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Biomedical subjects

S H Levitt

Publications and source records attributed to S H Levitt.

At least 37 records · Page 2Linked to original sources
PubMed1996

Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience.

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Adult↗
PubMed1995

Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study.

PURPOSE: Since 1985, the University of Minnesota Hospital and Clinic has investigated the efficacy and safety of 8 MHz radiofrequency (RF) capacitive hyperthermia using the Thermotron RF-8. This study reports the thermometric and clinical results of 119 patients treated with RF hyperthermia in combination with radiotherapy (RT). METHODS AND MATERIALS: Of 119 patients, 69 received high-dose RT and 50 patients received low-dose RT because of previous irradiation to the treatment site. The most common anatomic sites treated were within the pelvic cavity or head and neck area. Thirty-three percent and 24% of tumors treated were > 7 cm and > 10 cm in largest diameter, respectively. Forty percent of the patients had deep-seated tumors (depth > 6 cm). Hyperthermia was given as soon as possible after RT twice weekly, allowing at least 72 h between treatments. The objective was to raise intratumoral temperatures to 42-43 degrees C or above for 30-50 min while keeping normal tissue temperatures below 40-41 degrees C. RESULTS: Of 119 patients, 40% achieved a Tmax tumor temperature of > 42 degrees C and 40% achieved 40-42 degrees C Tmax. Higher Tmax) tumor temperatures were observed as tumor size increased. Tumors > 10 cm in largest diameter had a Tmax of 42.2 degrees C. Tumor depth was not a significant factor for the tumor temperatures achieved. Of 119 patients, 11% achieved complete response and 38% achieved partial response. Of the no-response patients, 34% had symptomatic palliation and 15% had stable disease for at least 12 months after treatment. We were able to treat tumors of patients with subcutaneous fat as thick as 3 cm by precooling the fat for 20 min with 10-15 degrees C saline-filled boluses prior to the initiation of heating. During treatment, 60% of patients complained of varying degrees of pain and 19% had pain that was a factor in limiting treatment. Vital signs were relatively stable and not a factor in limiting treatment. CONCLUSION: The Thermotron RF-8 is a useful hyperthermia device that can raise tumor temperatures to a therapeutic level (i.e., 42 degrees C) in a significant proportion of patients with superficial, subsurface, and deep-seated tumors, with minimal adverse effects, complications, and systemic stress. Further clinical studies using improved thermometry systems are warranted.

Adenocarcinoma↗
PubMed1995

Proctitis after conventional external radiation therapy for prostate cancer: importance of minimizing posterior rectal dose.

PURPOSE: To identify factors associated with the prevalence of radiation proctitis in patients with prostate cancer treated with external radiation therapy and to determine if a dose-response relationship exists. MATERIALS AND METHODS: The study included 101 prostate cancer patients treated at the University of Minnesota Hospital and Clinics between 1970 and 1987. Radiation therapy at a daily dose of 175-200 cGy was given for 5 consecutive days per week for 7 weeks with a 10-24-MV linear accelerator. Mean dose to the prostate was 6,795 cGy (range, 5,579-7,417 cGy). Simulation radiographs obtained with rectal barium were analyzed in 51 patients. Doses were calculated at specific points in the boost field. RESULTS: Radiation proctitis developed in 19 patients. No pretreatment or treatment factors were associated with a higher prevalence of proctitis. Statistically significant correlation (P < .042) was found between the development of proctitis and dose to the posterior rectum. At chi 2 analysis, proctitis was statistically significantly (P < .005) associated with posterior rectal doses of > 5,000 cGy. CONCLUSION: A high posterior rectal dose (> 5,000 cGy) is associated with increased prevalence of proctitis after radiation therapy.

Aged↗
PubMed1995

The importance of local control in the conservative treatment of breast cancer.

The purpose of this study was to examine the meaning of local control, especially on survival, in breast cancer patients treated by lumpectomy with or without radiotherapy. We analyzed the survival results of four major published randomized trials that compare conservation surgery with or without radiation using three different statistical approaches: p-values, confidence intervals, and Bayesian techniques. All four trials report statistically significant increased local control and improved survival for the irradiated patients. Survival based on p-values and confidence intervals shows statistical significance for long-term follow-up of the NSABP-B06 trial, but not for the other trials, probably because of small sample sizes and short follow-up. At 10 years, the overall survival rates for the NSABP-B06 were 65% and 71% for lumpectomy alone or with radiation respectively. Interpreted in a Bayesian framework, the expected advantage in 10-year survival was 6% (the mean of NSABP-B06 10-year survival) with an 83% probability that the 10-year survival difference may lie between 2% and 10%. An 85% probability that 3% of patients will survive at 10 years because of irradiation translates into a 30% reduction in annual odds of death several years after treatment in stage I good prognosis patients and 15% in stage I poor prognosis patients. Analysis of the randomized trials comparing lumpectomy with or without radiation indicate a clear improvement in survival for the irradiated patients associated with increased local control. Combination of improved survival with the reduced psychological and economic costs associated with local recurrence argues well for the inclusion of radiation for many breast cancer patients.

Bayes Theorem↗
PubMed1994

Quality assurance in radiation oncology.

Quality assurance in radiation oncology attempts to prescribe consistent, safe, and optimal delivery of radiation to treat disease. It encompasses three major areas of treatment: clinical, physical, and technical. Although national approaches and guidelines of quality assurance in radiation oncology are available, they usually are not adequate to deal with the particular needs of individual institutions, nor are they adequate to ensure uniform standards of diagnosis and treatment among institutions. Therefore, it is important for individual institutions to develop and implement strict quality assurance standards, based on national guidelines as well as their own strengths and needs, to ensure that patients receive the highest quality of radiotherapy and that the successes and failures of treatment are statistically reliable. This paper addresses the importance of quality assurance in radiation oncology and examines the quality assurance program in the Department of Therapeutic Radiology-Radiation Oncology at the University of Minnesota as an example of a program tailored to the needs of an individual institution.

Breast Neoplasms↗
PubMed1994

The role of radiation therapy in the treatment of colorectal cancer. Implications for the older patient.

Radiation therapy plays an important role in the treatment of patients with colorectal cancer. Randomized trials show that patients with rectal cancer have an 8% improved local control rate with postoperative radiation and an 11-13% improved local control rate with combined postoperative radiation and chemotherapy. Survival is also improved for these patients. Ongoing randomized trials may clarify the role of postoperative radiation therapy for patients with colon cancer. Although there is little specific information regarding the tolerance and response of the older patient to radiation therapy, there is no reason to believe that cancer in the older patient is more sensitive to ionizing radiation. Therefore, treatment decisions should be based on the available data. The older patient may be at an increased risk for radiation-related small bowel damage, and the clinician should pay particular attention to techniques to limit the amount of small bowel in the irradiated field.

Aged↗
PubMed1994

The importance of locoregional control in the treatment of breast cancer and its impact on survival.

BACKGROUND: Different schools of thought regarding the natural history of breast cancer and how it relates to the importance of local control in affecting survival have generated controversy over the optimal treatment of early breast cancer. Parting with traditional thinking that some disease is localized, in which cases local control is important for survival, another view of the natural history of the disease argues that local control is not of value to survival. This commentary will review the evidence and attempt to evaluate the effect of modern adequate local treatment on survival. METHODS: A review of the pertinent literature on the treatment of breast cancer and an analysis of recent clinical trials and meta-analysis are presented. RESULTS: Evaluation of the recent literature and meta-analysis demonstrates that adequate local regional treatment, especially radiation therapy in the treatment of breast cancer, does effect survival significantly. CONCLUSIONS: Results of modern effective local treatment of breast cancer substantiate the claim that some breast cancer is localized. Data show that tumor size, lymph node involvement, tumor grade, and other prognostic factors are important predictors of whether a tumor is localized and therefore amenable to local treatment. Smaller tumors generally are most likely to be localized. Recent studies on modern irradiation techniques show that adequate effective irradiation of localized disease, including appropriate treatment of all nodal areas when needed and limited radiation to sensitive organs, can significantly improve survival and, in high-risk patients, enhance the effect of systemic treatment in improving survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Influences on inferences. Effect of errors in data on statistical evaluation.

BACKGROUND: Inadvertent random and systemic errors introduced into data sets and manipulation of data are well-defined sources of discrepancies in statistical evaluation of clinical trials. In this study, the authors show the influence of errors on the widely used statistical result, P values. METHODS: Using data from a retrospective study of patients with Hodgkin disease treated at the University of Minnesota between 1970 and 1984 and observed to 1988, we introduced various errors into the data to study the impact on results. RESULTS: Inadvertent random and systemic errors affect statistical results. Data entry and transcription errors, vague definitions of endpoints and prognostic factors, and the omission and selection of patients are examples of frequent errors that affect statistical evaluation. CONCLUSION: The results and inferences of many studies are sensitive to systemic errors and data manipulation. Great care must be given to the clear definitions of terms, exclusion and inclusion criteria, group assignments, treatment protocols, and the subgroups on which statistical analysis is performed. Clinicians and statisticians must work together to improve the performance and interpretation of clinical trials.

Clinical Trials as Topic↗
PubMed1993

Improved tumour oxygenation and radiosensitization by combination with nicotinamide and pentoxifylline.

We hypothesized that the combination of pentoxifylline (PTX) and nicotinamide (NA) can reduce the radioresistance of FSaII murine fibrosarcoma by improving oxygenation of the hypoxic tumour cells. The purpose of this study was to test the hypothesis; first, tumour blood flow after treatment with NA, PTX, and the combination (PTX+NA) was measured using laser Doppler flowmetry. Second, intratumour pO2 after various treatments was measured polarographically using O2 microelectrodes. Third, the radiation response was also measured, i.e. after an exposure to 20 Gy, the time required to reach a four-fold increase in initial tumour volume was 18 days in the saline-treated control group, 21 days in the NA-treated group, 26 days in the PTX-treated group, but was 36 days in PTX+NA treated group. Interestingly, tumour blood flow significantly increased at 10 min after injection of PTX+NA. The mean pO2 in untreated control tumours was 7.5 mmHg, increasing to 13.1 mmHg after 500 mg/kg of NA alone. Repeated injections of PTX with 100 mg/kg/day for 3 days significantly increased intratumour pO2 to 17.2 mmHg. Compared with PTX alone, PTX+NA slightly increased intratumour pO2 from 17.2 to 18.5 mmHg. However, the percentage of regions having values < 2.5 mmHg significantly decreased from 5% with PTX alone to 1% with PTX+NA. In conclusion, single or multiple injections of PTX may increase available O2 in the tumour and thus ameliorate hypoxia in tumour microregions. As previously reported, the subsequent injection of NA may efficiently oxygenate acutely hypoxic cells. Consequently, PTX+NA may increase the radioresponse of tumours by oxygenating chronic as well as acutely hypoxic cells. PTX alone or in combination with NA is potentially useful to radiosensitize tumours.

Animals↗
PubMed1993

The in vitro radiosensitization of human glioblastoma with pentoxifylline.

There is evidence that pentoxifylline may be both a radioprotector of normal tissue and a radiosensitizer of tumor cells. This article reviews this evidence and then describes our own laboratory study to determine whether pentoxifylline is a radiosensitizer of human glioblastoma cells in vitro. Human glioblastoma multiforme cells (SNB19 cell line) were irradiated in vitro with and without pentoxifylline. Regression of the log ratios (quotient of surviving colonies) revealed greater tumor cell kill in the PTX group, and the difference increased as the radiation dose increased (p < 0.01 at the 750 and 1000 cGY doses). Before the hypothesis that PTX is a radiosensitizer of hypoxic tumor cells can be confirmed or denied, it must be determined if the agent also has a separate mechanism of tumoricidal activity. Whereas in vivo models allow the well-documented rheologic, immunologic and oxygen-related effects of PTX to be active simultaneously, the in vitro model described herein excludes the effects of such systemic actions and focuses on mechanisms at the cellular or subcellular level. These data suggest there exists such a mechanism of tumoricidal activity of PTX that has not been previously identified.

Cell Survival↗