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Biomedical subjects

E Glatstein

Publications and source records attributed to E Glatstein.

At least 19 recordsLinked to original sources
PubMed1997

Phase I trial of photodynamic therapy in the treatment of recurrent superficial transitional cell carcinoma of the bladder.

OBJECTIVES: A Phase I trial of photodynamic therapy (PDT) in the treatment of superficial transitional cell carcinoma (TCC) of the bladder was performed. METHODS: Twenty patients with recurrent superficial TCC of the bladder after receiving a mean of 2.6 (range 1 to 6) courses of intravesical therapy were treated with PDT. The photosensitizer Photofrin II dose was 1.5 or 2.0 mg/kg. A 630-nm intravesical red laser was used to activate the photosensitizer 2 days after administration of Photofrin II. A 0.01% intralipid solution was used as a bladder-filling medium to scatter light and achieve more homogeneous light distribution. Light doses from 5.1 to 25.6 J/cm2 (total dosage 1500 to 5032 J) were used to illuminate the bladder. RESULTS: Twenty patients underwent 21 treatments with PDT. Complications included asymptomatic reflux in 4 patients. One other patient, treated at the highest total light dose, experienced bladder contraction and fibrosis. Nine patients (45%) had no tumor evident at cystoscopy, on random biopsies, or in urinary cytology at the 3-month evaluation after treatment. Four patients remained without recurrent disease for 23 to 56 months. Sixteen of 20 (80%) patients experienced recurrence, and 8 of the 16 underwent cystectomy. CONCLUSIONS: An intravenous photosensitizer dose of 1.5 mg/kg Photofrin II followed by light energy in the range of 13 J/cm2 (total light dose 2500 to 3250 J) was defined as a safe treatment parameter and resulted in tumor responses. With present technologies, administration of PDT requires careful dosimetry.

Adult↗
PubMed1996

Radiation biology of lung cancer.

The enormous problem that is lung cancer still defies satisfactory therapeutic strategy. This article summarizes some of the more important laboratory efforts directed at understanding the biology of this complex disease. The radiation sensitivities of established lung cancer cell lines are outlined. The effect of radiation dose rate and chemotherapy is explored. The emerging biology of oncogenetic alterations is explored as it relates to radiation sensitivity in general, and lung cancer in particular. Finally, novel therapeutic approaches including photodynamic therapy are introduced.

Antineoplastic Agents↗
PubMed1996

Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine.

PURPOSE: A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. PATIENTS AND METHODS: Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. RESULTS: Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have had progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival time is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. CONCLUSION: This combined modality regimen for patients with limited-stage small-cell lung cancer results in a 2-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths.

Adult↗
PubMed1995

Dosimetric considerations in treating mediastinal disease with mantle fields: characterization of the dose under mantle blocks.

PURPOSE: While the rationale for using mantle fields is well understood and the prescription of these fields is straightforward, the underlying complexity of the dose distributions that result is not generally appreciated. This is especially true in the choice of lung block design, which affects the dose to both the target volume as well as to the normal lung tissue. The key to the design of optimal lung blocks is the physician's perception of the complex relationship between the geometric and dosimetric aspects of heavily modified fields, as well as how the physical and anatomical properties of the target volume and the shape of the patient's lungs relate to the images visualized on simulator films. METHODS AND MATERIALS: Depth doses and cross-beam profiles of blocks ranging in width from 1 cm to 10 cm were taken using an automated beam scanning system. These data were then converted to "shadow fields." The results were compared to open fields of the same size using standard methodology. RESULTS: Shadow fields behave quite similarly to small, open fields in terms of x-ray-light field congruence, flatness, symmetry, and penumbra. There is a 2-3 mm rim between the edge of the block and the point at which it becomes nominally effective. The dose at the center of a block, which gives the normalization of the shadow fields, is given by a block transmission factor (BTF), which produces results in excellent agreement with measurements over a wide variety of block sizes and tissue depths. CONCLUSION: The radiation dose under shielding blocks can be considerably higher than expected, and care must be exercised when drawing blocks close to critical structures. The effects of blocks can be described in terms of normalized shadow fields, which behave similar to narrow, open fields, but with a divergence characteristic of their position relative to the radiation source. The normalization value for these fields, which gives the relative dose under the block, can be obtained from a straightforward analytical expression, the BTF.

Lung↗
PubMed1995

Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer.

BACKGROUND: Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. METHODS: Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. RESULTS: At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P = 0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P = 0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P = 0.17) after recurrences successfully treated by mastectomy were censored from the analysis. CONCLUSIONS: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy.

Breast Neoplasms↗
PubMed1995

A diffusing sphere which delivers homogeneous laser light for use in photodynamic therapy.

Photodynamic therapy (PDT) exploits the selective uptake of a photosensitizer in tumors and other hyperproliferative target tissues, as well as the ability to direct the treatment light beam to a specific region. Since the photodynamic effect depends on light dose, tissue optical properties and photosensitizer concentration, uniform delivery of light is crucial to attain optimal photodynamic effect. Many commonly used methods for delivering laser light during photodynamic therapy, such as a free fiber or microlens, require fiber and laser adjustments to obtain a highly uniform beam. In this study, we test the ability of a diffusing sphere to improve the uniformity of a light field coming from an argon laser coupled to a free fiber, in which no attempt has been made to optimize beam characteristics. Light fields from the free fiber, a microlens and the diffusing sphere are compared for uniformity via light intensity readings. An in vivo comparison between the sphere and the free fiber is also made in guinea pigs given Photofrin-II. The diffusing sphere decreases problems with shielding, allows quick and easy application of light by simply applying the device over the desired treatment area, and optimizes the desired photodynamic effect by producing ad highly uniform beam of light with no necessity to optimize light delivery by vibrating, looping or re-cleaving fibers.

Animals↗
PubMed1995

Electron beam treatment for cutaneous T-cell lymphoma.

Total skin electron radiation has proven efficacy in treating MF. It is a complex technique that requires a dedicated radiation team, involving physicists, radiotherapists, and radiation oncologists. A center must treat a sufficiently high volume of patients to justify the development of TSE, with appropriate organization, time, and expense. The radiation team should be an integral part of a multidisciplinary clinical group, including medical oncologists, dermatologists, pathologists, and nurses. In these contexts, TSE has appropriately been developed in a limited number of centers. Cooperation between these centers is essential for further refinement of TSE techniques and for evolution of the role of TSE in the management of most patients with MF.

Combined Modality Therapy↗
PubMed1994

Treatment of locally advanced cancer of the head and neck with 5'-iododeoxyuridine and hyperfractionated radiation therapy: measurement of cell labeling and thymidine replacement.

BACKGROUND: The halogenated pyrimidines 5'-iododeoxyuridine (IdUrd) and 5'-bromodeoxyuridine (BrdUrd) are under active study as radiation sensitizers for a variety of malignancies. Head and neck neoplasms may also be suitable for halogenated pyrimidine-mediated sensitization; previous regimens using intra-arterial BrdUrd delivery, however, were poorly tolerated. PURPOSE: A pilot study was undertaken with the use of intravenous IdUrd with hyperfractionated radiotherapy to assess tolerance. In addition, serial tumor biopsy specimens were obtained to determine the kinetics of IdUrd labeling and incorporation. METHODS: Twelve patients with squamous cell carcinomas of the head and neck (one patient had stage II cancer, one had stage III, and 10 had stage IV) were treated with hyperfractionated radiation therapy at a dose of 1.2 or 1.5 Gy twice a day, to a total dose in the range of 70-76 Gy. IdUrd (1000 mg/m2 per day) was infused for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. A tumor biopsy specimen was obtained from 11 patients following initiation of treatment with IdUrd. Eight patients consented to serial biopsy to allow the study of IdUrd-labeling indices and thymidine replacement over time. Incorporation of IdUrd into tumor DNA was determined by high-performance liquid chromatography, and cell labeling was determined with the use of an anti-BrdUrd/IdUrd monoclonal antibody in conjunction with flow cytometry. Patients continue to be followed to assess local control. RESULTS: A plot of corrected IdUrd replacement as a function of infusion time suggests the possibility of a plateau after 5-7 days of infusion at 7.5%-8%. The average rate of replacement from days 1 to 5 was 1.3% per day and was determined by linear regression analysis. Acute toxic effects, especially mucositis, were severe enough to require delays in the radiation therapy. Eleven of 12 patients treated had complete clinical remissions. Seven of these patients remain clinically free of local disease at the time of death or most recent follow-up. CONCLUSIONS: The level of IdUrd incorporation and cell labeling should be adequate to produce sensitization. However, the treatment as prescribed in this study (two 14-day infusions of IdUrd during radical radiotherapy with only one planned split) was not completed in a single patient because of either dose-limiting hematologic toxicity or severe mucositis necessitating treatment break. Since this particular regimen is not tolerable, future protocols will have shorter exposures to IdUrd. IMPLICATIONS: Previous regimens using halogenated pyrimidine radiosensitizers have generally used protracted drug delivery schedules. In this study, a high level of IdUrd labeling was measured after 5-7 days of drug infusion. The halogenated pyrimidines deserve further study with the use of repetitive short courses to reduce toxicity and possibly improve efficacy.

Adult↗
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↗