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S H Levitt

Publications and source records attributed to S H Levitt.

At least 73 records · Page 4Linked to original sources

Radiosensitization of murine tumors by Fluosol-DA 20%.

The effect of perfluorochemicals in combination with carbogen breathing on the response of SCK tumors of mice to fractionated irradiation was investigated. The SCK tumors of A/J mice were irradiated twice a day at 3 Gy per fraction (6 Gy per day), with a total dose of 18 Gy over 3 days. When the host animals were treated with an intravenous (iv) injection of 12 ml/kg of Fluosol-DA 20% before the first daily tumor irradiation and carbogen breathing during every X irradiation with Fluosol-DA 20% injection without carbogen breathing. The hypoxic cell fraction, as determined by an in vivo-in vitro cloning assay, decreased significantly, and the intratumor pO2, as determined with microelectrodes, was markedly increased by Fluosol-DA 20% injection and carbogen breathing. It was concluded that oxygenation of hypoxic cells in SCK tumors during the course of fractionated irradiation was improved by the iv injection of Fluosol-DA 20% and carbogen breathing.

Adenocarcinoma↗

The kinetics of vascular thermotolerance in SCK tumors of A/J mice.

Development of thermotolerance has been observed in diverse biological systems. Despite the important role of blood circulation in heat-induced tissue damage, little is known about vascular thermotolerance. The kinetics of vascular thermotolerance in SCK tumors of A/J mice was investigated in this study. A single heating at 43.5 degrees C or 44.5 degrees C for 1 hr caused marked damage in tumor vasculature, as demonstrated by a marked decrease in Rb-86 uptake (% of injected dose/g of dried tissue). The tumor vasculature became resistant or tolerant to subsequent heatings at those temperatures when the tumors were preheated at 42.5 degrees C for 1 hr. Vascular thermotolerance became significant at 5 hr and reached its maximum at 18 hr after preheating at 42.5 degrees C. When the vascular thermotolerance was at its peak, heating at temperatures as high as 44.5 degrees C for 1 hr could not reduce the tumor blood flow. The vascular thermotolerance decayed considerably but not completely at 72 hr after the preheating. The vascular thermotolerance may exert a profound implication on the response of tissues, including tumors, to multiple heatings.

Adaptation, Physiological↗

Effects of temperature on blood circulation measured with the laser Doppler method.

The effects of local heating or cooling on skin microcirculation in volar aspect of human forearms was studied using laser Doppler flowmetry. When the skin was heated to 40 degrees C from a normal temperature of 32 degrees C, red cell flow (laser Doppler flow, blood flow) momentarily increased several fold and then temporarily decreased. The flow subsequently resumed a gradual increase reaching 10-15 times that of control in 30-40 min. When the skin temperature was returned to 32 degrees C after 60 min of heating, the blood flow momentarily declined but soon increased for several minutes before it began its major descent. When cooled from 32 degrees C to 5 degrees C, the flow momentarily decreased, but soon increased, surpassing the pre-cooling level. The flow began to decline when the cooling was prolonged for more than 15-20 min. The changes in flow corresponded well with the changes in number (volume) and speed of red cells. Laser Doppler flowmetry was found to be very useful for continuously monitoring microcirculatory blood flow in human skin.

Adult↗

Clinical experience with thermotron RF-8 capacitive heating for bulky tumors: University of Minnesota experience.

We conducted a phase I clinical trial of the feasibility of using the Thermotron RF-8, a capacitative heating device utilizing 8-MHz RF, for the treatment of deep-seated and bulky human tumors. Preclinical studies with agar phantoms demonstrated that deep heating can be achieved with this device when the electrode diameters are sufficiently large relative to the thickness of the heated object. In the clinical application of capacitive heating with radiofrequency, excessive heating of subcutaneous tissue has often been a problem. However, this could be minimized by continuous cooling of the subcutaneous fat with a 10 degrees C saline bolus, beginning more than 20 minutes prior to the start of heating. It was often possible to raise the temperature of deep-seated tumors even in obese patients by applying this pre-cooling method. The mean achieved temperature during 30 to 40 minutes of heating was higher than 42 degrees C and 40 degrees C to 42 degrees C in 26% and 50% of 58 tumors treated, respectively. A combination of hyperthermia (four to ten sessions, twice a week) with full-course or a limited dose of radiotherapy resulted in complete tumor remission in 7% of patients, and partial tumor remission in 50% of patients. In the full-course radiotherapy group, 69% of the tumors were judged to show complete or partial regression, and in the low-dose group, 43% of the tumors regressed completely or partially. Histologic examination of many of the tumors that did not regress showed massive necrosis, indicating that tumor size after hyperthermia is not an accurate criterion of the treatment result. Side effects were minimal, and vital sign changes during heating were insignificant. Our data, together with those reported by Japanese investigators, clearly demonstrated that hyperthermia with the Thermotron RF-8 in combination with radiotherapy is useful in treating deep-seated and bulky tumors that fail to respond to conventional treatment modalities.

Adult↗

The consensus statements on adjuvant chemotherapy in breast cancer. Fact or artifact.

The decision of the National Cancer Institute, in November of 1985, in favor of adjuvant chemotherapy in the treatment of the premenopausal patient was based on the analysis of randomized clinical trials. The authors have carefully evaluated five papers dealing with the trials and found in each of them some problem in the performance or statistics which makes us question the interpretation of the findings of a statistically significant advantage for adjuvant chemotherapy in premenopausal patients. In view of this, we suggest that all the studies being considered need to be checked for their validity and if a significant number have similar flaws to those in the five trials noted, then we suggest that it is not possible to come to conclusions reported by the consensus panel.

Antineoplastic Combined Chemotherapy Protocols↗

Difference in the thermotolerance of mouse mammary carcinoma cells in vivo and in vitro.

The kinetics of thermotolerance development were compared for cells in the SCK mammary carcinoma of A/J mice, and the same cells cultured in vitro. Tumors in the legs of mice or cells in culture flasks were conditioned with heat in a water bath at 43 degrees C for 30 min and the cells were left in the tumors or the culture flasks for various lengths of time after heat conditioning. The magnitude of thermotolerance was determined by preparing single cells and subjecting them to a test heating in a controlled environment in vitro at 43 degrees C, and the survival of the cells was determined by measuring the colony-forming ability in vitro. Thermotolerance in tumors reached its maximum 12 h after heat conditioning, at which time the survival response was characterized by Do (the duration of heating required for exponential cell inactivation to 1/e) of 116 min. This changed to a Do of 170 min when the cells in tumors were incubated in culture medium of neutral pH during the development of thermotolerance. In contrast, the thermotolerance of cells cultured in vitro was fully developed within 8 h, at which time the Do was 306 min. The kinetics of thermotolerance development, therefore, varied significantly between the cells of the same origin but grown in vivo or in vitro. Killing of tumor cells in vivo caused by the heat-conditioning dose was about three times greater than that for tumor cells in vitro, but the greater damage did not result in a greater development of thermotolerance. The above results indicate that the development of thermotolerance in tumors is suppressed by the influence of intratumor environment.

Animals↗

Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen.

The potential usefulness of i.v. injection of perfluorochemicals and breathing carbogen (95% O2 and 5% CO2) to improve the radiation-induced control of tumors was investigated. When C3H mice, bearing RIF-1 tumors in the legs, were given i.v. injections of Fluosol-DA (20%) at 12 ml/kg, and allowed to breathe carbogen for 1 h before and during a single dose of X-irradiation, the curability of tumors increased by a dose modification factor of 1.47 +/- 0.03 (SE). Such a treatment also increased the radiation-induced skin damage by a factor of 1.15 +/- 0.12, resulting in a therapeutic gain of 1.28 +/- 0.04. Measurement of intratumor pO2 by oxygen microelectrodes demonstrated small increases in pO2 when the animals breathed carbogen, and marked increases in pO2 when Fluosol-DA (20%) was injected into the animals and the animals breathed carbogen. It was concluded that i.v. injection of Fluosol-DA (20%) followed by carbogen breathing significantly improved the oxygen supply to hypoxic cells in the RIF-1 tumors and thus increased the control of tumors by radiation.

Animals↗

Hodgkin's disease: a reassessment of prognostic factors following modification of radiotherapy.

Between 1970 and 1982, 175 patients with Stage IA, B, IIA, B, or IIIA Hodgkin's disease were treated with curative radiotherapy following surgical staging. The patients treated prior to 1975 received either regular extended or total nodal field treatments (Treatment Group 1, N = 65). Unsatisfactory results from this treatment program led to treatment modification in 1975. The modified protocols consisted of low-dose lung irradiation in patients having large mediastinal masses and/or hilar disease, and low-dose liver irradiation for Stage IIIAS+ patients (Treatment Group 2, N = 110). Recurrence-free survival rates improved significantly for various risk groups. Univariate analysis indicated that age, stage, symptoms, mediastinal mass size, number of sites involved, hilar disease, stage, and symptoms were significant risk factors in Treatment Group 1. In Treatment Group 2, only sex was a statistically significant risk factor. Stepwise Cox regression analysis for risk factors selected mediastinal mass size and stage as the most significant prognostic factors in Treatment Group 1. In Treatment Group 2, number of initial disease sites and sex were the most significant risk factors. The results of the study show significant improvement in recurrence-free survival rates in Treatment Group 2. It is concluded that these improvements are due to the modification in treatment.

Adolescent↗

Increase in tumor pO2 by perfluorochemicals and carbogen.

The effects of perfluorochemicals (Fluosol-DA) in combination with carbogen (95% O2 and 5% CO2) breathing on the tumor pO2 was investigated. The pO2 in RIF-1 tumors grown in the leg of C3H mice was determined by polarographic method using oxygen microelectrodes with diameters of 50-60 micron. The average and median pO2 in the control RIF-1 tumors was about 13 mm Hg and 6 mm Hg, respectively. Carbogen breathing alone could cause a significant increase in pO2 in some tumors and Fluosol-DA injection (i.v.) alone caused a slight change in tumor pO2. When the animals were treated with both Fluosol-DA injection and carbogen breathing, the pO2 markedly increased in most of the tumors resulting in an average and median tumor pO2 of 80 mm Hg and 60 mm Hg, respectively. Such an increase in tumor pO2 may account for the previous observations by us and others that the response of experimental tumors to radiation could be markedly increased by treating the tumor-bearing animals with carbogen and Fluosol-DA.

Animals↗

Unfortunate trends.

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Breast Neoplasms↗

Radical treatment of Hodgkin disease with radiation therapy: results of a 15-year clinical trial. The 1985 Erskine lecture.

In 1970, the University of Minnesota Hospitals instituted a policy for treatment of patients with stage I, II, and IIIA Hodgkin disease that required complete staging including laparotomy and extended field or total nodal radiation. Evaluation of the results of this policy in 1974 led to modifications of treatment based on analysis of disease recurrences. Since 1974, patients with large mediastinal masses or hilar disease have been treated with whole-lung or half-lung radiation. In addition, patients with stage IIIA disease with positive spleens were treated with liver irradiation. Sixty-five patients with Hodgkin disease treated with extended or total nodal fields and 126 patients treated with the radical radiation approach are evaluated. The use of this treatment modification has changed the prognostic factors and produced an improvement in recurrence-free survival that is statistically significant. The authors suggest that radical radiation therapy is the treatment of choice in patients with stage IA, IIA, or IIIA Hodgkin disease.

Adolescent↗