given at a daily dose of 1.8 Gy to a total of less than 20 Gy in 14 patients, greater than 20 less than or equal to 30 Gy in 6, and greater than 30 Gy in 1. CT consisted of 5-Fluorouracil by way of Hepatic Artery Infusion (HAI) in 9 patients, i.v. cisplatin in 5, and doxorubicin HAI in 3. Objective tumor regression (CR + PR) was seen in 6 (12%) patients. An additional 10 (20%) patients had less than 50% greater than 25% tumor regression, and 10 (20%) had complete or partial pain relief. The median duration of CR and PR was 26 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗