Search PubMed⌕ Search

Biomedical subjects

J R Oleson

Publications and source records attributed to J R Oleson.

At least 19 recordsLinked to original sources
PubMed1996

Radiation plus local hyperthermia versus radiation plus the combination of local and whole-body hyperthermia in canine sarcomas.

PURPOSE: The purpose of this study was to assess the effect of increasing intratumoral temperatures by the combination of local hyperthermia (LH) and whole body hyperthermia (WBH) on the radiation response of canine sarcomas. METHODS AND MATERIALS: Dogs with spontaneous soft tissue sarcomas and no evidence of metastasis were randomized to be treated with radiation combined with either LH alone or LH + WBH. Dogs were accessioned for treatment at two institutions. The radiation dose was 56.25 Gy, given in 25 2.25 Gy daily fractions. Two hyperthermia treatments were given; one during the first and one during the last week of treatment. Dogs were evaluated after treatment for local recurrence, metastasis, and complications. RESULTS: Sixty-four dogs were treated between 1989 and 1993. The use of LH+WBH resulted in statistically significant increases in the low and middle regions of the temperature distributions. The largest increase was in the low temperatures with median CEM 43 T90 values of 4 vs. 49 min for LH vs. LH + WBH, respectively (p<0.001). There was no difference in duration of local tumor control between hyperthermia groups (p = 0.59). The time to metastasis was shorter for dogs receiving LH + WBH (p = 0.02); the hazard ratio for metastatic disease for dogs in the LH + WBH group was 2.4 (95% confidence interval, 1.2-5.4) with respect to dogs in the LH group. Complications were greater in larger tumors and in tumors treated with LH + WBH, CONCLUSION: The combination of LH + WBH with radiation therapy, as described herein, was not associated with an increase in local tumor control in comparison to use of LH with radiation therapy. The combination of LH + WBH also appeared to alter the biology of the metastatic process and was associated with more complications than LH. We identified no rationale for further study of LH + WBH in combination with radiation for treatment of solid tumors.

Animals↗
PubMed1995

Anaphylactoid reactions with intraperitoneal cisplatin.

OBJECTIVE: To report the occurrence of anaphylactoid reactions to intraperitoneal cisplatin in 3 patients. CASE SUMMARIES: While conducting a protocol evaluating the efficacy of intraperitoneal cisplatin and hyperthermia in the treatment of recurrent ovarian cancer, 3 patients were noted to exhibit anaphylactoid reactions. A 43-year-old woman received cisplatin 60 mg/m2 in 15 minutes during her sixth cycle of therapy. She developed pruritus, edema, and urticaria over both hands. The reaction subsided after treatment with diphenhydramine and dexamethasone. A 57-year-old woman received 400 mL (62.4 mg) of a cisplatin solution concentrated to deliver cisplatin 100 mg/m2 during her first attempted therapy. At this point, she developed whole body urticaria and pruritus with edema of the extremities. The reaction was aborted with diphenhydramine and dexamethasone. Despite premedication with dexamethasone prior to a second attempt at therapy, she again experienced similar symptoms after receiving 500 mL (78 mg) of cisplatin solution. A 55-year-old woman received 2 cycles of therapy with cisplatin 100 mg/m2 without difficulty. During her third cycle, she again received cisplatin 100 mg/m2 over 30 minutes and developed palmar pruritus, urticaria, and edema. Symptomatology resolved with diphenhydramine. Despite premedication with diphenhydramine and dexamethasone, she experienced generalized pruritus and urticaria, as well as headache and chest pain/tightness, after her next infusion. For both the second and third patients, symptomatology failed to resolve until the intraperitoneal cisplatin solution was withdrawn. DISCUSSION: Anaphylactoid reactions have been described previously with cisplatin administration. No dose-rate effect has been reported, however. We observed 5 reactions in 3 patients that appear to be related to a high dose-infusion time ratio, indicating that dose and rate of infusion may be important factors in precipitating anaphylactoid reactions with cisplatin. CONCLUSIONS: We conclude that a high dose combined with a short infusion time increases the risk of anaphylactoid reactions with the administration of intraperitoneal cisplatin. There was no indication that the increase in anaphylactoid reactions was associated with the use of hyperthermia.

Adult↗
PubMed1994

Therapy monitoring in human and canine soft tissue sarcomas using magnetic resonance imaging and spectroscopy.

PURPOSE: The goals of this study were to determine whether magnetic resonance parameters (a) can identify early during therapy those patients most likely to respond to hyperthermia and radiotherapy, (b) can provide prior to or early during therapy information about the temperature distributions which can be obtained in patients receiving hyperthermia, and (c) can provide an understanding of the effects of hyperthermia on tumor metabolic status. METHODS AND MATERIALS: Twenty-one human patients and 10 canine patients with soft tissue sarcomas treated with preoperative hyperthermia and radiation had a series of magnetic resonance imaging and phosphorous spectroscopy studies done. To address the goals for both the human and canine populations, changes in mean T2 relaxation times, pH, and various phosphometabolite ratios from the pretreatment (Study 1) to the post first hyperthermia study (Study 2) were correlated with treatment outcome; pretreatment magnetic resonance parameters and changes in magnetic resonance parameters (Study 2-Study 1) were compared with various cumulative thermal descriptors; and thermal descriptors of the first hyperthermia were compared with changes in magnetic resonance phosphometabolite ratios. RESULTS: A decrease in adenosine triphosphate/phosphomonoester from study 1 to study 2 is associated with a greater chance of > or = 95% necrosis in surgical resected tumors from human patients, but no significant relationships were observed between changes in tumor pH or phosphometabolite ratios and time to local failure in dogs. Pretreatment magnetic resonance parameters correlated with various thermal dose descriptors in canines but not in humans. Change in adenosine triphosphate/inorganic phosphate and phosphomonoester signal to noise ratio correlated with cumulative thermal descriptors in dogs and humans, respectively. In dogs only, increases in thermal dose resulted in decreases in high energy phosphometabolites. CONCLUSION: Changes in magnetic resonance parameters early during therapy may be predictive of treatment outcome. Pretreatment and changes in magnetic resonance parameters appear to predict how well a tumor will be heated during hyperthermia. Magnetic resonance spectroscopy also appears to be a useful tool to study the effects of various thermal doses on tumor metabolic status.

Adenosine Triphosphate↗
PubMed1994

Clinical outcome after neoadjuvant thermoradiotherapy in high grade soft tissue sarcomas.

In the treatment of soft tissue sarcomas, hyperthermia has been demonstrated to enhance tumor necrosis from radiation therapy. The current study reports the clinical course of patients treated with this neoadjuvant therapy regimen. Forty-four patients with deep, undisturbed, nonmetastatic, high grade soft tissue sarcomas completed a neoadjuvant treatment protocol with combined hyperthermia and radiation therapy followed by wide surgical resection. Negative surgical margins were obtained in 40 patients. There was one local recurrence, thus yielding a local control rate of 97.5%. All other failures were either through regional lymphatic spread or pulmonary metastasis. As a group, the patients at 36 months had a 72% overall and a 58% disease-free survival. The most common pathologic diagnosis was malignant fibrous histiocytoma (MFH), which demonstrated a 36-month survival of 52% vs. 82% for others (P = 0.02). Tumor size was not prognostically significant for disease free or overall survival (P = 0.13). Those patients with surgical margins < 1 cm had a significantly lower disease-free survival and overall survival in a multivariate analysis (P = 0.02 and P = 0.006, respectively). Overall survival did not correlate with either the number of hyperthermia treatments received or the amount of tumor necrosis. Although this neoadjuvant protocol results in excellent local control rates, overall survival rates are comparable to adjuvant therapy employing radiation alone.

Adult↗
PubMed1993

Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.

PURPOSE: To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. METHODS AND MATERIALS: Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C. Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. RESULTS: Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7 degrees C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30-35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. CONCLUSION: Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7 degrees C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Cumulative minutes with T90 greater than Tempindex is predictive of response of superficial malignancies to hyperthermia and radiation.

PURPOSE: To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. METHODS AND MATERIALS: Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0 degrees C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24-70 Gy at 1.8-2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. RESULTS: One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T90) was > or = 40.0 degrees C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. CONCLUSIONS: These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer.

Adult↗
PubMed1993

Sensitivity of hyperthermia trial outcomes to temperature and time: implications for thermal goals of treatment.

PURPOSE: In previous work we have found that the cumulative minutes of treatment for which 90% of measured intratumoral temperatures (T90) exceeded 39.5 degrees C was highly associated with complete response of superficial tumors. Similarly, the cumulative time for which 50% of intratumoral temperatures (T50) exceeded 41.5 degrees C was highly associated with the presence of > 80% necrosis in soft tissue sarcomas resected after radiotherapy and hyperthermia. In the present work we have calculated the time for isoeffective treatments with T90 = 43 degrees C and T50 = 43 degrees C, respectively, using published thermal isoeffective dose formulae. The purpose of these calculations was to determine the sensitivity of treatment outcome to variations in thermal isoeffective dose. METHODS AND MATERIALS: The basis for the calculations were the thermal parameters and treatment outcomes in three patient populations: 44 patients with moderate or high grade soft tissue sarcoma treated preoperatively with hyperthermia and radiation; 105 patients with superficial tumors treated with hyperthermia and radiation, and 59 patients with deep tumors treated with hyperthermia and radiation. RESULTS: The thermal dose values calculated are strongly associated with outcome in multivariate logistic regression analysis. Simple dose-response equations result from the analysis, and we use these equations to assess the sensitivity of outcome upon variations in thermal dose. This information, in turn, allows us to estimate the number of patients required in Phase II and III trials of hyperthermia and radiation therapy. CONCLUSIONS: For regimens of 5 to 10 hyperthermia treatments, improvements in median T90 (superficial tumors) and T50 (deep tumors) parameters by 1.2-1.5 degrees C could result in response rates high enough (compared to radiotherapy alone) to justify Phase III trials. A similar improvement in response rates would require an increase in overall duration of treatment by a factor of 3 to 5. This would be difficult to achieve while also avoiding thermal tolerance induction. Achieving these temperature goals may be possible with improvements in hyperthermia technology. Alternatively, there may be ways to increase the sensitivity of cells to temperatures that can be achieved currently, such as pH reduction or chemosensitization.

Combined Modality Therapy↗
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↗