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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 199 records · Page 11Linked to original sources

Randomized trial comparing single dose versus fractionated irradiation for prevention of heterotopic bone: a preliminary report.

Radiation therapy has been shown to prevent heterotopic bone formation in high risk patients undergoing total hip replacement. A number of doses have been used without a randomized trial comparing one dose regimen against another. A prospective randomized trial was undertaken comparing 10 Gy in 5 fractions versus 8 Gy in 1 fraction. Forty-seven patients have been randomized at the time of this evaluation with 37 patients eligible for analysis. The pre-operative, immediate post-operative and 2 month post-operative radiographs were graded. At the time of this analysis, 17 patients were randomized to the 8 Gy arm with 20 patients in the 10 Gy arm. Patients were treated with limited fields so as to only cover the area at risk for development of heterotopic bone to prevent adverse effects on biologic fixation of uncemented implants. When comparing the pre-operative, operative, and 2 month post-operative radiographs, only four patients (1 patient in the 8 Gy arm and 3 patients in the 10 Gy arm), had an increase in the score. No patient had an increase in score to a clinically significant level, usually grade 3 or 4. These preliminary results appear to show that 8 Gy in a single fraction can be as effective as 10 Gy in 5 fractions in preventing heterotopic bone in susceptible individuals. Further follow-up of the remaining patients may confirm this.

Female↗

Radiation effects on left ventricular function and myocardial perfusion in long term survivors of Hodgkin's disease.

We evaluated systolic and diastolic indices of left ventricular performance by radionuclide angiocardiography and myocardial perfusion with exercise/rest thallium scintigraphy in 16 patients previously irradiated for Hodgkin's disease. These commonly used indices of left ventricular (LV) performance included LV ejection fraction (LVEF) as a measure of systolic function, and LV peak filling rate (PFR) as a measure of diastolic function. The presence of coronary artery disease (CAD) was evaluated by ECG treadmill testing (13 patients) and by quantitative planar thallium scintigraphy (12 patients). Patients were 16-38 years old (mean 24.9 +/- SD 6.2) at the tim eof irradiation, and were evaluated 2.5-21.5 years (mean 9.3 +/- 6.3) after radiation therapy (RT). RT was delivered with beam energies of 2-18 MV, equally weighted AP-PA mantle fields with both fields treated daily for most patients (13 patients), and fraction sizes of 1.5-2.0 Gy. Six patients received radiation to th entire cardiac volume, most commonly via left-sided partial transmission lung blocks (PTLB). Patient data were analyzed according to the volume of heart treated. Individuals who had the entire cardiac volume irradiated were assigned to group I (N = 6), and those patients who had some portion of the heart shielded throughout treatment comprised group II (N = 10). In this series, no perfusion defects were evident in either group by quantitative planar thallium scintigraphy. Mean LVEF for all patients studied was 60% (normal LVEF greater than or equal to 50%). Patients in group I had a lower mean LVEF than those in group II, 55 +/- 4% versus 63 +/- 6% (p = 0.01). Mean PFR for all patients studied was normal at 3.5 EDV/sec (normal PFR greater than or equal to 2.54 EDV/sec). Patients in group I had a lower mean PFR than those in group II, 3.0 +/- 0.6 vs 3.8 +/- 0.7 EDV/sec (p = 0.04). Thus, patients irradiated to large cardiac and pulmonary volumes had lower LVEF and PFR within the normal range compared to patients who had some portion of the cardiac volume shielded. These differences are statistically significant in the relatively small groups studied but do not appear to be associated at the present time with clinically significant effects.

Adolescent↗

Fetal hypothalamic transplants into brain irradiated rats: graft morphometry and host behavioral responses.

This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, & 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis in the fimbria, internal capsule, and other areas of the brain. These results suggest that grafts of fetal neural tissue exert a beneficial influence on the host brain, although the mechanism by which the implant exerts its effect is still unknown. Evidence supporting the role of trophic factors is reviewed. These preliminary results suggest a potential for tissue grafts in the treatment of CNS irradiated patients.

Animals↗

Effects of an oncology elective on first-year medical students' knowledge and attitudes about cancer.

This study examined cognitive knowledge and attitudes about cancer for three consecutive classes of first-year medical students who were enrolled in an elective oncology course. Analyses of the data indicated that knowledge about oncologic anatomy and cancer spread patterns increased and attitudes about various aspects of cancer tended to be positive; however, the two parameters were not correlated. Our observations and findings led us to believe that although we did not attempt to "teach" attitudes, factors in addition to cognitive skills could be associated with students' attitudes about cancer. Exposure to cancer patients in an appropriate setting may be as important as instruction. These findings are discussed and placed within the context of the literature. Further research is suggested to compare this group to students who may have similar exposure to cancer patients, but no didactic presentations.

Curriculum↗

Comparison of long-term safety of ketorolac tromethamine and aspirin in the treatment of chronic pain.

A double-blind, randomized trail was conducted in 823 patients who required long-term analgesic therapy for chronic pain such as that caused by osteoarthritis, fibromyopathies or fibromyalgias, other nonarticular chronic soft tissue pain syndromes, or headaches. The safety and analgesic efficacy of ketorolac tromethamine 10 mg 4 times a day as needed was compared with that of aspirin 650 mg 4 times a day as needed. The primary emphasis of this 52-week study was on evaluating the safety of the drugs. Patients returned to the clinics at 2, 5, 10, 15, 20, 28, 36, 44, and 52 weeks for assessments of safety and efficacy. Both patients' and investigators' evaluations of overall efficacy and safety favored ketorolac over aspirin. The probability of early withdrawal from the study was significantly higher with aspirin than with ketorolac, primarily because of lack of efficacy. Early withdrawal for safety-related reasons alone was similar for those taking aspirin and ketorolac.

Adult↗

Correlation of prostate-specific acid phosphatase and prostate-specific antigen immunocytochemistry with survival in prostate carcinoma.

Prostate-specific acid phosphatase, a secretory product of prostatic cells, may be a secondary product of the interaction of hormones with their receptor proteins. In this study we have examined two independent patient populations to see whether the intensity or extent of prostate-specific acid phosphatase and/or prostate-specific antigen staining correlated with survival and hormonal manipulation. One population of 24 patients was selected from patients undergoing surgical resection for adenocarcinoma Stage B or C at the Mayo Clinic. The second population of 123 patients was obtained from Radiation Therapy Oncology Group Protocols 75-06 and 77-06. Tissue from both populations was analyzed. In both populations, the intensity of prostate-specific acid phosphatase staining correlated with survival in a statistically significant manner. Staining with prostate-specific antigen was present in greater than 90% of specimens; data was therefore not analyzed. In those patients who subsequently relapsed and were subjected to hormonal manipulation, there appeared to be a higher likelihood of response to hormones with intense prostate-specific acid phosphatase staining.

Acid Phosphatase↗

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation.

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

Adult↗

Sequential hemibody radiotherapy in poor prognosis localized adenocarcinoma of the prostate gland: a preliminary study of the RTOG.

Ten patients with poor prognosis localized adenocarcinoma of the prostate gland received local regional radiotherapy to the prostate gland followed by sequential radiation therapy to the lower hemibody and the upper hemibody. The treatment technique is presented and its feasibility demonstrated. Five patients are alive, free of disease, with a minimum of 20 months follow-up. The most common adverse effect was prolonged reversible bone marrow suppression.

Adenocarcinoma↗

Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience.

The development of second malignant tumors (SMTs), in patients who have had their first tumor treated successfully, represents a serious limitation of current therapeutic strategies for head and neck cancers. To improve our understanding of the current magnitude of the problem and the various factors that might influence its importance, we reviewed the Radiation Therapy Oncology Group's (RTOG) prospectively collected registry of all head and neck patients seen in participating member institutions between February 1977 and April 1980. A total of 928 patients were identified who had squamous cell carcinomas of the head and neck region, no prior or coincident history of another malignant tumor, and whose planned treatment consisted of radiation therapy only. A total of 110 second, independent, malignant tumors occurred in these patients. Overall, the estimated risk of developing a second tumor within 3 years of radiotherapy was 10%, within 5 years 15%, and within 8 years 23%. Minor differences in frequency were observed for different primary sites. These SMTs unquestionably influenced subsequent survival adversely. Analysis of the database also revealed that the extent of the primary tumor influenced the risk of a second; most occurred in patients who presented with the smallest primary tumors because of their better survival. Our data indicate that preventive medicine should have its greatest impact in those patients who are treated for an early stage primary tumor.

Carcinoma, Bronchogenic↗

Second malignant tumors in patients with laryngeal carcinoma: diagnosis, treatment, and prevention.

Although the survival rates reported for patients with larynx carcinoma are quite good, there is a risk of developing second malignant tumors (SMT) in this population. The prognosis for SMT is poor, particularly with tumors of the lung and esophagus. The Rochester series was analyzed for larynx stage and specific SMT sites, possible common etiologic factors, and survival of the population as a whole, as well as for the SMT group. From a total of 235 patients with larynx carcinoma and a median follow-up of 10 years, 50 patients with 61 SMT were identified. The overall incidence of developing a SMT was 21%, with 44% of the SMT in the lung. The median survival from SMT diagnosis was 8.74 months and the 2-year survival was only 26%. More than twice as many SMT were observed than would be expected in the population at risk, with an observed-to-expected ratio (OER) for lung SMT of 5.3, and 8 times as many head and neck SMT occurring in our population. These SMT are not treatment related but are most likely caused by a combination of exposure to a common carcinogen, that is, tobacco smoke and alcohol, and to inherent factors, notably "condemned mucosa syndrome." Follow-up procedures, from the perspective of SMT development in larynx cancer patients, are addressed in an attempt to improve survival. The focus of this study is the high incidence of lung primaries that could be mistaken for metastatic disease, which is relatively uncommon in early larynx cancer patients.

Adult↗

Serum markers for prediction of pulmonary radiation syndromes. Part I: Surfactant apoprotein.

Detection of a biochemical marker indicating radiation lung injury prior to the onset of clinical pathologic events could prove valuable in patient management. An increased level of alveolar surfactant is one of the earliest detectable changes following lung irradiation, starting within hours of irradiation and persisting a maximum of 2-6 weeks. However, because broncho-alveolar lavage is impracticable and endothelial cell damage due to radiation results in changes in permeability of vessel wall with leakage of alveolar proteins into serum, identification of serum markers was sought. A series of experiments in rabbits are described that clearly demonstrate serum surfactant apoprotein is an accurate marker and predictor for later lethal radiation pneumonitis. At 3-7 days after graded single doses to lung, surfactant was found in the serum paralleling the dose response for lethality. Control studies with a physiologic agent such as terbutaline release alveolar surfactant, but no serum surfactant was detected. Monitoring serum surfactant could direct preventive intervention prior to clinicopathologic manifestation of pulmonary radiation syndromes.

Animals↗

Quality assurance problems in clinical hyperthermia and their impact on therapeutic outcome: a Report by the Radiation Therapy Oncology Group.

Since February 1981, 300 patients with superficial measurable tumors were randomized on an RTOG protocol (81-04) involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (42.5 degrees C, 60 min). This is a report of 218 eligible patients with single lesions: 107 treated with radiotherapy alone (RT), 111 with radiotherapy plus hyperthermia (RT + HT). Only 56% of the 24 tumors less than 3 cm and 36% of the 53 lesions larger than 3 cm received what was felt to be "adequate" therapy (greater than or equal to 29 Gy and 8 heating sessions). Overall complete response (CR) was observed in 28% of the patients treated with RT, and 32% of the patients receiving RT and heat. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (less than 3 or greater than or equal to 3 cm) and site/histology (breast/adenocarcinoma, head and neck/squamous, or other site/histologies). In the head and neck tumors less than 3 cm in diameter there was no difference in CR with irradiation alone or combined with hyperthermia (46% vs 43%). However, in the breast, and trunk and extremities a better CR rate was noted with irradiation and heat (55% and 67%) than with irradiation alone (33% and 0). In lesions less than 3 cm treated with irradiation and heat the probability of remaining in response was 80% compared with 15% with irradiation alone. In lesions larger than 3 cm no difference in CR was observed in either treatment group. It has been hypothesized that the response rate is higher in patients with smaller lesions (less than 3 cm) and in breast/chest wall, trunk/extremity lesions because these tumors and anatomical sites are easier to heat adequately. Problems encountered in correlating tumor response with quality of heating include less than optimal heating in larger lesions and the limited ability of current thermometry to accurately represent the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because of short survival of some patients and occasionally rapid tumor regression that may cause necrosis which may be misinterpreted as persistent tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Hormonal cytoreduction in locally advanced carcinoma of the prostate treated with definitive radiotherapy: preliminary results of RTOG 83-07.

RTOG 83-07 is a Phase II randomized protocol designed to compare the efficacy and toxicity of Megestrol vs Diethylstilbestrol (DES) used as cytoreductive agents prior to and during radiotherapy. The end-points of this study include tumor clearance rate, effect on serum testosterone, local-regional control, disease-free interval, and survival. Eligible patients were those with histologically confirmed locally advanced adenocarcinoma, clinical Stage B2 and C without regional lymph node involvement, or with lymph node involvement limited to the pelvis. Patients with medical conditions potentially predisposing to cardiovascular (thromboembolic) sequelae of endocrine therapy were not eligible. Patients were stratified by clinical stage, histological grade, and nodal status and were randomized to receive either Megestrol 40 mg PO tid or Diethylstilbestrol 1 mg PO tid. The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course. Radiotherapy consisted of 44 to 46 Gy, 1.8 to 2 Gy per day to the regional lymphatics followed by a boost to the prostate consisting of 20 to 25 Gy, 1.8 to 2 Gy per day to a total of 65 to 70 Gy. Serum testosterone levels were recorded throughout the treatment course. Tumor response was assessed clinically and radiographically (CT scan). From March 1983 through June 1986 a total of 203 patients were accessioned to the study; 197 were analyzable. Correlation of the incidence of drug related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol (DES) arm. The most prominent were the differences in the incidence of gynecomastia (55% vs 7%) and fluid retention (21% vs 6%). The incidence of thromboembolic phenomena was comparable (8% vs 5% in the Megestrol arm). Although patients on the DES arm demonstrated a significantly greater median decrease in testosterone level, correlation of the treatment assigned to the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms. At 3 years only 6.5% of the evaluable patients manifested evidence of local failure. The results of the study indicate comparable efficacy (using tumor clearance as an end-point) of DES and Megestrol. While DES appears more effective in suppressing testosterone it is also associated with a higher incidence of toxicity. The cytoreduction (using either DES, Megestrol, or an alternative regimen) concept remains to be tested in a Phase III study comparing it to radiotherapy alone.

Adenocarcinoma↗