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G T Chen

Publications and source records attributed to G T Chen.

At least 55 records · Page 3Linked to original sources

Tumor and target delineation: current research and future challenges.

In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target. The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties.

Forecasting↗

Evaluation of changes in the size and location of the prostate, seminal vesicles, bladder, and rectum during a course of external beam radiation therapy.

PURPOSE: To document the size and location of the prostate, seminal vesicles, bladder, and rectum throughout the course of external beam radiotherapy. The frequency and range of motion of these organs are quantified. METHODS AND MATERIALS: Ten patients with localized carcinoma of the prostate had conventional simulation followed immediately by a treatment planning computed tomography scan (TPCT0). Once treatment was initiated, each patient had a weekly CT (TPCT1-N) before or after his daily treatment. Anatomical structures from CT were delineated on a computer workstation for analysis. The serial CT sets were spatially registered to the initial scan using image correlation software that brings into congruence the bony pelvis of the different scans. The location of the prostate, seminal vesicles, bladder, and rectum on subsequent scans were compared to TPCT0, as well as to each other. RESULTS: Prostate volumes were observed to vary by an average of +/- 10% during the course of radiation therapy, while the seminal vesicle volumes varied by as much as 100%. Bladder and rectal volumes varied by +/- 30%. Compared to TPCT0, movement of the prostate was demonstrated in all patients. Quantitation of the center-of-mass (CM) showed motion of less than 1 mm in the left-right direction, while motion ranging from 0 to +/- 1 cm was observed in the anterior-posterior and superior-inferior directions. The individual standard deviations of these motions varied from approximately 1-5 mm. These variations were correlated to changes in the dimensions of the bladder and rectum. CONCLUSIONS: Changes in the location of the prostate, seminal vesicles, and normal tissue volumes during the course of radiation therapy occur and have dosimetric consequences that may impact tumor control and normal tissue complication probabilities. Conformal therapy for prostate cancer will require the incorporation of knowledge of the anatomic relationships of these structures as a function of time. Therefore, these uncertainties must be taken into account when designing treatment plans and in considering dose escalation trials.

Humans↗

Comparison of static conformal field with multiple noncoplanar arc techniques for stereotactic radiosurgery or stereotactic radiotherapy.

PURPOSE: Compare the use of static conformal fields with the use of multiple noncoplanar arcs for stereotactic radiosurgery or stereotactic radiotherapy treatment of intracranial lesions. Evaluate the efficacy of these treatment techniques to deliver dose distributions comparable to those considered acceptable in current radiotherapy practice. METHODS AND MATERIALS: A previously treated radiosurgery case of a patient presenting with an irregularly shaped intracranial lesion was selected. Using a three-dimensional (3D) treatment-planning system, treatment plans using a single isocenter multiple noncoplanar arc technique and multiple noncoplanar conformal static fields were generated. Isodose distributions and dose volume histograms (DVHs) were computed for each treatment plan. We required that the 80% (of maximum dose) isodose surface enclose the target volume for all treatment plans. The prescription isodose was set equal to the minimum target isodose. The DVHs were analyzed to evaluate and compare the different treatment plans. RESULTS: The dose distribution in the target volume becomes more uniform as the number of conformal fields increases. The volume of normal tissue receiving low doses (> 10% of prescription isodose) increases as the number of static fields increases. The single isocenter multiple arc plan treats the greatest volume of normal tissue to low doses, approximately 1.6 times more volume than that treated by four static fields. The volume of normal tissue receiving high (> 90% of prescription isodose) and intermediate (> 50% of prescription isodose) doses decreases by 29 and 22%, respectively, as the number of static fields is increased from four to eight. Increasing the number of static fields to 12 only further reduces the high and intermediate dose volumes by 10 and 6%, respectively. The volume receiving the prescription dose is more than 3.5 times larger than the target volume for all treatment plans. CONCLUSIONS: Use of a multiple noncoplanar conformal static field treatment technique can significantly reduce the volume of normal tissue receiving high and intermediate doses compared with a single isocenter multiple arc treatment technique, while providing a more uniform dose in the target volume. Close conformation of the prescription isodose to the target volume is not possible using static uniform conformal fields for target shapes lacking an axis of rotational symmetry or plane of mirror symmetry.

Brain Neoplasms↗

A method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy.

PURPOSE: To develop a method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy. METHODS AND MATERIALS: Dose-surface histograms of the rectum, which state the rectal surface area irradiated to any given dose, were calculated for a group of 27 patients treated with a four-field box technique to a total (tumor minimum) dose ranging from 68 to 70 Gy. Occurrences of rectal toxicities as defined by the Radiation Therapy Oncology Group (RTOG) were recorded and examined in terms of dose and rectal surface area irradiated. For a specified end point of rectal complication, the complication probability was analyzed as a function of dose irradiated to a fixed rectal area, and as a function of area receiving a fixed dose. Lyman's model of normal tissue complication probability (NTCP) was used to fit the data. RESULTS: The observed occurrences of rectal complications appear to depend on the rectal surface area irradiated to a given dose level. The patient distribution of each toxicity grade exhibits a maximum as a function of percentage surface area irradiated, and the maximum moves to higher values of percentage surface area as the toxicity grade increases. The dependence of the NTCP for the specified end point on dose and percentage surface area irradiated was fitted to Lyman's NTCP model with a set of parameters. The curvature of the NTCP as a function of the surface area suggests that the rectum is a parallel structured organ. CONCLUSIONS: The described method of analyzing rectal surface area irradiated yields interesting insight into understanding rectal complications in prostate conformal radiotherapy. Application of the method to a larger patient data set has the potential to facilitate the construction of a full dose-surface-complication relationship, which would be most useful in guiding clinical practice.

Dose-Response Relationship, Radiation↗

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PURPOSE: To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. METHODS AND MATERIALS: Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? RESULTS: There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume(s). Such definitions should make implementation of 3DCRT more complex, yet will make high-dose delivery a possibility. There are many sites in which single and multiinstitutional studies are ongoing that include prostate, lung, head and neck, and brain. In other areas, cooperative group trials are required because of the inability of single institutions to accrue enough patients to answer clinically relevant questions with statistical validity. Although implementation of 3DCRT will require multiple steps, these multiple steps can be brought into clinical practice gradually and one does not have to wait until all steps required for implementation of 3DCRT are available. In this respect, "3DCRT" should be used in a very broad sense, from beam's eye view blocking, use of multibeam dose distribution, use of dose-volume histograms in choosing alternative plans, noncoplanar beam arrangements, intensity modulation, inverse planning, to totally automated implementation of 3DCRT. To transfer the 3DCRT capabilities to the community from the University Centers, there is a necessity to develop quality assurance programs. RTOG and the Three-Dimensional Oncology Group are spearheading these efforts. Three-dimensional conformal radiation therapy has potential not only to improve local control and decrease toxicity, but also to improve the cost benefit ratio in the use of radiotherapy as well as in improving quality of life in patients with cancer. CONCLUSIONS: Achieving many potential benefits of 3DCRT (improvement in local control, decreasing toxicity, organs-function preservation, improvement in cost effectiveness) will require further physics-related and clinical research in carefully conceived and successfully completed future clinical trials.

Humans↗

The potential for normal tissue dose reduction with neoadjuvant hormonal therapy in conformal treatment planning for stage C prostate cancer.

PURPOSE: Preirradiation hormonal cytoreduction of prostate cancer has been proven to reduce exposure of normal structures by decreasing the size of the target volume. Dose-volume histogram (DVH) analysis, however, does not always appear to demonstrate a strong positive benefit with the use of neoadjuvant hormone therapy. This study analyzes various other factors influencing dose to normal organs, which may determine the success or failure of neoadjuvant hormonal therapy in achieving its goals. METHODS AND MATERIALS: Patients with bulky clinical Stage C adenocarcinoma of the prostate were given 3 months of hormone treatment consisting of oral Flutamide and monthly Zoladex injections prior to irradiation. Computerized tomography (CT) scans of the pelvis were obtained both prior to and following hormonal treatment. Treatment plans were generated by three-dimensional (3D) conformal treatment planning. The change in the volume of the prostate was assessed along with the percentage of prescribed dose delivered to the rectum and bladder. Various factors such as prostate size, bladder/rectum size, and organ shape were studied. Both dose-volume histograms (DVH) and dose-surface area histograms (DSH) were used for analysis. RESULTS: Six of seven patients had reduction in the size of their prostates. The mean volumes of the prostate before and after hormonal manipulation were 129.1 +/- 32.9 standard deviation (SD) cm3 and 73.0 +/- 29.5 SD cm3, respectively (p = 0.0059). The volume of rectum receiving 80% of the prescribed dose was reduced in five of seven patients from a mean of 83.2 to 59.9 cm3 (p = 0.045). The volume of bladder receiving 80% of the prescribed dose was also reduced in five out of seven patients from a mean of 74.5 to 40.2 cm3 (p = 0.098). Correlation between the size of the prostate and volume of rectum and bladder treated was not always consistent: greater reduction in prostate size did not necessarily result in large decreases in dose to bladder or rectum. The total size of the bladder and rectum were found to be important factors in normal tissue radiation exposure; the benefits of hormone therapy may be lost if the bladder and rectum are allowed to decrease in size. Also, the bladder may be prone to sagging into the pelvis of some patients following hormone therapy, resulting in a less optimal therapeutic ratio. CONCLUSION: Reduction in prostate size by neoadjuvant hormonal manipulation does decrease the amount of normal tissue irradiated in most patients. However, the correlation between the reduction in prostate size and amount of rectum or bladder treated is not linear if other variables are not controlled. Factors such as the shape of the organs, as well as the distensible nature of the bladder and rectum, play major roles in dose to normal tissues. These facts may mask the benefits of cytoreduction and could be obstacles in realizing consistent benefits from preirradiation hormonal treatment in the clinical setting if they are ignored.

Adenocarcinoma↗

Dose-surface histograms as treatment planning tool for prostate conformal therapy.

Dose-surface histograms are studied and compared with dose-volume histograms, as an evaluation tool for prostate treatment planning. For thin walled hollow organs, such as the rectum and bladder, the surface area irradiated is a more appropriate measure of the biological effect than the full volume. It is also more accurate and efficient to define the surface for a hollow structure and compute the surface area histograms. Application of the dose-surface histograms provide new insights into prostate treatment planning. A simple idealized geometry model demonstrates that the percentage surface area intersected by the geometric beam edge differs from the percentage volume intersected. For a group of prostate patients, it is shown that the dose-surface histograms yield substantially different results from the dose-volume histograms in ranking four-, six-, and, eight-field treatment plans and in calculating the fraction of the rectum irradiated to high dose. The difference in terms of surface area between these plans in the high-dose region is usually less than that in terms of the volume, and a reverse of plan ranking order can consequently occur. The percentage of organ surface irradiated to high dose is typically greater than the percentage volume by 5% to 10%. The use of the dose-surface histograms in analysis of organ motion and/or patient setup uncertainty, and analysis of rectal complications, is also discussed.

Biophysical Phenomena↗

Role of the AGA/AGG codons, the rarest codons in global gene expression in Escherichia coli.

AGA and AGG codons for arginine are the least used codons in Escherichia coli. Previous findings have shown that these codons are used preferentially within the first 25 codons in E. coli genes. More than 100 genes having a single AGA/AGG codon within the first 25 codons were identified to be associated with various essential cellular functions. The lacZ gene, containing 5 AGG codons after the tenth codon from the initiation codon, was constructed as a model system. The production of beta-galactosidase was inhibited almost completely during the stationary phase, whereas the production of the control beta-galactosidase without AGG codons was not. The inhibitory effect by the 5 AGG codons was substantially suppressed either by coexpressing the argU gene for tRNA(ArgUCU/CCU) or by moving the 5 AGG codons by > 50 codons away from the initiation codon. In addition, the production of a number of proteins resolved by two-dimensional gel electrophoresis was enhanced significantly during the stationary phase in the cells harboring a plasmid containing argU. At least one of them was identified as the hns product encoded by an ORF having an AGA codon at the nineteenth position. On the basis of these results, it is proposed that the expression of a group of essential genes for various cellular functions that have a single AGA/AGG codon very close to the initiation codon are globally regulated by the availability of the least abundant tRNA(ArgUCU/CCU). A model for this regulation is proposed.

Arginine↗

Unfolding patient motion with biplane radiographs.

A method of unfolding patient movement between biplane radiographs is presented. This method requires biplane projections of two points with a known separation to determine a translation motion or biplane projections of two or three point pairs to determine a general patient motion. Such a point pair can be provided by two ends of a line source or two radiopaque marks, with a fixed distance between them. The point pairs can be taped on skin, implanted in the target volume, or embedded in the bony structures. After obtaining the point locations on each film, the three-dimensional coordinates of points of interest at the instant of each view can be reconstructed, with an error of less than 0.5 mm. The motion parameters, characterized by a pseudotranslation vector and three axial rotational angles for the region of interest relative to the machine coordinate system, are also provided. In comparing with some other reconstruction algorithms, the point pair method can significantly improve source localization or point reconstruction in the presence of patient motion. Computer simulations and phantom experiments demonstrates the feasibility and accuracy of the method.

Brachytherapy↗

Computer-aided geometric reconstruction of Fletcher-Suit source positions.

A computer-aided method for reconstruction of the source positions of a Fletcher-Suit applicator has been developed. The tandem source positions are determined by digitizing of the tip and two arbitrary points on the shaft from each of two orthogonal simulator films. A colpostat source position is reconstructed by digitizing of a single point on the endcap and three arbitrary points on the cylindrical sidewalls of the colpostat on the films. This computer-aided method considers the true projection geometry and applicator shape and permits localization of the source positions to within a mean error of less than 1 mm. Compared with the conventional method, the new approach (1) is more time efficient because only a few easily identified points are digitized, (2) allows localization when the tandem sources are shifted by a spacer or when colpostat sources are difficult to visualize on the lateral film, and (3) is more accurate than the conventional technique because no manual drawing of source positions on films is involved.

Algorithms↗

Medical physics.

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Diagnosis, Computer-Assisted↗

Pain on injection of propofol.

A controlled randomized double-blinded clinical study was undertaken to evaluate and compare the efficacy of three methods of preventing pain during injection of propofol on induction of anesthesia. Patients were randomly allocated to six groups: saline pretreatment, followed by induction with propofol at room temperature plus saline; lidocaine pretreatment, followed by induction with propofol at room temperature plus saline; saline pretreatment, followed by induction with propofol at a temperature of 4 degrees C plus saline; lidocaine pretreatment, followed by induction with propofol at a temperature of 4 degrees C plus saline; saline pretreatment, followed by induction with propofol at room temperature plus lidocaine 40 mg; saline pretreatment, followed by induction with propofol at a temperature of 4 degrees C plus lidocaine 40 mg. Pretreatment with lidocaine reduced the incidence of pain and discomfort significantly compared with unpretreated groups. Groups which received propofol mixed with lidocaine also showed a significant reduced incidence of pain. induction with cold 4 degrees C propofol showed no significant difference in reduction of injection pain.

Adult↗

Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and 2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic activity.

Synthetic routes to difluorinated analogs of the adrenergic agonists, norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed. The syntheses were based on elaboration of the ethanolamine side chains from the appropriately polyfunctionalized benzaldehydes. The benzaldehydes were prepared from precursor difluorinated benzenes by sequential regioselective lithiations and reaction with electrophiles to introduce hydroxyl and carboxaldehyde functionalities. Binding and functional assay data demonstrate that the 2,6-difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic receptors. These results are consistent with earlier observations that 2-fluoro substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6-fluoro substitution decreases beta-adrenergic activity.

Animals↗

Online repositioning during treatment of the prostate: a study of potential limits and gains.

PURPOSE: With on-line portal imaging devices and image registration tools, the verification of radiation field position prior to each treatment becomes technically feasible. In this paper, we analyze the impact of pre-treatment verification and field position adjustment on target coverage and normal tissue sparing. METHODS AND MATERIALS: Port films were compared with corresponding simulation films to determine the magnitude of setup variations in patients treated for prostate cancer. From these data, an analytic function was determined between geometric coverage of the target and field margin size. A paradigm for on-line patient repositioning was employed to generate a new relationship between margin and target coverage. Margins were selected for the situations of normal treatment and on-line repositioning to ensure target coverage. Dose-volume histograms were generated for a typical prostate treatment using these margins. RESULTS: On-line repositioning, when setup errors exceed 1 cm, results in a 6 mm reduction in margin, suggesting that 10% of the volume of bladder and rectum may be spared of high dose. CONCLUSION: The use of on-line imaging and image registration to guide adjustment of patient setup may lead to a reduction in the volume of normal tissues irradiated, and possibly improve the probability of complication-free survival in future treatments.

Computer Simulation↗

Acute toxicity during external-beam radiotherapy for localized prostate cancer: comparison of different techniques.

PURPOSE: The chronic and acute toxicities associated with conventional radiotherapy of localized prostate cancer are well documented. However, the degree and incidence of toxicities with conformal techniques are not known. Studying side effects associated with modern radiotherapeutic techniques is more important now since there has been a general trend to use computerized tomography-based techniques in recent years; beam's eye view-based conformal techniques are also becoming more commonplace. It is possible that the local disease control can be improved with the delivery of higher doses than currently used. Conformation of the treatment volume to the target volume may facilitate such dose-escalation. However, prior to such dose-escalation, it is important to know the toxicities associated with such techniques with conventional doses. METHODS AND MATERIALS: We have compared week-by-week acute toxicities associated with conventional (Group A, 16 patients), computerized tomography-based, manual (Group B, 57 patients) and beam's eye view-based (Group C, 43 patients) techniques during 7 weeks of radiotherapy. Group B and C patients were treated contemporaneously (1988-1990). RESULTS: Acute side effects gradually increased from week 1 through weeks 4-5 and generally declined or plateaued after that. The incidence of acute toxicities was significantly less with the beam's eye view/based technique than with the other two methods. For instance, the percentages of Grade 2 acute genitourinary toxicities for Groups A, B, and C were as follows: Week 1-0, 0, 0; Week 2-6, 0, 0; Week 3-6, 9, 2; Week 4-12, 14, 9; Week 5-35, 14, 9; Week 6-31, 16, 7; Week 7-33, 8, 8, respectively. The p values associated with differences in acute genitourinary toxicities for Weeks 1-7 using chi-square test were 0.072, 0.627, 0.389, 0.538, 0.123, 0.06, and 0.012; the p values for acute gastrointestinal toxicities were 0.512, 0.09, 0.031, 0.031, 0.003, < 0.0001, and 0.004, respectively. Pairwise comparison (Wilcoxon rank-sum test) showed statistically significant lower acute toxicity in Group C than Group B (e.g., p values, Weeks 1-7 for gastrointestinal toxicity: 0.633, 0.056, 0.010, 0.014, < 0.0001, < 0.0001, and < 0.0001, respectively) in the latter part of the treatment course. No correlation was found between the extent of toxicity and the patient age or the overall treatment time. Also, no correlation was found between the degree of toxicity and the radiation dose and fraction size, within the narrow ranges used (65-70 Gy and 180-200 cGy, respectively). A trend suggesting increased severity of toxicity with increase in the volume of treatment was seen. CONCLUSION: The findings in this retrospective study need to be confirmed by other prospective studies.

Acute Disease↗

An analysis of image segmentation time in beam's-eye-view treatment planning.

In this work we tabulate and histogram the image segmentation time for beam's eye view (BEV) treatment planning in our center. The average time needed to generate contours on CT images delineating normal structures and treatment target volumes is calculated using a data base containing over 500 patients' BEV plans. The average number of contours and total image segmentation time needed for BEV plans in three common treatment sites, namely, head/neck, lung/chest, and prostate, were estimated.

Computer Peripherals↗

A frameless stereotactic approach to neurosurgical planning based on retrospective patient-image registration. Technical note.

A frameless stereotactic device interfacing an electromagnetic three-dimensional (3-D) digitizer to a computer workstation is described. The patient-image coordinate transformation was found by retrospectively registering a digitizer-derived model of the patient's scalp with a magnetic resonance (MR) imaging-derived model of the same surface. This procedure was performed with routine imaging data, eliminating the need to obtain special-purpose MR images with fiducial markers in place. After patient-image fusion was achieved, a hand-held digitizing stylus was moved over the scalp and tracked in real time on cross-sectional and 3-D brain images on the computer screen. This device was used for presurgical localization of lesions in 10 patients with meningeal and superficial brain tumors. The results suggest that the system is accurate enough (typical error range 3 to 8 mm) to enable the surgeon to reduce the craniotomy to one-half the size advisable with conventional qualitative presurgical planning.

Adult↗