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Biomedical subjects

B Emami

Publications and source records attributed to B Emami.

At least 73 records · Page 4Linked to original sources
PubMed1993

Analysis of early and late deaths on RTOG non-small cell carcinoma of the lung trials: comparison with CALGB 8433.

UNLABELLED: In a major study that showed a treatment advantage for induction chemotherapy followed by radiation therapy (CALGB 8433), there was a significantly (P = 0.02) lower proportion of patients dying within 105 days of registration in the chemotherapy/radiation arm than the radiation therapy arm; without this difference, the overall survival was marginally better (P = 0.059) for the chemotherapy/radiation group. A retrospective analysis of RTOG trials sought explanations for the phenomenon. MATERIALS AND METHODS: Patients who fit the CALGB eligibility criteria and received radiation therapy alone in four prospective trials of the RTOG conducted between 1983 and 1989 were analyzed to determine factors that distinguished patients dying within 105 days from longer survivors. Two were trials of altered fractionation and two used standard fractionation. Of 683 patients identified, 107 (15.7%) died within 105 days after registration. The log linear model was used to evaluate relationships between death within 105 days and known prognostic factors. Karnofsky performance status (KPS), < 90 vs. > or = 90, was the only factor significantly related to death within 105 days (P = 0.0052). A Cox model with the same factors plus fractionation and total dose found KPS and T-stage associated with overall survival (P = 0.0005 and 0.025, respectively). The choice of the hyperfractionation arm (HFX) for Phase III study (69.6 Gy at 1.2 Gy b.i.d.) was based in part on comparison with standard fractionation (STD) from a concurrent RTOG protocol, 8321. Review of early deaths showed that this HFX arm had a lower proportion of patients dying within 105 days (7.9%) than STD in 8321 (21.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Evaluation of 45 degrees C hyperthermia and irradiation. I. Studies in a murine rhabdomyosarcoma model.

This report describes biologic experiments using transplanted RIF-1 tumors (diameter 0.5 or 1 cm) in C3H/He inbred mice (12 to 20 per treatment group) to compare the results with heat alone (43 degrees C for 60 minutes or 45 degrees C for 15 minutes, twice weekly via radiofrequency electrodes), irradiation alone (400 cGy twice weekly for a total of 4,000 cGy with 140 kVp x-rays), or a combination of both therapies. Animals receiving combined treatment had significantly greater complete regression than those treated with either therapy alone. Tumor regrowth curves were equivalent for 43 degrees C or 45 degrees C following irradiation. In tumors 0.5 cm in diameter the overall tumor cure rates were 17% for 43 degrees C for 60 minutes and 25% for 45 degrees C for 15 minutes with heat alone and 8% with irradiation alone; the combination of irradiation and heat at both temperatures yielded comparable complete cure rates (75 and 67%). With 1-cm tumors the corresponding cure rates were 0% with heat alone (either temperature), 5% for irradiation alone, 33% for irradiation and 43 degrees C heat, and 64% for irradiation and 45 degrees C heat (p = .3). Approximately 20% of the animals in the various groups developed moist or dry desquamation in the area treated, whereas 40 to 66% exhibited moist desquamation. There was a slight increase in this sequela (73%) for mice that received irradiation and 45 degrees C compared with 50% in mice treated with 43 degrees C, but the difference was not statistically different (p = .54). Experimental studies demonstrated equivalent efficacy of 10 hyperthermia sessions at 43 degrees C or 45 degrees C combined with irradiation. Caution must be exercised in the clinical application of thermal iso-effect heat dose concepts until further clinical trials have been performed and there is a better understanding of the time-temperature relationship.

Animals↗
PubMed1993

Evaluation of 45 degrees C hyperthermia and irradiation. II. A phase I clinical trial in humans by the Radiation Therapy Oncology Group.

This report describes the experience in 40 evaluable patients entered into a Radiation Therapy Oncology Group (RTOG) study to evaluate the feasibility of administering 45 degrees C for 15 minutes for superficial malignant lesions: 18 patients (45%) tolerated only 1 heat session at 45 degrees C; 7 (17.5%), 2 sessions; 4 (10%), 3 sessions; and 3 (7.5%) tolerated > or = 4 sessions. The overriding reason for discontinuing at 45 degrees C treatment was pain. Of the 40 evaluable patients, 22 (55%) had complete tumor regression, and 8 (20%) had partial regression. Tumors < or = 3 cm in diameter had significantly better complete tumor response than lesions > 3 cm (85% vs 41%) (p = .02). We conclude that 45 degrees C heating is difficult to use in patients chiefly because of pain; this may be due in part to inadequacy of currently available external hyperthermia equipment. Caution must be exercised in the application of thermal isoeffect heat dose concepts in clinical practice until further trials have been performed and a better understanding of the time-temperature relationship is established.

Adenocarcinoma↗
PubMed1992

Retinoic acid-resistant HL-60R cells harbor a point mutation in the retinoic acid receptor ligand-binding domain that confers dominant negative activity.

Retinoic acid (RA) induces granulocytic differentiation of acute promyelocytic leukemia (APL) cells and is a useful therapeutic agent for patients with this disease. In the HL-60 promyelocytic leukemia cell line, this RA-induced granulocytic differentiation appears to be directly mediated through the RA receptor (RAR-alpha). We have previously identified a mutant subclone of HL-60 (designated HL-60R) that exhibits relative resistance to RA and that harbors RA receptors with markedly reduced affinity for RA. In the present study, we have now identified the genetic basis for this aberrant RA receptor activity. DNA sequencing of polymerase chain reaction-amplified cDNA products corresponding to the RAR-alpha ligand-binding domain shows a point mutation in RAR-alpha codon 411 in this mutant HL-60R subclone. This specific C-->T mutation generates a termination codon resulting in the truncation of 52 amino acids at the COOH terminal end of RAR-alpha. In cotransfection studies, expression vectors harboring this mutated RAR-alpha exhibit dominant negative activity with respect to the trans-activating function of the normal RAR-alpha. Although our observations are limited to HL-60 cells, similar RA receptor mutations might play an important role in the acquisition of RA resistance in RA-treated APL patients.

Amino Acid Sequence↗
PubMed1992

Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.

BACKGROUND: The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited. The median survival is less than 10 months, and less than 10 percent of patients survive for 5 years. Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival. METHODS: This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy. RESULTS: The median survival was 8.9 months in the radiation-treated patients, as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy. In the former group, the survival rates at 12 and 24 months were 33 percent and 10 percent, respectively, whereas they were 50 percent and 38 percent in the patients receiving combined therapy (P less than 0.001). Seven patients in the radiotherapy group and 25 in the combined-therapy group were alive at the time of the analysis. The patients who received combined treatment had fewer local (P less than 0.02) and fewer distant (P less than 0.01) recurrences. Severe and life-threatening side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined therapy, as compared with 25 percent and 3 percent of those treated with radiation alone. CONCLUSIONS: Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus, as measured by control of local tumors, distant metastases, and survival, but at the cost of increased side effects.

Adenocarcinoma↗
PubMed1992

Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk).

From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.

Adult↗
PubMed1992

Multiple members of the retinoic acid receptor family are capable of mediating the granulocytic differentiation of HL-60 cells.

The complex and diverse biological effects of retinoic acid (RA) are mediated through specific receptors that are members of the steroid hormone family of nuclear transcription factors. The RA receptor family consists of multiple structurally distinct RA receptors, which diverge primarily at the NH2-terminal domain. The evolutionary conservation of this divergent region in individual RA receptors among different species together with their tissue-specific patterns of expression suggest that the biological function and activity of the individual RA receptors may be confined to specific tissues. To test this hypothesis in hematopoietic cells, we used retrovirus-mediated gene transduction to introduce the RA receptors RAR-alpha, RAR-beta, and RAR-gamma as well as RXR-alpha into a mutant subclone of the HL-60 promyelocytic leukemia cell line (designated HL-60R) that is relatively resistant to RA-induced granulocytic differentiation. We found that each of these structurally distinct RA receptors could restore sensitivity of the HL-60R cells to RA. A critical threshold number of transduced receptors per cell appears to be necessary to restore this functional activity. Thus, the capability to mediate granulocytic differentiation of HL-60 cells is shared among distinctly different RA receptors.

Carrier Proteins↗
PubMed1991

Tolerance of normal tissue to therapeutic irradiation.

The importance of knowledge on tolerance of normal tissue organs to irradiation by radiation oncologists cannot be overemphasized. Unfortunately, current knowledge is less than adequate. With the increasing use of 3-D treatment planning and dose delivery, this issue, particularly volumetric information, will become even more critical. As a part of the NCI contract N01 CM-47316, a task force, chaired by the primary author, was formed and an extensive literature search was carried out to address this issue. In this issue. In this manuscript we present the updated information on tolerance of normal tissues of concern in the protocols of this contract, based on available data, with a special emphasis on partial volume effects. Due to a lack of precise and comprehensive data base, opinions and experience of the clinicians from four universities involved in the contract have also been contributory. Obviously, this is not and cannot be a comprehensive work, which is beyond the scope of this contract.

Bone and Bones↗
PubMed1991

Fitting of normal tissue tolerance data to an analytic function.

During external beam radiotherapy, normal tissues are irradiated along with the tumor. Radiation therapists try to minimize the dose of normal tissues while delivering a high dose to the target volume. Often this is difficult and complications arise due to irradiation of normal tissues. These complications depend not only on the dose but also on volume of the organ irradiated. Lyman has suggested a four-parameter empirical model which can be used to represent normal tissue response under conditions of uniform irradiation to whole and partial volumes as a function of the dose and volume irradiated. In this paper, Lyman's model has been applied to a compilation of clinical tolerance data developed by Emami et al. The four parameters to characterize the tissue response have been determined and graphical representations of the derived probability distributions are presented. The model may, therefore, be used to interpolate clinical data to provide estimated normal tissue complication probabilities for any combination of dose and irradiated volume for the normal tissues and end points considered.

Humans↗
PubMed1991

Numerical scoring of treatment plans.

This is a report on numerical scoring techniques developed for the evaluation of treatment plans as part of a four-institution study of the role of 3-D planning in high energy external beam photon therapy. A formal evaluation process was developed in which plans were assessed by a clinician who displayed dose distributions in transverse, sagittal, coronal, and arbitrary oblique planes, viewed dose-volume histograms which summarized dose distributions to target volumes and the normal tissues of interest, and reviewed dose statistics which characterized the volume dose distribution for each plan. In addition, tumor control probabilities were calculated for each biological target volume and normal tissue complication probabilities were calculated for each normal tissue defined in the agreed-upon protocols. To score a plan, the physician assigned a score for each normal tissue to reflect possible complications; for each target volume two separate scores were assigned, one representing the adequacy of tumor coverage, the second the likelihood of a complication. After scoring each target and normal tissue individually, two summary scores were given, one for target coverage, the second reflecting the impact on all normal tissues. Finally, each plan was given an overall rating (which could include a downgrading of the plan if the treatment was judged to be overly complex).

Humans↗
PubMed1991

Three-dimensional treatment planning for lung cancer.

The experience of four institutions involved in a three-dimensional treatment planning contract (NCI) for lung cancer is described. It was found that three-dimensional treatment planning has a significant potential for optimization of treatment plans for radiotherapy of lung cancer both for tumor coverage and sparing of critical normal tissues within the complex anatomy of the human thorax. Evaluation tools, such as dose-volume histograms, and three-dimensional isodose displays, such as multiple plane views, surface dose displays, etc., were found to be extremely valuable in evaluation and comparison of these complex plans. It is anticipated that with further developments in three-dimensional simulation and treatment delivery systems, major progress towards uncomplicated local regional control of lung cancer may be forthcoming.

Humans↗
PubMed1991

Characteristics of improved microwave interstitial antennas for local hyperthermia.

The heating potentials of two newly-developed microwave interstitial antennas are reported in this paper. The longitudinal (parallel to the antenna) and transverse (over a plane perpendicular to the antenna) specific absorption rate (SAR) distributions of single and an array of four parallel antennas were measured in a muscle equivalent phantom and their performance characterized at 915 MHz in terms of the following parameters: peak depth (location of the profile peak with respect to the surface), 50% HL (effective heating length over which SAR greater than 50% of the peak normalized SAR), dead length (axial length at the antenna tip with SAR less than 50% of peak normalized SAR), and the variations of the specific absorption rate pattern relative to the depth of insertion. The results are analyzed and discussed in terms of these parameters and other factors important in the clinical use of these antennas for effective interstitial hyperthermia.

Equipment Design↗
PubMed1991

N2 (clinical) non-small cell carcinoma of the lung: prospective trials of radiation therapy with total doses 60 Gy by the Radiation Therapy Oncology Group.

Clinical Stage III (N2) non-small cell carcinoma of the lung encompasses a large group of patients, frequently treated with radiation therapy alone, who are now considered to have borderline-resectable tumors. Pilot studies are proceeding which use combinations of resection, radiation therapy, and chemotherapy. To place trials of combination therapy in perspective with contemporary results of radiation therapy alone, recently completed trials of the RTOG were analyzed specifically for clinical Stages T1-3N2. A prospective randomized trial of hyperfractionated radiation therapy (HFX), conducted from 1983 through 1987, compared total doses of 60.0, 64.8, and 69.6 Gy using 1.2 Gy bid with greater than or equal to 4 hr interval. After acute and late effects were considered tolerable, 74.4 Gy and 79.2 Gy arms supplanted the two lowest dose arms. Survival was compared among the five total dose arms, and with 60 Gy in 30 fractions in 6 weeks (standard fractionation-STD) from earlier RTOG studies. Of 516 HFX patients analyzed, 296 (57.3%) with Performance Status (PS) 70-100 and less than 5% weight loss (favorable) had a significantly (p = .001) better survival than those with PS 50-69 or weight loss greater than 5%. Patients with RTOG Stage III (361, 70.0%) experienced better survival (p = .027) than RTOG Stage IV M0. The 69.6 Gy total dose arm was significantly (p = .031) better in favorable RTOG Stage III patients than all other total dose arms: the 1-year survival rate was 58% and the 3-year rate was 20%. The 69.6 Gy HFX results were significantly (p = .002) better than results with STD fractionation in comparable patients from earlier RTOG trials (1-year survival = 30%, 3-year survival = 7%). A prospective, randomized Phase III comparison of STD with 60 Gy versus HFX with 69.6 Gy is underway. These results provide benchmarks for studies of surgical resection combined with chemotherapy and/or radiation therapy until results of prospective comparisons with concurrent controls are available.

Adenocarcinoma↗
PubMed1991

Phase I/II study, combination of radiotherapy and hyperthermia in patients with deep-seated malignant tumors: report of a pilot study by the Radiation Therapy Oncology Group.

This is a report of a Phase I/II study activated in March 1984 and completed in October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity of hyperthermia in patients with deep-seated malignant tumors. The main objective of this study was to evaluate the morbidity of regional hyperthermia (systemic and regional, acute and late effects); a secondary objective was to evaluate tumor response to combined irradiation and regional hyperthermia. A total of 54 patients with locally advanced abdominal or pelvic malignancy were accrued to this study; 42% were male and 58% female. Seventy-five of the patients had pelvic tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3 (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one, and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the course of hyperthermia was terminated, primarily because of patient discomfort. Tumor response was assessed by physical examination or radiological studies. Of 44 patients evaluable for response, there were 17 (39%) complete responses and 6 (14%) partial responders. Significant technical problems in heat delivery and thermometry remain.

Abdominal Neoplasms↗
PubMed1991

RTOG quality assurance guidelines for clinical trials using hyperthermia administered by ultrasound.

Clinical quality assurance guidelines are established for RTOG hyperthermia protocols in which unfocused planar ultrasound may be used to administer hyperthermia. Measurement of temperature at a few fixed points is no longer considered to be adequate. Thermal mapping is required to obtain profiles of the temperature across the tumor dimensions, including margins of normal tissue. The thermometry strategies established for microwaves are to be adhered to with oblique insertion of the probes recommended. Two types of errors arise which are generally not present with microwaves. A measurement error, commonly referred to as a temperature artifact, arises because of absorption and/or viscous heating of the probe. Another error arises when thermocouples are used due to the conduction of heat along the wire leads, especially the copper wire. Several thermometry systems are evaluated with regard to the expected artifact and conduction errors. Acceptable systems include: a) indexing a polyurethane sheathed single sensor thermocouple in a polyurethane catheter, b) indexing a fiberoptic probe in a steel needle, c) indexing a single sensor thermocouple in a steel needle, and d) use of manganin-constantan multisensor thermocouples. Unacceptable systems include: a) fixed or static probes that do not provide profiles of the temperature across the tumor dimensions, b) copper-constantan multisensor thermocouples, and c) teflon sheathed thermocouples inserted into a teflon catheter.

Clinical Protocols↗
PubMed1991

RTOG quality assurance guidelines for clinical trials using hyperthermia for deep-seated malignancy.

Quality assurance has been vague or lacking in many previous hyperthermia trials. Recent publications by the Hyperthermia Physics Center, the Center for Devices and Regulatory Health, and the Radiation Therapy Oncology Group have described general guidelines for quality assurance in equipment reliability and reproducibility, superficial applications, and microwave techniques. The present report details quality assurance factors that are believed to be important for hyperthermia of deep clinical sites, defined as extending at least 3 cm beyond the skin surface. This document will discuss patient and physician factors, as well as thermometric accuracy, assessment of specific absorption rates (SAR), assurance of adequate coverage of tumors by the energy deposition pattern of the treatment device, and recommended documentation of the location, quantity, and frequency of treatment, specifically oriented to deep hyperthermia. The recommendations are structured to facilitate compliance in multiinstitutional trials.

Clinical Protocols↗
PubMed1991

RTOG quality assurance guidelines for interstitial hyperthermia.

This document specifies the current recommendations for quality assurance for hyperthermia administration with interstitial techniques as specified by the Radiation Therapy Oncology Group (RTOG). The document begins by providing a brief description of the physical principles behind the use of the three most commonly used methods of interstitial hyperthermia: radiofrequency (RF-LCF), microwave antennas, and ferromagnetic seeds. Emphasis is placed on features that effect quality assurance. Specific recommendations are provided for: a) Pretreatment planning and equipment performance checks, b) Implant considerations and documentation, c) Thermometry, and d) Safety procedures. Specific details regarding quality assurance issues that are common to all local and regional hyperthermia methods are outlined in previous documents sponsored by the RTOG. It is anticipated that technological advances may lead to future modifications of this document.

Documentation↗