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R A Steeves

Publications and source records attributed to R A Steeves.

At least 19 recordsLinked to original sources
PubMed2000

On the use of virtual simulation in radiotherapy of the intact breast.

In this paper a method of breast cancer treatment planning using virtual simulation implemented at the Department of Human Oncology at the University of Wisconsin is described. All patients in this procedure are placed in a custom vacuum mold in treatment position with both arms up to avoid collision with the CT scanner aperture. For all patients a CT scan of 5-mm-slice thickness is acquired. The ipsilateral and contralateral breast, the ipsilateral lung and the heart are delineated and a three-dimensional plan is generated that tries to minimize the dose to the ipsilateral lung and heart while ensuring adequate coverage of the affected breast. Digitally reconstructed radiographs are used to verify the patient setup on the treatment machine.

Breast Neoplasms↗
PubMed1998

Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.

PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

Animals↗
PubMed1997

Radiation therapy for squamous cell carcinoma in dystrophic epidermolysis bullosa: case reports and literature review.

Dystrophic epidermolysis bullosa (DEB) is a debilitating systemic disease frequently associated with biologically aggressive secondary squamous cell carcinomas arising from affected skin or mucosal surfaces. Treatment of these carcinomas with surgery, chemotherapy, or radiation is complicated by inherently poor wound healing. We report on two DEB patients treated with radiation therapy for locally advanced squamous cell carcinoma, and retrospectively analyze 10 DEB patients treated with radiation, reported in the literature. Of the 11 fully available and described case results from radiation therapy, six (54%) patients demonstrated a partial tumor response. All patients receiving > 4,500 cGy developed moist skin desquamation and delayed skin healing. Radiation therapy may be of benefit in palliating DEB patients who have locally advanced carcinoma, but has been associated with enhanced normal tissue toxicity, suggesting a narrow or absent therapeutic index between irradiated carcinoma and skin.

Adult↗
PubMed1997

Temperature distributions during thermoradiotherapy: a sensitivity study with a transient numerical model of the rabbit eye.

An approach to the treatment of medium-sized choroidal melanomas combines radiation with ferromagnetic hyperthermia. The study herein discusses results with a numerical thermal model of a choroidal melanoma in the rabbit eye as treated with episcleral, thermoradiotherapy plaques. The sensitivity of a temperature-dependent blood perfusion model is investigated.

Animals↗
PubMed1996

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Animals↗
PubMed1995

Thermoradiotherapy of intraocular tumors in an animal model: concurrent vs. sequential brachytherapy and ferromagnetic hyperthermia.

PURPOSE: To compare concurrent vs. sequential ferromagnetic thermoradiotherapy in vivo. METHODS AND MATERIALS: Greene melanomas were implanted subretinally in rabbits and observed until they were 3-5 mm in diameter. Episcleral plaques were assembled with 125I seeds for radiation therapy, or with ferromagnetic (FM) thermoseeds and nonradioactive I seeds for hyperthermia. Rabbits were implanted by centering a plaque over the intraocular melanoma. After a given dose of radiation had been delivered, the plaque was removed and a nonradioactive plaque containing FM thermoseeds was inserted into the same extrascleral space. One hour later, hyperthermia (46-47 degrees C at the plaque-scleral interface) was initiated and continued for a period of 1 h by placing the rabbits in a magnetic induction coil powered to 1200 W. Tumor size was determined at 1- to 2-week intervals by indirect ophthalmoscopy and by ultrasound. RESULTS: Dose-response analysis of 27 treated eye melanomas showed 50% local tumor control at 43 Gy for 125I alone and 29.4 Gy for 125I followed by FM hyperthermia. The thermal enhancement ratio was 1.4. CONCLUSION: Comparison with a previously published thermal enhancement ratio of 4.4 (for concurrent 125I and FM hyperthermia) leads us to conclude that thermal enhancement of 125I brachytherapy is more efficient in this tumor model system when hyperthermia is delivered during, rather than after, the irradiation process.

Animals↗
PubMed1995

Retroperitoneal paragangliomas: natural history and review of the literature.

Retroperitoneal paragangliomas are uncommon neoplasms that arise from neural crest cells. Typical retroperitoneal sites of origin include adrenal medulla, organs of Zuckerkandl, and along sympathetic and parasympathetic nerves. We present a case of a woman diagnosed with retroperitoneal paraganglioma treated with debulking, intraoperative radiotherapy and external beam radiation therapy. She experienced a 7-year disease-free interval prior to symptomatic metastatic recurrence. Such remissions are consistent with the natural history for paragangliomas. The purpose of this report and literature review is to summarize the pertinent biologic and therapeutic options for these uncommon tumors.

Adult↗
PubMed1994

The use of generalized cell-survival data in a physiologically based objective function for hyperthermia treatment planning: a sensitivity study with a simple tissue model implanted with an array of ferromagnetic thermoseeds.

PURPOSE: A physiologically based objective function for identifying a combination of ferromagnetic seed temperatures and locations that maximizes the fraction of tumor cells killed in pretreatment planning of local hyperthermia. METHODS AND MATERIALS: An objective-function is developed and coupled to finite element software that solves the bioheat transfer equation. The sensitivity of the objective function is studied in the optimization of a ferromagnetic hyperthermia treatment. The objective function has several salient features including (a) a physiological basis that considers increasing the fraction of cells killed with increasing temperatures above a minimum therapeutic temperature (Tmin,thera), (b) a term to penalize for heating of normal tissues above Tmin,thera, and (c) a scalar weighting factor (gamma) that has treatment implications. Reasonable estimates for gamma are provided and their influence on the objective function is demonstrated. The cell-kill algorithm formulated in the objective function is based empirically upon the behavior of published hyperthermic cell-survival data. The objective function is shown to be independent of normal tissue size and shape when subjected to a known outer-surface, thermal boundary condition. Therefore, fractions of cells killed in tumors of different shapes and sizes can be compared to determine the relative performance of thermoseed arrays to heat different tumors. RESULTS: In simulations with an idealized tissue model perfused by blood at various rates, maxima of the objective function are unique and identify seed spacings and Curie-point temperatures that maximize the fraction of tumor cells killed. In ferromagnetic hyperthermia treatment planning, seed spacing can be based on maximizing the minimum tumor temperature and minimizing the maximum normal tissue temperature. It is shown that this treatment plan is less effective than a plan based on seed spacings that maximize the objective function. CONCLUSIONS: It is shown that under the assumptions of the model and based on a desired therapeutic goal, the objective function identifies a combination of thermoseed temperatures and locations that maximizes the fraction of tumor cells killed.

Cell Survival↗
PubMed1994

A practical alternative to conventional five-field irradiation postmastectomy for locally advanced breast cancer.

A combination of electron and photon beams has been used as an alternative for the conventional five-field method to irradiate patients postmastectomy for locally advanced breast cancer. Anterior and posterior opposed photon beams treat in continuity the lateral chest wall, axilla, and supraclavicular lymph nodes. An adjacent anterior electron beam is used at an energy matched to the depth of the internal mammary nodes. It includes the anterior chest wall, but bolus is used in the lateral aspect to spare underlying lung. This electron beam eliminates the diverging junction between the internal mammary and medial tangential fields used in the conventional five-field technique. Overlaps along the junction between the photon and electron beams are minimized by placing the center of the photon field along its medial border. Measurements with an Alderson-Rando phantom show dose-distribution advantages for this technique over the conventional five-field approach. There is less chance of underdosing tumor cells or of overdosing normal tissue along beam junctions. Clinical studies on 29 patients treated by this technique between July 1985 and December 1989 show increased rates of acute skin reactions, but otherwise similar side effects compared with 57 breast cancer patients treated with the five-field technique over the same time period. Local recurrence rates and patient survival rates were similar for the two groups. Given the dose-distribution advantages of this technique and its simple adaptation to accommodate unusual surgical scars or cancer recurrences, its use should be considered for postmastectomy patients with locally advanced breast cancer in well-equipped cancer treatment centers.

Breast Neoplasms↗
PubMed1994

Effect of interseed spacing, tissue perfusion, thermoseed temperatures and catheters in ferromagnetic hyperthermia: results from simulations using finite element models of thermoseeds and catheters.

Finite element heat-transfer models of ferromagnetic thermoseeds and catheters are developed for simulating ferromagnetic hyperthermia. These models are implemented into a general purpose, finite element computer program to solve the bioheat transfer equation. The seed and catheter models are unique in that they have fewer modeling constraints than other previously developed thermal models. Simulations are conducted with a 4 x 4 array of seeds in a multicompartment tissue model. The heat transfer model predicts that fractions of tumor greater than 43 degrees C are between 8 and 40% lower when seed temperatures depend on power versus models which assume a constant seed temperature. Fractions of tumor greater than 42 degrees C, in simulations using seed and catheter models, are between 3.3 and 25% lower than in simulations with bare seeds. It is demonstrated that an array of seeds with Curie points of 62.6 degrees C heats the tumor very well over nearly all blood perfusion cases studied. In summary, results herein suggest that thermal models simulating ferromagnetic hyperthermia should consider the power-temperature dependence of seeds and include explicit models of catheters.

Catheterization↗
PubMed1991

Hyperthermia and irradiation for locally recurrent previously irradiated breast cancer.

From March 1981 to June 1989, 44 patients with locally recurrent, previously irradiated adenocarcinoma of the breast were treated with hyperthermia and irradiation. Treatment sites were chest wall (35) or nodal (nine), with an average tumor area of 29.44 cm2 (range 0.16 to 252 cm2) prior to treatment. Concurrent radiation doses varied from 16 to 56 Gy (mean = 29.4 Gy). Externally applied microwave hyperthermia was given twice weekly, aiming at 43 degrees C for 60 min. Evaluation at one month post treatment revealed 41% complete response (CR), 23% partial response (PR), and 36% no response (NR), and 67% of patients with a CR sustained that response for greater than 12 months. Tumors heated to a mean thermal dose (equivalent-minutes at 42.5 degrees C) greater than 50 had a 53% CR rate, significantly better than the 14% CR rate observed in patients whose tumors received a mean thermal dose less than 50. Among patients with tumors less than or equal to 6 cm2 in area, 65% achieved CR, significantly better than the 26% CR rate noted for patients with tumors greater than 6 cm2 in area. Only four patients (7.4%) experienced complications: one developed a catheter-related infection, two had ulcerated infections, and one had a severe blister. In summary, higher thermal doses delivered and smaller tumor areas were associated with more favorable tumor responses.

Adenocarcinoma↗
PubMed1990

Adjunctive therapy (whole body hyperthermia versus lonidamine) to total body irradiation for the treatment of favorable B-cell neoplasms: a report of two pilot clinical trials and laboratory investigations.

Based on earlier clinical and preclinical investigations, we designed two different pilot trials for patients with nodular lymphoma or chronic lymphocytic leukemia. These studies evaluated the use of either 41.8 degrees C whole body hyperthermia (WBH), or the nonmyelosuppressive chemotherapeutic drug, lonidamine (LON), as an adjunct to total body irradiation (TBI) (12.5 cGy twice a week, every other week for a planned total dose of 150 cGy). Whole body hyperthermia was initiated approximately 10 min after total body irradiation; lonidamine was administered orally (420 mg/m2) on a daily basis. Although entry to the studies was nonrandomized, the two patient populations were accrued during the same time frame and were comparable in terms of histology, stage of disease, performance status, and prior therapy. Of 8 patients entered on the TBI/WBH study, we observed 3 complete responses (CR), 4 partial responses (PR), and 1 improvement (i.e., a 48% decrease in tumor burden). Of 10 patients entered in the TBI/LON study, there was 1 CR and 4 PR. For the TBI/WBH study, myelosuppression was not treatment-limiting; there were no instances of infection or bleeding and platelet support was never required. The median survival time for the TBI/WBH study is 52.5 months based on Kaplan Meir estimates. Two patients remain in a CR. The median time to treatment failure (MTTF) is 9.4 months (90% confidence interval = 7-15.4 months). In the TBI/LON study, 50% of patients receiving TBI required treatment modification due to platelet-count depression during therapy, but there were no instances of infection or bleeding. Frequently observed LON-related toxicities included myalgias, testicular pain, photophobia and ototoxicity. For the TBI/LON study, median survival is 7.6 months; MTTF was 2.4 months. In analyzing the results of these pilot studies, our subjective clinical impressions lead to the hypothesis that WBH protected against TBI-induced thrombocytopenia during therapy, whereas LON had no effect on TBI-induced myelosuppression. This speculation was tested and confirmed in a series of in vitro and in vivo experiments.

Adult↗
PubMed1989

"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas.

Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.

Adult↗
PubMed1989

Ferromagnetic hyperthermia and iodine 125 brachytherapy in the treatment of choroidal melanoma in a rabbit model.

Hyperthermia has been combined with conventional radiation methods to achieve enhanced tumor destruction. We combined iodine 125 seeds with ferromagnetic thermoseeds in a single plaque to simultaneously deliver radiation and heat in a rabbit model of choroidal melanoma. Initially, six ferromagnetic thermoseeds were placed in parallel on a 14-mm episcleral plaque. The plaques were placed on normal rabbit eyes and on eyes containing transvitreally implanted choroidal melanoma. The heating response was assessed in both normal and tumor-containing eyes. Rigid copper-constantan and flexible Baily thermocouples were used to monitor temperature responses. The animals were subjected to an electromagnetic field of 100 kHz, with power of 1100 to 1500 W. The thermoseeds autoregulated at 48.2 degrees C. Scleral temperatures stabilized at 45.8 degrees C +/- 0.4 degrees C (SD), while temperatures at the base of the tumor stabilized at 43.6 degrees C +/- 0.1 degrees C. Ferromagnetic thermoseeds were then combined with iodine 125 seeds. Similar temperature responses were recorded, and autoradiographic findings confirmed a uniform radiation distribution. Varying the amount or type of ferromagnetic material in the thermoseeds allows the delivery of heat at virtually any temperature. Ferromagnetic hyperthermia may provide a more simplified approach over currently available methods of heat delivery.

Animals↗
PubMed1989

Cosmesis and local control after irradiation in women treated conservatively for breast cancer.

One hundred twenty-two patients (124 tumor sites) with breast carcinoma (T1 to T3, N0 to N2, M0) were treated by a lumpectomy and radiation therapy at the University of Wisconsin, Madison, from June 1978 to December 1986. Irradiation to the breast and regional lymph nodes was carried out with cobalt 60 teletherapy in 2-Gy fractions to 50 Gy, followed by an additional boost of 10 Gy to the tumorectomy site with coned electrons. Cosmesis was analyzed by scoring the effects of surgery, as well as the effects of irradiation, and by photographic assessment. After a follow-up of 24 to 119 months (median, 36 months), 82% of the patients were found to have good or excellent cosmetic scores. There was a trend that favored better cosmetic results in younger patients and in patients with outer-quadrant lesions. No significant impact of adjuvant chemotherapy on the cosmetic outcome or on the complications of treatment was demonstrated. There were six local recurrences (5.2%), three of which were true recurrences and the other three that were new primary tumors; 11 distant failures (9%) occurred. The following side effects from irradiation developed in only 5 patients (4.1%): match-line fibrosis (n = 2), soft-tissue necrosis (n = 1), and persistent tenderness (n = 2). The conditions of the two patients with persistent tenderness responded favorably with conservative management. We concluded that a lumpectomy, followed by radiation therapy, provides good cosmetic results without compromising the local control rate. If adjuvant chemotherapy is planned, we recommend that it be administered before radiation therapy in favor of concomitant therapy with both modalities.

Adult↗
PubMed1989

Eight-drugs-in-one-day chemotherapy in postirradiated adult patients with malignant gliomas.

Fifteen patients, 12 with glioblastoma multiforme and 3 with anaplastic astrocytoma, were treated with "eight-drugs-in-one-day" chemotherapy [methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 (maximum of 2 mg/cycle), CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3,000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2]. All patients had prior brain irradiation but none had previous chemotherapy. The population included 10 patients with progressive disease after irradiation and 5 who presented within 2 months of completing radiation. Patients received an average of 5 monthly cycles of chemotherapy. Three patients achieved a complete and 2 a partial response (CR + PRrate was 33%). The median survival time was 46 weeks. Myelosuppression was the dose-limiting toxicity. Leucocyte counts between 2.0-4.5 x 10(3)/mm3 were observed in 40% of patients, between 1.0- less than 2.0 x 10(3)/mm3 in 33%, and less than 1.0 x 10(3)/mm3 in 7%. Platelet counts between 50-130 x 10(3)/mm3 were observed in 27% of patients, and less than 50 x 10(3)/mm3 in 33%. Six patients suffered infections, 4 had reversible renal toxicity, 2 developed paresthesias, and one a debilitating myopathy related to treatment with dexamethasone. Ototoxicity was seen in 3 patients. Two patients developed pulmonary emboli. Nine patients had nausea and vomiting, in one case associated with Candida esophagitis. One long-term survivor developed necrosis of the corpus callosum and dementia. Four patients discontinued treatment after an average of 3.5 cycles because of toxicity. Although extremely toxic, this regimen has modest activity in previously irradiated adult patients with malignant glioma.

Adult↗