Incorporation of functional status into dose-volume analysis.

The dose-volume histogram (DVH) has gained wide acceptance as a mechanism for reducing the voluminous data of a three-dimensional dose distribution into a two-dimensional graph. These graphs are often converted to a single figure of merit. This data reduction technique is used both for clinical treatment plan evaluation and as part of proposed systems for estimating control and complication probabilities. It has long been recognized that a major shortcoming of the DVH as an analysis tool is that all spatial information is discarded. A subtler problem, which is addressed in this work, is that the DVH also implies homogeneity of biological consequence of irradiation in what may be a functionally heterogeneous volume of tissue. An extension to the DVH, the functional dose-volume histogram, or dose-function histogram (DFH), is proposed, that explicitly includes quantitative three-dimensional functional information. The concept is illustrated by the use of SPECT imaging to assess the functional status of irradiated lung.

Quantification of radiation-induced regional lung injury with perfusion imaging.

PURPOSE: To better understand the dose and time dependence of radiation therapy (RT)-induced regional lung dysfunction as assessed by changes in regional lung perfusion. METHODS AND MATERIALS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Regional function was assessed pre- and post-RT with single photon emission computed tomography (SPECT) lung perfusion scans, obtained following the intravenous administration of approximately 4 mCi of technetium-99m macroaggregated albumin. Pre-RT computed tomography (CT) scans were used to calculate the three-dimensional (3D) dose distribution, reflecting tissue density inhomogeneity corrections. Each SPECT scan was correlated with the pre-RT CT scan, and the 3D dose distribution. Changes in regional lung perfusion were correlated with regional RT dose, at various time intervals following radiation. RESULTS: The data from 20 patients (7 breast cancer, 5 lymphoma, 1 esophagus, 1 sarcoma, and 6 lung cancer) have been analyzed. Patients with gross intrathoracic lung cancers causing obstruction of regional pulmonary arteries were not included. For most patients, there is a statistically significant dose-dependent reduction in regional blood flow at all time points following radiation. While a time dependence is suggested in the high dose range, the limited amount of data prevents meaningful statistical evaluation. CONCLUSIONS: Radiation therapy-induced regional lung dysfunction occurs in a dose-dependent manner and develops within 3-6 months following radiation. In contrast to classical "sigmoid" dose-response curves, described mainly for changes following whole lung irradiation, these data suggest a more gradual relationship between regional dysfunction and RT dose. Retraction of irradiated lung with secondary movement of unirradiated lung into the "3D-defined irradiated volume" may have introduced inaccuracies into this analysis. Additional studies are currently underway to assess this possibility and better refine this dose-response curve. Studies are underway to determine if changes in assessments of whole lung function, such as pulmonary function tests, can be predicted by summing the regional changes observed.

Conformal radiation therapy with fixed shaped coplanar or noncoplanar radiation beam bouquets: a possible alternative to radiosurgery.

PURPOSE: Three-dimensional (3D) geometric conformation of the therapeutic dose volume to the shape of a target tissue volume is the motivation for both conformal radiotherapy and radiosurgery. Although noncoplanar arcs have a clear physical and geometric advantage over fixed fields for small spherical targets, those advantages are reduced for large or irregularly shaped targets where static fields can be individually shaped. We have developed a system that allows efficient and flexible design and reliable delivery of customized "bouquets" of fixed nonopposed coplanar or noncoplanar shaped fields, resulting in highly uniform dose distributions. This report describes our initial experience using beam bouquets to treat intracranial lesions. METHODS AND MATERIALS: Patients with primary (11) or metastatic (4) intracranial lesions with a maximum diameter less than approximately 6 cm, most of whom candidates for single-fraction radiosurgery, were treated with beam bouquets of four to eight nonopposed coplanar or noncoplanar beams. Doses ranged from 16-20 Gy in four fractions for recurrent lesions (8) to 45 to 68 Gy in 25 to 34 fractions for primary lesions (7). The patients were immobilized with custom foam head supports and face masks attached to a fixed base plate. Planning computed tomography scans were acquired, from which the physician developed the custom beam bouquet using 3D treatment-planning tools. The bouquet was designed based primarily on geometric concerns. The bouquet was subsequently modified to add wedge filters chosen by vector analysis of dose gradients to achieve uniform dose over the volume of beam crossfire. At the time of treatment, the isocenter was placed using the instructions provided by the treatment-planning system and pretreatment orthogonal port films were compared to digitally reconstructed radiographs (DRR) to assure proper isocenter placement. For several situations, the 3D dose distributions resulting from alternative coplanar and noncoplanar plans were compared. RESULTS: Each patient was treated without incident. Daily pretreatment port films showed excellent reproducibility of isocenter placement in 87% of setups. With short follow-up (0-12 months), two patients with recurrent glioblastoma experienced clinical deterioration 2 to 4 weeks following treatment. One had increased edema on scans and responded to steroids. Six patients clinically improved following radiation therapy. Review of alternative treatment plans reveals that the relative utility of coplanar vs. noncoplanar beams is likely dependent on the location of the lesion. Noncoplanar beam bouquets are likely preferable to coplanar beams when the target is located in the central regions of the head. Coplanar beams are likely adequate, and possibly preferable, for peripherally located targets. CONCLUSION: The biological advantages of fractionation and the physical advantages of radiosurgery are exploited with this approach. The use of multiple nonopposed coplanar or noncoplanar conformal wedged fields provides a uniform dose to the target and acceptable dose gradient at the target edge. This technique may prove to be an alternative to arc-based radiosurgery in some settings and has the potential advantages that fractionation should improve the therapeutic ratio, and each beam can be individually shaped to conform to irregularly shaped targets. Additional studies are underway to improve this system and better define its utility.

The role of three dimensional functional lung imaging in radiation treatment planning: the functional dose-volume histogram.

PURPOSE: During thoracic irradiation (XRT), treatment fields are usually designed to minimize the volume of nontumor-containing lung included. Generally, functional heterogeneities within the lung are not considered. The three dimensional (3D) functional information provided by single photon emission computed tomography (SPECT) lung perfusion scans might be useful in designing beams that minimize incidental irradiation of functioning lung tissue. We herein review the pretreatment SPECT scans in 86 patients (56 with lung cancer) to determine which are likely to benefit from this technology. METHODS AND MATERIALS: Prior to thoracic XRT, SPECT lung perfusion scans were obtained following the intravenous injection of approximately 4 mCi of 99mcTc-labeled macro-aggregated albumin. The presence of areas of decreased perfusion, their location relative to the tumor, and the potential clinical usefulness of their recognition, were scored. Patients were grouped and compared (two-tailed chi-square) based on clinical factors. Conventional dose-volume histograms (DVHs) (DVFHs) are calculated based on the dose distribution throughout the computed tomography (CT)-defined lung and SPECT-defined perfused lung, respectively. RESULTS: Among 56 lung cancer patients, decreases in perfusion were observed at the tumor, adjacent to the tumor, and separate from the tumor in 94%, 74%, and 42% of patients, respectively. Perfusion defects adjacent to the tumor were often large with centrally placed tumors. Hypoperfusion in regions separate from the tumor were statistically most common in patients with relatively poor pulmonary function and chronic obstructive pulmonary disease (COPD). Considering all SPECT defects adjacent to and separate from the tumor, corresponding CT abnormalities were seen in only approximately 50% and 20% of patients, respectively, and were generally not as impressive. Following XRT, hypoperfusion at and separate from the tumor persisted, while defects adjacent to the tumor improved in several patients. In four patients who achieved a complete response scored by CT with chemotherapy prior to XRT, persistent hypoperfusion was present at and adjacent to the tumor site in three. Among 30 patients with cancers not arising in the lung (14 breast, 12 lymphoma, 4 others), perfusion defects were seen in only 4 (2 adjacent and 2 apart). Recognition of decreases in perfusion mainly impacted on treatment planning for a few patients with poor pulmonary function and limited target volumes. DVFHs have been useful in beam selection for patients with marked perfusion heterogeneities. CONCLUSIONS: Lung perfusion scans provide functional information not provided by CT scans that can be useful in designing radiation treatment beams that minimize incidental irradiation of the function regions of the lung. This approach appears to be most helpful in patients with gross intrathoracic lung cancer, especially those with small targets and relatively poor pulmonary function. One limitation of this approach is that some of the defects adjacent to the tumor site reperfuse following treatment, indicating that these scans identify perfusion rather than potential perfusion. Three dimensional functional data can be used to generate DVFHs that may be more predictive of the physiological consequences of the radiation than conventional DVHs. Additional work is currently underway to test this hypothesis.

A customized head and neck support system.

PURPOSE: To describe a customized head and neck immobilization system for patients receiving radiotherapy including a head support that conforms to the posterior contour of the head and neck. METHODS: The system includes a customized headrest to support the posterior head and neck. This is fixed to a thermoplastic face mask that molds to the anterior head/face contours. The shape of these customized head and neck supports were compared to "standard" supports. RESULTS: This system is comfortable for the patients and appears to be effective in reproducing the setup of the treatment. CONCLUSIONS: The variability in the size and shape of the customized posterior supports exceeded that of "standard" headrests. It is our clinical impression that the customized supports improve reproducibility and are now a standard part of our immobilization system. The quantitative analysis of the customized headrests and some commonly used "standard" headrests suggests that the customized supports are better able to address variabilities in patient shape.

The effectiveness of immobilization during prostate irradiation.

PURPOSE: To evaluate the effect of a hemibody foam cradle on the reproducibility of patient setup during external beam radiation treatment of prostate cancer. METHODS AND MATERIALS: Between January 1992 and April 1993, 74 patients received external beam radiation treatment to the prostate +/- nodes, generally with a four-field box technique. Forty-four of the 74 patients had a custom-made hemibody foam cast used in an attempt to improve setup accuracy. A review of the routine weekly port films was performed following the completion of therapy to determine the reproducibility of patient setup in all 74 patients. The physician's request of an isocenter shift was used as an indicator of reproducibility. Neither the treating technologists nor the physicians knew at the time the films were taken that the port films would be reviewed for setup reproducibility at a later date. The results were compared between the patients treated with (44) and without (30) an immobilization device. RESULTS: In the 44 immobilized patients, 213 routine checks of the isocenter were performed during the 7-week course of radiation therapy. In 17.4% of these instances (37 out of 213), an isocenter shift was requested. This rate is compared to 23.1% (30 out of 130) in the 30 patients who did not have the immobilization device (p < 0.2). There was a statistically significant reduction in isocenter shifts requested in the anterior to posterior direction in the patients who were immobilized, 5.1% (9 out of 175) vs. 12.6% (13 out of 103) (p < 0.05, two tailed chi-square test). There was no significant improvement in the reproducibility of isocenter placement in the cephalad to caudal or right to left directions. CONCLUSIONS: This custom-made hemibody foam cradle appears to improve the reproducibility of patient setup during the 7-week course of fractionated external beam irradiation for patients with adenocarcinoma of the prostate. This type of immobilization device is now routinely used in our clinic and is recommended for all patients receiving pelvic radiotherapy. These devices are likely to be particularly useful when contemplating dose escalation to minimize the volume of bladder and rectum included in the treatment fields.

To treat or not to treat the internal mammary nodes: a possible compromise.

PURPOSE: A method for designing partly wide tangential fields that irradiate the superiorly placed internal mammary nodes, yet exclude the inferiorly placed internal mammary nodes and the cardiac tissue, is described for patients receiving tangential radiation for breast cancer. METHODS AND MATERIALS: Patients are immobilized in hemibody foam cradles. A CT study is performed with a series of fiducial markers. The CT data set can then either be transferred to the three-dimensional treatment planning computer for sophisticated treatment planning, or can be viewed to design partly wide tangential fields "by hand." This latter method is far less time consuming and, we believe, usually adequate, given the uncertainties in identifying the location of the internal mammary nodes. RESULTS: This technique has been implemented in our clinic and has been used to treat approximately 15 patients. In four of these patients, a formal dose-volume histogram analysis revealed that these partly wide tangential fields can adequately exclude the cardiac volume and include the superiorly placed internal mammary nodes. Modest reductions in the pulmonary volume that is incidentally irradiated are seen compared to conventional wide tangents that irradiate the entire length of the internal mammary chain. CONCLUSION: While controversy remains regarding the appropriateness of internal mammary nodal irradiation for patients with breast cancer, the technique described represents an attractive compromise. Selective irradiation of the superiorly placed internal mammary nodes (which are those at greatest risk for involvement) with customized "partly wide" tangential fields is possible. This treatment technique may provide the survival advantage that might be seen with internal mammary node irradiation, yet avoid the possible cardiac morbidity.

The utility of SPECT lung perfusion scans in minimizing and assessing the physiologic consequences of thoracic irradiation.

PURPOSE: Three-dimensional single photon emission computed tomography lung perfusion scans (SPECT) provide a unique quantitative 3-dimensional map of the distribution of functioning pulmonary vascular/alveolar subunits, information not provided by other imaging modalities. This report describes our initial experience utilizing these scans to assist in the design of radiation treatment beams and to assess changes in regional lung function following irradiation. METHODS AND MATERIALS: Patients were immobilized and scanned in the treatment position with appropriate fiducial markers. Four millicuries of technetium 99M microaggregated albumin were injected and SPECT images of the lung were generated. Pre-treatment SPECT images were used to help design radiation beams to minimize irradiation of functioning lung. Pre- and post-treatment scans were compared to assess changes in regional function. These changes in function were then correlated with the regional radiation dose. RESULTS: Pre-radiotherapy SPECT scans were obtained in 18 patients (11 with lung cancer). Marked variations in regional function were frequently noted. In patients with primary lung tumors, these variations were not necessarily immediately adjacent to the tumor volume. In general, patients with poor pulmonary function pre-treatment, in whom one would like to spare as much normal lung as possible, had the most non-uniform distribution throughout the lung of functioning vascular/alveolar subunits. In these cases, pre-treatment scans were most useful in designing radiation portals to minimize irradiation of functioning lung. SPECT scans were also used to detect changes in regional lung function secondary to radiotherapy in four patients. With doses in excess of 40 Gy, reductions in regional function were noted 1-6 months following completion of radiotherapy. These reductions were not necessarily accompanied by reductions in conventional pulmonary function tests, which are assessments of whole lung function and may not reflect regional lung injury if the volume affected is small. CONCLUSIONS: SPECT lung scans provide an excellent means of assessing regional lung function, superior to that obtainable with planar images. The functional data provided by the SPECT images is useful in designing "optimal" radiation treatment beams and in assessing the effect of radiotherapy on regional lung functions. Efforts are continuing in our laboratory to develop a dose response curve for regional lung damage using the tools of SPECT scanning and 3-dimensional dose calculations.

A mathematical basis for selection of wedge angle and orientation.

The treatment plan optimization criterion that dose be homogeneous over an irradiated volume is equivalent to the criterion that the magnitude of the dose gradient be zero throughout that volume. If the dose gradient due to an individual beam is represented by a vector, the dose gradient due to an ensemble of beams is given by the weighted vector sum of the constituent beams' individual gradients. Given a fixed ensemble of beams, the two ways in which the total dose gradient can be modified are (1) by changes in relative beam weights and/or (2) by changes in the direction and/or magnitude of the dose gradient of one or more of the individual beams. Conventional wedges provide a simple mechanism for altering the dose gradient of a single beam. This paper describes a mathematical basis for the selection of wedge angles, wedge orientations, and relative beam weights, with the goal of producing a field of zero gradient over the volume of beam intersection. The approach is based on 3-dimensional vector analysis of dose gradients, and is valuable not only for its formalism, but also for the conceptual basis it provides for discussing and solving general wedge selection problems.

Craniospinal irradiation for trilateral retinoblastoma following ocular irradiation.

A case study is presented. Craniospinal radiotherapy and a three-fold pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

Coordinate transformation as a primary representation of radiotherapy beam geometry.

An approach to both geometric specification of radiotherapy beams and computerized solution of geometric treatment planning problems using coordinate transformations is presented. It is demonstrated that the specification of the geometric relationship of a treatment beam to a patient can be uniquely given by a 4 x 4 coordinate transformation matrix, and that the matrix representation can be translated from (and to) the more conventional machine-based specification of geometry. This approach enables a compact representation of the patient/beam geometry which is independent of the specific labeling conventions of the treatment machine and which can be directly exploited in the solution of treatment planning problems. Beam geometry can be easily described either in terms of the natural degrees of freedom of a therapy machine or in terms of alternative, problem-specific frames of reference. The ability to use these various frames of reference interchangeably allows the designer of treatment design software to present appropriate task-specific user interfaces for arbitrarily complex tasks, and thus reduce the cognitive burden on users of the software.

A comparison of postoperative techniques for carcinomas of the larynx and hypopharynx using 3-D dose distributions.

If a head and neck cancer originates low in the neck with a primary site below the shoulders, a technical challenge to the radiation oncologist exists in that the entire neck needs treatment while avoiding overlap of multiple fields on the spinal cord. No standard solution to this problem exists. We have developed a 3-D treatment planning tool that can be used to develop and compare 3-D treatment plans and dose distributions. Using this tool, we have studied the following techniques for the postoperative treatment of carcinomas of the larynx and hypopharynx, tumors that often embody the problems discussed above: (a) the mini-mantle technique used at the Massachussetts General Hospital, (b) a 3-field technique used at the University of Florida at Gainesville (UF 3-field), (c) a 3-field technique used at our institution and at many others (standard 3-field), and (d) the kicked out lateral technique used at our institution and at others. The 3-D dose distributions from these plans are compared. With 100% delivered just anterior to the vertebral body at mid-neck, the mini-mantle technique results in large 120% hot spots laterally and anteriorly in the neck. Near the mastoid tips, however, the dose falls to 100%. The upper neck nodes may be underdosed since this is 20% cooler than the lateral-anterior neck dose (where a large 120% hot spot exists). The spinal cord is adequately blocked. The two 3-field techniques result in small hot spots at the junction of the lateral and anterior fields. Because different methods are used to prevent overlap at the spinal cord, these hot spots occur anteriorly in the standard 3-field technique and laterally in the UF 3-field technique. The spinal cord block results in untreated neck tissue which can be supplemented with electrons in the standard 3-field technique, but is left untreated in the UF 3-field technique. Both techniques result in a generous length of spinal cord which does not receive full dose. The kicked out lateral technique treats the entire neck and reconstructed pharynx without matching fields at midneck. The upper mid mediastinum is underdosed 10-20% despite being within the posterior inferior portion of the beam. This could be minimized by using a tissue compensator. Unless there is significant subglottic extension or significant risk of disease in the upper mediastinum, we favor treating these malignancies with the kicked out lateral technique, which avoids the problem of junctioning lateral and anterior fields and provides a fairly homogeneous dose distribution.

The portable virtual simulator.

The Virtual Simulator is a software tool for support and management of the geometric component of 3-dimensional radiotherapy treatment design. The Virtual Simulator is a software implementation of a physical simulator with additional functionality not currently available on physical simulators. Treatment of a virtual patient, derived from CT or other source, is simulated using the Virtual Simulator in the same way a physical simulator would be used. The intent of this approach is to provide the user with a familiar working environment for radiotherapy treatment design. Key features include an effective and efficient user interface, and the use of computing techniques and software standards which enhance portability to a variety of computer workstations. The Virtual Simulator is implemented in the C programming language using the X Window System, and has been written with the generic UNIX workstation in mind. It has been demonstrated that it can be installed and run without modification on workstations from a number of vendors.

Virtual simulation: initial clinical results.

We have developed a graphics-based three-dimensional treatment design system that permits the physician to easily understand which anatomy will be treated for any arbitrary beam orientation. Our implementation of this system differs from others in that the software (the Virtual Simulator) simulates the full functionality of a (physical) radiation therapy simulator allowing it to be easily used by physicians. The details of the of our initial clinical experience with virtual simulation are presented in this paper. Virtual simulation was attempted in 71 patients and completed in 65. In 41/71 patients (58%), the beam orientations chosen differed significantly from those traditionally used in our department. Although virtual simulation lead to traditional radiation portals in the remaining patients, in 23/71 (32%) secondary blocking was designed which was different from that which would have been conventionally employed. Thus, overall, virtual simulation lead to treatment changes in 64/71 (90%) of the patients in whom it was attempted. In 78% of evaluable patients the treatment designed with virtual simulation could be implemented on the physical simulator with a precision of +/- 5 mm (+/- 3 mm for brain and head and neck). Thus virtual simulation allowed both accurate planning and execution of treatment plans that would be difficult to achieve with conventional methods.

Recent advances in radiotherapy treatment planning.

Radiation treatment planning is currently in a state of rapid change. Dissatisfaction with past planning technology stems from the growing realization that: (1) Increases in the local regional tumor control rate will increase the cure rate in many malignancies. (2) Even at the best treatment centers geometric tumor misses are commonplace. (3) Traditional constraints on treatment techniques, originally imposed for simplicity and reproducibility, are no longer necessary, and can result in suboptimal treatment. (4) Treatment plans judged "optimal" in two dimensions may be far from optimal when viewed over the entire treatment volume. (5) Lack of treatment reproducibility is also commonplace, and can be demonstrated to adversely affect treatment outcome. On the positive side, recent developments in computer graphics, image processing, radiation physics, and radiation biology are now making it possible to define, design, and deliver sophisticated 3D radiation treatments. However, because many of these technologies are being developed for other disciplines, their applicability to radiation therapy treatment planning is not widely appreciated. We outline the current status and new developments in radiation therapy treatment planning.

Virtual simulation in the clinical setting: some practical considerations.

Virtual simulation departs from normal practice by replacing conventional treatment simulation with 3-dimensional image data and computer software. Implementation of virtual simulation requires the ability to transfer the planned treatment geometry from the computer to the treatment room in a way which is accurate, reproducible, and efficient enough for routine use. We have separated this process into: (a) immobilization of the patient; (b) establishment and alignment of a practical coordinate system for the patient/couch system; and (c) setup of the patient/couch been addressed by the use of hemi- or full-body foam casts, the second by use of an alignment jig on the treatment couch, and the third with the aid of a patient coordinate system referenced to easily located landmarks. Phantom studies and clinical practice have shown these techniques to be practical and effective within reasonable clinical bounds.

Computation of digitally reconstructed radiographs for use in radiotherapy treatment design.

The increasing use of 3-dimensional radiotherapy treatment design has created greater reliance on methods for computing images from CT data which correspond to the conventional simulation film. These images, known as computed or digitally reconstructed radiographs, serve as reference images for verification of computer-designed treatments. Used with software that registers graphic overlays of target and anatomic structures, digitally reconstructed radiographs are also valuable tools for designing portal shape. We have developed radiograph reconstruction software that takes full advantage of the contrast and spatial detail inherent in the original CT data. This goal has been achieved by using a ray casting algorithm which explicitly takes into account every intersected voxel, and a heuristic approach for approximating the images that would result from purely photoelectric or Compton interactions. The software also offers utilities to superimpose outlines of anatomic structures, field edges, beam crosshairs, and linear scales on digitally reconstructed radiographs. The pixel size of the computed image can be controlled, and several methods of interslice interpolation are offered. The software is written in modular format in the C language, and can stand alone or interface with other treatment planning software.

Three-dimensional display techniques in radiation therapy treatment planning.

Good radiation treatment planning requires that the target volume be treated with a high and uniform dose of radiation while irradiating normal tissue as little as possible. Even if the merits of a given treatment plan are judged only on the appearance of isodose lines in one or a few planes it can sometimes be difficult for the experienced radiation oncologist to select the best of several alternative plans. If consideration is given to the entire spatial distribution of dose, however, the problem becomes far more difficult because of the enormous amount of data that must be evaluated. We believe that the lack of suitable methods to display these data has greatly contributed to the slow incorporation of 3D considerations into routine radiation treatment planning. In the past few years there have been great advances in both the theory of how to produce effective 3D displays and in the display hardware itself. In this paper we survey some of the methods used at the University of North Carolina, and show specific examples of how these displays can be used in radiation therapy treatment planning.