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Biomedical subjects

M L Kessler

Publications and source records attributed to M L Kessler.

At least 19 recordsLinked to original sources
PubMed1997

Long-term results of hepatic artery fluorodeoxyuridine and conformal radiation therapy for primary hepatobiliary cancers.

PURPOSE: We have previously shown that conformal radiation therapy (RT) combined with hepatic artery (HA) fluorodeoxyuridine (FdUrd) had encouraging hepatic control and survival rates for patients with nondiffuse primary hepatobiliary malignancies. With longer follow-up, we were particularly interested if long-term hepatic control and disease-free survival could be achieved, and if late hepatic complications due to radiation therapy were observed. METHODS AND MATERIALS: Patients with unresectable primary hepatobiliary cancer were treated with concurrent HA FdUrd (0.2 mg/kg/day) and conformal RT (1.5-1.65 Gy per fraction, twice a day), directed only to the liver abnormalities. Three-dimensional treatment planning was used to define both the target and normal liver volumes. The total dose of radiation (48 or 66 Gy) was determined by the fractional volume of normal liver excluded from the high dose volume. Patients were followed routinely for response, patterns of failure, long-term toxicity, and survival. The median potential follow-up was 54 months. RESULTS: A total of 22 patients (11 with hepatocellular carcinoma and 11 with cholangiocarcinoma) were treated. There were 10 objective responses in the 11 evaluable patients. The overall freedom from hepatic progression at more than 2 years was about 50%. The median survival was 16 months with an actuarial 4-year survival of about 20%. Gastrointestinal bleeding was the most common long-term toxicity. Late hepatic toxicity was not observed; in fact, hypertrophy of the untreated liver was seen. CONCLUSIONS: Combined conformal RT and HA FdUrd can produce long-term freedom from hepatic progression and survival in patients with unresectable, nondiffuse primary hepatobiliary malignancies. There were no long-term liver complications observed.

Adult↗
PubMed1996

Optimal placement of radioisotopes for permanent prostate implants.

PURPOSE: To determine which of four loading techniques most efficiently yields the prescribed dose to the prostate volume while limiting dose to the central urethral volume. MATERIALS AND METHODS: The four techniques included (a) equal activity and equal spacing with nomogram, (b) differential loading, (c) peripheral loading, and (d) spiked loading of the lobes. They were evaluated with regard to target coverage urethra dose, tolerance to error, and complexity of procedure. RESULTS: All ideal plans delivered the prescribed dose of 160 Gy to 99% of the prostate volume. With prostate-volume expansion and source-placement errors, all strategies indicated that at least 71% of the target volume received the prescribed dose and greater than 92% of the target volume received 120 Gy. CONCLUSION: With source-placement errors and glandular swelling, peripheral loading yields the best target coverage while limiting dose to the central urethral volume.

Brachytherapy↗
PubMed1995

A computer-controlled conformal radiotherapy system. II: Sequence processor.

PURPOSE: A sequence processor (SP) is described as part of a larger computer-controlled conformal radiotherapy system (CCRS). The SP provides the means to accept and then translate highly sophisticated radiation therapy treatment plans into vendor specific instructions to control treatment delivery on a computer-controlled treatment machine. METHODS AND MATERIALS: The sequence processor (SP) is a small workstation computer that interfaces to the control computer of computer-controlled treatment machines, and to other parts of the larger CCRS system. The system reported here has been interfaced to a computer-controlled racetrack microtron with two treatment gantries, and also to other linear accelerator treatment machines equipped with multileaf collimators. An extensive design process has been used in defining the role of the SP within the context of the larger CCRS project. Flexibility and integration with various components of the project, including databases, treatment planning system, graphical simulator, were key factors in the development. In conjunction with the planned set of treatment fields, a procedural scripting language is used to define the sequence of treatment events that are performed, including operator interactions, communications to other systems such as dosimetry and portal imaging devices, and database management. RESULTS: A flexible system has been developed to allow investigation into procedural steps required for simulating and delivering complex radiation treatments. The system has been used to automate portions of the acceptance testing for the control system of the microtron, and is used for routine daily quality assurance testing. The sequence processor system described here has been used to deliver all clinical treatments performed on the microtron system in 2 years of clinical treatment (more than 200 patients treated to a variety of treatment sites). CONCLUSIONS: The sequence processor system has enabled the delivery of complex treatment using computer-controlled treatment machines. The flexibility of the system allows integration with secondary devices and modification of procedural steps, making it possible to develop effective techniques for insuring safe and efficient computer-controlled conformal radiation therapy treatments.

Computer Simulation↗
PubMed1995

A computer-controlled conformal radiotherapy system. III: Graphical simulation and monitoring of treatment delivery.

PURPOSE: Safe and efficient delivery of radiotherapy using computer-controlled machines requires new procedures to design and verify the actual delivery of these treatments. Graphical simulation and monitoring techniques for treatment delivery have been developed for this purpose. METHODS AND MATERIALS: A graphics-based simulator of the treatment machine and a set of procedures for creating and manipulating treatment delivery scripts are used to simulate machine motions, detect collisions, and monitor machine positions during treatment. The treatment delivery simulator is composed of four components: a three-dimensional dynamic model of the treatment machine; a motion simulation and collision detection algorithm, user-interface widgets that mimic the treatment machine's control and readout devices; and an icon-based interface for creating and manipulating treatment delivery scripts. These components are used in a stand-alone fashion for interactive treatment delivery planning and integrated with a machine control system for treatment implementation and monitoring. RESULTS: A graphics-based treatment delivery simulator and a set of procedures for planning and monitoring computer-controlled treatment delivery have been developed and implemented as part of a comprehensive computer-controlled conformal radiotherapy system. To date, these techniques have been used to design and help monitor computer-controlled treatments on a radiotherapy machine for more than 200 patients. Examples using these techniques for treatment delivery planning and on-line monitoring of machine motions during therapy are described. CONCLUSION: A system that provides interactive graphics-based tools for defining the sequence of machine motions, simulating treatment delivery including collision detection, and presenting the therapists with continual visual feedback from the treatment machine has been successfully implemented for routine clinical use as part of an overall system for computer-controlled conformal radiotherapy treatment, and is considered a necessary part of the routine treatment methodology.

Computer Graphics↗
PubMed1995

A computer-controlled conformal radiotherapy system. I: Overview.

PURPOSE: Equipment developed for use with computer-controlled conformal radiotherapy (CCRT) treatment techniques, including multileaf collimators and/or computer-control systems for treatment machines, are now available. The purpose of this work is to develop a system that will allow the safe, efficient, and accurate delivery of CCRT treatments as routine clinical treatments, and permit modifications of the system so that the delivery process can be optimized. METHODS AND MATERIALS: The needs and requirements for a system that can fully support modern computer-controlled treatment machines equipped with multileaf collimators and segmental or dynamic conformal therapy capabilities have been analyzed and evaluated. This analysis has been used to design and then implement a complete approach to the delivery of CCRT treatments. RESULTS: The computer-controlled conformal radiotherapy system (CCRS) described here consists of a process for the delivery of CCRT treatments, and a complex software system that implements the treatment process. The CCRS system described here includes systems for plan transfer, treatment delivery planning, sequencing of the actual treatment delivery process, graphical simulation and verification tools, as well as an electronic chart that is an integral part of the system. The CCRS system has been implemented for use with a number of different treatment machines. The system has been used clinically for more than 2 years to perform CCRT treatments for more than 200 patients. CONCLUSIONS: A comprehensive system for the implementation and delivery of computer-controlled conformal radiation therapy (CCRT) plans has been designed and implemented for routine clinical use with multisegment, computer-controlled, multileaf-collimated conformal therapy. The CCRS system has been successfully implemented to perform these complex treatments, and is considered quite important to the clinical use of modern computer-controlled treatment techniques.

Equipment Design↗
PubMed1995

Advanced interactive planning techniques for conformal therapy: high level beam descriptions and volumetric mapping techniques.

PURPOSE: To aid in design of conformal radiation therapy treatment plans involving many conformally shaped fields, this work investigates the use of two methodologies to enhance the ease of interactive treatment planning: high-level beam constructs and beam's-eye view volumetric mapping. METHODS AND MATERIALS: High-performance computer graphics running on various workstations using a graphical visualization system (AVS) have been used in this work. Software specific to this application has been written in standard FORTRAN and C languages. A new methodology is introduced by defining radiation therapy "fields" to be composed of multiple beam "segments." Fields can then be defined as higher-level entities such as arcs, cones, and other shapes. A "segmental cone" field, for example, is defined by a symmetry axis and a cone angle, and can be used to rapidly place a series of beam segments that converge at the target volume, while reducing the degree of overlap elsewhere. A new beam's-eye view (BEV) volumetric mapping technique is presented to aid in selecting the placement of conformal radiation fields. With this technique, the relative average dose within an organ of interest is calculated for a sampling of isocentric, conformally shaped beams and displayed either as a "globe," which can be combined with the display of anatomical surfaces, or as a two-dimensionally mapped projection. The dose maps from multiple organs can be generated, stacked, or composited with relative weightings to aid in the placement of fields that minimize overlap with critical structures. RESULTS: The use of these new methodologies is demonstrated for prostate and lung treatment sites and compared to conventional planning techniques. DISCUSSION: The use of many beams for conformal treatment delivery is difficult with current interactive planning. The use of high-level beam constructs provides a means to quickly specify, place, and configure multiple beam arrangements. The BEV volumetrics aids in the placing of fields, which minimize involvement with critical normal tissues. CONCLUSIONS: Early experience with the new methodologies suggest that the new methods help to enhance (or at least speed up) the ability of a treatment planner to create optimal radiation treatment field arrangements.

Evaluation Studies as Topic↗
PubMed1995

A computer-controlled conformal radiotherapy system. IV: Electronic chart.

PURPOSE: The design and implementation of a system for electronically tracking relevant plan, prescription, and treatment data for computer-controlled conformal radiation therapy is described. METHODS AND MATERIALS: The electronic charting system is implemented on a computer cluster coupled by high-speed networks to computer-controlled therapy machines. A methodical approach to the specification and design of an integrated solution has been used in developing the system. The electronic chart system is designed to allow identification and access of patient-specific data including treatment-planning data, treatment prescription information, and charting of doses. An in-house developed database system is used to provide an integrated approach to the database requirements of the design. A hierarchy of databases is used for both centralization and distribution of the treatment data for specific treatment machines. RESULTS: The basic electronic database system has been implemented and has been in use since July 1993. The system has been used to download and manage treatment data on all patients treated on our first fully computer-controlled treatment machine. To date, electronic dose charting functions have not been fully implemented clinically, requiring the continued use of paper charting for dose tracking. CONCLUSIONS: The routine clinical application of complex computer-controlled conformal treatment procedures requires the management of large quantities of information for describing and tracking treatments. An integrated and comprehensive approach to this problem has led to a full electronic chart for conformal radiation therapy treatments.

Data Display↗
PubMed1995

The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy.

PURPOSE: Whole-liver radiation, with or without chemotherapy, has been of modest benefit in the treatment of unresectable hepatic metastases from colorectal cancer. A Phase I/II study combining escalating doses of conformally planned radiation therapy (RT) with intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd) was performed. METHODS AND MATERIALS: Twenty-two patients with unresectable hepatic metastases from colorectal cancer, 14 of whom had progressed after previous chemotherapy (2 with prior IAH FdUrd), were treated with concurrent IAH FdUrd (0.2 mg/kg/day) and conformal hepatic radiation therapy (1.5-1.65 Gy/fraction twice a day). The total dose of radiation given to the tumor (48-72.6 Gy) depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for response, toxicity, hepatobiliary relapse, and survival. Median potential follow-up was 42 months. RESULTS: Eleven of 22 patients demonstrated an objective response, with the remainder showing stable disease. Actuarial freedom from hepatic progression was 25% at 1 years. The most common acute toxicity was mild to moderate nausea and transient liver function test abnormalities. There were three patients with gastrointestinal bleeding (none requiring surgical intervention) after the completion of treatment. Overall median survival was 20 months. The presence of extrahepatic disease was associated with decreased survival (p < 0.01). CONCLUSIONS: Combined conformal radiation therapy and IAH FdUrd can produce an objective response in 50% of patients with hepatic metastases from colorectal cancer. However, response was not durable, and hepatic progression was frequent. Improvements in hepatic tumor control for patients with metastatic colorectal cancer may require higher doses of conformal radiation and/or improved radiosensitization. In an effort to increase radiosensitization, we have recently initiated a clinical trial combining IAH bromode-oxyuridine, a thymidine analog radiosensitizer, with conformal high dose radiation therapy.

Adult↗
PubMed1995

Analysis of clinical complication data for radiation hepatitis using a parallel architecture model.

PURPOSE: The detailed knowledge of dose volume distributions available from the three-dimensional (3D) conformal radiation treatment of tumors in the liver (reported elsewhere) offers new opportunities to quantify the effect of volume on the probability of producing radiation hepatitis. We aim to test a new parallel architecture model of normal tissue complication probability (NTCP) with these data. METHODS AND MATERIALS: Complication data and dose volume histograms from a total of 93 patients with normal liver function, treated on a prospective protocol with 3D conformal radiation therapy and intraarterial hepatic fluorodeoxyuridine, were analyzed with a new parallel architecture model. Patient treatment fell into six categories differing in doses delivered and volumes irradiated. By modeling the radiosensitivity of liver subunits, we are able to use dose volume histograms to calculate the fraction of the liver damaged in each patient. A complication results if this fraction exceeds the patient's functional reserve. To determine the patient distribution of functional reserves and the subunit radiosensitivity, the maximum likelihood method was used to fit the observed complication data. RESULTS: The parallel model fit the complication data well, although uncertainties on the functional reserve distribution and subunit radiosensitivity are highly correlated. CONCLUSION: The observed radiation hepatitis complications show a threshold effect that can be described well with a parallel architecture model. However, additional independent studies are required to better determine the parameters defining the functional reserve distribution and subunit radiosensitivity.

Hepatitis↗
PubMed1995

Aspects of enhanced three-dimensional radiotherapy treatment planning.

Advances in computer technology have led to the availability of sophisticated three-dimensional treatment planning systems for use in many radiotherapy centers. However, additional complexity in both the planning and delivery of treatments has accompanied their use. Thus, even more computer-aided tools are beginning to appear to address these needs. Aspects of recent enhancements to 3-D treatment planning at the University of Michigan are presented.

Dose-Response Relationship, Radiation↗
PubMed1994

Expanding the use and effectiveness of dose-volume histograms for 3-D treatment planning. I: Integration of 3-D dose-display.

PURPOSE: A technique is presented for overcoming a major deficiency of histogram analysis in three-dimensional (3-D) radiotherapy treatment planning; the lack of spatial information. METHODS AND MATERIALS: In this technique, histogram data and anatomic images are displayed in a side-by-side fashion. The histogram curve is used as a guide to interactively probe the nature of the corresponding 3-D dose distribution. Regions of dose that contribute to a specific dose bin or range of bins are interactively highlighted on the anatomic display as a window-style cursor is positioned along the dose-axis of the histogram display. This dose range highlighting can be applied to two-dimensional (2-D) images and to 3-D views which contain anatomic surfaces, multimodality image data, and representations of radiation beams and beam modifiers. Additionally, as a range of histogram bins is specified, dose and volume statistics for the range are continually updated and displayed. RESULTS: The implementation of these techniques is presented and their use illustrated for a nonaxial three field treatment of a hepatic tumor. CONCLUSION: By integrating displays of 3-D doses and the corresponding histogram data, it is possible to recover the positional information inherently lost in the calculation of a histogram. Important questions such as the size and location of hot spots in normal tissues and cold spots within target volumes can be more easily uncovered, making the iterative improvement of treatment plans more efficient.

Humans↗
PubMed1994

Three-dimensional reconstruction of monoclonal antibody uptake in tumor and calculation of beta dose-rate nonuniformity.

BACKGROUND: The measurement of the heterogeneity of radiolabeled monoclonal antibody uptake in tumor has an essential role in the calculation and interpretation of the absorbed dose of radiation. Large data arrays and long calculation times have been limiting factors in the calculation of three-dimensional dose-rate distributions used to study the relationship between uptake heterogeneity and dose. METHODS: Serial autoradiographs of tumor sections were digitized with approximately 100 microns resolution using a laser densitometer. The section images were aligned to form a registered tumor-image data set. The image data were corrected for film response versus activity density to create a three dimensional activity density distribution using features of a three-dimensional radiotherapy treatment planning system. Dose-rate distributions were formed by convolution with a beta dose kernel using fast Fourier transforms. RESULTS: Differential dose-rate-volume histograms (derived from the dose-rate distribution) were created to summarize the dose-rate nonuniformity throughout the tumor volume. Effects of section sampling interval, interpolation methods between section planes, and calculation resolution on the dose-rate-volume histograms were illustrated. CONCLUSIONS: The several orders of magnitude improvement in calculational speed provided by the fast Fourier transform technique allowed an investigation of the effects of the calculational parameters. This investigation enabled tuning of both data acquisition and dose computation. These studies can lead to further enhancements in the calculational efficiency of three-dimensional dose-rate distributions. These improvements will allow the study of summing techniques to yield average total dose distributions.

Animals↗
PubMed1994

An automated image-registration technique based on multiple structure matching.

A new image-registration technique that matches multiple structures on complementary imaging data sets (e.g., CT and MRI) has been developed and tested with both phantom and patient data. The algorithm assumes a rigid-body transformation and is suitable for correlating structures within the cranium or at the skull base. The basic premise of the new technique is that an optimum transformation is achieved when the relative volume lying outside of the intersection between a structure and its transformed counterpart is a minimum. This relative volume is calculated numerically using a random sampling approach, and a binary searching algorithm was used to step through the nine-dimensional parameter space consisting of three rotation angles, three scaling factors and three components of a translation vector. For the nine tests using phantom data, the automated structure-matching technique was able to predict the correct rotation angles to within +/- 1 degree. The expected clinical performance of the new technique was assessed by comparing results obtained with the new method to those obtained using other techniques for 12 patients who were treated with charged particles at Lawrence Berkeley Laboratory (LBL) and who had image-registration studies performed as part of their treatment plan. For 9 of the 12 patients considered, the new structure-matching technique produced a significantly better registration than the older methods, as measured by the resultant average relative volume lying outside of the intersection between any structure and its transformed counterpart. For the other three patients, results were not significantly different for the new structure-matching method and the older techniques.

Algorithms↗
PubMed1994

CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody therapy of lymphoma patients.

UNLABELLED: A method for performing 131I quantitative SPECT imaging is described which uses the superimposition of markers placed on the skin to accomplish fusion of computed tomography (CT) and SPECT image sets. METHODS: To calculate mean absorbed dose after administration of one of two 131I-labeled monoclonal antibodies (Mabs), the shape of the time-activity curve is measured by daily diagnostic conjugate views, the y-axis of that curve is normalized by a quantitative SPECT measurement (usually intra-therapy), and the tumor mass is deduced from a concurrent CT volume measurement. The method is applied to six B-cell non-Hodgkin's lymphoma patients. RESULTS: For four tumors in three patients treated with the MB1 Mab, a correlation appears to be present between resulting mean absorbed dose and disease response. Including all dosimetric estimates for both antibodies, the range for the specific absorbed dose is within that found by others in treating B-cell lymphoma patients. Excluding a retreated anti-B1 patient, the tumor-specific absorbed dose during anti-B1 therapy is from 1.4 to 1.7 mGy/MBq. For the one anti-B1 patient, where quantitative SPECT and conjugate-view imaging was carried out back to back, the quantitative SPECT-measured activity was somewhat less for the spleen and much less for the tumor than that from conjugate views. CONCLUSION: The quantitative SPECT plus conjugate views method may be of general utility for macro-dosimetry of 131I therapies.

Adult↗
PubMed1993

Use of Veff and iso-NTCP in the implementation of dose escalation protocols.

PURPOSE: This report investigates the use of a normal tissue complication probability (NTCP) model, 3-D dose distributions, and a dose volume histogram reduction scheme in the design and implementation of dose escalation protocols for irradiation of sites that are primarily limited by the dose to a normal tissue which exhibits a strong volume effect (e.g., lung, liver). METHODS AND MATERIALS: Plots containing iso-NTCP contours are generated as a function of dose and partial volume using a parameterization of a NTCP description. Single step dose volume histograms are generated from 3-D dose distributions using the effective-volume (Veff) reduction scheme. In this scheme, the value of Veff for each dose volume histogram is independent of dose units (Gy, %). Thus, relative dose distributions (%) may be used to segregate patients by Veff into bins containing different ranges of Veff values before the assignment of prescription doses (Gy). The doses for each bin of Veff values can then be independently escalated between estimated complication levels (iso-NTCP contours). RESULTS AND CONCLUSION: Given that for the site under study, an investigator believes that the NTCP parameterization and the Veff methodology at least describe the general trend of clinical expectations, the concepts discussed allow the use of patient specific 3-D dose/volume information in the design and implementation of dose escalation studies. The result is a scheme with which useful prospective tolerance data may be systematically obtained for testing the different NTCP parameterizations and models.

Humans↗