Sensitivity analysis for lexicographic ordering in radiation therapy treatment planning.

PURPOSE: To introduce a method to efficiently identify and calculate meaningful tradeoffs between criteria in an interactive IMRT treatment planning procedure. The method provides a systematic approach to developing high-quality radiation therapy treatment plans. METHODS: Treatment planners consider numerous dosimetric criteria of varying importance that, when optimized simultaneously through multicriteria optimization, yield a Pareto frontier which represents the set of Pareto-optimal treatment plans. However, generating and navigating this frontier is a time-consuming, nontrivial process. A lexicographic ordering (LO) approach to IMRT uses a physician's criteria preferences to partition the treatment planning decisions into a multistage treatment planning model. Because the relative importance of criteria optimized in the different stages may not necessarily constitute a strict prioritization, the authors introduce an interactive process, sensitivity analysis in lexicographic ordering (SALO), to allow the treatment planner control over the relative sequential-stage tradeoffs. By allowing this flexibility within a structured process, SALO implicitly restricts attention to and allows exploration of a subset of the Pareto efficient frontier that the physicians have deemed most important. RESULTS: Improvements to treatment plans over a LO approach were found by implementing the SALO procedure on a brain case and a prostate case. In each stage, a physician assessed the tradeoff between previous stage and current stage criteria. The SALO method provided critical tradeoff information through curves approximating the relationship between criteria, which allowed the physician to determine the most desirable treatment plan. CONCLUSIONS: The SALO procedure provides treatment planners with a directed, systematic process to treatment plan selection. By following a physician's prioritization, the treatment planner can avoid wasting effort considering clinically inferior treatment plans. The planner is guided by criteria importance, but given the information necessary to accurately adjust the relative importance at each stage. Through these attributes, the SALO procedure delivers an approach well balanced between efficiency and flexibility.

Inverse plan optimization accounting for random geometric uncertainties with a multiple instance geometry approximation (MIGA).

Radiotherapy treatment plans that are optimized to be highly conformal based on a static patient geometry can be degraded by setup errors and/or intratreatment motion, particularly for IMRT plans. To achieve improved plans in the face of geometrical uncertainties, direct simulation of multiple instances of the patient anatomy (to account for setup and/or motion uncertainties) is used within the inverse planning process. This multiple instance geometry approximation (MIGA) method uses two or more instances of the patient anatomy and optimizes a single beam arrangement for all instances concurrently. Each anatomical instance can represent expected extremes or a weighted distribution of geometries. The current implementation supports mapping between instances that include distortions, but this report is limited to the use of rigid body translations/ rotations. For inverse planning, the method uses beamlet dose calculations for each instance, with the resulting doses combined using a weighted sum of the results for the multiple instances. Beamlet intensities are then optimized using the inverse planning system based on the cost for the composite dose distribution. MIGA can simulate various types of geometrical uncertainties, including random setup error and intratreatment motion. A limited number of instances are necessary to simulate Gaussian-distributed errors. IMRT plans optimized using MIGA show significantly less degradation in the face of geometrical errors, and are robust to the expected (simulated) motions. Results for a complex head/neck plan involving multiple target volumes and numerous normal structures are significantly improved when the MIGA method of inverse planning is used. Inverse planning using MIGA can lead to significant improvements over the use of simple PTV volume expansions for inclusion of geometrical uncertainties into inverse planning, since it can account for the correlated motions of the entire anatomical representation. The optimized plan results reflect the differing patient geometry situations which can be important near the surface or heterogeneities. For certain clinical situations, the MIGA optimization approach can correct for a significant part of the degradation of the plan caused by the setup uncertainties.

Effects of fractionated irradiation of endocrine aspects of testicular function.

We have examined the hormonal alterations of testicular function in 27 males (14 to 67 years of age) with soft-tissue sarcoma who were treated with surgery and high-dose radiation to the tumor bed. The testicular dose from scatter radiation ranged from 1 to 2,500 rad. There was a dose-dependent increase in the median per patient difference from baseline in serum follicle-stimulating hormone (FSH) values following irradiation, with the maximal difference seen at 6 months. Recovery of serum FSH level was biphasic with a decline in the median difference in values between 6 and 12 months, followed by a gradual descent toward baseline. Only patients receiving less than 50 rad show early complete recovery 12 months after radiation therapy. Radiation injury also induced dose-dependent increases in serum luteinizing hormone (LH) concentration, with the maximal median difference from baseline level occurring at 6 months. Only those patients receiving greater than 200 rad showed statistically significant LH changes from baseline levels at each time interval up to 30 months. No significant changes were observed in total testosterone values. These data provide quantitative guidelines for predicting seminiferous tubule injury and germ cell depletion in men exposed to fractionated radiation. The effects on seminiferous tubule and Leydig cell function, as judged by serum FSH and LH concentrations, suggest that subtle Leydig cell dysfunction, in addition to germ cell depletion, may also occur at exposures greater than 200 rad.

Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy.

Intensity-modulated radiation therapy (IMRT) may be performed with many different treatment delivery techniques. This article summarizes the clinical use and optimization of multisegment IMRT plans that have been used to treat more than 350 patients with IMRT over the last 4.5 years. More than 475 separate clinical IMRT plans are reviewed, including treatments of brain, head and neck, thorax, breast and chest wall, abdomen, pelvis, prostate, and other sites. Clinical planning, plan optimization, and treatment delivery are summarized, including efforts to minimize the number of additional intensity-modulated segments needed for particular planning protocols. Interactive and automated optimization of segmental and full IMRT approaches are illustrated, and automation of the segmental IMRT planning process is discussed.

A large screen digitizer system for radiation therapy treatment planning.

PURPOSE: This paper describes a new technique for manually drawing contours of anatomy over image data for the purposes of radiation therapy treatment planning. METHODS AND MATERIALS: A large area rear-projectible digitizer tablet is used together with a projection TV system to display computer graphics and image data. Large images of computed tomography or magnetic resonance cross-sections are displayed and the digitizer is used to directly trace outlines of important organs. Digitizer menus allow multiple functions for selecting images and structures, for changing the grayscale level and window, and for zooming and roaming the image. RESULTS: This device has been in clinical operation for many years and has proven to greatly increase the speed of entering cross-sectional outlines defined for serial computed tomography images sets. A small timing study of clinical usage demonstrates up to a factor of ten improvement in the speed of contour entry. CONCLUSION: For 3-dimensional radiation therapy, tumor, and target volumes, as well as important critical organs, must be delineated from serial sets of computed tomography or magnetic resonance images. Often 30 or more slices must be considered and the process of outlining structures on this number of slices can represent a significant fraction of the total treatment planning time. The device described in this paper greatly improve the ease and speed of manual contour entry for 3-dimensional radiation therapy planning.

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.

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.

Full integration of the beam's eye view concept into computerized treatment planning.

A complete set of beam's eye view (BEV) and beam portal design features have been integrated into a computerized 3-dimensional radiotherapy treatment planning system. Among the features implemented is the ability to mix BEV graphics with gray-scale images such as simulator and verification radiographs, and digital reconstructed radiographs. Image processing techniques have been developed to both enhance verification images and to detect radiation field boundaries. These portal simulation and presentation techniques are being used clinically to design and verify radiation fields with manual or automatically-designed field shaping blocks. The ability to perform computer dose calculations for planes which are parallel or perpendicular to a specified beam's central axis is available and this feature has also proven useful for treatment plan evaluation and optimization. Finally, direct comparison of computer-generated portal images with actual simulation and verification radiographs is also possible. These techniques allow the direct integration of "CT-directed treatment planning" with block design, simulator films and port films, and other Beam's Eye View-type displays.

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result.

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.

Dose to the contralateral breast due to primary breast irradiation.

The radiation dose received by the contralateral breast during primary breast irradiation is of concern because breast tissue is subject to cancer induction from low to moderate doses of radiation. In this paper the dose to the opposite breast has been studied in detail for common breast treatment techniques. Measurements have been made on 16 patients, a water phantom, a polystyrene phantom with cork inserts to simulate lung tissue, and a body-shaped phantom with wax breasts. Thermoluminescent dosimeters (TLD), ion chambers, diodes, and film have been used in the various configurations. The patient measurements have shown that there is a wide variation in the opposite breast dose received by patients, even when all are treated with, for example, tangential fields alone. Addition of more radiation fields, such as supraclavicular/axillary and internal mammary fields, may increase the dose to the opposite breast for a particular patient. Variations in the details of the technique such as what wedges are used, the use of blocks, and the orientation of the field edges are all important to the final dose received by the patient's contralateral breast. With the phantom measurements, it has been possible to determine the contributions to the opposite breast dose from each of the relevant factors. This makes it possible to explain the wide variation in patient dose measurements, and to make some relatively simple recommendations that will allow the reduction of the dose to the opposite breast from several hundred cGy to about 50 cGy for a typical treatment course dose of 5000 cGy.

Peripheral dose to the testes: the design and clinical use of a practical and effective gonadal shield.

A simple and practical gonadal shield has been developed for use near megavoltage radiation fields. The lead shield encloses only the testes, allowing its use with nearly any radiation field that does not include the testes. The dose to the testes with and without the shield has been measured extensively both in phantoms and on patients. The gonadal shield allows a 3 to 10-fold reduction in dose to the testes depending primarily on the distance from the field edge to the gonads. When the shield is used, the gonadal dose is always less than 1% of the patient's prescription dose. Based on our patient studies of testicular injury following conventionally-fractionated irradiation, a dose of less than 50 cGy (1% of a typical 5000 cGy treatment regimen) should preserve normal testicular function.

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.

The imaging revolution and radiation oncology: use of CT, ultrasound, and NMR for localization, treatment planning and treatment delivery.

The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This has forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume. This increase in precision and accuracy will presumably improve the results of radiation therapy.

Clinical use of a match-line wedge for adjacent megavoltage radiation field matching.

The divergence and sharp penumbra of linear accelerator beams pose notorious problems when joining such beams side by side. One way of reducing the dose distribution nonuniformity in the matching region is to create a wide pseudo-penumbra with the use of a "match-line wedge." A single match-line wedge shape has been developed for 6 MV and 10 MV photon beams. The wide pseudo-penumbra created by the wedge drastically reduces the effect of random set-up errors. Special attention has been paid to ensure simple and reliable clinical use of the wedge. Details of the design, construction, dosimetry, and rules of practical application are presented. Comparisons of several matching methods are made.

A technique for field matching in primary breast irradiation.

The intrinsic divergence of photon beams presents serious matching problems in three-field treatment of the breast and the adjoining supraclavicular area. A method is presented in which appropriate beam blocking combined with suitable isocentric rotation of the treatment couch neutralize the affects of divergence so that proper matching is achieved at all depths. The geometric principles and the set-up procedures are discussed and illustrated.

Television system for verification and documentation of treatment fields during intraoperative radiation therapy.

Intraoperative radiation therapy (IORT) involves direct treatment of tumors or tumor beds with large single doses of radiation. The verification of the area to be treated before irradiation and the documentation of the treated area are critical for IORT, just as for other types of radiation therapy. A television system which allows the target area to be directly imaged immediately before irradiation has been developed. Verification and documentation of treatment fields has made the IORT television system indispensable.

Three-dimensional treatment planning of astrocytomas: a dosimetric study of cerebral irradiation.

To demonstrate that 3-dimensional planning is both practical and applicable to the treatment of high-grade astrocytomas, 50 patients over a 2-year period have received cerebral irradiation delivered in focussed, non-axial techniques employing from 2 to 5 beams. Astrocytomas have been planned using rapid, practical incorporation of CT data to define appropriate tumor volumes. Tumor + 3.0 cm and tumor + 1.5 cm volumes have been treated to conventional doses of 4500 cGy and 5940 cGy, respectively, using beam orientations that maximally spared normal remaining parenchyma. Analyses of 3-dimensionally calculated plans have been performed using integral dose-volume histograms (DVH) to help select treatment techniques. Using identical CT-based volumetric data as input for generation of Beam's Eye View (BEV) designed blocks, DVH curves demonstrate dosimetric advantages of non-axial techniques over conventional parallel-opposed orientations. Assessment of the non-axial techniques in selected cases indicates that uniform target volume coverage could be maintained with a typical reduction of 30% in the total amount of brain tissue treated to high dose (95% isodose line).

Is uniform target dose possible in IMRT plans in the head and neck?

PURPOSE: Various published reports involving intensity-modulated radiotherapy (IMRT) plans developed using automated optimization (inverse planning) have demonstrated highly conformal plans. These reported conformal IMRT plans involve significant target dose inhomogeneity, including both overdosage and underdosage within the target volume. In this study, we demonstrate the development of optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements for all target volumes (e.g., +/-5%), while also sparing the parotids and other normal structures. METHODS AND MATERIALS: The treatment plans of 15 patients with oropharyngeal cancer who were previously treated with forward-planned multisegmental IMRT were planned again using an automated optimization system developed in-house. The optimization system allows for variable sized beamlets computed using a three-dimensional convolution/superposition dose calculation and flexible cost functions derived from combinations of clinically relevant factors (costlets) that can include dose, dose-volume, and biologic model-based costlets. The current study compared optimized IMRT plans designed to treat the various planning target volumes to doses of 66, 60, and 54 Gy with varying target dose homogeneity while using a flexible optimization cost function to minimize the dose to the parotids, spinal cord, oral cavity, brainstem, submandibular nodes, and other structures. RESULTS: In all cases, target dose uniformity was achieved through steeply varying dose-based costs. Differences in clinical plan evaluation metrics were evaluated for individual cases (eight different target homogeneity costlets), and for the entire cohort of plans. Highly conformal plans were achieved, with significant sparing of both the contralateral and ipsilateral parotid glands. As the homogeneity of the target dose distributions was allowed to decrease, increased sparing of the parotids (and other normal tissues) may be achieved. However, it was shown that relatively few patients would benefit from the use of increased target inhomogeneity, because the range of improvement in the parotid dose is relatively limited. Hot spots in the target volumes are shown to be unnecessary and do not assist in normal tissue sparing. CONCLUSION: Sparing of both parotids in patients receiving bilateral neck radiation can be achieved without compromising strict target dose homogeneity criteria. The geometry of the normal tissue and target anatomy are shown to be the major factor necessary to predict the parotid sparing that will be possible for any particular case.

Dose-volume histogram and 3-D treatment planning evaluation of patients with pneumonitis.

PURPOSE: Tolerance of normal lung to inhomogeneous irradiation of partial volumes is not well understood. This retrospective study analyzes three-dimensional (3-D) dose distributions and dose-volume histograms for 63 patients who have had normal lung irradiated in two types of treatment situations. METHODS AND MATERIALS: 3-D treatment plans were examined for 21 patients with Hodgkin's disease and 42 patients with nonsmall-cell lung cancer. All patients were treated with conventional fractionation, with a dose of 67 Gy (corrected) or higher for the lung cancer patients. A normal tissue complication probability description and a dose-volume histogram reduction scheme were used to assess the data. Mean dose to lung was also calculated. RESULTS: Five Hodgkin's disease patients and nine lung cancer patients developed pneumonitis. Data were analyzed for each individual independent lung and for the total lung tissue (lung as a paired organ). Comparisons of averages of mean lung dose and normal tissue complication probabilities show a difference between patients with and without complications. Averages of calculated normal tissue complication probabilities for groups of patients show that empirical model parameters correlate with actual complication rates for the Hodgkin's patients, but not as well for the individual lungs of the lung cancer patients treated to larger volumes of normal lung and high doses. CONCLUSION: This retrospective study of the 3-D dose distributions for normal lung for two types of treatment situations for patients with irradiated normal lung gives useful data for the characterization of the dose-volume relationship and the development of pneumonitis. These data can be used to help set up a dose escalation protocol for the treatment of nonsmall-cell lung cancer.

Three-dimensional treatment planning of intracavitary gynecologic implants: analysis of ten cases and implications for dose specification.

PURPOSE: Results of 3-dimensional treatment planning for ten intracavitary gynecologic implants and implications for dose specification are presented. METHODS AND MATERIALS: Using a computed tomographic (CT) compatible intracavitary applicator we have performed CT scans during gynecologic brachytherapy in 10 cases. A CT-based treatment planning system with 3-dimensional capabilities was used to calculate and display dose in three dimensions. Conventional point doses including the estimated bladder and rectal maximum doses and dose to Point A were acquired from orthogonal simulation films. CT maximum bladder and rectal doses and minimum cervix doses were ascertained from isodose lines displayed on individual CT images. Dose volume histograms for the bladder, rectum and cervix were generated and used to obtain volume of the cervix target volume receiving less than the prescribed dose and the volume of bladder and rectum receiving more than the orthogonal maximum doses. The 5 cc volume of bladder and rectum receiving the highest dose were also calculated. RESULTS: Average values of CT point doses and volumes are compared with the traditionally obtained doses. As demonstrated by others, much higher bladder and rectal doses are found using the CT information. The minimum dose to the cervix target volume is lower than the dose to Point A in each case. CT maximum bladder and rectum and minimum cervix target doses may not be the best index doses to correlate with outcome because of the small volumes receiving the dose. CONCLUSION: We hypothesize that clinically useful bladder, rectal and cervix target volume doses will include volume information which is obtainable with dose volume histogram analysis.