The clinical cyclotron facility in Seattle continues to provide beams for neutron therapy and PET isotope production. Over 2000 patients have so far been treated using an isocentric gantry with multi-leaf collimator. Downtime remains below 2%. A new therapy control system has been in operation for nearly two years now and works efficiently and reliably. Developments to extend the therapeutic window for neutron therapy by adding a boron neutron capture dose component selectively to the tumor are continuing. Several beryllium-tungsten target combinations have been investigated with regard to neutron spectrum, dosimetry and radiobiology. The project of an external ion source to increase flexibility to accelerate other particle beams, in particular He has been abandoned. The change-over to such a system would have created too serious an interruption in the therapy schedule. Instead, modifications to the existing internal cold cathode pig source are being investigated. Substantial progress has been made and the goal of 50 μA at an external target station appears achievable.

This reportdescribesa new computercontrolsystemfor a radiationtherapy machinewith an isocentricgantryanda multileaf collimator. It discussesthe motivation andrationalefor someof the featuresanddevelopmentactivities, andreportsseveralmeasuresof development effort, performance, andquality, determinedafteralmosttwo yearsof operatingexperience. Notable featuresof the control systeminclude constructionbasedon standard(vendorindependent) hardwareandsoftwarecomponentsconnectedbyanetwork,asimpleandefficient userinterface,closeintegrationwith thetreatmentplanningsystem,automatedrecordkeeping for patientqualityassuranceandmachinemaintenance, andeaseof maintenanceandupgrading. Separationof control functionsfrom datamanagement functionsresultsin a control program which is small,fast,andfeasibleto analyzethoroughly. Choiceof featuresandinternaldesign wereinformedby fifteenyearsexperienceusingandmaintainingcomputercontrolledtherapy machines. Thedevelopmentmethodwaschosento ensureexceptionalsafety, reliability, andclinical acceptability. Much of thedetailedspecificationwasexpressedin formal (mathematical)notation. This formal specification(not theprosedescription)servedasthebasisfor mostcoding, testplanning,andsafetyanalysis.Testingandreviews weresupplementedby new automated analysesmethodsincluding theoremprovingandmodelchecking.

The clinical cyclotron facility in Seattle continues to provide beams for neutron therapy and PET isotope production. Over 2000 patients have so far been treated using an isocentric gantry with multi-leaf collimator. Downtime remains below 2%. A new therapy control system has been in operation for nearly two years now and works efficiently and reliably. Developments to extend the therapeutic window for neutron therapy by adding a boron neutron capture dose component selectively to the tumor are continuing. Several beryllium-tungsten target combinations have been investigated with regard to neutron spectrum, dosimetry and radiobiology. The project of an external ion source to increase flexibility to accelerate other particle beam, in particular He-4(++) has been abandoned. The change-over to such a system would have created too serious an interruption in the therapy schedule. Instead, modifications to the existing internal cold cathode pig source are being investigated. Substantial progress has been made and the goal of 50 muA at an external target station appears achievable.

A control program has been developed for use with an existing radiation therapy machine used to treat cancer patients with neutrons. The system is safety-critical, multitasking, meets real-time deadlines and replaces existing control system hardware and software in use since 1984. The program allows therapists to treat patients in a safe and timely manner. The system controls various wedges, filters, and a collimator that shape the therapy beam dose distribution. It checks the actual machine state against a database of prescribed machine setups, and records accumulating dose for each patient across multiple treatment sessions, and updates logs used for patient record keeping and machine quality assurance. Development involved both formal and traditional methods, including extensive use of the Z formal specification language. Since the therapy equipment is in daily clinical use with the original control system, access to real machine hardware is very limited. This limited access necessitated the use of portable components such as X windows and ANSI C to allow for most development and testing to be done on a general purpose workstation and operating system. The program was written only in ANSI C using minimal support (X Windows, the real time operating system, and ANSI C libraries) to reduce the dependence on other third party products and software. This was done to ensure stability over the lifespan of the system and for quality control of safety critical functions. Experiences with testing the program and actual clinical use is reported.

The clinical cyclotron facility in Seattle continues its operation with traditional fast neutron therapy and production of PET isotopes. System availability remains high. Improvements to the extraction efficiency resulted in an increased beam intensity and a 3.5 kW beam is now routinely used for neutron production with the beryllium target in the therapy head. Neutron spectrum measurements have been performed using foil activation techniques. These measurements are part of the effort to enhance fast neutron therapy by baron neutron capture of moderated slow neutrons in the patient. Dosimetric measurements and animal experiments ate being conducted for this modality. Improvements were made to the control system, power supplies and the neutron collimation system, where radiation damaged components had to be replaced. Plans for an external ion source for improved operation with different particle beams for production of experimental medical radionuclides are actively pursued.

Purpose: Three-dimensional treatment planning depends upon exact and consistent delineation of target volumes, This study tested whether different physicians from different institutions vary significantly in their creation of planning target volumes (PTVs),Methods and Materials: Eight physicians from three different institutions created partial planning target volumes for nine clinical test cases. Their target volumes were evaluated qualitatively and quantitatively. Quantitative results were tested for significant differences.Results: Qualitative analysis showed the physicians to vary in (a) the margin placed around the clinical target volume, (b) the margin used near critical structures, and (c) handling of concavities in the clinical target volume, Quantitative analysis showed these variations to result in statistically significant differences in the measured volume of the physicians' planning target volumes,Conclusions: Individual physicians and institutions differ significantly in their creation of planning target volumes, suggesting individual and institutional differences in the working definition for the PTV, Implications of this fact are discussed, along with areas where standardization can be improved. (C) 1997 Elsevier Science Inc.

Purpose: Three dimensional (3D) target volumes are an essential component of conformal therapy because the goal is to shape the treament volume to the target volume. The planning target volume (PTV) is defined by ICRU 50 as the clinical target volume (CTV) plus a margin to ensure that the CTV receives the prescribed dose. The margin must include all interfractional and intrafractional treatment variations. This paper describes a software tool that automatically generates 3D PTVs from CTVs for lung cancers and immobile head and neck cancers.Methods and Materials: Values for the interfractional and intrafractional treatment variations were determined by a literature review and by targeted interviews with physicians. The software tool is written in Common LISP and conforms to the specifications for shareable software of the Radiotherapy Treatment Planning Tools Collaborative Working Group.Results: The tool is a rule-based expert system in which the inputs are the CTV contours, critical structure contours, and qualitative information about the specific patient. The output is PTV contours, which are a cylindrical expansion of the CTV. A model for creating PTVs from CTVs is embedded in the tool. The interfractional variation of setup uncertainty and the intrafractional variations of movement of the CTV (e.g., respiration) and patient motion are included in the model. Measured data for the component variations is consistent with modeling the components as independent samples from 3D Gaussian distributions. The components are combined using multivariate normal statistics to yield the cylindrical expansion factors. Rules are used to represent the values of the components for certain patient conditions (e.g., setup uncertainty for a head and neck patient immobilized in a mask). The tool uses a rule interpreter to combine qualitative information about a specific patient with rules representing the value of the components and to enter the appropriate component values for that patient into the cylindrical expansion formula.Conclusion: The portable software tool allows the rapid, consistent, and automatic generation of 3D PTVs and automatic from CTVs.

Purpose: Software tools are seeing increased use in three-dimensional treatment planning, However, the development of these tools frequently omits careful evaluation before placing them in clinical use, This study demonstrates the application of a rigorous evaluation methodology using blinded peer review to an automated software tool that produces ICRU-50 planning target volumes (PTVs).Methods and Materials: Seven physicians from three different institutions involved in three-dimensional treatment planning participated in the evaluation, Four physicians drew partial PTVs on nine test cases, consisting of four nasopharynx and five lung primaries, Using the same information provided to the human experts, the computer tool generated PTVs for comparison, The remaining three physicians, designated evaluators, individually reviewed the PTVs for acceptability, To exclude bias, the evaluators were blinded to the source (human or computer) of the PTVs they reviewed. Their scorings of the PTVs were statistically examined to determine if the computer tool performed as well as the human experts.Results: The computer tool was as successful as the human experts in generating PTVs, Failures were primarily attributable to insufficient margins around the clinical target volume and to encroachment upon critical structures. In a qualitative analysis, the human and computer experts displayed similar types and distributions of errors.Conclusions: Rigorous evaluation of computer-based radiotherapy tools requires comparison to current practice and can reveal areas for improvement before the tool enters clinical practice. (C) 1997 Elsevier Science Inc.

Purpose: To evaluate the effectiveness of variable multileaf collimation, three-dimensional treatment planning, and computer-controlled conformal radiation therapy of prostate cancer.Methods and Materials: Two hundred and forty-five patients with locally advanced prostate cancer have completed treatment over a 9-year time span using a multileaf collimator and conformal treatment techniques on the University of Washington cyclotron. All patients had three-dimensional treatment planning with computed tomography scans in the treatment position, and had treatment fields individually shaped to the target volume with a continuously variable multileaf collimator. Treatment was delivered under computer control with network transfer of the multileaf collimator settings from the treatment planning computer to the cyclotron control system.Results: The multileaf collimator combined with three-dimensional treatment planning results in elegant dose distributions. These neutron dose distributions resulted in a reduced local/regional tumor failure rate vith no increase in complications when compared to control treatment with photons in a randomized trial. Neutron treatment delivered at other institutions without conformal beam shaping resulted in the same improvement in local-regional tumor control rates, but was associated with a significantly higher normal tissue complication rate than seen with conformal neutron beam delivery techniques (grade 3 and 4 cumulative late normal tissue toxicity rates of 39% vs. 10%, p = 0.0007).Conclusions: Conformal treatment of prostate cancer using a multileaf collimated neutron beam results in increased local/regional tumor control rates with low normal tissue toxicities. This experience is directly applicable to the conformal treatment of prostate cancer with photons.

Purpose: For many years neutron radiation has been used to treat malignant disease both as fast neutron radiotherapy and as thermal neutron induced boron neutron capture therapy (BNCT). To date, these two approaches have been used independently of one another due to the large difference in neutron energies each employs. In this paper we discuss the potential application of BNCT to enhance the therapeutic effectiveness of a fast neutron radiotherapy beam.Methods and Materials: Measurements are presented for the thermal neutron component that is spontaneously developed as the University of Washington fast neutron radiotherapy beam penetrates a water phantom. The biological effect of this thermalized component on cells ''tagged'' with boron-10 (B-10) is modeled mathematically and the expected change in cell survival calculated. The model is then extended to estimate the effect this enhanced cell killing would have for increased tumor control.Results: The basic predictions of the model on changes in cell survival are verified with in vitro measurements using the V-79 cell line. An additional factor of 10-100 in tumor cell killing appears achievable with currently available B-10 carriers using our present neutron beam. A Poisson model is then used to estimate the change in tumor control this enhanced cell killing would produce in various clinical situations and the effect is sufficiently large so as to be clinically relevant. It is also demonstrated that the magnitude of the thermalized component can be increased by a factor of 2-3 with relatively simple changes in the beam generating conditions.Conclusion: BNCT may provide a means of enhancing the therapeutic effectiveness of fast neutron radiothearapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued.

Both fast neutron radiotherapy and boron neutron capture therapy (BNCT) have been utilized to treat malignant disease. Herein we discuss the potential of combining these treatments to enhance the effectiveness of fast neutron therapy through a concomitant BNCT boost. Using a fast neutron beam generated from a 50 MeV proton on beryllium reaction, me have determined that 0.1% of the beam per microgram of boron-10 per gram of tissue (mu g/g) can be deposited via BNCT. Our mathematical modeling predicts that BNCT enhancement of our beam will lead to an additional 1-2 logs of tumor cell kill for boron-10 concentrations of 30-50 mu g/g. We have validated this via V-79 cell line in vitro measurements. A Poisson model estimation of how this additional cell kill will influence local tumor control, predicts that BNCT enhancement of fast neutron radiation will lead to a clinically significant improvement in outcome.

A 3-D treatment planning system is one that can represent all radiation therapy treatment machine motions, and which can calculate the dose at any point in the patient treatment volume. As a corollary to these two requirements, a 3-D planning system must also be able to display 3-D plan geometry and doses in some useful way. This article reviews three visible aspects of 3-D planning systems: graphic displays, dose computation methods, and ease of use. It also discusses a less visible, but no less important, aspect: the underlying software engineering. Although 3-D planning systems first appeared in research institutions more than a decade ago, and potential benefits have been demonstrated, they are used only rarely in routine clinical practice. This review concludes that adequate displays and computation techniques are now available, but improved packaging, engineering, and ease of use are required before 3-D planning will be practiced widely.

This report describes a systematic effort to test all functions of a large 3-D radiation therapy planning program, including graphics and user interaction. Previous studies in quality assurance for radiation therapy programs do not adequately address the problem of programming errors. They compare dose estimates calculated by planning programs to actual doses measured in phantoms, so they cannot distinguish programming errors from measurement errors or physical unsoundness of the beam model. Moreover, they fail to exercise graphics and user interaction functions. This report describes a different methodology[ test cases are derived from the program specification, results are calculated by an independent technique, and compared to program output. Derivation of test cases is described in detail. Effectiveness of testing is assessed by reporting the number of errors revealed by testing and comparing to the number of errors discovered during routine use in five successive program versions. The size of the test set is related to the total program size, and the effort devoted to deriving and performing tests is compared to the total program development effort. We conclude that systematic testing can reveal errors that are not found by informal testing, routine program use, or comparison with measurements. However, additional errors remain that are only discovered during use. This study suggests that a typical large planning system may include more than 100 errors when it is released for clinical use. Methods for increasing testing effectiveness are recommended.