Radiat Environ Biophys (1992) 31:219-231
Radiation and Environmental Biophysics © Springer-Verlag 1992
Beam delivery systems for charged particles* H. Blattmann PSI Paul Scherrer Institute, Abteilung Strahlenmedizin,CH-5232 Villigen PSI, Switzerland Received December 12, 1991 / Accepted in revised form February 26, 1992
Summary. Heavy charged particle therapy, started at research institutes three decades ago, is now on the verge of entering a clinical phase. This phase has resulted from the evolution and development of various beam delivery systems and techniques with existing research accelerators and with newly built accelerators. For the first thirty years, heavy charged particle therapy was administered with a fixed horizontal beam line. In 1991, the first treatment with an isocentric gantry was administered. The development of the isocentric gantry, the newest beam delivery system, and clearly a consequence of all the experience gained at the earlier facilities has many advantages. It offers advantageous physical properties of the particles as well as being equal in the flexibility of dose delivery to the modern photon radiotherapy gantries. Introduction For the last three decades, heavy charged particles, protons, light ions up to argon and pions, have been considered ideal for radiotherapy especially for treatment of well delineated lesions. The first 30 patients were treated with protons from 1955 to 1957 at Lawrence Berkeley Laboratory (Lawrence 1957; Lawrence et al. 1962). In 1957 Uppsala, Sweden, started a proton therapy program (Larsson 1988). The use of heavy charged particles has been limited to few centers up to now due to the large and expensive accelerators needed. All present projects except for one, are based on machines built for physics research experiments and most of the therapy projects continue to run in parallel with physics research. This fact has not only limited the number of patients treated, but has also influenced the application techniques used in particle therapy, since all the beam lines were fixed and horizontal. In the future, however, * Paper given on the fourth workshop on "HeavyCharged Particles in Biologyand Medicine" GSI, Darmstadt, FRG, September 23-25, 1991
220 Table 1. Patients treated with heavy charged particles by middle of 1991 World wide charged particle patient totals July 1, 1991 Berkeley 184 CA. USA Berkeley CA. USA Uppsala Sweden Harvard MA. USA Dubna USSR Moscow USSR Los Alamos NM. USA Leningrad USSR Berkeley CA. USA Chiba Japan TRIUMF Canada PSI Switzerland Tsukuba Japan PSI Switzerland Dubna USSR Uppsala Sweden Clatterbridge England Loma Linda CA. USA Louvain-la-Neuve Belgium
p He p p p p p heavy p n n p p p p p p p n ions protons TOTAL
1955 57 since 1957 195%76 since 1961 1964-74 since 1969 1974-82 since 1975 since 1975 since 1979 smce 1979 since 1980 since 1983 smce 1984 since 1987 since 1988 since 1989 since 1990 since 1991
30 2054 73 5268 84 2135 230 685 433 65 253 478 229 1035 13 20 158 19 6 961 2487 9820 13268
this is likely to change. Clinical facilities within research institutes and hospital based facilities, for protons and light ions, are being planned and/or under construction in numerous places in the world, and therefore b e a m line designs will be optimized for medical use. New delivery techniques are under investigation for routine operation in a clinical environment in view of the increasing capabilities of diagnostics and hence increased expectations, as well as computer control. Initially, for treatment of small lesions in the brain, 200 MeV p r o t o n pencil beams were cross fired to yield a small volume of high dose with sharp edges to the t u m o r volume (Larsson 1988). The same technique was later used in Leningrad with p r o t o n beams of much higher energies and, therefore, penetration. For this technique, protons produce a much better dose distribution than photons due to the sharp lateral dose fall off, therefore, giving a sharper penumbra in the area of overlapping beams. These thirty years of development and experience from all the charged particle centers in the world paved the way for the newest p r o t o n beam delivery system - the isocentric gantry. This gantry at L o m a Linda University Medical Center, USA, is also the first hospital based beam delivery system for charged particle therapy in the world. Treatments started operation in 1991 (Slater et al.
1988). In conclusion, it can be said that there has been substantial experience and development in charged particle patient treatment over the last three decades,
221 TREATMENTVOLUMESHAPING BEAMWIDENING
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Fig. 1. Beam delivery systems. The treatment volume can be fitted in two dimensions in the beams eye view to the shape of the target volume by various combinations of beam widening and depth control techniques. As the depth modulation is uniform over the whole field, some of the volume elements outside the target volume are exposed to the full target volume dose. The relevance of this unwanted exposure is reduced by multi-port irradiation. For conformation therapy the dose distribution is shaped in three dimensions for each port. For multi-port irradiation this results in an optimal reduction of the integral dose. With help of a multi-leaf collimator and a bolus to fit the distal shape of the dose distribution, the two dimensional shaping of the beam cross section can be developed into a three dimensional shaping. The same result can be achieved directly, without patient specific hardware, by voxel or spot scanning despite all is entering Minakowa et al. 1985)
the hard work and difficult conditions is has encountered, and it a new decade o f growth and development. (Chuvilo et al. 1984; et al. 1990; Munzenrider et al. 1985; Suit et al. 1982; Tsunemoto (Table 1).
Beam delivery Beam delivery can be divided into two categories - b e a m widening techniques and conformal techniques. Beam widening techniques give a homogeneous dose distribution in a field of the appropriate size and shape, combined with range modulators and shaped collimators to achieve a flat, regularly shaped high dose volume enclosing the target volume. For an individual beam it is unavoidable that also some adjacent normal tissue is included in the high dose volume. Conformal techniques give three dimensionally shaped high dose distributions conformal to the target volume (Figs. 1 to 3).
Beam widening techniques
Scattering techniques For the first treatments, small volumes were irradiated by geometrically overlapping multiple proton beams in the plateau region of their depth dose profile thereby not making use of the well defined range of the heavy charged particles. The knowledge of the exact integrated stopping power along the entire track
222 Beam delivery techniques
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of the particle from the surface to the target volume was not within easy reach before the availability of CT scanners and not necessary for the cross-over technique. The first center to use the Bragg peak was Lawrence Berkeley Laboratory in 1960 (Lawrence et al. 1962). To irradiate large volumes, the p r o t o n beams from the accelerator have to be defocussed or scattered to widen the useful beam cross section. This technique gives bell shaped b e a m profiles in which the central flat region is used for treatment, and results in a large fraction of the particles being lost because the tails of the profile are cut by the collimators. To improve the use of the particles, the double scattering technique was developed at the H a r v a r d Cyclotron L a b o r a t o r y (Koehler et al. 1977). While single scattering results in a dose distribution with a high intensity in the center of the irradiated field, a second scatterer placed at a well defined distance upstream reduces the n u m b e r of particles in this central region and an annulus, arranged around the center piece, scatters particles which otherwise would fall outside the useful area into the fall-off region of the dose. For a specific geometrical arrangement of first and second scatterer and target volume, and with optimized scatterer thickness and diameter, this results in a circular dose distribution with a larger radius and a reduced loss of primary particles. This technique has recently been further improved (Gottschalk et al. 1991), instead of a central scatterer and a ring, a contoured scatterer which is thick in the center
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Fig. 3a-h. Illustration of the principle of different scanning techniques. For raster scanning (a) and (b) and also for wobbling (e) the beam is scanned on a regular pattern with constant velocity, independent of the shape of the target volume. With individually prepared collimators the fractions of the path of the pencil beam outside the area of interest are cut off (dashed lines)• Fixed range modulation leads to uniform depth of the high dose volume, exposing substantial areas outside the target volume (g). With a multi leaf collimator this area can be reduced. Discrete voxel or spot scanning (d) and (e) deposite the full dose only inside the target volume• The dose per spot is optimized to yield uniform dose inside the target volume while the dose outside is minimized• For variable scan velocity a homogeneous dose distribution is achieved by uninterrupted scanning (f). A prerequisite is a stable beam intensity. For (d), (e) and (f) the depth of the target volume is covered by variing the range in steps, no bolus is needed. These techniques are particularly adventageous for large irregularly shaped target volumes and gets thinner with increasing radius is now used. This scatterer made of lead is combined with a plastic piece with radially dependent thickness which makes energy loss of the particle independent of the radius. Further, placing all the scattering and range modulation elements upstream, results in an increase in efficiency of approximately 46% and a sharper dose fall off. The dose area is still circular and must be larger in diameter than the largest projection of the target contour. A relative long drift distance between scatterer and patient is necessary. Scattering techniques have been predominantly used for the patient treatments with protons by all centers, with the only exception of a few patient at N I R S in Japan, who have been treated with a scanned b e a m for superficial lesions (Kanai et al. 1983). Differences between the p r o t o n treatment facilities exist mainly in the energy ranges available. While Harvard, Uppsala, and Moscow have energies in the range of 160-200 MeV, some facilities, especially the newer ones, can only treat ocular m e l a n o m a or superficial tumors with low energy p r o t o n beams of less than 100 MeV. Although treatments with light ions were initially done with scattered beams at Lawrence Berekely Laboratory, the treatments for the past 6 years have been with a dynamic b e a m widening technique (Chu et al. 1985; Chu et al. 1988).
224 For ions as well as for protons, most of the available beam lines are horizontal. Vertical beam lines were introduced in Japan, at NIRS for low energy protons of 70 MeV and at Tsukuba for treatment of deep seated tumors with energies from 150 to 300 MeV, produced by degrading a 500 MeV beam (Kurihara et al. 1983). At Tsukuba, a scatterer and ridge filters as well as a dynamic range modulator are used. Besides a block-collimator a multi leaf collimator is also available. Even for their new hospital based facility the present design includes fixed beams only: one room with both a vertical and a horizontal beam line and one room with a vertical beam line only (Fukumoto et al. 1990). The same philosophy is also being pursued at the HIMAC project, planned to begin operation in 1993, at Chiba, Japan where a dedicated heavy ion therapy facility is under construction (Kawachi et al. 1989). Featuring a double synchrotron as the accelerator, three treatment rooms are provided with vertical and horizontal beam lines. One of the rooms will have both a vertical and horizontal beam focused isocentrically. Each of the beam lines, initially, will use a scattering system with the possibility of using a dynamic application technique in the future. The proton facility at the hospital of Loma Linda is equipped with the widest spectrum of proton beams. Besides one room with two horizontal beam lines, one for eye treatment and one for small volume cranial lesions, three rooms have isocentric gantries installed (Slater et al. 1988). At the present time one gantry is in service and the other two will be operational soon. All three gantries are identical and have a diameter of more than 12 m. They are equipped with a scattering beam delivery system, which at a later stage may be upgraded to provide raster scanning or conformation therapy.
Dynamic beam widening techniques Wobbling. A new, dynamic technique has been developed at Berkeley for heavy ion beams at the BEVALAC. By wobbling the particles of a beam pulse are smeared out on a circular ring by use of a pair of dipole magnets with sinoidal fields with a phase difference of 90 °. Several circles of optimized radii and doses are added dependent on the field size to be achieved (Fig. 3 c). Flat fields of up to 30 cm diameter have been reached with less than 5% dose variation. This technique results in economizing the particles, as double scattering, but it depends strongly on constant pulse intensities or on large numbers of pulses for each ring. This system has been used for routine radiotherapy at Lawrence Berkeley Laboratory since 1985 (Chu et al. 1985). Besides the higher efficiency, wobbling has additional advantages of importance for light ions. Wobbling uses less material in the beam upstream of the patient and therefore substantially reduces the adverse effects of fragmentation. This results in a sharper dose fall off with depth, a beam with smaller tails, and a higher RBE in the distal areas of the treatment volume. Less contamination with lighter fragments with a longer range also results in a lower integral dose for the same target volume and target dose. Raster scanning. Raster scanning, first used for protons at Uppsala in the sixties (Graffman et al. 1985) and developed later at Berkeley for heavy ions (Chu et al. 1988), is a similar, but more flexible technique to yield large homogeneous
225 dose distributions. Instead of scanning on circles, the scans are performed on a rectangular grid with a high frequency in one direction and a lower frequency in the direction perpendicular to it (Fig. 3 a and b). Rectangular fields of different shapes can be scanned in this way giving a field more closely related to the target volume projection, and, therefore, further reducing the losses. Up to 40 × 40 cm 2 fields can be scanned at Berkeley with scanning rates of 40 and I Hz for the two axes respectively. The final shape of the dose field is tailored by an individual collimator, cutting unwanted beam areas. As with wobbling, raster scanning has additional advantages for light ions compared to scattering due to the reduced fragmentation. Both wobbling and raster scanning operate with fixed range modulation either with a ridge filter or a rotating absorber wheel or with a combination of both. This results in a dose distribution which can at best be conformed to the target volume contour distally, by using a patient specific compensator bolus. With this technique, normal tissue is exposed to the same dose as the target in the proximal area (Fig. 3g). In principle, this could be avoided by the use of a multi-leaf collimator, which has been mentioned by several authors but not yet been introduced in practice.
Conformation therapy Spot or voxel scanning Conformation therapy is the tailoring of the high dose volume in three dimensions to the target volume. Various slightly different techniques and different names have been proposed by several centers. It is often referred to as spot, pixel or voxel scanning at PSI whereas at GSI it is called raster scanning (Fig. 3 d to f and h). These technique can be regarded as further refinement of the raster scan described above. Instead of irradiating regularly shaped areas, mostly rectangles, the scans are covering only the cross section of the target volume including a margin around it and this is achieved without the need of individual collimators. This can either be accomplished by depositing dose to discrete volumes (Fig. 3 d and e) or by scanning a small beam with a variable speed (Fig. 3 f). NIRS has developed this technique for 70 MeV protons of the range of approx. 3 cm where the aim was primarily to save range of the protons due to reduced energy loss in the scatterer (Kanai et al. 1983). For deep seated tumors the first patients have been treated with a three dimensional conformation therapy with pions in the Piotron at PSI, Villigen (Blattmann 1979; Pedroni et al. 1983; Von Essen et al. 1985). Almost 500 patients since 1982 have been treated for various indications in the abdomen and in the head with this technique. Spot scanning has been developed for treatment with the Piotron to minimize dose to normal tissue. The aim was not to rely purely on the biological advantage of the secondaries of the pion capture in tissue but to optimize in addition the physical dose distribution as far as possible with the relatively light particles. Dose spots in the Piotron are formed by overlapping the stopping region of 60 converging beams entering the treatment chamber in a vertical plane. The patients contour is fitted to a cylinder with tissue equivalent material and the patient placed in a couch
226 on the axis of the treatment device inside a water bolus. It is possible to shape the distribution of the high dose volume in three dimensions to the contour of the target volume. The scanning is performed in the Piotron by translation of the patient in three axes. The limitations of the dose distributions of the Piotron are the gradual fall off of dose to all sides. Due to the relatively large range necessary, the straggling of the pions contributes substantially to the spot size, resulting in beam profiles on the axis of the Piotron of 5.5 cm F W H M in all three directions, which in turn results in a gradual, uniform dose fall of to all directions, leaving no flexibility to trade a sharp fall-off in the direction of a critical normal tissue for a shallow fall-off in a less important area. For 200 MeV protons at PSI (Blattmann et al. 1990; Pedroni et al. 1990) and light ions at GSI (Haberer et al. 1991 ; Kraft et al. 1991) magnetic scanning of the beam has been tested. Similar techniques are under development or proposed at Uppsala, Moscow and by IBA as well as for E U L I M A , the European light in medical accelerator (Farley and Carli 1991 ; Grusell et al. 1991 ; Jongen 1991 ; K h o r o s h k o v et al. 1991). Characteristic for all these techniques is, that they irradiate small volume elements with a narrow beam scanned in three dimensions. To be able to shape the dose according to the target volume well enough, approximately ten thousand voxels have to be irradiated per liter volume, As all the projects aim at treatment times similar to those in contemporary photon therapy, i.e. a few minutes, these spots have to be delivered in small fractions of a second. A fast control of the beam is therefore necessary to either vary the scan speed of the fastest axis accordingly or to switch the beam on and off. Depending on the duty cycle of the accelerator this may be a requirement which is hard to achieve. The fastest scan axis for all of the projects except for the IBA facility is magnetic scanning. The scan speed of this axis is on the order to 1000 cm/s or much more for the synchrotron planned at Moscow with a duty cycle in the few percent region. The second axis may be, again, magnetic scanning as for GSI, Uppsala, Moscow and IBA or it may be range shifting as for the PSI beam. The scan speed for this axis is a factor of approx. 25 times slower. The third and slowest motion is done either by range shifting (Uppsala), energy variaton (Moscow, also planned for GSI) rotational movement of the bending magnet (IBA) or movement of the patient (PSI). C o m m o n to all these solutions is the need for a fast and reliable monitoring and control system.
Dynamic collimators Conformation therapy in three dimensions can also be performed with fixed range modulation. In is then necessary to use a compensating bolus to shape the dose at the distal surface of the target volume and to use a multi-leaf dynamic collimator to shape the field size at the proximal surface of the tumor (Ludewigt et al. 1991).
Clinical implications of the delivery technique The relevance of the clinical results of the application technique is still under debate. No clinical comparison of fixed range modulation technique with three
227 la
o
Fig. 4. a Target volume cross sections for a tumor which has been treated with pion conformation therapy, b and e CT cross sections at the levels I and II for this patient with isodose lines of 95, 85, 65, 45 and 25% simulated for a conformal single port irradiation with protons. In slice c all the tissues in the entrance region of the beam would be included in the 95% isodose for fixed range modulation techniques
dimensional conformation therapy has been possible up to now. The only way to estimate the gain of the improved dose distribution is by calculating dose distributions for various techniques and comparing the results either in the f o r m of isodose lines or calculating integral doses or dose volume histograms for specific tissues. Depending on the organ at risk, one m a y also choose to compare the m a x i m u m dose delivered to a certain minimal volume element. To fully exploit the potential of conformation therapy, m o r e data relating dose volume histograms to complication rate for different tissues has to be compiled or determined as reported in the workshop by Tatzuzaki et al. (Tatzuzaki et al. 1991). These calculations are done either for geometrical shapes of target volumes or for specific patients. The conclusions will strongly depend on treatment site, complexity of the shape of the target volume as well as the critical normal tissue under consideration. Several papers have estimated the difference in cure rate to be expected from conformation radiotherapy c o m p a r e d to fixed range modulation techniques. Comparisons were based on either assumed geometrical shapes of target volumes (Goitein and Chen 1983) or on specific cases which have been planned for different treatment modalities (Urie and Goitein 1989). The gain o f variable range modulation versus fixed modulation turns out to be of the order of up to 15% integral dose reduction for ellipsoidal target volumes for various light ions or protons. The study which used actual cases for intercomparison (Urie and Goitein 1989) came to the conclusion that the
228 gain was again on the same order of magnitude however, much smaller than for the transition from photon treatment to protons with fixed modulation. The advantage of conformation therapy may not be very large for the dose distributions for small target volumes. The gain in general of conformation therapy is probably significantly underestimated if only cases which are treated today with photons with conventional techniques are analyzed. An example of conformation therapy with pions may illustrate that substantially more complex target volumes are defined if the treatment possibility is given (Fig. 4). Protons with their sharper dose fall-off applied with an isocentric gantry, would further increase the spectrum of treatable volumes compared to pions. Another significant advantage of conformed treatment compared with fixed range modulation treatment may be the fact that equally favorable dose distributions can be reached with less treatment ports (Daftari 1991) making the treatment more practical and more economical. Gantries for dynamic proton therapy can be made considerably smaller than for scattered beam therapy which may facilitate the installation in a hospital environment.
Patient or organ movement during treatment
Patient and organ movement have to be taken into account in every radiotherapy treatment but is clearly more important if the goal is a precision treatment and if the application technique is dynamic, independent of beam widening or conformation technique. The relevance of the relative movement depends on the frequency, direction and size of the movement of the tissue as well as the speed and direction of the dose spot and its size. It affects the dose distribution in the target volume as well as the dose fall-off at the edge of the target and the dose to adjacent normal tissues (Levin et al. 1988). The coverage of the target volume is accounted for by choosing a planning target volume which takes the movement into account. More critical is the dose inhomogeneity inside the target volume which may lead for small spot sizes to intolerable dose deviations, socalled hot or cold spots (Phillips et al. 1990).
Discussion
The interest for heavy charged particles for radiotherapy today is related primarily to the capacity of shaping the physical dose distribution. For this, the heavier the particle, the smaller the multiple scattering and the sharper the lateral dose fall-off. Distally the heavier ions demonstrate an increasing tail in the depth dose produced by light fragments, an optimal mass of the particle is considered to be that of carbon or oxygen. The acceleration of light ions to energies high enough to penetrate anywhere in the body needs larger accelerators, because of the stiffness of the particles. Where for protons and He, the dose distribution characteristics were the only incentive, light ions and pions promised additional advantages through their higher ionization density and the corresponding higher biological efficiency. For some of these particles the high LET portion was even expected to be limited to the target volume whereas the normal tissue in the entrance region experiences low LET radiation. The biological advantage of high LET in addi-
229
tion to the dose distribution is considered to be important in 10 to 20% or even more of the patients, judging from the neutron therapy results (Wambersie 1988). Light ion irradiation offers the advantage of verification of the penetration of the particles by substituting the therapy ion by a positron emitting nuclide of almost the same mass (Enghardt et al. 1991). The new facilities and technique will be compared to the best available technique with photons, including new developments like conformation therapy or combinations of external irradiation with brachytherapy and it is therefore of utmost importance to make optimal use of all the characteristics of the heavy charged particles. Scattering techniques have been improved to more efficiently use the particles accelerated. Their advantage is a lower sensitivity on the time structure of the proton or light ion beam than for the dynamic techniques. The reduced flexibility in shaping the dose distribution in three dimensions may be less important for small or relative regularly shaped target volumes. Dynamic delivery techniques result in higher flexibility of dose shaping. Dependent on the specific technique, they are expected to use minimal or no individual hardware such as collimators and boli. The ability to shape the dose distribution in three dimensions to the target volume results in the potential of reducing radiation burden to normal tissues and hence increasing the therapeutic gain (Goitein and Chen 1983; Urie and Goitein 1989). In common with all dynamic application techniques they may be sensitive to movements of the patient or organs during treatment (Levin et al. 1988; Phillips et al. 1990). Dynamic application techniques need more stringent safety precautions. The availability of particles with deep enough range and more flexible application techniques will widen the spectrum of indications which significantly profit from heavy charged particle therapy. Voxel scanning opens possibilities which cannot yet be exploited, as it will be perfectly feasible to shape the dose distribution even inside the target volume if new insight into tumor growth pattern or tumor cell viability asks for it. Precise conformation therapy will be of increasing importance when more efficient therapies for scattered tumor cells will be available. Tighter target volumes might not immediately improve the treatment results, a period of adaptation of the treatment strategy according to the new experience gained might be needed to optimize the therapy. For some indications, safety margins may need to be altered, for others an additional regional therapy may be chosen to control local spread of tumor cells. More specific diagnostic techniques as MRI, PET or diagnostics with labelled antibodies may help to optimize the therapy.
References Blattmann H (1979) Therapy planning and dosimetry for the pion applicator at the Swiss Institute for Nuclear Research (SIN). Radiat Environ Biphys 16:205-209 Blattmann H, Coray A, Pedroni E, Greiner R (1990) Spot scanning for 250 MeV protons. Strahlenther Onkol 166: 45-48 Chuvilo IV, Goldin LL, Khoroshkov VS et al. (1984) ITEP Synchrotron proton beam in radiotherapy. Int J Radiat Oncol Biol Phys 10:185-195 Chu WT, Curtis SB, Llacer J, Renner TR Sorensen RW (1985) Wobbler facility for biomedical experiments at the Bevalac. IEEE Trans Nucl Sci NS-32:3321-3323
230 Chu WT, Renner TR, Ludewig BA (1988) Dynamic beam delivery for three-dimensional conformal therapy. Proceedings of the EULIMA Workshop on the potential value of light ion beam Therapy. Chauvel P, Wambersie A (eds) Nice November 3-5, 295-328, EUR 12165 EN Daftari I (1991) Private communication Enghart W, Fromm WD, Manfrass P, Pawelke J, Sobiella M, Geissel H, Schardt D, Keller H, Kraft G, Magel A, Mfinzenberg G, Nickel F, Pffitzner M, Voss B, Sastri C (1991) In-beam PET imaging of implanted positron emitting ions. Extended Abstracts, Fourth Workshop on Heavy Particles in Biology and Medicine, GSI-91-29 Report September ISSN 0171-4546, G3 von Essen CF, Blattmann H, Bodendoerfer G, Mizoe J, Pedroni E, Walder E, Zimmermann A (1985) The Piotron: II. Methods and initial results of dynamic pion therapy in phase II studies. Int J Radiat Oncol Biol Phys 11:217-226 Farley FJM, Carli C (1991) EULIMA beam delivery. Proceedings of the Proton Radiotherapy Workshop at PSI, Feb 28, March 1, PSI, Villigen Switzerland, PSI-Report 111, pp 21-24 Fukumoto S, Endo K, Muto K, Akisada M, Kitagawa T, Inada T, Tsujii H, Maruhashi A, Hayakawa Y, Takada Y, Tada J, Tsukuba medical proton synchrotron. Proc Int Heavy Particle Therapy Workshop (PTCOG, EORTC, ECNEU) Sept 18-20, 70-74, 1989, Blattmann H (ed). PSI-Report Nr. 69 Goitein M, Chen TY (1983) Beam scanning for heavy charged particle radiotherapy. Med Phys 10:831-840 Gottschalk B, Koehler AM, Sisterson JM, Wagner MS (1991) The case for passive beam spreading. Proceedings of the Proton Radiotherapy Workshop at PSI, Feb 28, March 1, PSI, Villigen Switzerland, 50-53, PSI-Report 111 Graffman S, Brahme A, Larsson B (1985) Proton radiotherapy with the Uppsala cyclotron. Experience and plans. Strahlentherapie 161:764-770 Grusell E et al. (1991) The proton therapy project of the Swedberg Laboratory in Uppsala. Proceedings of the Proton. Radiotherapy Workshop at PSI, Feb 28, March 1, PSI, Villigen Switzerland, 43-45, PSI-Report 111 Haberer Th, Becher W, B6hne D, Kraft G, Langenbeck B, Lenz G, Loos D, R6sch W, Schardt D, Steiner R, Stelzer H (1991) Magnetic scanning system for heavy ion therapy. Extended Abstracts, Fourth Workshop on Heavy Particles in Biology and Medicine, GSI-9129 Report September ISSN 0171-4546, G2 Hirao Y (1988) HIMAC project at NIRS. Proceeding of the EULIMA Workshop on the potential value of light ion beam Therapy. Chauvel P, Wambersie A (eds) Nice November 3-5, 381-397, EUR 12165 EN Jongen Y (1991) Status report of IBA's proton therapy program. Proceedings of the Proton Radiotherapy Workshop at PSI, Feb 28, March 1, PSI, Villigen Switzerland, 43-45, PSIReport 111 Kanai T, Kawachi K, Matsuzawa H, Inada T (1983) Three-dimensional beam scanning for proton therapy. Nucl Instrum Methods 214:491-496 Kawachi K, Kanai T, Endo M, Hirao Y, Tsunemoto H (1989) Radiation oncological facilities of the HIMAC. J Jpn Soc Ther Radiol Oncol 1:19-29 Khoroshkov VS, Goldin LL, Onosovsky KK, Klenov GI (1991) Soviet Project of proton therapy facility with several treatment rooms. Proceedings of the Proton Radiotherapy Workshop at PSI, Feb 28, March 1, PSI, Villigen Switzerland, 37 42, PSI-Report 111 Koehler AM, Schneider RJ, Sisterson JM (1977) Flattening of proton dose distributions for large-field radiotherapy. Med Phys 4:297-301 Kraft G, Becher W, Blasche K, B6hne D, Fischer B, Gademann G, Geissel H, Haberer Th, Klabunde J, Kraft-Weyrather W, Langenbeck B, Mfinzenberg G, Ritter S, R6sch W, Schardt D, Stelzer H, Schwab Th. GSI-91-15, Preprint Kurihara D, Suwa S, Tachikawa A, Takada Y, Takikawa K (1983) A 300-MeV Proton beam line with energy degrader for medical science. Japanese J Appl Phys 22:1599-1605 Larsson B (1988) Proton Therapy: Review of the Clinical Results. Proceeding of the EULIMA Workshop on the potential value of light ion beam Therapy. Chauvel P, Wambersie A (eds) Nice November 3-5, 139-164, EUR 12165 EN Lawrence JH (1957) Proton irradiation of the pituitary. Cancer 10:795-798 Lawrence JH, Tobias CA, Born JL et al. (1962) Heavy-particle irradiation in neoplastic and neurologic disease. J Neurosurg 19 : 717-722
231 Levin CP, Gonin R, Wynchank S (•988) Computed limitations of spot scanning for therapeutic proton beams. Int J Biomed Comput 23 : 33-4• Ludewigt BA, Chu WT, Renner TR (•99•) 3-D conformal dose delivery with ion beams. Extended Abstracts, Fourth Workshop on Heavy Particles on Biology and Medicine, GSI9Â-29 Report September ISSN 0171-4546 Minakova Ye I, Twenty Years Clinical Experience of Narrow Proton Beam Therapy in Moscow. Proc Int Heavy Particle Therapy Workshop (PTCOG, EORTC, ECNEU) Sept 18-20, 154-157, 1989, Blattmann H (ed) PSI-Report Nr. 69, July •990 Munzenrider JE, Austin-Seymour M, Blitzer P J, Gentry R, Goitein M, Gragoudas ES, Johnson K, Koehler AM, McNulty P, Moulton G, Osborne E, Seddon JM, Suit HD, Urie M, Verhey L J, Wagner M (1985) Proton therapy at Harvard. Strahlentherapie •6•:756-763 Pedroni E, Blattmann H, Salzmann M, Walder E, Crawford JF, Dietlicher R, Cordt I, Sch~ippi K, von Essen CF, Perret C (1983) Treatment planning and dosimetry for the pi-meson therapy facility at SIN. Proc Int Conf on Application of Physics to medicine and Biology. Alberi G, Bajzer Z, Baxa P (eds) World Scientific, Singapore, pp 1-25 Pedroni E, Bacher R, Blattmann H, Boehringer T, Coray A, Egger E, Phillips M, Scheib S (1990) The 200 MeV Proton Therapy Project at PSI: A Status Report Proc Int Heavy Particle Therapy Workshop (PTCOG, EORTC, ECNEU) Sept 18-20, 1-8, •989, Blattmann H (ed) PSI-Report Nr 69, July Phillips M, Pedroni E, Bacher R, Blattmann H, Boehringer T, Coray A, Scheib S (1990) Charged particle spot scanning method: Effect of motion on dose homogeneity. Proceedings of the EPAC Meeting, Nice, June 11-16 Sisterson J (•99•) Particles No 8, PTCOG Newsletter. Sisterson J (ed) Harvard Cyclotron Lab Cambridge MA 02•38, USA Slater JM, Miller DW, Arachambeau JO (1988) Development of a hospital-based proton beam treatment center. Int J Radiat Oncol Biol Phys •4:76•-775 Suit H, Goitein M, Munzenrider J, Verhey L, Blitzer P, Gragoudas E, Koehler AM, Urie M, Gentry R, Shipley W, Urano M, Duttenhaver J, Wagner M (•982) Evaluation of the clinical applicability of proton beams in definitive fractionated radiation therapy. Int J Radiat Oncol Biol Phys 8:2199-2205 Tatsuzaki H, Arimoto T, Uwamimo Y, Nakamura T, Yaguchi M, Inada T (1991) Partial volume irradiation on murine leg by y 30 MeV proton beam. Extended Abstracts, Fourth Workshop on Heavy Particles in Biology and Medicine, GSI-91-29 Report, ISSN 0171-4546, G5 Tsunemoto H, Morita S, IshikawaT, Furukawa S, Kawachi K, Kanai T, Ohara H (•985) Proton therapy in Japan. Radiat Res 104:S-235-S-243 Urie M, Goitein M (•989) Variable versus fixed modulation of proton beams for treatments in the cranium. Med Phys 16:593-601 Wambersie A (1988) The future of High-LET radiation in cancer therapy. Justification of the heavy-ion therapy programs. Proceedings of the EULIMA Workshop on the potential value of light ion beam Therapy. Chauvel P, Wambersie A (eds) Nice November 3-5, XIX-LIII, EUR 12165 EN
Radiation and Environmental Biophysics © Springer-Verlag 1992
Beam delivery systems for charged particles* H. Blattmann PSI Paul Scherrer Institute, Abteilung Strahlenmedizin,CH-5232 Villigen PSI, Switzerland Received December 12, 1991 / Accepted in revised form February 26, 1992
Summary. Heavy charged particle therapy, started at research institutes three decades ago, is now on the verge of entering a clinical phase. This phase has resulted from the evolution and development of various beam delivery systems and techniques with existing research accelerators and with newly built accelerators. For the first thirty years, heavy charged particle therapy was administered with a fixed horizontal beam line. In 1991, the first treatment with an isocentric gantry was administered. The development of the isocentric gantry, the newest beam delivery system, and clearly a consequence of all the experience gained at the earlier facilities has many advantages. It offers advantageous physical properties of the particles as well as being equal in the flexibility of dose delivery to the modern photon radiotherapy gantries. Introduction For the last three decades, heavy charged particles, protons, light ions up to argon and pions, have been considered ideal for radiotherapy especially for treatment of well delineated lesions. The first 30 patients were treated with protons from 1955 to 1957 at Lawrence Berkeley Laboratory (Lawrence 1957; Lawrence et al. 1962). In 1957 Uppsala, Sweden, started a proton therapy program (Larsson 1988). The use of heavy charged particles has been limited to few centers up to now due to the large and expensive accelerators needed. All present projects except for one, are based on machines built for physics research experiments and most of the therapy projects continue to run in parallel with physics research. This fact has not only limited the number of patients treated, but has also influenced the application techniques used in particle therapy, since all the beam lines were fixed and horizontal. In the future, however, * Paper given on the fourth workshop on "HeavyCharged Particles in Biologyand Medicine" GSI, Darmstadt, FRG, September 23-25, 1991
220 Table 1. Patients treated with heavy charged particles by middle of 1991 World wide charged particle patient totals July 1, 1991 Berkeley 184 CA. USA Berkeley CA. USA Uppsala Sweden Harvard MA. USA Dubna USSR Moscow USSR Los Alamos NM. USA Leningrad USSR Berkeley CA. USA Chiba Japan TRIUMF Canada PSI Switzerland Tsukuba Japan PSI Switzerland Dubna USSR Uppsala Sweden Clatterbridge England Loma Linda CA. USA Louvain-la-Neuve Belgium
p He p p p p p heavy p n n p p p p p p p n ions protons TOTAL
1955 57 since 1957 195%76 since 1961 1964-74 since 1969 1974-82 since 1975 since 1975 since 1979 smce 1979 since 1980 since 1983 smce 1984 since 1987 since 1988 since 1989 since 1990 since 1991
30 2054 73 5268 84 2135 230 685 433 65 253 478 229 1035 13 20 158 19 6 961 2487 9820 13268
this is likely to change. Clinical facilities within research institutes and hospital based facilities, for protons and light ions, are being planned and/or under construction in numerous places in the world, and therefore b e a m line designs will be optimized for medical use. New delivery techniques are under investigation for routine operation in a clinical environment in view of the increasing capabilities of diagnostics and hence increased expectations, as well as computer control. Initially, for treatment of small lesions in the brain, 200 MeV p r o t o n pencil beams were cross fired to yield a small volume of high dose with sharp edges to the t u m o r volume (Larsson 1988). The same technique was later used in Leningrad with p r o t o n beams of much higher energies and, therefore, penetration. For this technique, protons produce a much better dose distribution than photons due to the sharp lateral dose fall off, therefore, giving a sharper penumbra in the area of overlapping beams. These thirty years of development and experience from all the charged particle centers in the world paved the way for the newest p r o t o n beam delivery system - the isocentric gantry. This gantry at L o m a Linda University Medical Center, USA, is also the first hospital based beam delivery system for charged particle therapy in the world. Treatments started operation in 1991 (Slater et al.
1988). In conclusion, it can be said that there has been substantial experience and development in charged particle patient treatment over the last three decades,
221 TREATMENTVOLUMESHAPING BEAMWIDENING
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Fig. 1. Beam delivery systems. The treatment volume can be fitted in two dimensions in the beams eye view to the shape of the target volume by various combinations of beam widening and depth control techniques. As the depth modulation is uniform over the whole field, some of the volume elements outside the target volume are exposed to the full target volume dose. The relevance of this unwanted exposure is reduced by multi-port irradiation. For conformation therapy the dose distribution is shaped in three dimensions for each port. For multi-port irradiation this results in an optimal reduction of the integral dose. With help of a multi-leaf collimator and a bolus to fit the distal shape of the dose distribution, the two dimensional shaping of the beam cross section can be developed into a three dimensional shaping. The same result can be achieved directly, without patient specific hardware, by voxel or spot scanning despite all is entering Minakowa et al. 1985)
the hard work and difficult conditions is has encountered, and it a new decade o f growth and development. (Chuvilo et al. 1984; et al. 1990; Munzenrider et al. 1985; Suit et al. 1982; Tsunemoto (Table 1).
Beam delivery Beam delivery can be divided into two categories - b e a m widening techniques and conformal techniques. Beam widening techniques give a homogeneous dose distribution in a field of the appropriate size and shape, combined with range modulators and shaped collimators to achieve a flat, regularly shaped high dose volume enclosing the target volume. For an individual beam it is unavoidable that also some adjacent normal tissue is included in the high dose volume. Conformal techniques give three dimensionally shaped high dose distributions conformal to the target volume (Figs. 1 to 3).
Beam widening techniques
Scattering techniques For the first treatments, small volumes were irradiated by geometrically overlapping multiple proton beams in the plateau region of their depth dose profile thereby not making use of the well defined range of the heavy charged particles. The knowledge of the exact integrated stopping power along the entire track
222 Beam delivery techniques
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of the particle from the surface to the target volume was not within easy reach before the availability of CT scanners and not necessary for the cross-over technique. The first center to use the Bragg peak was Lawrence Berkeley Laboratory in 1960 (Lawrence et al. 1962). To irradiate large volumes, the p r o t o n beams from the accelerator have to be defocussed or scattered to widen the useful beam cross section. This technique gives bell shaped b e a m profiles in which the central flat region is used for treatment, and results in a large fraction of the particles being lost because the tails of the profile are cut by the collimators. To improve the use of the particles, the double scattering technique was developed at the H a r v a r d Cyclotron L a b o r a t o r y (Koehler et al. 1977). While single scattering results in a dose distribution with a high intensity in the center of the irradiated field, a second scatterer placed at a well defined distance upstream reduces the n u m b e r of particles in this central region and an annulus, arranged around the center piece, scatters particles which otherwise would fall outside the useful area into the fall-off region of the dose. For a specific geometrical arrangement of first and second scatterer and target volume, and with optimized scatterer thickness and diameter, this results in a circular dose distribution with a larger radius and a reduced loss of primary particles. This technique has recently been further improved (Gottschalk et al. 1991), instead of a central scatterer and a ring, a contoured scatterer which is thick in the center
223
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Fig. 3a-h. Illustration of the principle of different scanning techniques. For raster scanning (a) and (b) and also for wobbling (e) the beam is scanned on a regular pattern with constant velocity, independent of the shape of the target volume. With individually prepared collimators the fractions of the path of the pencil beam outside the area of interest are cut off (dashed lines)• Fixed range modulation leads to uniform depth of the high dose volume, exposing substantial areas outside the target volume (g). With a multi leaf collimator this area can be reduced. Discrete voxel or spot scanning (d) and (e) deposite the full dose only inside the target volume• The dose per spot is optimized to yield uniform dose inside the target volume while the dose outside is minimized• For variable scan velocity a homogeneous dose distribution is achieved by uninterrupted scanning (f). A prerequisite is a stable beam intensity. For (d), (e) and (f) the depth of the target volume is covered by variing the range in steps, no bolus is needed. These techniques are particularly adventageous for large irregularly shaped target volumes and gets thinner with increasing radius is now used. This scatterer made of lead is combined with a plastic piece with radially dependent thickness which makes energy loss of the particle independent of the radius. Further, placing all the scattering and range modulation elements upstream, results in an increase in efficiency of approximately 46% and a sharper dose fall off. The dose area is still circular and must be larger in diameter than the largest projection of the target contour. A relative long drift distance between scatterer and patient is necessary. Scattering techniques have been predominantly used for the patient treatments with protons by all centers, with the only exception of a few patient at N I R S in Japan, who have been treated with a scanned b e a m for superficial lesions (Kanai et al. 1983). Differences between the p r o t o n treatment facilities exist mainly in the energy ranges available. While Harvard, Uppsala, and Moscow have energies in the range of 160-200 MeV, some facilities, especially the newer ones, can only treat ocular m e l a n o m a or superficial tumors with low energy p r o t o n beams of less than 100 MeV. Although treatments with light ions were initially done with scattered beams at Lawrence Berekely Laboratory, the treatments for the past 6 years have been with a dynamic b e a m widening technique (Chu et al. 1985; Chu et al. 1988).
224 For ions as well as for protons, most of the available beam lines are horizontal. Vertical beam lines were introduced in Japan, at NIRS for low energy protons of 70 MeV and at Tsukuba for treatment of deep seated tumors with energies from 150 to 300 MeV, produced by degrading a 500 MeV beam (Kurihara et al. 1983). At Tsukuba, a scatterer and ridge filters as well as a dynamic range modulator are used. Besides a block-collimator a multi leaf collimator is also available. Even for their new hospital based facility the present design includes fixed beams only: one room with both a vertical and a horizontal beam line and one room with a vertical beam line only (Fukumoto et al. 1990). The same philosophy is also being pursued at the HIMAC project, planned to begin operation in 1993, at Chiba, Japan where a dedicated heavy ion therapy facility is under construction (Kawachi et al. 1989). Featuring a double synchrotron as the accelerator, three treatment rooms are provided with vertical and horizontal beam lines. One of the rooms will have both a vertical and horizontal beam focused isocentrically. Each of the beam lines, initially, will use a scattering system with the possibility of using a dynamic application technique in the future. The proton facility at the hospital of Loma Linda is equipped with the widest spectrum of proton beams. Besides one room with two horizontal beam lines, one for eye treatment and one for small volume cranial lesions, three rooms have isocentric gantries installed (Slater et al. 1988). At the present time one gantry is in service and the other two will be operational soon. All three gantries are identical and have a diameter of more than 12 m. They are equipped with a scattering beam delivery system, which at a later stage may be upgraded to provide raster scanning or conformation therapy.
Dynamic beam widening techniques Wobbling. A new, dynamic technique has been developed at Berkeley for heavy ion beams at the BEVALAC. By wobbling the particles of a beam pulse are smeared out on a circular ring by use of a pair of dipole magnets with sinoidal fields with a phase difference of 90 °. Several circles of optimized radii and doses are added dependent on the field size to be achieved (Fig. 3 c). Flat fields of up to 30 cm diameter have been reached with less than 5% dose variation. This technique results in economizing the particles, as double scattering, but it depends strongly on constant pulse intensities or on large numbers of pulses for each ring. This system has been used for routine radiotherapy at Lawrence Berkeley Laboratory since 1985 (Chu et al. 1985). Besides the higher efficiency, wobbling has additional advantages of importance for light ions. Wobbling uses less material in the beam upstream of the patient and therefore substantially reduces the adverse effects of fragmentation. This results in a sharper dose fall off with depth, a beam with smaller tails, and a higher RBE in the distal areas of the treatment volume. Less contamination with lighter fragments with a longer range also results in a lower integral dose for the same target volume and target dose. Raster scanning. Raster scanning, first used for protons at Uppsala in the sixties (Graffman et al. 1985) and developed later at Berkeley for heavy ions (Chu et al. 1988), is a similar, but more flexible technique to yield large homogeneous
225 dose distributions. Instead of scanning on circles, the scans are performed on a rectangular grid with a high frequency in one direction and a lower frequency in the direction perpendicular to it (Fig. 3 a and b). Rectangular fields of different shapes can be scanned in this way giving a field more closely related to the target volume projection, and, therefore, further reducing the losses. Up to 40 × 40 cm 2 fields can be scanned at Berkeley with scanning rates of 40 and I Hz for the two axes respectively. The final shape of the dose field is tailored by an individual collimator, cutting unwanted beam areas. As with wobbling, raster scanning has additional advantages for light ions compared to scattering due to the reduced fragmentation. Both wobbling and raster scanning operate with fixed range modulation either with a ridge filter or a rotating absorber wheel or with a combination of both. This results in a dose distribution which can at best be conformed to the target volume contour distally, by using a patient specific compensator bolus. With this technique, normal tissue is exposed to the same dose as the target in the proximal area (Fig. 3g). In principle, this could be avoided by the use of a multi-leaf collimator, which has been mentioned by several authors but not yet been introduced in practice.
Conformation therapy Spot or voxel scanning Conformation therapy is the tailoring of the high dose volume in three dimensions to the target volume. Various slightly different techniques and different names have been proposed by several centers. It is often referred to as spot, pixel or voxel scanning at PSI whereas at GSI it is called raster scanning (Fig. 3 d to f and h). These technique can be regarded as further refinement of the raster scan described above. Instead of irradiating regularly shaped areas, mostly rectangles, the scans are covering only the cross section of the target volume including a margin around it and this is achieved without the need of individual collimators. This can either be accomplished by depositing dose to discrete volumes (Fig. 3 d and e) or by scanning a small beam with a variable speed (Fig. 3 f). NIRS has developed this technique for 70 MeV protons of the range of approx. 3 cm where the aim was primarily to save range of the protons due to reduced energy loss in the scatterer (Kanai et al. 1983). For deep seated tumors the first patients have been treated with a three dimensional conformation therapy with pions in the Piotron at PSI, Villigen (Blattmann 1979; Pedroni et al. 1983; Von Essen et al. 1985). Almost 500 patients since 1982 have been treated for various indications in the abdomen and in the head with this technique. Spot scanning has been developed for treatment with the Piotron to minimize dose to normal tissue. The aim was not to rely purely on the biological advantage of the secondaries of the pion capture in tissue but to optimize in addition the physical dose distribution as far as possible with the relatively light particles. Dose spots in the Piotron are formed by overlapping the stopping region of 60 converging beams entering the treatment chamber in a vertical plane. The patients contour is fitted to a cylinder with tissue equivalent material and the patient placed in a couch
226 on the axis of the treatment device inside a water bolus. It is possible to shape the distribution of the high dose volume in three dimensions to the contour of the target volume. The scanning is performed in the Piotron by translation of the patient in three axes. The limitations of the dose distributions of the Piotron are the gradual fall off of dose to all sides. Due to the relatively large range necessary, the straggling of the pions contributes substantially to the spot size, resulting in beam profiles on the axis of the Piotron of 5.5 cm F W H M in all three directions, which in turn results in a gradual, uniform dose fall of to all directions, leaving no flexibility to trade a sharp fall-off in the direction of a critical normal tissue for a shallow fall-off in a less important area. For 200 MeV protons at PSI (Blattmann et al. 1990; Pedroni et al. 1990) and light ions at GSI (Haberer et al. 1991 ; Kraft et al. 1991) magnetic scanning of the beam has been tested. Similar techniques are under development or proposed at Uppsala, Moscow and by IBA as well as for E U L I M A , the European light in medical accelerator (Farley and Carli 1991 ; Grusell et al. 1991 ; Jongen 1991 ; K h o r o s h k o v et al. 1991). Characteristic for all these techniques is, that they irradiate small volume elements with a narrow beam scanned in three dimensions. To be able to shape the dose according to the target volume well enough, approximately ten thousand voxels have to be irradiated per liter volume, As all the projects aim at treatment times similar to those in contemporary photon therapy, i.e. a few minutes, these spots have to be delivered in small fractions of a second. A fast control of the beam is therefore necessary to either vary the scan speed of the fastest axis accordingly or to switch the beam on and off. Depending on the duty cycle of the accelerator this may be a requirement which is hard to achieve. The fastest scan axis for all of the projects except for the IBA facility is magnetic scanning. The scan speed of this axis is on the order to 1000 cm/s or much more for the synchrotron planned at Moscow with a duty cycle in the few percent region. The second axis may be, again, magnetic scanning as for GSI, Uppsala, Moscow and IBA or it may be range shifting as for the PSI beam. The scan speed for this axis is a factor of approx. 25 times slower. The third and slowest motion is done either by range shifting (Uppsala), energy variaton (Moscow, also planned for GSI) rotational movement of the bending magnet (IBA) or movement of the patient (PSI). C o m m o n to all these solutions is the need for a fast and reliable monitoring and control system.
Dynamic collimators Conformation therapy in three dimensions can also be performed with fixed range modulation. In is then necessary to use a compensating bolus to shape the dose at the distal surface of the target volume and to use a multi-leaf dynamic collimator to shape the field size at the proximal surface of the tumor (Ludewigt et al. 1991).
Clinical implications of the delivery technique The relevance of the clinical results of the application technique is still under debate. No clinical comparison of fixed range modulation technique with three
227 la
o
Fig. 4. a Target volume cross sections for a tumor which has been treated with pion conformation therapy, b and e CT cross sections at the levels I and II for this patient with isodose lines of 95, 85, 65, 45 and 25% simulated for a conformal single port irradiation with protons. In slice c all the tissues in the entrance region of the beam would be included in the 95% isodose for fixed range modulation techniques
dimensional conformation therapy has been possible up to now. The only way to estimate the gain of the improved dose distribution is by calculating dose distributions for various techniques and comparing the results either in the f o r m of isodose lines or calculating integral doses or dose volume histograms for specific tissues. Depending on the organ at risk, one m a y also choose to compare the m a x i m u m dose delivered to a certain minimal volume element. To fully exploit the potential of conformation therapy, m o r e data relating dose volume histograms to complication rate for different tissues has to be compiled or determined as reported in the workshop by Tatzuzaki et al. (Tatzuzaki et al. 1991). These calculations are done either for geometrical shapes of target volumes or for specific patients. The conclusions will strongly depend on treatment site, complexity of the shape of the target volume as well as the critical normal tissue under consideration. Several papers have estimated the difference in cure rate to be expected from conformation radiotherapy c o m p a r e d to fixed range modulation techniques. Comparisons were based on either assumed geometrical shapes of target volumes (Goitein and Chen 1983) or on specific cases which have been planned for different treatment modalities (Urie and Goitein 1989). The gain o f variable range modulation versus fixed modulation turns out to be of the order of up to 15% integral dose reduction for ellipsoidal target volumes for various light ions or protons. The study which used actual cases for intercomparison (Urie and Goitein 1989) came to the conclusion that the
228 gain was again on the same order of magnitude however, much smaller than for the transition from photon treatment to protons with fixed modulation. The advantage of conformation therapy may not be very large for the dose distributions for small target volumes. The gain in general of conformation therapy is probably significantly underestimated if only cases which are treated today with photons with conventional techniques are analyzed. An example of conformation therapy with pions may illustrate that substantially more complex target volumes are defined if the treatment possibility is given (Fig. 4). Protons with their sharper dose fall-off applied with an isocentric gantry, would further increase the spectrum of treatable volumes compared to pions. Another significant advantage of conformed treatment compared with fixed range modulation treatment may be the fact that equally favorable dose distributions can be reached with less treatment ports (Daftari 1991) making the treatment more practical and more economical. Gantries for dynamic proton therapy can be made considerably smaller than for scattered beam therapy which may facilitate the installation in a hospital environment.
Patient or organ movement during treatment
Patient and organ movement have to be taken into account in every radiotherapy treatment but is clearly more important if the goal is a precision treatment and if the application technique is dynamic, independent of beam widening or conformation technique. The relevance of the relative movement depends on the frequency, direction and size of the movement of the tissue as well as the speed and direction of the dose spot and its size. It affects the dose distribution in the target volume as well as the dose fall-off at the edge of the target and the dose to adjacent normal tissues (Levin et al. 1988). The coverage of the target volume is accounted for by choosing a planning target volume which takes the movement into account. More critical is the dose inhomogeneity inside the target volume which may lead for small spot sizes to intolerable dose deviations, socalled hot or cold spots (Phillips et al. 1990).
Discussion
The interest for heavy charged particles for radiotherapy today is related primarily to the capacity of shaping the physical dose distribution. For this, the heavier the particle, the smaller the multiple scattering and the sharper the lateral dose fall-off. Distally the heavier ions demonstrate an increasing tail in the depth dose produced by light fragments, an optimal mass of the particle is considered to be that of carbon or oxygen. The acceleration of light ions to energies high enough to penetrate anywhere in the body needs larger accelerators, because of the stiffness of the particles. Where for protons and He, the dose distribution characteristics were the only incentive, light ions and pions promised additional advantages through their higher ionization density and the corresponding higher biological efficiency. For some of these particles the high LET portion was even expected to be limited to the target volume whereas the normal tissue in the entrance region experiences low LET radiation. The biological advantage of high LET in addi-
229
tion to the dose distribution is considered to be important in 10 to 20% or even more of the patients, judging from the neutron therapy results (Wambersie 1988). Light ion irradiation offers the advantage of verification of the penetration of the particles by substituting the therapy ion by a positron emitting nuclide of almost the same mass (Enghardt et al. 1991). The new facilities and technique will be compared to the best available technique with photons, including new developments like conformation therapy or combinations of external irradiation with brachytherapy and it is therefore of utmost importance to make optimal use of all the characteristics of the heavy charged particles. Scattering techniques have been improved to more efficiently use the particles accelerated. Their advantage is a lower sensitivity on the time structure of the proton or light ion beam than for the dynamic techniques. The reduced flexibility in shaping the dose distribution in three dimensions may be less important for small or relative regularly shaped target volumes. Dynamic delivery techniques result in higher flexibility of dose shaping. Dependent on the specific technique, they are expected to use minimal or no individual hardware such as collimators and boli. The ability to shape the dose distribution in three dimensions to the target volume results in the potential of reducing radiation burden to normal tissues and hence increasing the therapeutic gain (Goitein and Chen 1983; Urie and Goitein 1989). In common with all dynamic application techniques they may be sensitive to movements of the patient or organs during treatment (Levin et al. 1988; Phillips et al. 1990). Dynamic application techniques need more stringent safety precautions. The availability of particles with deep enough range and more flexible application techniques will widen the spectrum of indications which significantly profit from heavy charged particle therapy. Voxel scanning opens possibilities which cannot yet be exploited, as it will be perfectly feasible to shape the dose distribution even inside the target volume if new insight into tumor growth pattern or tumor cell viability asks for it. Precise conformation therapy will be of increasing importance when more efficient therapies for scattered tumor cells will be available. Tighter target volumes might not immediately improve the treatment results, a period of adaptation of the treatment strategy according to the new experience gained might be needed to optimize the therapy. For some indications, safety margins may need to be altered, for others an additional regional therapy may be chosen to control local spread of tumor cells. More specific diagnostic techniques as MRI, PET or diagnostics with labelled antibodies may help to optimize the therapy.
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