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Biomedical subjects

E Glatstein

Publications and source records attributed to E Glatstein.

At least 55 records · Page 3Linked to original sources
PubMed1994

Postmastectomy radiotherapy in the management of operable breast cancer.

There is a long and detailed history of radiation therapy as an adjuvant to surgery in operable breast cancer. The results of a large number of randomized clinical trials will be reviewed. They can be summarized by saying that although the trials show a reduction in local-regional failure with the use of postoperative radiotherapy, a survival advantage has not been clearly identified. Many of the older trials used techniques and radiation doses inadequate by current standards, which may have affected the results. Recent trials that used therapeutic doses of radiation, however, did demonstrate a survival advantage among patients who received postoperative radiotherapy. These trials generally have included chemotherapy and required careful integration of radiotherapy and systemic therapy. Although all trials have not demonstrated a survival benefit by the addition of radiotherapy, the ability to maintain local-regional control after mastectomy is an important goal. Administration of prophylactic chest wall and nodal radiotherapy to patients at high risk for local-regional recurrence significantly reduces the chance of a local treatment failure. Because a chest wall recurrence is a distressing event that dramatically affects quality of life, improved local-regional control with postoperative radiotherapy is a highly significant end point.

Breast Neoplasms↗
PubMed1994

Is c-erb B-2 a predictor for recurrent disease in early stage breast cancer?

PURPOSE: To assess the prognostic importance of c-erb B-2 expression in early stage breast cancer. METHODS AND MATERIALS: Immunohistochemical analysis for c-erb B-2 over-expression was retrospectively performed on 107 paraffin-embedded specimens of women with Stage I or II breast cancer entered in a randomized trial. Results were correlated with known prognostic factors such as pathologic axillary involvement, T-size, estrogen and progesterone receptor status, and nuclear grade. Immunohistochemical staining for c-erb B-2 protein expression was also correlated with breast/chest wall failure as well as survival without evidence of disease (NED) and overall survival. RESULTS: C-erb B-2 overexpression was positive in 21% of the biopsy specimens. A significant association was found between c-erb-2 positivity and lesions containing an intraductal component, with 62% of lesions staining positively for c-erb B-2 having an intraductal component compared to only 36% of lesions with an intraductal component staining negatively for the c-erb B-2 protein (p2 = .031). A significant correlation between c-erb B-2 protein over-expression and axillary nodal status, primary tumor size, nuclear grade, and estrogen and progesterone receptor status was not identified. Cox proportional hazards model did not show a significant effect of c-erb B-2 expression for NED or overall survival. CONCLUSION: Our study did not find over-expression of c-erb B-2 to reliably predict for recurrent disease in early stage breast cancer. This data can be added to other series comparing erb B-2 expression and disease outcome among node-positive and node-negative women with carcinoma of the breast.

Adult↗
PubMed1994

Healing impairment of open wounds by skin irradiation.

BACKGROUND: Ionizing radiation is frequently used for the treatment of malignancy. Sequelae of therapeutic radiation frequently present clinical problems in the form of poor wound healing and easy injury of treated tissue in response to mild trauma. OBJECTIVE: We describe a radiation-impaired wound healing model in guinea pigs, developed to determine the effect of cutaneous irradiation on wound contraction. METHODS: Guinea pigs were anesthetized and a flap of skin was isolated and treated with x-rays to 18 Gy. Circular wounds of identical size were made in irradiated and control skin, and average wound size was recorded. RESULTS: Our results demonstrate that a statistically significant wound healing deficit is produced in open wounds by surface irradiation of skin. CONCLUSION: Radiation of skin results in slower healing of open wounds, and provides an in vivo system for evaluation of topical dressings and growth factors in radiation-impaired wounds.

Animals↗
PubMed1994

Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy.

PURPOSE: To examine behavioral dimensions of treatment outcomes for patients receiving cranial irradiation. Radiation encephalopathy is one of these and refers to significant cognitive and emotional dysfunction following radiation therapy to the brain. Issues of definition, estimated incidence, pathophysiologic mechanisms, and recommended research designs are reviewed in relationship to functional neurobehavioral outcomes. PATIENTS AND METHODS: Twenty-nine studies of adults receiving therapeutic cranial irradiation (TCI) involving 748 patients and 18 studies of prophylactic cranial irradiation (PCI) involving 368 patients are reviewed. Assessment of patient outcomes are summarized for research published since 1980, with specific attention to adverse changes in cognitive and emotional functioning. RESULTS: Analyses revealed that 213 TCI patients and 100 PCI patients showed encephalopathy attributed to radiation. Manifestations of the late delayed effects of radiotherapy on brain function are related to patient age, total dose of irradiation, fraction sizes, and timing of chemotherapy. Radiation encephalopathy appears to be more common than the pathologic tissue injury of radiation necrosis. Accurate diagnosis of these neurobehavioral sequelae can require follow-up over a period of years with sensitive assessment procedures. CONCLUSIONS: It is likely that the true incidence of treatment-related side effects of cranial irradiation in adults who survive more than 6 months without brain tumor growth or recurrence has been significantly underestimated. Research designs that include formal neuropsychologic assessment in conjunction with other neurodiagnostic tests can provide more comprehensive evaluation of long-term neurobehavioral outcomes.

Brain↗
PubMed1994

Clinical applications of photodynamic therapy.

This is a review of photodynamic therapy, which is a classic binary system involving the use of a photosensitizer and light of very specific wavelength, consistent with the absorption characteristics of that sensitizer. As a binary system, its effects are almost entirely limited to tumour cells, but the major drawback is its limited penetration because it utilizes physical light within the visible spectrum. For Photofrin II, which is the only approved sensitizer for clinical use in this country, the effects are limited to approximately 0.5 cm or less, depending on the tissue and the amount of blood, etc. Newer sensitizers offer more penetration and the opportunity to repeat treatments, because the newer sensitizers do not have the very long (up to 10 weeks) period of enhanced skin sensitivity to sunlight. A summary of the results of photodynamic therapy by individual sites is included. The use of newer sensitizers, which represent much purer substances than Photofrin II, should give an opportunity for repeated treatments, which should eventually make this form of treatment far more important than it has been up to now.

Animals↗
PubMed1993

Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors.

PURPOSE: Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors. METHODS AND MATERIALS: Patients received dihematoporphyrin ethers (DHE) 1.5-2.5 mg/kg by i.v. injection prior to surgery. Patients resected to < or = 5 mm of residual disease underwent laser light delivery to all peritoneal surfaces. RESULTS: Fifty-four patients entered the study. Thirty-nine underwent resection and light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8-3.0 J/cm2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10-15 J/cm2 red light or 5-7.5 J/cm2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7-9 days, while one had a gastric perforation. At potential follow-up times of 3.8-43.1 months (median 22.1 months), 30/39 patients are alive and 9/39 are free of disease. CONCLUSION: The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0-7.5 J/cm2 of 514 nm green light or 10-15 J/cm2 of 630 nm red light to sites of gross disease encountered at surgery.

Adult↗
PubMed1993

Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial.

Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospective, randomized, clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose (35- to 40-Gy) external-beam radiotherapy with postoperative high-dose (50- to 55-Gy) external-beam radiotherapy alone. Chemotherapy with doxorubicin hydrochloride, cyclophosphamide (anhydrous), and methotrexate sodium was used for a portion of the trial. Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years (median follow-up, 8 years). Median survival times were similar for the group that received intraoperative radiotherapy (45 months) and the control group (52 months). There were no indications of benefit from adjunctive chemotherapy. The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy (six of 15) than control patients (16 of 20). Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis (two of 15) than control patients (10 of 20), but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy (nine of 15) than among control patients (one of 20).

Adult↗
PubMed1993

Long-term outcome in 87 patients with low-grade soft-tissue sarcoma.

OBJECTIVE: To describe the long-term clinical outcome of patients with low-grade soft-tissue sarcoma and identify factors that may predict or determine their prognosis. DESIGN: Retrospective chart review with multivariate analysis. SETTING: Large research hospital and referral center. PATIENTS: All patients treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who had a confirmed diagnosis of low-grade soft-tissue sarcoma. INTERVENTIONS: Surgery and radiation therapy. MAIN OUTCOME MEASURES: Local recurrence and overall survival. RESULTS: For patients with nonretroperitoneal lesions, overall survival was excellent, with a history of recurrence, a positive surgical margin, and an absence of adjuvant radiation therapy significantly associated with increased risks of local recurrence. Patients with retroperitoneal lesions not only had an increased risk of local recurrence, but significantly poorer overall survival. CONCLUSIONS: Low-grade soft-tissue sarcomas are associated with excellent overall survival, especially those confined to nonretroperitoneal sites. The risk of local recurrence after resection with negative margins and/or adjuvant radiation therapy is very low and most recurrences can be controlled with further therapy.

Adolescent↗
PubMed1993

Randomized trial of intraoperative radiotherapy in carcinoma of the stomach.

A prospectively randomized controlled clinical trial was performed comparing surgical resection and intraoperative radiotherapy (IORT) with conventional therapy in adenocarcinoma of the stomach. Patients in the experimental group underwent gastrectomy, and IORT was administered to their gastric bed (20 Gy using 11 to 15 MeV electrons). Patients in the control group underwent gastrectomy alone for early-stage lesions confined to the stomach (stages I to II) or resection and postoperative external beam radiotherapy to the upper abdomen (50 Gy using 6 to 10 mV photons) for advanced-stage lesions extending beyond the gastric wall (stages III to IV). One hundred patients were screened for the study, of whom 60 were randomized and underwent exploratory surgery. Nineteen patients were excluded intraoperatively because of unresectability or metastatic disease, leaving 41 patients in the study. Seven patients (17%) died of complications. The median survival for patients with tumors of all stages was 25 months for the IORT group and 21 months for the control group (p = 0.99). Locoregional disease failures occurred in 7 of 16 (44%) IORT patients and in 23 of 25 (92%) control patients (p < 0.001). Complication rates were similar between IORT and control patients. Although IORT failed to afford a significant advantage over conventional therapy in overall survival, IORT did significantly improve control of locoregional disease.

Actuarial Analysis↗
PubMed1993

Biology of chronic radiation effect on tissues and wound healing.

Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed.

Animals↗
PubMed1992

Tempol, a stable free radical, is a novel murine radiation protector.

Nitroxide compounds are stable free radicals which were previously investigated as hypoxic cell radiosensitizers. The stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) has recently been shown to protect aerated cells in culture against superoxide generated from hypoxanthine/xanthine oxidase, hydrogen peroxide, and radiation-induced cytotoxicity and to modestly sensitive hypoxic cultured cells. To extend these observations from the cellular level to the whole animal, the toxicity, pharmacology, and in vivo radioprotective effects of Tempol were studied in C3H mice. The maximum tolerated dose of Tempol administered i.p. was found to be 275 mg/kg, which resulted in maximal Tempol levels in whole blood 5-10 min after injection. Mice were exposed to whole-body radiation in the absence or presence of injected Tempol (275 mg/kg) 5-10 min after administration. Tempol treatment provided significant radioprotection (P less than 0.0001); the dose of radiation at which 50% of Tempol-treated mice die at 30 days was 9.97 Gy, versus 7.84 Gy for control mice. Tempol represents a new class of in vivo, non-sulfur-containing radiation protectors. Given the potential for hypoxic radiosensitization and aerobic cell radioprotection, Temporal or other analogues may have potential therapeutic application.

Animals↗
PubMed1992

Measurement of thymidine replacement in patients with high grade gliomas, head and neck tumors, and high grade sarcomas after continuous intravenous infusions of 5-iododeoxyuridine.

Based upon the radiation sensitization properties of the halogenated pyrimidines, 5-iododeoxyuridine (IdUrd) and 5-bromodeoxyuridine, long term i.v. infusions of halogenated pyrimidines in conjunction with fractionated radiation therapy have been evaluated in the treatment of a variety of human malignancies. While clinical studies have attempted to measure the halogenated pyrimidine incorporation, few have successfully related tumor response to the incorporation of IdUrd by the tumor. The present study reports the continuous IdUrd labeling index (number of cells labeled) and the IdUrd corrected replacement (percentage of thymidine replacement in the labeled cells of the population) from the tumors of 17 patients who received continuous infusions of IdUrd (1000 mg/m2/24 h). The tumors treated included four high grade gliomas, five head and neck tumors, four high grade sarcomas, and five other tumors of varying types. Less than 25% of the cells in three of four gliomas incorporated IdUrd after 5-7-day IdUrd infusion time. Corrected replacement for the gliomas ranged from 0 to 4%. In contrast, 63-85% of the cells in the head and neck biopsies were labeled with IdUrd after 3-7-day IdUrd infusions suggesting that these large tumors (3-12 cm diameter) have a high fraction of dividing cells. Corrected replacements values for the head and neck tumor patients ranged from 2.9 to 26.3%. The high grade sarcomas also demonstrated a high percentage of IdUrd labeled cells (57-79%) with three patients having corrected replacements of 7.5-14.2%. The continuous labeling and thymidine replacement data for four patients from whom serial biopsies were taken during IdUrd infusion demonstrated both an increasing IdUrd replacement and continuous labeling index with an increasing duration of IdUrd infusion. The clinical response of both the high grade glioma and head and neck tumor patients indicate that the IdUrd replacement and labeling data may provide some important predictive information with regard to the successful use of the halogenated pyrimidines in clinical radiation trials.

Animals↗
PubMed1992

Persistent or recurrent acromegaly. Long-term endocrinologic efficacy and neurologic safety of postsurgical radiation therapy.

As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml.

Acromegaly↗