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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 253 records · Page 14Linked to original sources
PubMed1985

Prophylactic versus no brain irradiation in regional small cell lung carcinoma.

Among 104 complete responders entered in a randomized prospective trial of treatments for regional small cell undifferentiated carcinoma of the lung, 52 received prophylactic irradiation of the brain, 3,000 rad in 10 fractions, and 52 did not. The median survivals were 53 and 52 weeks respectively, and the incidences of brain metastases were 5% and 20%. Prophylactic brain irradiation was not associated with significant long-term toxicity.

Brain Neoplasms↗
PubMed1985

Misonidazole and hemibody irradiation in the palliation of widespread metastases. Final report of an RTOG study.

The radiation therapy oncology group conducted a phase I/II trial of hemibody irradiation combined with high-dose misonidazole in the management of metastatic solid tumors. Thirty-seven patients received 39 hemibody irradiation treatments, each preceded by 4 g/m2 or 5 g/m2 misonidazole orally. One fraction of 600 cGy was delivered to a half-body volume. Objective tumor response occurred in 21% of evaluable patients, including one complete response. Pain relief was documented in only 36%. Acute toxicity consisting of nausea and vomiting was significant; 54% of patients experienced severe or very severe reactions. Other toxicities were acceptable. The low response rate and high acute toxicity contraindicate the use of misonidazole with hemibody irradiation for palliation.

Administration, Oral↗
PubMed1985

Birth defects in three common pediatric malignancies; Wilms' tumor, neuroblastoma and Ewing's sarcoma.

During the period 1965-1980, 84 patients with Wilms' tumor, neuroblastoma and Ewing's sarcoma were treated at the University of Rochester Medical Center. All patients were evaluated for the presence of congenital abnormalities. Ten of 34 (29%) patients with Wilms' tumor, 3 of 32 (9%) patients with neuroblastoma, and 0 of 18 patients with Ewing's sarcoma were so effected. In the patients with Wilms' tumor, 5 children had more than one abnormality. In this group, types of defects included genitourinary in 10 patients, central nervous system in 3, and other structural defects in 7. In the patients with neuroblastoma, the abnormalities were dissimilar. As expected, most of the 13 patients with congenital malformations were detected as having defects prior to the diagnosis of malignancy. For the patients with Wilms' tumor, median age at diagnosis for the entire group and for the subgroup with defects was 3 years, with age ranges similar. Male to female ratios were 1.3:1 and 1:1, respectively. Seventy percent of each group survived more than 5 years. For the patients with neuroblastoma, median age (range) for the entire group was 16 months (0-12 years). The patients with defects had ages of 5 days, 1 month and 9 months at diagnosis. Male to female ratio for the entire group was 0.6:1 and survival was 63% at 3 years (range 3-23 years). Those with defects are alive 3-8 years from diagnosis.

Adolescent↗
PubMed1984

Once-a-week radiation therapy for locally advanced lung cancer. Final report.

Forty-nine patients with very advanced locoregional lung cancer, metastatic in 41% of the instances, were treated with 5 Gy once weekly to a total dose of 50 to 60 Gy (1826-2050 ret). The overall tumor response rate was 68% (27% complete response and 41% partial response). The largest number of responders and the majority of complete responses were seen with the higher doses (60 Gy). The response rates of the major histologic variants were 100%, 75%, and 47% for small cell, large cell, squamous, and adenocarcinomas. The time to achieve more than 50% reduction in tumor size was 2, 2, 6, and 9 weeks for these histologic variants, respectively. The overall incidence of local failures was 22%, with only 10% of the patients demonstrating exclusive in-field local failures. There are 13 long-term survivors and the main cause of patient deaths was metastatic disease. The technique was extremely well tolerated, and, in fact, practically no acute radiation-induced complications were observed during the 10 to 12 weeks' treatment duration. Only one patient developed a symptomatic but transient radiation pneumonitis. Radiation fibrosis of various degrees has occurred, but it has been mostly asymptomatic and analogous to what is normally seen using conventional continuous schedules delivering similar doses. Once-a-week irradiation emerges as a practical and convenient alternative for the treatment of lung cancer, and appears to achieve similar results to conventional continuous schedules.

Aged↗
PubMed1984

External radiation in the management of superior sulcus tumor.

Thirty-one patients with superior sulcus tumor (Pancoast's syndrome) treated with radiation between 1967 and 1980 were reviewed. Doses ranged from 2000 to 7000 cGy delivered with a continuous schedule (23 patients) and a split course regimen (8 patients). The overall survival at 5 years was 18% (median, 17 months). Patients without bone erosion or scalene lymph node involvement (13 patients) had the best 5-year survival rate of 40%. Local control tended to correlate with the total dose and tumor extent; doses below 5000 cGy or bone invasion were associated with a higher rate of local failure. Primary external radiation is not only useful for palliation but can also cure some patients with superior sulcus tumor.

Adenocarcinoma↗
PubMed1984

Predicting the response of head and neck cancers to radiation therapy with a multivariate modelling system: an analysis of the RTOG head and neck registry.

Two thousand and sixty-six patients with primary head and neck cancers were entered in the RTOG Head and Neck Cancer Registry between 1977 and 1980. Nine hundred and ninety-seven (997) evaluable patients were treated initially with radiation therapy alone. Tumor site, T-stage, N-stage, histology, degree of infiltration, degree of differentiation, patient age, sex and Karnofsky performance score were all prospectively recorded. T-stage (p less than .001), N-stage (p = .007), primary site (p less than .001), and initial Karnofsky performance score (p less than .001) proved to be significant factors independently predictive of primary tumor clearance. Using these factors, a multivariate response model was constructed to predict primary tumor response. The predictive accuracy of the model proved to be highly reliable, and was tested by comparing the predicted vs. observed complete tumor clearance rates for each independent variable. For primary sites, the predicted number of complete responses vs. observed were: oral cavity, 139.8 predicted vs. 139 observed; nasopharynx, 51.8 predicted vs. 51 observed; oropharynx, 174.8 predicted vs. 176 observed, supraglottic larynx, 314.4 predicted vs. 318 observed; glottic larynx, 314.4 predicted vs. 318 observed; and hypopharynx, 49.4 predicted vs. 46 observed. For the entire group of patients predicted to have a 90% or better complete primary tumor response (including T3 and T4 tumors), 94% remained in initial complete remission at the primary site at one year, and 87% at two years. An accurate multivariate response model, such as the one presented in this paper, should prove to be a useful tool in selecting patients with head and neck cancers suitable for treatment with radiation therapy alone.

Adult↗
PubMed1984

Radiation induced secretion of surfactant from cell cultures of type II pneumocytes: an in vitro model of radiation toxicity.

The pathogenesis of pneumonitis and fibrosis secondary to lung irradiation is incompletely understood. The role of the type II alveolar epithelial pneumocyte in these processes has been under investigation. The type II pneumocyte has been shown in vivo to respond to radiation induced injury with release of pulmonary surfactant. The effect of irradiation on cell cultures of type II pneumocytes was studied to determine if this could be reproduced in vitro. Type II pneumocytes were found to release surfactant material with a threshold of radiation dose between 1000 and 1500 rad. This is similar to the dosage range over which the same effect has been demonstrated in vivo. Experimental results support the concept that the release of surfactant is not due to either cell disruption or non-specific release of phospholipid from cell membranes. Irradiation appears to trigger membrane receptor mediated surfactant release. In addition, irradiation abolishes the ability of cells to subsequently respond to a physiologic agonist, suggesting radiation induced damage to the secretory mechanism. These studies establish that surfactant release in response to irradiation in vivo is a direct effect on type II pneumocytes. Cell cultures of type II pneumocytes can serve as a laboratory model of lung cell radiation toxicity.

Animals↗
PubMed1984

Characterization of the biophysical properties of human tumor and bone marrow cells as a preliminary step to the use of centrifugal elutriation in autologous bone marrow transplantation.

The principle of centrifugal elutriation (CE) depends on a balance of an outwardly directed centrifugal force and inwardly directed fluid flow and buoyant forces. This method (CE) can be used effectively to separate cells on the basis of size. In the murine model, neoplastic cells from different tumors are generally larger than bone marrow cells and can be removed from bone marrow almost completely with centrifugal elutriation. In order to determine if CE is capable of eliminating human tumor cells from harvested bone marrow (BM), the biophysical characteristics of a variety of human tumor cells and bone marrow cells were determined. Human tumor cells were dispersed into single cell suspensions by several enzymatic digestion and mechanical dissociation methods. The size and density characteristics of these cells were determined with an electronic particle counter and channelyzer and density gradients. Of 40 solid tumors studied, 29 tumors had cell size distributions distinctively larger than BM, as was found in the experimental animal model. The cell size distributions of tumor cells from 11 solid tumors and 7 leukemias were not substantially different from that of BM. Mixtures of BM and cultured human hypernephroma, ovarian, and neuroblastoma cells, were separated into BM and tumor fractions by CE. The separation results as indicated by the labeling index and colony forming efficiency of tumor cells in each fraction showed that a BM fraction virtually free of tumor cells could be obtained. Thus, CE should be able to separate BM cells from most tumor cells metastatic to BM.

Bone Marrow↗
PubMed1984

Usefulness of postoperative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients.

Heterotopic ossification is a complication of total hip arthroplasty in 14 to 30% of patients. Significant functional impairment will occur in up to 28% of patients with ectopic bone. The high risk group includes those with preexisting heterotopic bone in either hip, those suffering from hypertrophic osteoarthritis or ankylosing spondylitis and patients who have had multiple procedures on the hip. Fifty-eight patients (67 hips) were irradiated after surgical removal of ectopic bone (53 hips) or received radiation prophylaxis of heterotopic ossification (14 hips). Ninety-five percent of patients had either no bone visible or insignificant amounts of ectopic bone visible on postoperative hip X-rays. Only 5% of patients showed significant persistence of ectopic bone. Postoperative hip function was dramatically improved compared to preoperative function in all patients treated. The importance of early commencement of irradiation is emphasized.

Adult↗
PubMed1984

The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 1. Different volumes and doses.

Bone marrow regeneration (BMR) following irradiation has been largely studied as a dose-effect phenomenon, however, a large literature has simultaneously developed utilizing a wide variety of volumes, both in clinical studies and in experimental studies. In human situations radiation treatment fields and the amount of bone marrow organ exposed have ranged from total body irradiation (small daily and total doses) to large field (half-body) single high doses encompassing 50% of the bone marrow, to segmental or localized field (50-25%). Volume factors, more than dose, determine patterns of suppression and regeneration which have been documented by a variety of assay systems. Experimental evidence is presented which indicates that high dose irradiation (500-1000 cGy) to large volumes of bone marrow (50%) does not completely suppress bone marrow regeneration but results in a rapid compensatory response. The nadir response of bone marrow CFUc-GM stem cell compartment was directly proportional to increasing doses of irradiation (200-2000 cGy) delivered to a single limb. Immediate depression of CFUc-GM was followed by an increase proliferative phase with the most notable difference observed in doses less than or greater than 1000 rad. Following doses of 500 and 1000 rad to large field (half-body), an immediate depression was again observed followed by an immediate and greater compensatory response particularly after the 1000 rad dose. Comparisons ae made between the small and larger volumes at similar doses and indicate a greater overall compensatory response after the larger field irradiation, being more rapid in onset particularly after the 1000 rad dose. Although in-field regeneration of bone marrow occurs after single dose radiation to different volumes of bone marrow, experimental and clinical evidence from protracted conventional doses of irradiation to different volumes of bone marrow (greater or less than 50%) indicate significantly different response mechanisms. From our laboratory and clinical investigations it can be determined that bone marrow is extremely sensitive to radiation insult and has different compensatory mechanisms to "fine tune" its response in proportion to the volume insulted.

Animals↗
PubMed1984

The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation. 2. Total body irradiation.

Low dose total body irradiation (TBI) administered in small fractional doses (5-10 cGy) for the treatment of disseminated malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma can be extremely toxic with substantial bone marrow depression. We elected to study bone marrow suppression following fractionated TBI in the rabbit. New Zealand white/female rabbits were thus treated with one of the following three schedules: (1) 3 fractions of 10 cGy per week; (2) 5 fractions of 10 cGy per week; and (3) 5 fractions of 25 cGy per week. Total doses ranged from 1050 to 2625 cGy and animals were sacrificed immediately, 4 weeks, or 8 weeks following completion of therapy. With the 10 cGy/day schedules, slight depression of total WBC counts and lymphocyte numbers occurred during and to the completion of irradiation followed by a rebound to greater than normal levels. With the 25 cGy schedule, a significant WBC and lymphocyte depression occurred at an accumulated dose of 1000 cGy and continued to decrease up to 2500 cGy, followed again by a rebound to greater than normal levels. The depression with the 25 cGy fractions was significantly greater than with the 10 cGy daily fractions. Thus, the severe and persistent peripheral blood count depression observed in CLL patients treated with TBI in small fractional doses was not reproduced in the normal rabbits. Possible explanations for this paradox are offered.

Animals↗
PubMed1984

Irradiation induces release of von Willebrand protein from endothelial cells in culture.

Human umbilical vein endothelial cells in tissue culture were irradiated with doses between 0 and 40 Gy, and the released von Willebrand (vW) protein and that which remained associated with the cells was quantitated. Doses of 20 Gy and higher produced a statistically significant increase in amount of vW protein secreted. This release was present whether the cells were labeled continuously throughout the experiment or just prelabeled before irradiation. An increase in fibronectin secretion was not observed. The release response to radiation was slow, reaching significance close to 24 hours after irradiation. The release of vW protein was not due to cell lysis, because the secreted vW protein contained very little of the large 260-kilodalton vW precursor subunit present in cell lysates and the cells appeared intact by immunofluorescence staining.

Blood Coagulation Factors↗
PubMed1983

Ocular and orbital complications following radiation therapy of paranasal sinus malignancies and review of literature.

During the period from March 1963 through March 1978, 30 patients with malignant neoplasms of the paranasal sinuses were treated with supervoltage technique at the University of Rochester Medical Center. Twenty-one patients had at least the medial portion of the orbit within the effective treatment volume and the rest of the patients had whole eye irradiation. In paranasal sinus malignancies, orbital involvement with ocular symptoms and signs is quite common; in many patients it can be the presenting problem. Enucleation is necessary in patients with gross orbital tumor. Eye preservation is worthwhile in patients with minimal orbital tumor. Anterior complications are a minimal risk if the technique is good. Posterior complications occur in almost all patients, but are rarely clinically significant until doses of 6000 rad or above are reached. In patients without gross orbital involvement, preservation of the eye can be considered optional treatment. It includes shielding of the anterior structures, but it is usually not possible to protect medial and posterior portions of the eye and orbit. In advanced cases, it is worthwhile to preserve the eye as cure rate is low and posterior eye complications are often late. Because the aim of treatment is cure, dose should not be compromised to prevent complications. Radiation injury to the optic nerve and retina is the major factor in visual loss, but it can be prevented by limiting the retinal and optic nerve dose to less than 6000 rad.

Aged↗