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Biomedical subjects

W G Connor

Publications and source records attributed to W G Connor.

At least 19 recordsLinked to original sources
PubMed1984

Importance of minimum tumor temperature in determining early and long-term responses of spontaneous canine and feline tumors to heat and radiation.

A total of 130 dogs and cats with squamous cell carcinomas, melanomas, fibrosarcomas, mammary adenocarcinomas, or mast cell sarcomas were randomized to receive radiation (XRT) or heat plus XRT. Time-temperature data for each monitored tumor location were converted to degree-minutes or equivalent min at 43 degrees (Eq43). Response rates and durations of response were compared for subgroups of histology, volume, site, and heat treatment method. Thermal gradients existed in all heated tumors. The influence of these gradients on tumor response was examined by correlation of response with degree-minutes and Eq43 minima, maxima, averages, and ranges. A pattern emerged from these analyses linking dose minima, maxima, and ranges with prognostic subgroups as classified by volume, site, or treatment method. The data indicated that the coolest part of the tumor governed the biological response to combined heat + XRT. Tumors which received a minimum of 35 Eq43 had significantly longer durations of response than did those receiving XRT alone or less than 3 Eq43 (p less than or equal to 0.006 and 0.014, respectively; log-rank test). Furthermore, broad temperature ranges were associated with power-limiting "hot spots" and invariably led to underheating in other areas of tumor. Multivariate analysis found minimum Eq43 on the first treatment to be the best predictor of long-term response (p less than 0.05). Other biological covariates of site, volume, and histology contributed strength to the model, which was independent of Eq43 (p less than 0.05).

Animals↗
PubMed1982

Clinical hyperthermia: results of a phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy.

Forty-three patients with advanced, locally accessible neoplasms were treated in a Phase I clinical trial employing hyperthermia alone or hyperthermia combined with either high-dose-rate external beam or low-dose-rate interstitial radiotherapy (interstitial thermoradiography). All patients had failed previous conventional therapeutic attempts, including various combinations of surgery, chemotherapy and radiation therapy. Many had received tolerance or near tolerance levels of prior radiation that restricted dose prescriptions in this trial to subcurative values. A number of tumors with different histologies were treated, including squamous cell carcinoma (14), adenocarcinoma (14), melanoma (8), malignant fibrous histiocytoma (2), and sarcoma (5). The response evaluation criteria used included no response (NR--less than 50% decrease in tumor volume), partial response (PR--50% less than or equal to tumor volume reduction less than 100%) and complete response (CR--complete tumor disappearance). For all tumor types, hyperthermia therapy alone resulted in a total response rate of 45% (27% PR, 18% CR). Hyperthermia combined with high-dose-rate external beam radiotherapy yielded a total response rate of 80% (53% PR, 27% CR). Seventeen patients treated with interstitial thermoradiography displayed a 100% total response rate (29% PR, 71% CR). By tumor histologies for all treatment groups, total response rates have ranged from 50% to 79% for all types except melanoma, which has shown a 100% (8/8) response rate to date. Response durations have varied from one to 24 months. Twelve of the 43 patients remain alive; three have no evidence of disease (NED) while nine have either stable local disease or are NED in the treated volumes but have metastatic disease. Complications have been minimal and have included one third-degree burn and three second-degree burns from fringing RF fields, one vaginal-rectal fistula, a superficial focal soft tissue necrosis, and some minor blistering. The results of this Phase I trial demonstrate that hyperthermia alone or combined with radiation can be safely applied in the treatment of malignant disease. Most importantly, the data suggest that hyperthermia, especially when combined with interstitial thermoradiography, can yield remarkable results in the eradication of local cancers.

Adenocarcinoma↗
PubMed1982

Preliminary results of a phase III trial of spontaneous animal tumors to heat and/or radiation: early normal tissue response and tumor volume influence on initial response.

A Phase III randomized trial was initiated to test the relative efficacies of heat alone, radiation alone and heat plus radiation using spontaneous malignancies in pet animals. Heat alone was inferior to the other two treatment arms as demonstrated by a significantly higher non-response rate and shorter response duration. The ratio of complete response rates (CR) for heat plus radiation to radiation alone or the thermal relative risk (TRR) was greater for tumors greater than 10 cm3 as compared to those less than 10 cm3 (TRR = 4.8 and 1.4, respectively). The overall TRR for complete responses was 2.3. The CR data for the combined therapy arm indicate at least an additive effect between heat and radiation for small tumors but most likely a synergistic effect in the larger tumor group. Based on the data currently available, no significant difference in response duration is observed between the two radiation arms, although a nonsignificant advantage to the combination therapy exists. Normal tissue effects were evaluated by incidence of full moist desquamation within the irradiated volume, late fibrosis and bone necrosis. Since the radiation skin dose depended upon the technique being used it was possible to estimate the dose to achieve moist desquamation in 50% of the animals (DD50) by a logistic regression model as being 3728 +/- 344 rad for radiation alone. Significant lowering of the DD50 was not observed for the addition of heat to radiation. Low patient numbers where intact skin was heated prevented an accurate analysis of the effect, however.

Animals↗
PubMed1980

Localized current field heating as an adjunct to radiation therapy.

The purpose of this paper is to report the results of a pilot study using hyperthermia as an adjunct to radiation therapy in the treatment of malignant disease, spontaneously occurring in domestic animals. Localized current fields (LCF) have been used to produce the hyperthermia. The aim of the pilot study was to establish a reasonable dose regime for testing in a randomized trial. The doses tested ranged from an equivalent 3,000 rads in 3 weeks to 6,000 rads in 6 weeks for the radiation treatments and 43 degrees C for 30 min to 45 degrees C for 30 min for the hyperthermia treatments. To date, there have been either complete or partial (over 50% tumor regression) responses in 82.9% of the animals and complete regression in 54.3% of the tumors. The details of the randomized trial are described.

Animals↗
PubMed1977

Prospects for hyperthermia in human cancer therapy. Part I: hyperthermic effects in man and spontaneous animal tumors.

Systemic hyperthermia in man may occur by accident, as in heat stroke or malignant hyperthermia during general anesthesia, or it may be therapeutically induced (fever therapy). The latter has been used infrequently since the advent of antibiotics, except recently for treatment of cancer. Local or regional heating combined with x irradiation for human cancer therapy has been sporadically reported for over 60 years, but has not found its place in clinical medicine possibly due to technical limitations in heat production and dosimetry. Preliminary results are reported for treatment of spontaneous animal tumors with radiofrequency current fields and x irradiation.

Animals↗
PubMed1977

Prospects for hyperthermia in human cancer therapy. Part II: implications of biological and physical data for applications of hyperthermia to man.

Laboratory data from studies of hyperthermia as a potential antitumor agent indicate that: (a) tumor cells may be more sensitive to heat than normal tissue; (b) hyperthermia enhances response to irradiation and can increase the therapeutic ratio; (c) cells are most sensitive to hyperthermia during the S-phase, when they are resistant to ionizing radiations; (d) the oxygen effect is absent for hyperthermic cell killing, and radiation effects are less oxygen-dependent when potentiated by heat treatment; and (e) biological damage changes more rapidly at temperatures above 43 degrees C. Methods of heat production and dosimetry need to be refined further before these findings can be put to practical use in tumor therapy.

Animals↗
PubMed1976

A transient thermotolerant survival response produced by single thermal doses in HeLa cells.

Continuous exposure of HeLa cells in culture to elevated temperatures (41-45 degrees) results in cell killing which increases exponentially as the time at the elevated temperature increases linearly. When cells are returned to 37 degrees after an initial thermal dose, cellular sensitivity to subsequent hyperthermic doses is reduced. Cell inactivation rates for cultures previously treated with 44 degrees for either 0.5 or 1 hr followed by incubation at 37 degrees for 2 hr, showed D0's of 1.1 and 1.5 hr, respectively, for subsequent thermal treatments at 44 degrees. Cultures receiving no prior hyperthermic dose had a D0 of 0.5 hr for treatments at 44 degrees for up to 3.5 hr. The viable progeny of cells treated with 44 degrees for 1 hr, however, had the same sensitivity to thermal doses at 44 degrees as did previously unheated cells. These results and others demonstrate that (a) single thermal dose produce a state of thermotolerance in HeLa cells to subsequent hyperthermic doses; (b) the degree of thermotolerance produced is dependent on the magnitude (i.e., temperature and time at the elevated temperature) of the first thermal dose; (cy thermotolerance does not develop at the elevated temperature but requires a return of culture temperatures to 37 degrees; (d) cellular acquisition of thermal tolerance is dependent on cell metabolism, as demonstrated by an inhibition of the effect at 0 degrees; and (e) this effect is a transient phenomenon which is lost as cells divide following the first thermal dose.

Cell Division↗
PubMed1975

The potential of localized heating as a adjunct to radiation therapy.

Experimental studies have shown that (a) tumor cells may be more sensitive to heat than normal cells; (b) hyperthermia inactivates cellular repair mechanisms for radiation damage; and (c) heat may lower the OER for ionizing radiation (anoxic cells are at least as sensitive to hyperthermia as oxygenated cells). Localized hyperthemia produced by localized current fields in the range of 100 kHz-10 MHz by direct contact electrodes offers two major advantages: the eletrode configurations may be manipulated to obtain desired thermal dose distributions, and, since the mode of heating is essentially instantaneous, accurate temperature control can be maintained during treatment.

Adolescent↗
PubMed1975

Evaluation of B-mode ultrasound as a means of improving radium dosimetry in the treatment of gynecologic cancer.

The radiation dose to the base of the bladder and anterior rectal wall during radium applications for gynecologic cancer is a function of the distances between the source and the bladder and rectum. Precise measurement of these distances depends on a number of factors and cannot be obtained with current radiographic localization techniques. B-mode ultrasound is useful as a means of supplementing available information. While it is not necessarily more accurate than standard radiographs, it offers a three-dimensional appreciation of pelvic anatomy and does appear to be more accurate than transverse axial tomography.

Female↗