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Biomedical subjects

E Cheng

Publications and source records attributed to E Cheng.

At least 55 records · Page 3Linked to original sources

c-Ki-ras mutations in dysplastic fields and cancers in ulcerative colitis.

A sensitive restriction fragment length polymorphism assay and DNA sequencing were used to detect c-Ki-ras mutations in 56 specimens of colonic epithelium from 18 patients with chronic ulcerative colitis. Mutations were not detected in biopsy specimens that were negative or indefinite for dysplasia. In 4 of 8 patients with high-grade dysplasia, a c-Ki-ras codon 12 or 13 mutation was detected. In three colectomy specimens, a wide area of dysplastic cells (greater than 10 cm2) contained a specific ras mutation. In two of these specimens, an invasive cancer contained a c-Ki-ras mutation identical to that found in adjacent dysplastic epithelium. These studies indicate that mutations of c-Ki-ras may be an excellent molecular genetic marker to map dysplastic fields and invasive cancer in ulcerative colitis.

Base Sequence↗

Contouring structures for 3-dimensional treatment planning.

Three-dimensional (3-D) treatment planning is a labor-intensive process with contouring of the target volume and critical normal tissues being a significant time-consuming component. The use of 3-D treatment planning on a routine basis may be limited by the time required to complete treatment plans. Despite the need to increase the efficiency of the process, there is little literature addressing the speed and accuracy of contouring systems. In an attempt to initiate systematic analysis of the contouring process, data sets consisting of 10 CT images each were developed on two patients with esophageal carcinoma. Nine different operators manually contoured structures (target volume, spinal canal, lungs) on the data sets using four different contouring systems present in our department. These included both commercially available systems and those developed by the authors. There was a wide variation in the hardware and software characteristics of these systems. The time required to contour the CT data sets was recorded and analyzed. The contouring accuracy was assessed by comparison with a standard template derived from the CT data set for each image. The contouring time was found to be dependent on the system design, previous contouring experience, and the type of drawing instrument (lightpen vs mouse). The mean contouring time ranged from 26 minutes per patient for the fastest system to 41 minutes for the slowest. Potential clinically significant errors in contouring were rare for the spinal canal and lungs but present at a greater rate for the target volume (30.3%). The implications of this finding are discussed.

Adenocarcinoma↗

Three-dimensional photon treatment planning for carcinoma of the nasopharynx.

The role of 3-D treatment planning for carcinoma of the nasopharynx was assessed in a four institution study. Two patients were worked up and had an extensive number of CT scans on which target volumes and normal tissues were defined. Treatment planning was then performed using state of the art dose planning systems for these patients to assess the value of the new technology. In general, it was demonstrated that multi-field conformal plans could achieve good tumor dose coverage, while at the same time reducing normal tissue doses, compared to standard treatment planning techniques. The role of inhomogeneity corrections, beam energy, and the use of CT vs. simulation films for defining target volumes were also discussed. In addition, techniques to evaluate 3-D plans for the nasopharynx were considered, and some analysis of this problem is presented in this paper.

Adult↗

Three-dimensional photon treatment planning in carcinoma of the larynx.

The role of three-dimensional (3-D) treatment planning in the definitive treatment of carcinoma of the larynx with radiation was evaluated at four institutions as part of an NCI contract. A total of 30 different treatment approaches were devised for two patients with larynx cancer. CT scans were obtained for both patients and various treatment planning tools were employed to optimize beam arrangements and to evaluate the resulting dose distribution. The effect on dose distribution of a number of factors was also examined: 1) the use of dose calculation algorithms which correct for tissue inhomogeneities, 2) the variation of the CT numbers used for inhomogeneity corrections to simulate inaccuracies in the knowledge of the CT numbers, and 3) the modification of beam energy. A multitude of data was used in plan evaluation and a numerical score was given to each plan to estimate the tumor control probability and the normal tissue complication probability. We found 3-D treatment planning to be of potential value in optimizing treatment plans in larynx cancer. Improved target coverage was achieved when complete information describing 3-D geometry of the anatomy was utilized. In some cases, the treatment planning tools employed, such as the beam's eye view, helped devise novel beam arrangements which were useful alternatives to standard techniques. We found little effect of change in CT number on dose distributions. A comparison between dose distributions calculated with tissue inhomogeneity corrections to those calculated without this correction showed little difference. We did find some improvement in the dose to the primary tumor volume at lower beam energies, but with an increased larynx volume potentially receiving doses above tolerance.

Adult↗

Three-dimensional photon treatment planning of the intact breast.

Three-dimensional treatment planning for the intact breast was performed on two patients who had undergone CT scanning. A total of 38 treatment plans were evaluated. Multiple plans were evaluated for each patient including plans with and without inhomogeneity corrections, plans using varying photon energies of 60Co, 4 MV, 6 MV, 10 MV, and 15 MV, and three-dimensionally unconstrained plans. Increased hot spots were appreciated in the central axis plane when lung inhomogeneity corrections were used. Additional hot spots were appreciated in off-axis planes towards the cephalad and caudad aspects of the target volume because of lung inhomogeneity corrections and changes in the breast contour. The use of 60Co was associated with an increase in the magnitude and volume of hot spots, whereas the use of higher energy photons such as 10 MV and 15 MV was associated with an unacceptable target coverage at shallow depths. Therefore, for the two patients studied, the use of a medium energy photon beam (such as from a 6 MV linear accelerator) appeared to be the energy of choice for treatment of the intact breast. The three-dimensionally unconstrained plans were able to improve slightly upon the standard plans, particularly with relationship of dose to normal tissue structures. Areas for future research were identified, including the use of tissue compensators.

Adult↗

Three-dimensional photon treatment planning for Hodgkin's disease.

A multi-institutional study was undertaken using computerized planning systems to develop three-dimensional (3-D) radiotherapy plans for Hodgkin's disease (H.D.). Two patients, the first afflicted with bulky stage II disease and another one with early stage I H.D., were studied. Three main categories of plan were produced for each patient: a) a traditional plan which modelled a conventional mantle treatment on the 3-D system, b) a 3-D standard plan where anterior and posterior fields were designed to cover 3-D target volumes, and c) a 3-D unconstrained plan where innovational techniques were employed. Three-dimensional planning provides information about the dose distribution throughout the large volume irradiated in patients with H.D. that is not available with conventional mantle planning. The use of 3-D techniques resulted in improved tumor coverage, but by allowing for uncertainties such as motion, the doses to normal tissues tended to be higher. The use of unorthodox beam arrangements introduced added complexities, and further increased the lung doses. The most even dose distributions were obtained by incorporating compensating filters into anterior fields. Clinicians showed wide variations in their assessment of the plans, possible reasons for which are addressed in this paper. In addition, calculated probabilities from models of tumor control and normal tissue damage are also presented.

Hodgkin Disease↗

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↗

Three-dimensional treatment planning for para-aortic node irradiation in patients with cervical cancer.

Three-dimensional treatment planning has been used by four cooperating centers to prepare and analyze multiple treatment plans on two cervix cancer patients. One patient had biopsy-proven and CT-demonstrable metastasis to the para-aortic nodes, while the other was at high risk for metastatic involvement of para-aortic nodes. Volume dose distributions were analyzed, and an attempt was made to define the role of 3-D treatment planning to the para-aortic region, where moderate to high doses (50-66 Gy) are required to sterilize microscopic and gross metastasis. Plans were prepared using the 3-D capabilities for tailoring fields to the target volumes, but using standard field arrangements (3-D standard), and with full utilization of the 3-D capabilities (3-D unconstrained). In some but not all 3-D unconstrained plans, higher doses were delivered to the large nodal volume and to the volume containing gross nodal disease than in plans analyzed but not prepared with full 3-D capability (3-D standard). The small bowel was the major dose limiting organ. Its tolerance would have been exceeded in all plans which prescribed 66 Gy to the gross nodal mass, although some reduction in small bowel near-maximum dose was achieved in the 3-D unconstrained plans. All plans were able to limit doses to other normal organs to tolerance levels or less, with significant reductions seen in doses to spinal cord, kidneys, and large bowel in the 3-D unconstrained plans, as compared to the 3-D standard plans. A high probability of small bowel injury was detected in one of four 3-D standard plans prescribed to receive 50 Gy to the large para-aortic nodal volume; the small bowel dose was reduced to an acceptable level in the corresponding 3-D unconstrained plan. An optimum beam energy for treating this site was not identified, with plans using 4, 6, 10, 15, 18, and 25 MV photons all being equally acceptable. Attempts to deliver moderate or high doses (50-66 Gy) to this region should be made only after careful analysis of the plan with techniques similar to those employed in this study.

Aged↗

Three-dimensional treatment planning considerations for prostate cancer.

Over 300 treatment plans for a total of eight disease sites based on 3-D treatment planning considerations utilizing serial CT delineated target volumes were generated by four institutions as part of an NCI supported contract to both assess the current state-of-the-art capabilities and point directions for future efforts. Two patients with stage C prostate cancer were evaluated with protocol plans which required treatment of the prostate to 70 Gy and the pelvic lymph nodes to 46 Gy. When full 3-D target definition and multiple beam arrangements were employed, all institutions were able to submit plans which scored higher on tumor coverage and had lower normal tissue complication scores compared to traditional plans. The 3-D plans using standard beam arrangements, however, were often rated as highly as the 3-D unconstrained plans due to the multiple beam arrangements already selected to optimize standard plans at most institutions. For this site, heterogeneity corrections, beam energy changes and changes in CT number did not substantially change plan scores.

Aged↗

Three-dimensional treatment planning for postoperative treatment of rectal carcinoma.

The role of three-dimensional (3-D) treatment planning for postoperative radiation therapy was evaluated for rectal carcinoma as part of an NCI contract awarded to four institutions. It was found that the most important contribution of 3-D planning for this site was the ability to plan and localize target and normal tissues at all levels of the treatment volume, rather than using the traditional method of planning with only a single central transverse slice and simulation films. There was also a slight additional improvement when there were no constraints on the types of plans (i.e., when noncoplanar beams were used). Inhomogeneity considerations were not important at this site under the conditions of planning, i.e., with energies greater than 4 MV and multiple fields. Higher beam energies (15-25 MV) were preferred by a small margin over lower energies (down to 4 MV). The beam's eye view and dose-volume histograms were found quite useful as planning tools, but it was clear that work should continue on better 3-D displays and improved means of translating such plans to the treatment area.

Combined Modality Therapy↗

IgG in murine intestinal secretions. Aging effect and possible physiological role.

To assess the role of, and age-associated alterations in, intraluminal IgG in the intestine, total IgG and subclass distribution in small intestinal perfusates and pilocarpine-stimulated intestinal secretions were measured under non-fasting conditions in three groups of BALB/c mice: 2-3, 12-14, and over 24 months old. Total intraluminal IgG and its subclasses (i.e. IgG1, IgG2a, and IgG2b) increased with age. However, the binding capacities of natural intraluminal IgG antibody (Ab) for outer membrane antigen (Ag) from normal habitant bacteria (Escherichia coli and Enterobacter agglomerans) were markedly reduced in the aged lavage samples as compared with such binding in samples from the other two age groups. The striking similarity to serum in the magnitude of the increase of intraluminal IgG and also in the distribution patterns of its subclasses in the small intestinal perfusates from all age groups suggests that the serum is a major source of the IgG. The intraluminal IgG may play some role in humoral immune protection under physiologic conditions of the gut lumen.

Aging↗