PubMed Health⌕ Search

Biomedical subjects

T H Wasserman

Publications and source records attributed to T H Wasserman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Stereotactic external beam irradiation using a linear accelerator: the Washington University experience.

From February 1989 to December 1993, 139 patients with a variety of brain lesions were treated with stereotactic external beam irradiation using a 6MV linear accelerator. The largest group consisted of patients with recurrent brain metastases (n = 46). Twenty seven patients had malignant gliomas, most of which were recurrent. Several benign conditions were treated, including arteriovenous malformations (n = 27), acoustic neuromas (n = 9), meningiomas (n = 7), and pituitary adenomas (n = 2). Durable responses were seen in the majority of patients with transient, mild, side effects. This experience suggests that stereotactic external beam irradiation is a safe, reliable, and effective method for non-invasive treatment of selected patients with small, localized brain lesions.

Academic Medical Centers↗
PubMed1994

Assurance of high quality linac-based stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery is generally a single, high-dose radiation treatment for the brain requiring targeting accuracy on the order of a millimeter. From the initial implementation of radiosurgery, therefore, quality assurance is an ongoing process of paramount importance. In this paper, we outline the basic elements of a quality assurance program for our linear accelerator that has been in use at Washington University Medical Center over the past 2 years. METHODS AND MATERIALS: Various devices and procedures have been developed to verify the accuracy and safety of the stereotactic radiosurgery regimen. Specifically, we present methods for assessing the attainment of spatially correct patient images, the reliability of the computerized treatment planning system, achieving physical safety for the patient, as well as the proper operation of the radiation treatment device. RESULTS: Our procedures have allowed us to assure quality patient treatments and, additionally, has permitted monitoring our performance for continual improvement. For example, a plot of targeting accuracy with the number of patients shows an asymptotic approach to a value within 0.6 mm of that ideally expected. CONCLUSION: To maintain high-quality patient care, one must review critical aspects of the treatment regimen on a periodic basis. Providing for the appropriate level of staff training, periodic reviews of procedures and maintenance of forms are also very important.

Humans↗
PubMed1994

Radiation therapy for stage I and IIA testicular seminoma.

PURPOSE: To review the survival, cure rate, treatment morbidity, and late sequelae of histologically confirmed seminoma patients who underwent orchiectomy and radiation therapy at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from 1964 to 1988. METHODS AND MATERIALS: There were 128 patients, with a median patient age of 37 years (range, 17-79 years). Follow-up ranged from 1-24 years, with a median of 6.7 years. There were 95 patients with Stage I and 33 with Stage IIA disease. All patients were treated with orchiectomy followed by iliac and paraaortic irradiation (median tumor dose: 2500 cGy for Stage I and 3400 cGy for Stage IIA patients). Twenty-five of 33 patients with Stage IIA disease received prophylactic mediastinal and left supraclavicular irradiation (median dose, 2700 cGy). RESULTS: For patients with Stage I disease, 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 97%, 100%, and 100%, respectively. For patients with Stage IIA disease, the 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 93%, 89%, and 97%, respectively. Four patients (3%) had recurrences; all were outside the radiation treatment field. Three of four were successfully salvaged with chemotherapy and rendered disease-free; the other patient refused treatment. There were no mediastinal recurrences whether prophylactic mediastinal irradiation was administered or not. Bowel obstruction and necrosis developed in one patient who received 3363 cGy midplane dose to the pelvic and paraaortic areas as well as additional intraperitoneal colloidal 198Au (150 mCi) for a ruptured seminoma from an undescended testis. CONCLUSION: In summary, radical orchiectomy and irradiation of the iliac and paraaortic lymphatics is the treatment of choice for patients with Stage I and IIA testicular seminoma.

Adolescent↗
PubMed1994

Radiation Therapy Oncology Group quality of life assessment: design, analysis, and data management issues.

The Radiation Therapy Oncology Group (RTOG) has embarked on seven phase II or phase III multicentre clinical trials involving a quality of life component. Each quality of life trial used questionnaires or examinations that have been tested for reliability and validity by independent investigators. Each trial includes questionnaires that examine the patient's physical, functional, social, and emotional status, and that measure a specific quality of life issue pertinent to the patient's diagnosis or treatment. Two trial designs have been implemented for studies with quality of life endpoints. One design involves companion trials to the primary treatment study pertaining solely to the quality of life endpoint. The second design integrates the quality of life component into the primary trial design. The RTOG has found a need for education of individuals and institutions expected to administer and obtain the quality of life data. Once the data have been collected several methods for the analysis of the quality of life data are available. However, there is no one best method for analysing quality of life data, thus more than one method should be used in order to provide insight into the data.

Analysis of Variance↗
PubMed1994

Non-Hodgkin lymphoma: whole-abdomen irradiation as an adjuvant to chemotherapy.

PURPOSE: To evaluate the efficacy and toxicity of whole-abdomen irradiation in the treatment of abdominal non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: Between 1978 and 1990, 39 patients with abdominal NHL were treated with modified three-way whole-abdomen irradiation as either an adjunct to chemotherapy (in 34 patients) or sole therapy (in five patients). RESULTS: The 5-year relapse-free survival rate in 36 patients who received at least 30 Gy was 38% and was 64% in 17 patients treated for consolidation of complete or partial response to chemotherapy. Treatment was terminated in four of 19 patients in whom treatment was interrupted because of acute toxicity. The major acute toxicities were decreased blood counts and enteritis. There were four grade 3 or 4 late toxicities. CONCLUSION: Whole-abdomen irradiation is a safe adjunct to chemotherapy in patients with NHL who are at high risk for intraabdominal failure.

Abdomen↗
PubMed1994

Radiotherapeutic studies with amifostine (Ethyol).

Radiotherapeutic studies with amifostine (WR-2721; Ethyol, US Bioscience, Inc, West Conshohocken, PA) are reviewed, with evidence that it offers clinical normal tissue protection and no evidence of any tumor protection. Conducting clinical trials with amifostine has been difficult because of the unique (toxicity) endpoints and concerns about tumor protection. The Radiation Therapy Oncology Group has conducted phase I studies and a phase II hemibody study, and is now in the process of conducting phase III amifostine studies. Amifostine remains the most promising compound for testing clinical radioprotection, and as new techniques are developed in radiation therapy to deliver higher doses of radiation, the protection of normal tissues will become even more important. This review will cover both the preclinical and clinical studies involving the use of amifostine with radiation therapy.

Amifostine↗
PubMed1993

Analysis of prognostic factors in localized gastric lymphoma: the importance of bulk of disease.

PURPOSE: To identify prognostic factors in localized gastric lymphoma patients for optimal therapy selection. METHODS AND MATERIALS: From 1974 to 1990, 77 patients with localized gastric lymphoma (38 Stage IE and 39 Stage IIE) were treated with radiation therapy, chemotherapy, surgery, or a combination. Univariate and multivariate local control and survival analyses were performed on possible prognostic factors, such as patient age, gender, histologic subtype, stage, tumor size, depth of penetration, multicentricity, and treatment modality. RESULTS: At 5 years, the relapse-free survival was 52%; 74% of the relapses occurred at local sites. Smaller tumor size was most strongly associated with local control (p = .001) and relapse-free survival (p < .001). Patients with tumor sizes < or = 5 cm had relapse-free survival of 87%, compared with 41% and 15% for those with tumor sizes of 5.1 cm to 10 cm and > 10 cm, respectively. The 47 patients who received combined-modality therapy had a relapse-free survival of 65%, compared with 24% for the 30 who received single-modality therapy (p < .01). Although patient age, stage, depth of penetration, and resective surgery affected the above endpoints, these factors were not independent predictors of outcome. Analysis of treatment subgroups showed that surgical resection combined with postoperative irradiation was associated with highest local control (p = .002) and the best relapse-free survival (p = .004), when compared with other treatment modalities. In 27 patients with tumor sizes < or = 5 cm, comparison of the 15 patients who had surgery with the 12 who did not failed to reveal a local control benefit from the addition of surgery. CONCLUSION: These data demonstrate that tumor bulk is an important prognostic determinant of local control and relapse-free survival in localized gastric lymphoma patients. Stage IE and IIE lymphoma of the stomach can be selectively treated with primary radiation, but surgical resection may be necessary for large tumors (> 5 cm), followed by adjuvant radiation.

Adult↗
PubMed1993

Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol.

PURPOSE: This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases; (b) to refine existing concepts of liver tolerance for fractionated external radiation employing a fraction size which might be appropriate in clinical protocols evaluating elective or adjuvant radiation of the liver. METHODS AND MATERIALS: One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. RESULTS: The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% (+/- 7.3% S.E.) at 6 months, resulting in closure of the study to patient entry. CONCLUSION: The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question.

Clinical Protocols↗
PubMed1993

Cost accounting in radiation oncology: a computer-based model for reimbursement.

PURPOSE: The skyrocketing cost of medical care in the United States has resulted in multiple efforts in cost containment. The present work offers a rational computer-based cost accounting approach to determine the actual use of resources in providing a specific service in a radiation oncology center. METHODS AND MATERIALS: A procedure-level cost accounting system was developed by using recorded information on actual time and effort spent by individual staff members performing various radiation oncology procedures, and analyzing direct and indirect costs related to staffing (labor), facilities and equipment, supplies, etc. Expenditures were classified as direct or indirect and fixed or variable. A relative value unit was generated to allocate specific cost factors to each procedure. RESULTS: Different costs per procedure were identified according to complexity. Whereas there was no significant difference in the treatment time between low-energy (4 and 6 MV) or high-energy (18 MV) accelerators, there were significantly higher costs identified in the operation of a high-energy linear accelerator, a reflection of initial equipment investment, quality assurance and calibration procedures, maintenance costs, service contract, and replacement parts. Utilization of resources was related to the complexity of the procedures performed and whether the treatments were delivered to inpatients or outpatients. In analyzing time motion for physicians and other staff, it was apparent that a greater effort must be made to train the staff to accurately record all times involved in a given procedure, and it is strongly recommended that each institution perform its own time motion studies to more accurately determine operating costs. Sixty-six percent of our facility's global costs were for labor, 20% for other operating expenses, 10% for space, and 4% for equipment. Significant differences were noted in the cost allocation for professional or technical functions, as labor, space, and equipment costs are higher in the latter. External beam treatment-related procedures accounted for more than 50% of all technical and professional revenues, simulation for 8% to 10%, and other physics/dosimetry procedures for 11% to 14% of revenues. Some discrepancies were identified between the actual cost and level of reimbursement of various procedures. Details are described in the manuscript. CONCLUSION: It is imperative to develop an equitable reimbursement system for radiation oncology services, based on cost accounting and other measures that may enhance productivity and reduce the cost per procedure unit, while at the same time preserving the highest quality of service provided to patients.

Accounting↗
PubMed1993

Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater. Results of Radiation Therapy Oncology Group 85-28.

BACKGROUND: Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity. METHOD: Radiation Therapy Oncology Group (RTOG) 85-28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4-8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy. RESULTS: Acute and late toxicities were acceptable. The median survival time and 1-year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant). CONCLUSION: A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis.

Adenocarcinoma↗
PubMed1992

Plasmacytoma. Treatment results and conversion to myeloma.

Forty-six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution.

Adult↗
PubMed1992

Logistics in designing clinical trials for etanidazole (SR 2508): an RTOG experience.

In a Phase II study of etanidazole (SR 2508), the dose of 17 x 2 g/m2 (total drug dose: 34 g/m2) was tested in 33 patients and the toxicity was deemed acceptable. A Phase III trial is now in progress comparing conventional radiotherapy with conventional radiotherapy plus etandizole (2 g/m2 i.v. 30 to 60 min before radiotherapy each Monday, Wednesday, and Friday to 34 g/m2 in 17 doses) in patients with unresectable head and neck carcinomas. A recent analysis showed only 14.7% grade 1 and 3.9% Grade 2 peripheral neuropathy. In the initial study design, 133 evaluable patients per treatment arm could achieve an 80% level of power of detecting a 15% difference in local-regional control rates between the radiotherapy arm (25% local-regional control at 2 years) and the radiotherapy plus etanidazole arm (assuming a 40% rate). Allowing for 20 ineligible cases in each arm, a total number of 306 was required. An interim analysis showed that 27% of the patients assigned to radiotherapy plus etanidazole are receiving less than 14 doses of the drug. It is assumed that less than 14 drug doses will not produce any therapeutic gain, therefore, a true 40% local-regional control rate in the radiotherapy plus etanidazole arm will be observed as a 36% rate when analyzed by assigned treatment. Using this information, the study was modified to have an 80% level of power in detecting a difference between a 25% local-regional control rate in the radiotherapy group and a 36% rate in the radiotherapy plus etanidazole group. Allowing for a 10% patient ineligibility rate, 518 patients are required. With 12 patients entered per month, it is estimated that patient accrual to this study will continue through October 1991.

Carcinoma, Squamous Cell↗
PubMed1992

The structure for a radiation oncology protocol. The Committee of Radiation Oncology Group Chairmen.

Multi-institutional Cooperative Group clinical trials involving radiotherapy require unambiguous therapeutic guidelines, so that patients entered from each of the participating institutions will receive essentially uniform treatment. The technical guidelines for a Radiation Oncology Protocol presented in this report represents a consensus of the Radiotherapy Committees in the major NCI funded Cooperative Groups and is derived from over a decade of experience. Although they have been written for external beam therapy, they are applicable to brachytherapy with appropriate technical considerations. It is anticipated that further evolution will occur with the introduction of new technologies such as 3-D treatment planning and delivery, multi-leaf collimation and small field irradiation.

Clinical Protocols↗
PubMed1991

Cure of early-stage Hodgkin's disease with subtotal nodal irradiation.

Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure.

Adolescent↗
PubMed1991

Clinical trials with etanidazole (SR-2508) by the Radiation Therapy Oncology Group (RTOG).

Following the completion of a phase I study of etanidazole (SR 2508), a new hypoxic cell sensitizer, the RTOG, began a phase II/III trial. The objectives of the study were to determine the toxicity and efficacy of SR 2508, combined with conventional radiotherapy for the management of unresectable stage III and IV head and neck squamous carcinomas. During the first step (or the Phase II portion) of the study, 33 patients received radiotherapy plus SR 2508 (RT + SR 2508). The incidence of drug toxicities was modest; including 24% grade I peripheral neuropathy (PN), 6% grade II PN, 27% grade I or II nausea and vomiting, 9% allergy and 15% reversible neutropenia. Because observed toxicities were deemed acceptable, the second step (or phase III portion) was then activated. Patients were randomized to receive either RT or RT + SR 2508. As of November 20, 1989, a total of 242 patients have been entered onto the Phase III portion of the study. One hundred twenty-two patients were randomized to the RT + SR 2508 arm and 120 patients were randomized to the RT alone arm. The analyses presented in this report are based on data available. The incidence of drug toxicities has been low, with 18% grade I or II PN, 26% nausea and vomiting (including one grade III), 14% allergy (including one grade III) and 13% reversible neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗
PubMed1991

The Radiation Therapy Oncology Group: an update of clinical research activities.

This paper provides an introduction into the clinical activities of the RTOG (Radiation Therapy Oncology Group), its goals, its organization, its format for protocol development, and presents major areas of achievement. It provides an organizational chart of the group, a disease site modality cross-reference for protocols, and appendices which provide the key published results of the Group's clinical activities. This paper presents an important overview of the RTOG clinical research activities, which are designed to improve the role of radiation therapy.

Clinical Protocols↗
PubMed1991

Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole.

Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis. We employed the novel hypoxic marker [18F]fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat. A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion. No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats. Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs. 20% decrease, P less than 0.05) and an increased retention of [18F]fluoromisonidazole in skeletal muscle of the septic rats. We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis. The greater reduction in muscle blood flow and the increased retention of [18F]fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia.

Animals↗