Inr. J. Rdatmn Oncology Bid Phys. Vol. 21. pp. 683-693 Pnnted in the U S.A All nghts reserved.

CopyrIght

0360.3016/91 $3.00 + .oO 0 1991 Pergamon Press plc

??Original Contribution

TREATMENT PLANNING FOR STEREOTACTIC RADIOSURGERY OF INTRA-CRANIAL LESIONS HANNEM. KOOY,PH.D. ,l,** LUCIENA. NEDZI,M.D. ,I,*, JAY S. LOEFFLER, M.D. ,I,*, EBEN ALEXANDERIII, M.D.,‘7293 CHEE-WAICHENG,PH.D.,‘,*, EDWARDG. MANNARINO, B.S.,‘,* EDWARD J. HOLUPKA, PH.D.’ AND ROBERT L. SIDDON, PH.D. ,1,2 ‘Joint Center for Radiation Therapy, and *the Stereotactic Radiosurgery Program, 3Division of Neurosurgery, Brigham and Woman’s Hospital, The Children’s Hospital, Harvard Medical School, Boston MA Stereotactic radiosurgery of intra-cranial lesions is a treatment modal&y where a well defined target volume receives a high radiation dose in a single treatment. Our technique delivers this dose using a set of nonrcoplanar arcs and small circular collimators. We use a standard linear accelerator in our treatments, and the adjustable treatment parameters are: isocenter location, gantry arc rotation interval, couch angle, collimator field size, and dose. The treatment planning phase of the treatment determines these parameters such that the target volume ls sufficiently irradiated, and dose to surrounding healthy tissue and critical, dose-limitlng structures is minimized. The attachment of a BRW localizing frame to the patient’s cranium combined with CT imaging (and optionally MRI or angiography) provides the required accuracy for localizing individual structures in the treatment volume. The treatment is fundamentally 3-dimensional and requires a volumetric assessment of the treatment plan. The selection of treatment arcs relies primarily on geometric constraints and the beam’s eye view concept to avoid irradiating critical structures. The assessment of a treatment plan involves lsodose distributions throughout the volume and integral dose-volume histograms. We present the essential concepts of our treatment planning approach, and illustrate these in three clinical cases. Stereotactic radiosurgery, 3-Dimensional treatment planning, Dose computation, Dose-volume histograms, Visualization.

INTRODUCTION

planning approach therefore emphasizes 3-dimensional computations and graphics. The main planning effort focuses on defining a set of beams and computing the volu-

The Swedish neurosurgeon Lars Leksell (10) introduced stereotactic radiosurgery in 195 1. The current increased interest in radiosurgery is in part related to the development of modified linear accelerators (6,12,19,21,24) and the availibility of Gamma Knife units (4,ll). In addition, charged particle beams (8,9) also produce dose distributions advantageous for the treatment of small lesions, but are by nature much less available. All of these methods rely on rigid localization and alignment to deliver the treatment beams through a well defined set of external portals. The efficacy of the different methods is an active area of study. Treatment planning for stereotactic radiosurgery is a fundamentally 3-dimensional task, and requires accurate determination of the target volume and its spatial relationship to nearby critical structures in the brain. Our treatment

metric dose distribution. The dosimetric results must be synthesized with the anatomical information to allow a clinical evaluation of the treatment plan. This synthesis assumes multiple forms allowing both qualitative evaluations, such as isodose surface displays, and quantitative evaluation, such as integral dose-volume histograms. Our examples demonstrate the importance of both in the clinical decision process. Because our delivery system (12) is a standard linear accelerator, the adjustable treatment parameters are isocenter location within the BRW stereotactic localization system, gantry arc rotation interval, couch angle for a given arc, collimator field size, and dose. Geometric considerations, such as available through the beam’s eye view method, determine the limits of the gantry rotation, and ensure that the tumor volume remains inside and

Reprint requests to: Hanne M. Kooy, Ph.D., Joint Center for Radiation Therapy, Harvard Medical School, 50 Binney St., Boston MA 0211.5. Acknowledgements-We thank Michael Goitein for his discussions on dose-volume

histograms

and sampling

methods.

3-dimensional anatomical renderings were made with the Application Visualization System on a Stardent ST1000 computer from Stardent Computer, Inc. Accepted

The

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for publication

22 February

1991.

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critical structures remain outside the beam portal. The dose computation is the most time-consuming component in the planning procedure and requires both the use of selective computational algorithms to preserve an interactive environment, and sufficiently powerful computational engines. METHODS AND MATERIALS The treatment planning process for stereotactic radiosurgery depends critically on the visualization and representation of 3-dimensional information. The planning process is iterative and requires interactive 3-dimensional graphics displays and fast dose computations. The sections below describe components of the planning process on a technical and individual basis, while the clinical cases illustrate the use of these components in an integrated manner.

August 1991, Volume 21, Number 3

isocenter defined by that procedure is simply “dialed” in, and we proceed by selecting the arcs. The initial isocenter location is the geometric center of the target volume. We center a sphere at this isocenter and determine the radius that encloses the target volume. Subsequent movement of the isocenter and adjustments to the sphere diameter provide a visual method for an initial optimization of the isocenter position and minimum geometric covering sphere. Dose distributions obtained from multiple non-coplanar arcs are highly spherical in the high dose region, with each isodose level forming a shell around the isocenter. A simple empirical relation thus relates the collimator diameter to the diameter of the geometric sphere enclosing the target volume given a treatment specification of desired coverage, say 80 or 90% to the target surface, and 100% dose delivered to the isocenter:

Data preparation

4kollimator

We use the Brown-Roberts-Wells CT stereotactic (BRW)* localization system for determining positions within the cranium, and follow the standard surgical and localization procedures defined for that system. We obtain a finely spaced (0.3-0.5 cm, continuous slices) CT scan throughout the full cranial volume from the superior edge of the BRW frame to the cranial vertex. A scan typically yields 35 to 40 transverse slices. We subsequently draw contours on each slice delineating the external cranial surface, the target volume(s), dose-limiting structures such as optic nerves and chiasm, eyes, postrema, and functional brain areas such as the brainstem. The definitions of planar contours on consecutive slices define the surface enclosures of the cranial volumes of interest. In addition, all nine rod intersections on each slice are digitized to define the transformation for each slice from the CT reference system to the BRW system. Isocenter definition

One or more sets of non-coplanar arcs irradiate the target volume. Each set of arcs centers at a single isocenter. The definition of these isocenters is such that the cumulative dose distribution of all arcs for all isocenters delivers sufficient dose to the target volume. A good initial estimate for a single isocenter location is the geometric center of the target volume with further manual adjustment. For multiple isocenters, in cases where a target volume dimension exceeds the largest available collimator size, each isocenter is manually positioned. For the purpose of this discussion we assume a single isocenter and address the problem of multiple isocenters in a case study. The discussion below applies only to target volumes defined by CT or MRI. The treatment of arterio-venous malformations relies primarily on angiography to determine both the isocenter location and the treatment field (2 1,22). The

*Radionics

Inc., Burlington

MA.

=

AL

+

&+s,,ere

(1)

where A, and BL are constants for a given isodose level L and 4Co,,imator and 4Sphere are the collimator and sphere diameters. Given the covering sphere diameter and the desired coverage, a collimator size closest to, but not less then 9 4sphere is selected. The value for BL is approximately 1, and the values for A, and A, are 2.8 and 4.2 mm respectively (values depend on details of the machine geometry and beam energy). The latter is an indication of the steep dose gradient present in stereotactic radiosurgery treatments, where a 1 mm change in position can change the minimum target volume dose on the order of lo%!?

Arc selection

Each isocenter defines the center of rotation for a set of non-coplanar arcs. Each arc is defined by a gantry rotation interval and a couch position. The construction of our delivery system (12) limits the gantry rotation angles to the -interval { - 120”, 120”) (with 0” at the anterior position of the BRW frame). The couch angle is within the interval { - 90”, 90”). The gantry rotation plane, that is, the plane for a single arc, is obviously fixed by the accelerator geometry, and the position of this plane with respect to the cranium is solely determined by the couch angle. The collimator size is fixed for a given arc, with diameter ranges from 12.5 mm to 40.0 mm in 2.5 mm increments. We specify arcs in terms of arc start angle, arc end angle, and couch angle, that is {GantryStart, GantryEnd, Couch}. The arcs in a set are constrained by the collimator size, the target location, and critical structures. The collimator size constrains the angular separation between arcs. The intersection volume between two arcs depends on the collimator size; for a given separation between two arc planes, increasing the collimator size will increase this volume.

‘This can be inferred from the values for A,, and A, where a 90 t 80 change occurs over a diameter change of 4.2-2.8 mm.

Stereotactic

radiosurgery

of intra-cranial

This volume can receive a clinically significant high dose, and we minimize this volume by increasing the angular separation between arc planes. We typically choose a 30” separation interval for smaller collimator sizes and 45” for larger collimator sizes, although often the choice depends on the case under consideration. We further constrain arcs not to cross the transverse (the BRW AP LAT) plane, and stop oblique arcs 20” away from the transverse plane. If we thus consider a 20 mm collimator, the set could contain upto six arcs with one large transverse 240” arc and five 100” arcs at 30” separation, for a total of 740” of arc rotation. We try to minimize the entrance depth over a given arc rotation, and thus the target location can remove some beams from this maximal set. This means that for a right lateral lesion, the left arcs are typically reduced or removed from the set, and the transverse arc is reduced. The total number of arc degrees becomes thus about 400”. Finally, we consider the intersection of each arc with critical structures. Using the Beam’s Eye View (BEV) method (5,13), we view each arc at each degree of rotation and eliminate those degrees of arc that involve a critical structure. This means that some arcs will be reduced, others may be split into disjoint arcs, and others may be removed altogether. A final set of arcs contains anywhere between 3 and 10 arcs, for a total of 250-500” of arc rotation. The selection of arcs described above is accomplished purely through the application of geometric constraints. The dose contribution from each arc is initially set as the relative number of arc degrees an arc contributes to the total number of arc degrees in the full set; if the total arc degrees is 400”, and one beam delivers IOO”,that one beam will deliver 25% of the dose to isocenter. Final specification of the arcs may involve additional adjustments in the dose contribution from each arc. Dose computation Rice et al. (20) and Bjarngard et al. (2) discuss the do-

simetric properties of the small fields used in stereotactic radiosurgery. The narrow beam geometry allows the field to be accurately modeled with a primary beam model only. In this model, dose to a point from a single, stationary, beam is: D(d,r,s)

= MS,(s)T M R(d,s)OAR(r)F2

(2)

where r is the radial distance from the central axis to the point of calculation, d is the depth in the cranium on the central axis from the source position to the calculation point, s is the field (collimator) size, M is the conversion from cGy to machine monitor units, S, is the output relative to the machine calibration geometry, T M R is the Tissue Maximum Ratio measured in water, 0 A R is the off-axis ratio, and F2 is the inverse square correction factor. Equation 2 is the dose to a point from a single static beam. The dose deposited by an arc is computed as the sum of a sufficiently large set of static beams approximating the rotation interval for the arc. The total dose to a

lesions

??H. M. Koov er al.

685

point is the sum of contributions from each arc. The dose to a point p for a single arc is: BeamsCArc) D,,,

(PJ = Oil,,

c k=l

D Cdk(PA

r&PA

+J

(3)

where 0, is the machine output for this arc required to deliver the fraction W,, of total dose delivered to isocenter, that is D,(p = Isocenter) = W,, X DTotal(p = Isocenter). Given the specification of dose to the isocenter and the fraction delivered by an arc, O,, is obtained by setting p to the isocenter position and applying equations 2 and 3. The total dose to a point is the sum over all arcs for all isocenters . These definitions provide a consistent normalization procedure if multiple isocenters are involved and only require that the dose specification for each isocenter uses the same absolute (cGy) or relative (%) units. During planning, we specify the dose delivered to each isocenter in units of lOO%, and use the terminology of normalizing to a given isodose level (for example 1,200 cGy to 80%) as a semantic shortcut for the correct statement of specifying that dose to an isocenter in units of 100% will be 125% of the dose delivered to the periphery (defined by the 80% surface) of the treatment volume. The main task is to compute the dose distribution in the volume and to combine the result with the anatomical data for a clinical evaluation of the plan. This is a 3-dimensional task that must be accomplished interactively. The resulting dose distribution can be synthesized in three formats: dose values on the surface of structures, planar isodose distributions and isodose surfaces, and integral dosevolume histograms. Surface doses allow a rapid assessment of target volume and critical structure coverage. The dose can be displayed relative to a threshold value in contrasting colors (red vs blue, for example) or as a continuous dose gradient display over the surface of the volume. Such a display allows a rapid assessment of target volume coverage by lowering the threshold incrementally until a section of the surface turns blue indicating the minimum target dose. A colorwash display, showing the dose gradient across the surface, is useful to assess the dose for a critical structure such as the brainstem. Planar isodose distributions show the precise relationship between dose gradients and critical structures. Isodose surfaces show the relationship of dose in the volume with anatomic structures. However, both planar and surface isodose displays do not provide a numerical assessment of the volume-dose relationship. Integral dose-volume histograms quantify the volume contained within an arbitrary isodose surface. We compute integral dose-volume histograms with Monte Carlo integration (16). By sampling dose values preferentially at points in regions of high dose gradients and in specific structures

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of interest, we can rapidly generate integral dose volume histograms for all contoured cranial volumes, including the healthy brain, with a high degree of accuracy using approximately 7,500 dose points (15). Because radiosurgery is critically concerned with dose-volume relationships, we present integral dose-volume histograms as a continuous function of absolute volume (in cc) versus normalized (in % of dose to isocenter) or absolute (in Gy) dose. Integral dose-volume histograms are critical to a complete assessment of a treatment plan (3). Isocenter optimization The position of the isocenter within a target volume often critically affects the dose on the surface of the target volume. Small movements of the isocenter can change the minimum surface dose by as much as 30%. We use an optimization procedure that computes the dose at points on the surface, finds the point of minimum dose, and suggests moving the isocenter in the direction of that point by an amount set by the planner. This procedure is repeated until the minimum surface dose is maximized. If the minimum dose to the target volume surface is unacceptably low, the collimator size must be increased. Treatment prescription A treatment prescription specifies the BRW AP, LAT, and VERT position of the isocenter(s) position(s) in the BRW system, the dose to each isocenter, the geometric parameters for each treatment arc (gantry start and end of rotation, couch angle, and collimator size), and machine monitor units for each arc. The dose prescription is specified as a minimum dose to be delivered to a given level encompassing the tumor volume. Occasionally, however, the integral dose-volume histogram will show that only a small fraction of the volume receives the minimum dose and that, for example, 99% of the volume receives a much higher dose. This is the case for highly irregularly shaped lesions, or lesions treated with multiple isocenters. In those situations, the dose prescription is often adjusted to reflect the dose delivered to the higher isodose level. Typical prescriptions range from 10 to 27.5 Gy to the 80% isodose level, and depend on the lesion histology, size, and the minimum dose that can be delivered to the target volume. Treatment planning process We treat typically four patients with stereotactic radiosurgery per week. The real limit is in our access to the linear accelerator, where we have to wait until the regular patient treatments have been completed. The treatment planning process involves four main components: CT data acquisition and transfer, treatment planning, quality assurance, and treatment. The CT data acquisition and transfer currently uses a magnetic tape that needs to be manually carried from the Radiology department to our center. We

August 1991, Volume 21, Number 3

recently obtained network access to the scanners and expect to reduce the transfer time from 1 hour to a simple transfer over high-speed network connections. The actual planning procedure takes anywhere from 30 minutes to 5 hours depending on the complexity and the various image studies used such as MRI and angiography. We subsequently review all aspects of our treatment plan before commencing the actual treatment. Elements of the quality assurance process have been described by Tsai et al. (23). A typical patient turn-around time is 4 hours, excluding the time we need to wait for access to the accelerator. The latter time will be eliminated in the near future when we complete the construction of a dedicated facility for radiosurgery, Until recently we used a VAX*-based treatment planning system. This system provided the basic functionality with sufficient computational speed. The evaluation of target positions and target position optimization were made in an interactive manner. Dose computations on 10 representative slices could be completed on the order of minutes. We have recently introduced a much higher performance environment based on the Stardents platform. The computational performance of the Stardent allows us to compute volume doses (at a rate of better than 30,000 points/set. beam on a GS2000 (7)) and generate isodose surface interactively to make 3-dimensional dose evaluations a reality in the treatment planning process. The treatment planning system is layered on top of the Application Visualization System by Stardent Computer which manages all aspects of user interface and visualization. Cases We demonstrate the various components of the planning process in three cases. These cases were chosen for their illustrative purpose and are somewhat more complex than the more than 300 cases we have treated to date. Case 1: single isocenter treatment. Patient 1 is a 13year-old boy with neurofibromatosis who was treated at the age of 3 with radiotherapy for an optic glioma causing visual compromise. The patient received 5,390 cGy (180 cay/day) with 5 X 5 cm2 opposed lateral fields on a 4 MV linear accelerator. This lesion regressed over 5 years and is no longer radiographically present. At the age of 9, he presented with nausea, vomiting, and headaches and was found to have a fourth ventricular tumor, which was subtotally resected and found to be an anaplastic astrocytoma. The tumor arose along the posterior field edge of his previous radiotherapy, and further radiotherapy was not recommended because of concern of significant dose overlap in the brain stem region with further therapy. At the age of 12 he was reoperated upon for tumor recurrence in the fourth ventricular region. The tumor invaded the floor of the fourth ventricle and a complete resection was not possible. Because of previous radiotherapy to this region, he

*Digital Equipment Corporation, Inc., Maynard MA. QStardent Computer, Inc., Concord, MA.

Stereotactic radiosurgery of intra-cranial lesions 0 H. M. KOOYer al

687

Superioi

Anterior

Fig. 1. Set of four arcs for case 1 for treatment of posterior fossa lesion. Collimator size is 37.5 mm. The optic chiasm constrains the arc rotation intervals to lateral positions. The patient is in a prone position due to the posterior position of the lesion, and hence the BRW anterior position corresponds to the patient’s posterior.

was referred for radiosurgety for the persistent disease in the posterior fossa. The dose to the area postrema was significant so the patient was premeditated with antiemetic therapy and corticosteroids to avoid the development of post-radiosurgery nausea and vomiting (1). The lesion has shown only slight reduction in the 7 months following radiosurgery . The patient has recently developed some edema in the right cerebral hemisphere causing slight ataxia and requiring the introduction of low doses of corticosteroids. We chose a collimator diameter of 37.5 mm for the treatment of the lesion (maximum diameter is 33 mm with a somewhat non-spherical shape and volume equal to 7.2 cc. The posterior location of the lesion required the patient to be placed in a prone position, that is, the BRW anterior position is the patient’s posterior. The geometric center of mass of the tumor is the first estimate for the isocenter location. Given the large collimator size, we chose four sets of arcs (Fig. 1) for the rotation with gantry start, gantry end, and couch angle given by: { - 120”, - 30”, O’}, {50”, 120”, O”}, {50”, 120”, 45”}, and {- 120”, -4O”, -45”}, respectively. The transverse arc (couch angle 0”) is split into two components as the gantry interval from { -30”. 50”) intersects the optic chiasm. Similar considerations, as evaluated through the Beam’s Eye View, constrain the gantry interval for the other beams. The sagittal arc (couch angle 90”) includes the optic chiasm for most of its rotation and was excluded. This set of arcs and with the isocenter at the geometric center of mass of the tumor (at a BRW {AP, LAT, VERT} = (37.3, - 15.7, - 12.8)) results in a minimum tumor dose of 61% (of dose to isocenter), and a maximum area postrema dose of 8 1%. This minimum tumor dose is less than typical for single isocenter treatments and can be significantly improved. Area postrema dose larger than 400 cGy has been correlated with severe nausea, requiring steriod and anticonvulsant prophylaxis (I), and an 81% dose level is not acceptable. Our first attempt is to optimize the tumor dose by the optimization procedure described above.

for case 1 in the coronal plane 1 mm anterior to the isocenter with the intersection of the target volume and the dose-critical area postrema. Results are shown in 10%

Fig. 2. Isodose distribution

increments, isocenter.

with 100% corresponding

to 1,846 cGy delivered to

This results in a 3 mm shift (to a BRW {AP, LAT, VERT} = (40.2, - 16.1, - 13.4}), mainly toward the anterior position of the BRW system (posterior with respect to the patient anatomy). The minimum tumor dose for this “optimal” isocenter is 81%. The maximum area postrema dose, however, is still unacceptably high at 85%! We therefore moved the isocenter away from area postrema to minimize the area postrema dose while maintaining adequate target volume coverage. The choice of treatment dose is thus constrained by (a) a minimum tumor dose for cure, and (b) a maximum postrema dose to avoid complications. The final “constrained” isocenter location was choosen at a 6.7 mm superior / right shift (BRW {AP, LAT, VERT} = (41.2, -20.8, -8.7)) relative to the optimal isocenter position, and results in a minimum tumor dose of 63% and a maximum area postrema dose of 49%. The final dose prescription was chosen at 1,200 cGy to the 65% isodose line. The minimum tumor dose is thus 1,163 cGy, and the maximum area postrema dose is 913 cGy. Single dose values for tumor and area postrema do not form as comprehensive a description as do isodose distributions and integral dose-volume histograms. Figure 2 shows the volume intersection of the target volume and the area postrema on the coronal plane 1 mm anterior of the isocenter, and shows the spherical distribution characteristic of these treatments and the transverse and oblique entry of the treatment arcs. Isodose distributions provide a geometric gauge for the extent of dose in the volume, but do not provide the quantitative information available in integral dose-volume histograms. Specifically, our isocenter selection away from the optimal isocenter (by 6.7 mm),

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Dose

(Gy)

August 1991, Volume 21. Number 3

Dose

(Gy)

Fig. 3.(A) Integral dose-volume histograms for case 1 for tumor for both the optimal target position (dashed line), and the final target position (solid line) constrained by the requirement of minimizing the dose to area postrema. The mean tumor doses are 1,815 cGy and 1,762 cGy for the optimal and constrained configurations, respectively. (B) Integral dose-volume histograms for case 1 for area postrema for both optimal (dashed) and constrained (solid line) target position. The mean area postrema doses are 1,203 cGy and 517 cGy for the optimal and constrained configurations, respectively. The difference in volume between the two distributions is due to statistical fluctuations present in the dose-volume sampling formalism.

results in practically identical isodose distributions that do not indicate what fraction of volume is affected by this move. Figure 3a shows the integral dose-volume histograms for the tumor for both the optimal isocenter (dashed line) and the constrained (by minimizing area postrema dose) isocenter (solid line). The integral dose-volume histograms show that approximately 0.5 cc (7%) of the tumor volume is affected by the chance of isocenter. The chance is largest for the high dose region, as expected from the sharp dose gradient. The mean doses for the optimal isocenter and the constrained isocenter are 1,815 cGy and 1,762 cGy respectively, indicating only a 50 cGy lower dose on the average. Figure 3b shows the integral dosevolume histograms for the area postrema, and clearly shows the dramatic decrease in dose for this dose sensitive structure. The mean (maximum) doses to the postrema for the optimal versus constrained isocenters are 1,203 (1,700) cGy and 517 (913) cGy, respectively. Case 2: dual isocenter treatment. Patient 2 was a 42year-old man who presented to his family physician after two episodes of severe headaches and visual seizures over a l-week period. A CT scan revealed a 2.5 cm enhancing lesion in the right basal ganglia which was stereotactically biopsied and revealed an anaplastic astrocytoma. The patient was treated with 100 cGy bid external beam therapy to a total dose of 7,200 cGy. BCNU chemotherapy was also given intravenously at &week intervals. Seven months following radiotherapy, the lesion began to expand and he was referred to us for either stereotactic brachytherapy or radiosurgery. It was the opinion of the stereotactic radiation committee that an implant in this area carried excessive risk and thus it was decided to treat the patient with radiosurgery. Six weeks after completing radiosurgery a

positron emission tomography (PET) scan showed no metabolic activity in the tumor region. However, tumor developed at the margin of radiosurgery volume in the interventricular septum and the patient died of progressive disease 9 months after radiosurgery. Figure 4 shows the right lateral location of the tumor relative to the optic chiasm and eyes, and its relatively large size. The stereotactic head frame was tilted lower on the side of the lesion and rotated to have the anterior frame portion on the patient’s right to allow the transverse arcs to exit above the optic chiasm and brain stem. The frame tilt can be seen in Figure 4 where the right eye lies superior to the left eye. The size (35 cc) and shape of the tumor preclude the usage of a single isocenter, and a dual isocenter treatment is required. A multi-isocenter treatment requires an approximation of the treatment volume by a set of spheres (corresponding to the dose distributions delivered by a single treatment field). The treatment volume, in general, can be well covered by such an approximation with almost ideal minimization of dose to the healthy surrounding brain. A serious concern, however, is the introduction of large dose inhomogeneities within the treatment volume where the spheres intersect. High dose inhomogeneities, and thus high doses (up to 200% of dose to isocenter) within the treatment volume are associated with an increased risk of complication for large lesions (14). The initial step determines the number of spheres required. For this patient, two isocenters with a collimator size of 37 mm (the largest collimator available at time of this patient’s treatment) was adequate. The initial isocenter positions and collimator sizes are solely determined by the requirement that the total volume enclosed by spheres is maximized, and the intersection between spheres is mini-

Stereotactic radiosurgery of in&a-cranial lesions 0 H. M.

689

KCOY ef al

Fig. 4. Perspective display of treatment volume for case 2. The relevant volumes are the target volume (blue) and the optic structures (pink). The target volume is located at a right lateral position superior to the chiasm. The display is intersected by a plane to show the internal detail of the treatment configuration. The target volume is enclosed by the I.200 cGy (50%) isodose surface (yellow). The 1,920 cGy (80%) isodose surface (yellow) partly intersects the target volume. The dual isocenter configuration is clearly shown by the two spheres representing the contribution of each isocenter. The 2,880 cGy (120%) isodose surface (red) is a high dose region typical in multi-isocenter treatments.

The next step of selecting arcs for each isocenter is a much more complicated procedure compared to the single isocenter case. Unlike single isocenter treatments, arc planes and segments for different isocenters can geometrically intersect, and such intersections must be minimized. For this patient, we chose a full 240” transverse arc (couch O”), an oblique arc (couch 45”), and a sagittal arc (couch 90”) for both isocenters. We were able to apply both transverse arcs due to the large vertical separation, thus minimizing the intersection between these arcs. Note that these specifications are with respect to the BRW system; the patient’s position within the frame means that BRW sagittal corresponds to patient coronal. The isocenter BRW AP, LAT, and VERT locations are 1:{20.4, 13.5, 35.8) and 11:{28.6, - 11.5, 12.1) and are obtained through optimizing the dose delivered to the tumor surface using the optimization procedure in the planning system and moving both isocenters independently. The vertical separation is 23.7 mm, and the transverse arcs overlap in a plane 13.3 mm thick. The oblique and sagittal arc for isocenter I are both full arcs of 100”. The oblique and sagittal arc for isocenter II were reduced at the BRW anterior (patient right lateral) portion because these arcs overlapped with the optic chiasm over their anterior portions. The superior position of isocenter I avoids the optic chiasm. Total degrees of arc for isocenter I is 440”, and for isocenter II is 360”. Both isocenters receive equal dose, and the dose prescription is 2,400 cGy to each isocenter (1,200 cGy to the 50% surface enclosing the target volume). Figure 4 shows three isodose surfaces with respect to the target volume (in mized.

blue). The volumes in Figure 5 have been disected by a plane to show the inner features of the distributions. The outer shell (green) represents the 1,200 cGy isodose surface (50%) and encloses the target volume. The 1,92 cGy isodose surface (80%, yellow) misses portions of the target volume, and clearly shows the two spheres packed together to fit the target volume. The inner surface (red) within the target volume is the 2,880 cGy (120%) isodose surface and is a consequence of the intersection of the dual isocenters dose regions. Figure 5 is the integral dose-volume histogram for the target volume, and shows that the

401 35: 30.. z 0 25. g 20. ,' 0 15.. > 10.. 5.. 0' 0

5

10

15 Dose

20

25

30

35

. 40

(Gy)

Fig. 5. Integral dose-volume histogram for case 2. The mean dose is 2,384 cGy with a range of 1,200 cGy to 3,600 cGy.

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target volume receiving between 1,200 cGy (50%) to 1,980 cGy (80%) is 3.1 cc (9%). The integral dose-volume histogram for the target volume shows a smooth distribution with a mean dose of 2,384 cGy (99.3%) and a tumor dose inhomogeneity (TDI), defined as D,, - Dmin of 2,400 cGy. The dose to the chiasm is less than 120 cGy (5%). Case 3: single isocenter treatment with brainstem involvement. Patient 3 is a 2-year-old girl who presented with nausea and vomiting and was found to have an enhancing lesion in the pineal region. The lesion was biopsied and shown to be an anaplastic ependymoma. A subtotal resection was performed and the patient received systemic chemotherapy followed by craniospinal irradiation. The craniospinal axis received 3,040 cGy followed by an 1,800 cGy boost to the primary tumor region with fractionated radiotherapy. The lesion initially regressed but recurred and the patient was referred to us for radiosurgery. At the time of radiosurgery the lesion was involving the posterior aspect of the midbrain. As for all pediatric patients, this patient was under full anesthesia from the time the BRW frame was attached until after the treatment was completed. Scans 6 weeks and 3 and 5 months after radiosurgery show a slight decrease in the overall mass with the development of a large central area of necrosis. The midbrain shows no evidence of radiation induced edema. The patient is alive and free of complications 7 months following radiosurgery. Figure 6 shows the location of the tumor relative to the brainstem, for which only the section at risk has been outlined on the CT scans. The brainstem constrains all beams to posterior lateral entry portals. Typically, we place patients with posterior lesions in a prone position, but this is not recommended for a patient under anesthesia. The tumor volume is 2.8 cc and the brainstem volume is 8.9 cc. The set of beams (see Fig. 9) consists of seven arcs with gantry start-end and couch angles: { - 40”, - loo”, - 60”}, { -5O”, - loo”, -3O”}, { -5O”, - 120”, 00}, {70”, 120”, O’}, {80”, 120”, 30”}, {40”, 120”, 60”}, and {40”, lOO”, 90”} for a total of 410” of arc rotation. The collimator size is 25.0 mm. Note that the transverse arc at couch angle 0” is split in two arcs, as the anterior portion of the arc from - 50” to 70” sweeps through the brainstem. Each beam intersects a small, unavoidable, portion of the brainstem. This arc configuration covers the target volume by 85% of dose to isocenter, and a treatment prescription of 1,750 cGy to the 85% isodose level was chosen. Figure 7 shows a 3-dimensional rendering of the volumes (from a left posterior view) with the dose on the surface displayed in red where the dose equals or is greater than 1,850 cGy (90%). These surface displays effectively communicate regions of high or low dose, and suggest how to adjust the isocenter or collimator size if necessary. They also show whether critical structures receive a certain dose, such as the brainstem surface behind the target volume receiving this dose. Figure 8 shows the same volumes with the 1,750 cGy (85%) isodose surface (orange) and the 1,030 cGy (50%) isodose surface (green, lines). Finally,

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Fig. 6. Sagittal cut through isocenter for case 3 showing the brainstem, the target volume, and the isodose distributions normalized to the isocenter dose of 2,059 cGy (1,750 cGy to 85%). The arc intervals are trimmed to avoid the brainstem, and the dose gradient between the target volume and the brainstem is sharper as a consequence when compared to the gradient in the inferior-superior direction.

Figure 9 shows the same volumes with the 100 cGy (5%) isodose surface. At this low dose the dose distribution is obviously non-spherical, and instead dramatically shows the individual traces of each arc through the cranial volume. The integral dose-volume histograms (Figs. 1Oa and lob) show the integral dose versus volume for both the tumor and the brainstem. These show excellent coverage for the target volume, and only a small volume of brainstem (1 cc) receiving critical dose of 1,000 cGy or more. Given the presence of the brainstem in the treatment field, we also computed what dose would be delivered to the brainstem if no limits were placed on the arc rotation interval. This generic treatment uses the same number of arc degrees, but places no restriction on the gantry start and end angles. The result is shown as generic in Figs 10a and lob, and clearly shows the importance of trimming arcs to avoid the brainstem. Our “generic” treatment is similar to results given by Phillips et al. (17) (see their Fig. 4) for charged particles, where we equate their lesion location to ours. Our “custom” treatment shows that the optimal treatment for a given lesion cannot always be determined by the particle type, and that photon radiosurgery can be competitive with charged particle therapy. DISCUSSION Our treatment planning process relies critically on the 3-dimensional displays of patient anatomical information combined with volumetric computational results for dosimetric information. These displays take various forms, and include isodose distribution on planar cuts through the treatment volume, integral dose-volume histograms, and superposition of dose information on the patient anatomical structures. The multiplicity of displays for what is in essence the same information allows the clinician to assess

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Fig. 7. 3-dimensional anatomical rendering for case 3, showing the optic chiasm, eyes, partially defined brainstem. and target volume. The surface in red receives a dose of 1,850 cGy (90%) or more, while the surface in blue receives

less than this dose.

the available choices critically. The planning process is complex, and requires highly interactive systems of sufficient computational power to effectively iterate through alternative treatment configurations, and to effectively provide real-time interaction with complex displays combining image data, 3-dimensional geometic data, and computational results such as dose in the treatment volume.

The treatment planning process manipulates multiple interrelated parameters and requires a treatment planning systern that efficiently manages these parameters to remove the possibility of error. Our treatment planning experience shows that the complementary information available from isodose distributions and integral dose-volume histograms, that is, spatial

Fig. 8. Same as in Figure 8, with the 1,750 cGy (85%, transparent

orange) and 1,030 cGy (50%) isodose surfaces.

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rendering of the treatment volume with the 5% isodose surface

versus volumetric, is indispensable to the clinician in effectively deciding between alternatives. For the treatment planner, the isodose distributions show where a given arc could be reduced, while the integral dose-volume histogram shows the effect of such a possible reduction. Isodose distributions often provide little information about how to adjust an isocenter position to increase the target volume dose coverage, and displays such as Figure 8 and 9 effectively communicate alternatives. A cold spot on the surface can be removed by simply moving the isocenter toward a cold spot shown in such a display. If this fails,

and other cold spots appear on the opposite position of the surface, the collimator size must be increased. All these displays must be interactive and require high-end graphics display capabilities coupled with sufficient computational power. We have treated various target volumes close to the brainstem, and, as shown in case 3, we can be competitive with charged particle therapy from a dosimetric assessment based on integral dose-volume histograms. The clinical dose-volume tolerance in radiosurgery for critical structures such as the brainstem is not well known, and remains of

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Fig. 10. (A) Integral dose-volume histogram for the target volume for case 3 for optimized and generic arcs. The generic arcs use the same number of arc degrees as for the optimized treatment arcs, but are equally distributed over the possible arcs. (B) Integral dose-volume histogram for brainstem for case 3 for optimized and generic arcs.

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great concern. We rely on patient-specific definition of the arc configuration to obtain our favorable dosimetric results. Hence, we rarely apply standard arc configurations such as the so-called “Boston system.” Furthermore, the question of dosimetric optimality as suggested by Pike et al. (18) must be considered on an individual basis. For example, the dose results for patient 3 (Fig. 8) more closely correspond to the isodose distribution obtained from a single transverse rotation, as one obviously desires a gradient as steep as possible between the brainstem and the tumor. Thus, while a 47r rotation is dosimetrically “optimal,” clinically it is probably sub-optimal for patient 3. Our treatment planning approach recognizes the need for standardization of reporting treatment parameters. At a

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minimum, in the absence of integral dose-volume histograms, the target volume minimum and maximum dose need to be reported. Our convention is to record the target volume (in cc), the target volume minimum and maximum doses (in cGy), dose normalization relative to isocenter as discussed above, and target volume dose inhomogeneity (TDI). Further studies are needed to standardize on the relevant clinical parameters. We do, if there are no other altematives, treat patients with multiple isocenters. However, our clinical data suggests that the risk for complications in such treatments is higher compared to single isocenter treatments. Hence we are actively pursuing alternative treatment delivery techniques to remove the need for such treatments.

REFERENCES 1. Alexander, E., III; Siddon. R. L.; Loeffler, J. S. The acute onset of nausea and vomiting following stereotactic radiosurgery: correlation with total dose to area postrema. Surg. Neurol. 3240-44; 1989. 2. Bjsjngard, B. E.; Tsai, J.-S.; Rice, R. K. Doses on the central axes of narrow 6 MV x-ray beams. Med. Phys. 17:795799; 1990. 3. Chen, G. T. Y. Dose volume histograms in treatment planning. Int. J. Radiat. Oncol. Biol. Phys. 14:1319-1320; 1988. 4. Dahlin, H.: Sarby, B. Destruction of small intracranial tumours with 6OCo gamma irradiation; physical and technical considerations. Acta Radiol. 14:209-227; 1975. 5. Goitein, M.; Abrams, M.; Rowell, D.; Pollari, H.; Wiles, J. Multidimensional treatment planning: II. Beams eye view. back projection, and projection through CT sections. Int. J. Radiat. Oncol. Biol. Phys. 9:789-797; 1983. 6. Hartmann, G. H.; Schlegel, W.; Sturm, V.; Kober, B.; Pastyr, 0.; Lorenz, W. J. Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. Int. J. Radiat. Oncol. Biol. Phys. 11: 1185-l 192; 1985. 7. Holupka, E. J.; Kooy, H. M. Spherical harmonic expansion of cranial surfaces. Med. Phys. (Accepted for publication). 8. Kjellberg, R. N.; Hanamura, T.; Davis, K. R.; Lyons, S. L.; Adams. R. D. Bragg peak proton-beam therapy for arteriovenous malformations of the brain. N. Eng. J. Med. 309: 269-274; 1983. 9. Larsson, B.; Leksell, L.; Rexed, B.; Sourander, P.; Mair. W.; Anderson, B. The high energy proton beam as a neurological tool. Nature 182:1222-1223, 1958. 10. Leksell. L. The stereotactic method and radiosurgery of the brain. Acta Chir Stand. 102:31&319, 1951. 11. Lunsford, L. D.; Flickinger, J.; Lindner, G.; Maitz, A. Stereotactic radiosurgery of the brain using the first United States 201 Cobalt-60 source gamma knife. Neurosurgery 24: 151-159, 1989. 12. Lutz, W. L.; Winston, K. R.; Maleki, N. A system for stereotactic radiosurgery with a linear accelerator. Int. J. Radiat. Oncol. Biol. Phys. 14:373-381; 1988. 13. McShan, D. L.; Silverman, A.; Lanze, D. N.; Reinstein, L. E.; Glicksman, A. S. A computerized three-dimensional treatment planning system utilizing interactive colour graph-

1979. its. Br. J. Radiol. 52:478481, 14. Nedzi, L. A.; Kooy, H. M.; Alexander, E.; Loeffler, J. S. Variables associated with the development of complications from radiosurgery of intracranial tumors. Int. J. Radiat. Oncol. Biol. Phys. (Accepted for publication). 15. Nedzi, L. A.; Kooy, H. M.; Alexander, E.; Loeffler, J. S. Application of nonuniform random sampling to the generation of integral dose-volume histograms for stereotactic radiosurgery (Abstract). Med. Phys. 17:530, 1990. 16. Niemierko, A.; Goitein, M. Random sampling for evaluating treatment plans. Med. Phys. 17:753-762; 1990. 17. Phillips, M. H.; Frankel, K.A.; Lyman, J. T.; Fabtikant, J. I.; Levy, R. P. Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 18:211-220; 1990. 18. Pike, G. B.; Podgorsak, E. B.; Peters, R. M.; Pla, C.; Olivier. A.: Souhami, L. Dose distributions in radiosurgery. Med. Phys. 17:296-304; 1990. 19. Podgorsak, E. B.; Olivier, A.; Pla, M.; Lefebre, P.Y .; Hazel, J. Dynamic stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 14:115-126; 1988. 20. Rice, R. K.; Hansen, J. L.; Svensson, G. K.; Siddon. R. L. Measurements of dose distributions in small beams of 6 MV x-rays. Phys. Med. Biol. 32:1087-1099; 1987. 21. Saunders, W. M.; Winston, K. R.; Siddon, R. L.; Svensson, G. K.; Kijewski, P. K.; Rice, R. K.; Hansen, J. L.: Barth, N. H. Radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: rationale and technique. Int. J. Radiat. Oncol. Biol. Phys. 15:441-147; 1988. 22. Siddon, R. L.; Barth, N. H. Stereotaxic localization of intracranial targets. Int. J. Radiat. Oncol. Biol. Phys. 13:12411246; 1987. 23. Tsai, J.-S.; Buck, B. A.; Alexander, E.; Svensson, G. K.; Cheng, C.-W.; Mannarino, E. G.; Loeffler, J. S. Quality assurance in stereotactic radiosurgery using a standard linear accelerator. Int. J. Radiat. Oncol. Biol. Phys. (Accepted for publication). 24. Winston, K. R.; Lutz, W. Linear accelerator as a neurosurgical tool for stereotactic radiosurgery. Neurosurgery 22:454464, 1988.