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A technique for fractionated stereotactic radiotherapy in the treatment of intracranial tumors
1111 J Au&mm Oncda~ Btol Phw Vol Pnnted in the U S A. All rights reserved.
0360.3016193 $6.00 + .oO Copyright 0 I993 Pergamon Press Ltd.
21, pp. 1225-1230
??Technical Innovations and Notes
A TECHNIQUE
FOR FRACTIONATED STEREOTACI’IC RADIOTHERAPY TREATMENT OF INTRACRANIAL TUMORS
IN THE
ERVIN B. PODGORSAK, PH.D., F.C.C.P.M.,* LUIS SOUHAMI, M.D.,?_ JEAN-LOUIS CARON, M.D.,+ MARINA PLA, M.Sc., M.C.C.P.M.,* BRENDA CLARK, PH.D., M.C.C.P.M.,* CONRADO PLA, PH.D., F.C.C.P.M.* AND PATRICK CADMAN, M.Sc.* Departments of *MedicalPhysics,tRadiationOncology,and SNeurosurgery, MontrealGeneralHospital, McGillUniversity, Montrial,Quebec, Canada Purpose: The excellent treatment results obtained with traditional radiosurgery have stimulated attempts to broaden the range of intracranial disorders treated with radiosurgical techniques. For major users of radiosurgery this resulted in a gradual shift from treating vascular diseases in a single session to treating small, well delineated primary tumors on a fractionated basis. In this paper we present the technique currently used in Montreal for the fractionated stereotactic radiotherapy of selected intracranial lesions. Methods and Materials: The regimen of six fractions given every other day has been in use for “fractionated stereotactic radiotherapy” in our center for the past 5 years. Our current irradiation technique, however, evolved from our initial method of using the stereotactic frame for target localization and first treatment, and a “halo-ring” with tattoo skin marks for the subsequent treatments. Recently, we developed a more precise irradiation technique, based on an in-house-built stereotactic frame which is left attached to the patient’s skull for the duration of the fractionated regimen. Patients are treated with the stereotactic dynamic rotation technique on a 10 MV linear accelerator (linac). Results: In preparation for the first treatment, the stereotactic frame is attached to the patient’s skull and the coordinates of the target center are determined. The dose distribution is then calculated, the target coordinates are marked onto a Lucite target localization box, and the patient is placed into the treatment position on the linac with the help of laser positioning devices. The Lucite target localization box is then removed, the target information is tattooed on the patient’s skin, and the patient is given the first treatment. The tattoo marks in conjunction with the target information on the Lucite target localization box are used for patient set-up on the linac for the subsequent 5 treatments. The location of the target center is marked with radio-opaque markers on the target localization box and verified with a computerized tomography scanner prior to the second treatment. The same verification is done prior to other treatments when the target center indicated by the target localization box disagrees with that indicated by the tattoo marks. The new position of the target center is then determined and used for treatment positioning. Conclusion: The in-house-built frame is inexpensive and easily left attached to the patient’s skull for the 12 day duration of the fractionated regimen. Positioning with the Lucite target localization box verified with tattoo marks ensures a high level of precision for individual fractionated treatments. Radiosurgery, Fractionated stereotactic radiotherapy, Small beam irradiation, Stereotactic frame, Brain irradiation.
INTRODUmION
radiosurgery. This has led to a gradual shift from the treatment of vascular brain diseases to the treatment of solitary metastatic tumors or well delineated primary tumors ( 11, 18) together with a move from dose delivery in a single session to fractionated dose regimens (4, 15, 17). Delivery of dose with stereotactic techniques in a single session continues to be referred to as stereotactic radiosurgery, while the fractionated regimens are referred to as
The recent introduction of radiosurgery to radiotherapy departments through linear accelerator-based techniques such as multiple converging arcs ( 1, 3, 9) or dynamic rotation (13, 14) has brought radiosurgery into the mainstream of radiotherapy. It also has stimulated attempts to broaden the range of intracranial disorders treated with
Presented at the 34th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), San Diego, CA, 9-13 November 1992. Reprint requests to: Ervin B. Podgorsak, Ph.D., Department of Medical Physics, Montreal General Hospital, 1650 Avenue Cedar, Montreal, Quebec H3G IA4 Canada.
Acknowledgements-This work was supported in part by a research grant MT-10830 from the Medical Research Council of Canada. Accepted for publication 16 June 1993.
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stereotactic radiotherapy. In the treatment of benign brain lesions such as arteriovenous malformations a single large dose of irradiation has been successfully used. However, for malignant intracranial tumors it is believed that the use of a fractionated regimen leads to an improved therapeutic ratio (7). Even small malignant tumors contain a proportion of hypoxic cells which are more resistant to killing by radiation. The use of multiple fractions increases the cellular depopulation of the tumor thereby improving the oxygenation of the hypoxic cells and making them more sensitive to the subsequent irradiation fractions. Moreover, because of the differences in shapes of the doseresponse curves between early responding normal and tumor tissues (rapidly proliferating) and late-responding normal tissues (slowly proliferating), fractionation reduces the damage to critical late-responding normal tissues (5, 7, 16). In 1987, in an attempt to improve the therapeutic ratio, we introduced a fractionated regimen using the dynamic radiosurgical technique for the treatment of selected tumors involving sensitive brain structures. Treatments are typically delivered in six sessions, every second day, resulting in a total treatment time of 12 days. In our original fractionated technique (2), the target localization was done with a stereotactic frame, which was then also used for the treatment set-up and patient immobilization during the first of the six treatments. After the first treatment, coordinates of the target center were marked on the patient’s skin with tattoos and the stereotactic frame was removed. Prior to the second treatment, 2 days later, a standard neurosurgical halo-ring was attached to the patient’s skull and used for patient set-up and immobilization during the 5 successive treatments. For these treatments the placement of the patient into the treatment position was achieved through the alignment of the tattoo marks on the skin with the laser positioning devices designating the linac isocenter in the treatment room. The halo-based fractionated treatment approach proved useful, yet somewhat cumbersome with regard to patient set-up on the treatment machine. In addition, the reliance on tattoo marks alone for patient placement into the linac isocenter was of some concern because of possible effects of tissue swelling on the position of tattoos relative to the target center which could adversely affect the accuracy of patient positioning. In the belief that the most reliable approach would be to treat all fractions with the help of the stereotactic frame, we developed a new technique in which an in-house-built stereotactic frame is left on the patient’s skull for the duration of treatments and all fractionated treatments are given with the stereotactic frame. In this note we describe
’Clinac- 18 linear accelerator, Varian Associates, Palo Alto, CA. * Leksell Stereotactic Frame, Model G, Electra Instrument AB, Stockholm, Sweden.
Volume 27, Number 5, 1993
our updated technique for the fractionated stereotactic treatments of well-defined solitary brain lesions with dimensions less than 4 cm. METHODS
AND MATERIALS
The stereotactic dynamic rotation treatments, which are characterized by simultaneous and continuous rotations of the gantry (300” from 30” to 330”) and couch (150” from 75’ to -75”) are given in our center with a 10 MV linear accelerator (linac)‘. Radiation fields are circular with diameters up to 4 cm. The dynamic stereotactic rotation technique has been described in detail elsewhere (13, 14). An in-house-built stereotactic frame, closely resembling the Leksell stereotactic frame,2 is used for the initial target localization procedure as well as for treatment set-up and patient immobilization during all 6 treatment procedures. The base of the in-house-built stereotactic frame is made of aluminum, the posts are made of plastic and the pins are made of aluminum with titanium tips. The frame is inexpensive, sturdy, weighs only 450 g, and is depicted in Figure 1. Since the frame is normally left attached to the patient for 12 days, our department has several of these frames so that we can have more than one patient on treatment at a given time. A commercial system3 is used for target localization in conjunction with computerized tomography (CT)- or magnetic resonance (MR) imaging procedures and the dose distributions are calculated with a treatment planning system developed locally and described in detail previously ( 12). For patients who require MR imaging we use a plastic in-house-built frame which is very similar to the aluminum frame. The coordinates of the target center are determined
Fig. 1. The in-house-built stereotactic frame with aluminum b&, plastic posts and aluminum screws.
3 Electra Instrument
AB, Stockholm, Sweden.
Stereotactic radiotherapy in the treatment of intracranial tumors 0 E. B. PODGORSAK
et al.
1221
with the standard procedure based on fiducial markers. The patient is positioned into the linac isocenter with the help of a Lucite target localization box containing the coordinates of the target center. Two different Lucite boxes, one with fiducial markers and the other with a target localization grid, may be used with the stereotactic frame, the former for target localization and the latter for treatment setup. However, to minimize the potential for errors, it is preferable to use only one box containing both the fiducial markers and the target localization grid. In Figure 2 we show the combined fiducial marker/ target localization box which we use in conjunction with the in-house-built stereotactic frame. The Cartesian coordinate system grids as well as fiducial marker lines are clearly visible on the right lateral side and the anterior side, as is a set of marks designating the location of a typical target. Similarly to our halo-based technique, tattoo marks are placed on the patient’s skin after the first treatment, but now they are only used for confirmation of the patient’s proper position during the subsequent treatments rather than for positioning itself. The positioning for all fractionated treatments is achieved with the Lucite target localization box, the stereotactic frame, and the laser positioning devices. Figure 3 shows the stereotactic frame affixed to a typical patient for the duration of the fractionated treatments. Although the frame is somewhat cumbersome for the patient during the 12 days of treatment, its use can be justified by several positive features. The frame enables an easy and fast patient set-up on the linac, it provides an excellent patient immobilization during the treatment, and, in conjunction with the target localization box, it gives an excellent reproducibility of treatments. Figure 4 shows the patient on the linac treatment couch in preparation for one of the fractionated treatments. The Lucite fiducial marker/target localization box, which is used to place the target center into the linac isocenter, is shown in the figure but is removed prior to treatment to decrease the interference of the stereotactic frame components with the radiation beam.
The experience with 49 patients who underwent fractionated treatments with the halo-ring in our center between 1987 and December 199 1 has shown that patients have no serious difficulty with the immobilization devices affixed to their skulls for the relatively short period of treatment time (2). Therefore, the switch from the haloring to the in-house-built stereotactic frame was justified easily, since the frame, even though slightly more inconvenient for the patient than the halo-ring, is affixed to the skull with exactly the same technique as was the haloring (local anaesthesia and 4 screws), yet it is much more practical and reliable for treatment setup and patient immobilization. Moreover, with the in-house frame the patient undergoes only one frame attachment procedure for all six treatments, while with the halo-ring there were 2; 1 to attach the stereotactic frame for the target localization
Fig. 2. The in-house-built stereotactic frame with the Lucite fiducial marker/target localization box attached. The location of a typical target is also shown.
Fig. 4. Patient set-up on the linac treatment couch, stereotactic frame fastened to the couch, the Lucite fiducial marker/target localization box attached to the stereo-tactic frame.
typical attachment of the stereotactic frame to patient’s skull. The frame remains attached to the patient for 12 days.
Fig. 3. A
RESULTS
AND DISCUSSION
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and first radiation treatment, and the other to attach the halo-ring for the subsequent 5 treatments. A concern could be raised that the simple in-housebuilt frame cannot be used to replace the sophisticated commercially available stereotactic frames. This is certainly true in the case of surgical procedures, such as stereotactic biopsies, and we would not advocate the use of the in-house-built frame for such procedures. In radiosurgery, however, it is the fiducial marker/target localization box that has to meet very stringent specifications; the base of the stereotactic frame is only of secondary importance. As long as the base of the frame meets the basic requirements, such as compatibility with imaging equipment, light weight, and sturdiness, it will be acceptable for radiosurgery. To ensure a high degree of accuracy in spatial dose delivery to the target for all 6 fractionated treatments, the target center points, as indicated by the 2 treatment room lateral lasers and by the vertical laser when the patient is in the proper treatment position, are tattooed onto the patient’s skin after the first treatment. During the 5 subsequent treatments, the 3 tattoo marks are used for confirmation of the treatment positions which are achieved with the help of the Lucite target localization box onto which the target information is marked, as shown in Figure 4. There are 2 possible causes for a discrepancy between the target information given by the Lucite target localization box and that given by the tattoo marks; either the frame has moved on the patient’s skull or the tattoo marks have shifted because of tissue swelling in the vicinity of the marks. The exact cause for the discrepancy can be determined easily with the CT-scanner through a repeat of the target localization procedure. To verify the reliability of the frame attachment to the patient’s skull during the 12 days of treatment, we tested the frame placement on the first 2 patients with 5 CTscanning procedures subsequent to the original one used for target localization. Thus, following the first treatment, a CT-target localization procedure was done before each of the 5 subsequent fractionated treatments. On the next 3 patients a CT-target localization procedure was done before the second, fourth, and last treatment. During each pretreatment scanning procedure, a series of transverse CT-slices is taken through the target volume and the position of the central slice is verified with the information that was calculated during the original target localization procedure and marked on the target localization box for all treatments. The verification of the central slice through the target confirms the axial coordinate of the target center. The other two coordinates lie in the transverse plane and are verified as follows: the horizontal (coronal) and vertical (sagittal) planes through the center of the target are defined on the Lucite target localization box with thin radio-opaque horizontal lines containing the target points as marked on the two lateral sides and the anterior side.
Volume 27, Number 5, 1993
The radio-opaque lines will appear as dots on the CT slice, similar to the fiducial marker dots obtained on transverse slices during the initial target localization procedure. In the target verification procedure, these dots on the central transverse slice show the position of the three target points on the target localization box, allowing us to verify the two coordinates of the target center in the transverse plane. In Figure 5 we show the results of the target verification procedure for the first patient. The patient was treated for an unresectable meningioma involving the right cavernous sinus. A central transverse CT-slice is shown for each of the 6 treatments. The slice for day 1 was used for the target localization procedure and the size of the tumor as well as the fiducial markers are clearly shown. Based on this information, the coordinates of the target center were determined and transferred to the Lucite target localization box to be used for patient set-up on the treatment machine for all six treatments. The other 5 slices (days 3, 5, 8, 10, 12) of Figure 5 represent the central slices obtained with the verification technique before each 1 of the 5 subsequent fractionated treatments, as described above. The 3 intercepts of the central slice with the radio-opaque lines defining the horizontal and vertical planes through the target center are clearly shown. On reconstruction, as indicated in Figure 5, the 2 coordinates of the target center in the transverse plane may be determined. For all 5 subsequent treatments, the pretreatment CT procedure resulted in target center coordinates within & 1 mm of the originally determined values and the tattoo marks agreed well with the target points marked on the target localization box. This result shows that for patient no. 1 during the 12-day duration of the treatment, neither of the 2 possibilities for error occurred, that is, the stereo-
Day 1
Day 3
Day 8
Day 10
Day 5
Day
12
Fig. 5. A series of transverse CT-scans through the center of the target volume. Scan on day 1 was used for the target localization procedure based on fiducial markers, the other scans were used for treatment set-up verification.
Stereotactic radiotherapy in the treatment of intracranial tumors 0 E. B.PODGORSAK etal.
tactic frame did not move relative to the skull, nor did the tattoo marks shift as a result of tissue swelling. All fractionated treatments were thus delivered with a high degree of reproducibility and precision. The results of the frame placement test for the second patient were also excellent, as were the results of the smaller scale tests performed on the next 3 patients. Based on these test results we concluded that the in-house-built stereotactic frame and the frame placement procedure are sufficiently reliable to allow us to reduce the routine use of pretreatment CT-scanning as a cost- and time-saving measure. Currently, target verification procedures are done on all patients prior to their second fractionated treatment, and for subsequent treatments only if the discrepancy between the target center indicated by the target localization box and the target center indicated by the tattoo marks exceeds 1 mm. New coordinates of the target center are then determined and used for subsequent treatments. To date, we have performed 48 fractionated treatments (8 patients) with in-house-built stereotactic frames, and only in 1 of the treatments observed a discrepancy between the target information given by the Lucite target localization box and that given by tattoo marks, necessitating the special target verification procedure to redefine the target center. The attachment of the stereotactic frame during the course of the fractionated regimen caused only minimal disturbances of patients’ daily activities or sleeping patterns and there were no acute complications, such as skin infection or hemorrhage. Fractionated stereotactic radiotherapy has also been used in other centers. The University of Miami (10, 15) has reported the use of a computer-controlled stereotactic radiotherapy system for fractionated treatments based on a halo-ring. Twenty-four patients underwent prolonged multifraction treatments (median number of fractions: 25.5) for benign or malignant brain lesions. Despite the long duration of the fractionated regimen (median duration: 40 days) no significant acute or chronic toxicity attributable to the stereotactic frame was observed. Others
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are advocating the use of noninvasive relocatable frames as a practical option for fractionated stereotactic radiotherapy (4, 6, 8). Noninvasive relocatable frames are certainly an elegant and practical solution for the discomfort caused by stereotactic frames left attached to patients’ skull for the duration of the fractionated regimens. Nevertheless, we believe that the inconvenience of the latter is outweighed by improved reliability and accuracy in the delivery of the fractionated treatment dose. Two promising new developments in dose delivery in radiotherapy are currently studied at various institutions and might prove useful in fractionated high precission radiotherapy. One, referred to as frameless radiosurgery, is based on a miniature megavoltage linac mounted on a robotic arm. The position of the radiation beam is controlled by on-line diagnostic x-ray images in conjunction with radiographs which were digitally reconstructed from CT axial images of the patient, obviating the need for a stereotactic frame in radiosurgery. The other approach uses intensity modulated radiation beams5 to obtain optimized dose distributions in irregular target volumes providing an excellent method for conformal radiotherapy on a fractionated basis. CONCLUSION The in-house-built stereotactic frame is simple to use, inexpensive, and yet it meets adequately the requirements for stereotactic frames used in radiosurgery. None of our patients had any serious difficulty with the frame attached to their skull during the 12 day duration of the fractionated treatments. For each patient, the combination of target information marked on the Lucite target localization box and target information provided by tattoo marks on patient’s skin gives a high degree of precision for all fractionated treatments. The stereotactic fractionated radiotherapy with the in-house-built stereotactic frame combines well the goals of the single fraction stereotactic radiosurgery with the aims of fractionation in the treatment of selected brain tumors.
REFERENCES Betti, 0. 0.; Derechinsky, V. E. Hyperselective encephalic irradiation with linear accel-erator. Acta Neurochirurgica 33 (Suppl.):385-390; 1984. Clark, B. G; Podgorsak, E. B; Souhami, L.; Olivier, A.; Sixel, K.; Caron, J.-L. A halo-ring technique for fractionated stereotactic radiotherapy. Br. J. Radio]. 66522-527; 1993. Colombo, F.; Benedetti, A.; Pozza, F.; Avanzo, R. C.; Marchetti, C.; Chierego, G.; Zanardo, A. External stereotactic irradiation by linear accelerator. Neurosurgery 16: 154- 160; 1985. Delannes, M.; Daly, N. J.; Bonnet, J.; Sabatier, J.; Tremoulet, M. Fractionated radio-therapy of small inoperable lesions of the brain using a noninvasive stereotactic frame. Int. J. Radiat. Oncol. Biol. Phys. 21:749-755; 1991. 4 Neurotron
1000, Accuray, Santa Clara, CA.
5. Fowler, J. F. What next in fractionated radiotherapy? Br. J. Cancer (Suppl.) 49:285-300; 1984. 6. Gill, S. S.; Thomas, D. G. T.; Warrington, A. P.; Brada, M. Relocatable frame for stereo-tactic external beam radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 20:599-603; 199 1. 7. Hall, E. J; Brenner, D. J. The radiobiology of radiosurgery: Rationale for different treatment regimens for AVMs and malignancies. Int. J. Radiat. Oncol. Biol. Phys. 25:381-385; 1993. 8. Harit, M. I.; Henriksson, R.; Lofroth, P.-O.; Laitinen, L.; Saberborg, N.-E. A noninvasive method for fractionated stereotactic irradiation of brain tumors with linear accelerator. Radioth. Oncol. 17:57-72; 1990. 9. Hartmann, G. H.; Schlegel, W.; Sturm, V.; Kober, B.; Pastyr, 5 Peacock System, Nomos Corp., Miami, FL.
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0.; Lorenz, W. J. Cerebral radiation surgery using moving field irradiation in a linear accelerator facility. Int. J. Radiat. Oncol. Biol. Phys. 1 I:1 185-l 192; 1985. IO. Houdek, P. V.; Schwade, J. G.; Serago, C. F.; Landy, H. J.; Pisciotta, V. J.; Wu, X.; Marboe, A.; Lewin, A. A.; Abitbol, A. A.; Bujnoski, J. L.; Marienberg, E. S.; Fiedler, J. A.; Ginsberg, M. S. Computer controlled stereotaxic radiotherapy system. Int. J. Radiat. Oncol. Biol. Phys. 22:175180; 1991. 11 McKenzie, M. R.; Souhami, L.; Podgorsak, E. B.; Olivier, A.; Caron, J.-L.; Villemure, J.-G. Photon beam radiosurgery; a clinical review. Can. J. Neurol. Sci. 19:212-221; 1992. 12. Pike, B.; Podgorsak, E. B.; Peters, T. M.; Pla, C. Dose distributions in dynamic stereotactic radiosurgery. Med. Phys. 14:780-789; 1987. 13. Podgorsak, E. B.; Olivier, A.; Pla, M.; Hazel, J.; de Lotbiniere, A.; Pike, G. B. Physical aspects ofdynamic stereotactic radiosurgery. Appl. Neurophysiol. 50:263-268; 1987.
Volume 27, Number 5, 1993 14. Podgorsak, E. B.; Olivier, A.; Pla, M.; Lefebvre, P. Y.; Hazel, J. Dynamic stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 14:115-125; 1988. 15. Schwade, J. G.; Houdek, P. V.; Landy, H. J.; Bujnoski, J. L.; Lewin, A. A.; Abitbol, A. A.; Serago, C. F.; Pisciotta, V. J. Small field stereotactic external beam radiation therapy of intracranial lesions: Fractionated treatment with a fixed halo immobilization device. Radiology 176:563-565; 1990. 16. Sheline, G. E; Wara, W. M; Smith, V. Therapeutic irradiation and brain injury. Int. J. Radiat. Oncol. Biol. Phys. 6: 1215-1228, 1980. 17. Souhami, L.; Olivier, A.; Podgorsak, E. B.; Villemure, J.-G.; Pla, M.; Sadikot, A. Fractionated stereotactic radiation therapy for intracranial tumors. Cancer 68:2 10 1-2 108; 1990. 18. Souhami, L.; Podgorsak, E. B. Radiosurgery: A review of clinical aspects. In Benulic, T., Sersa, G., Kovac, V., eds. Advances in radiology and oncology. Ljubljana, Slovenia, Radiologia Iugoslavica; 1992: 15 l- 166.
0360.3016193 $6.00 + .oO Copyright 0 I993 Pergamon Press Ltd.
21, pp. 1225-1230
??Technical Innovations and Notes
A TECHNIQUE
FOR FRACTIONATED STEREOTACI’IC RADIOTHERAPY TREATMENT OF INTRACRANIAL TUMORS
IN THE
ERVIN B. PODGORSAK, PH.D., F.C.C.P.M.,* LUIS SOUHAMI, M.D.,?_ JEAN-LOUIS CARON, M.D.,+ MARINA PLA, M.Sc., M.C.C.P.M.,* BRENDA CLARK, PH.D., M.C.C.P.M.,* CONRADO PLA, PH.D., F.C.C.P.M.* AND PATRICK CADMAN, M.Sc.* Departments of *MedicalPhysics,tRadiationOncology,and SNeurosurgery, MontrealGeneralHospital, McGillUniversity, Montrial,Quebec, Canada Purpose: The excellent treatment results obtained with traditional radiosurgery have stimulated attempts to broaden the range of intracranial disorders treated with radiosurgical techniques. For major users of radiosurgery this resulted in a gradual shift from treating vascular diseases in a single session to treating small, well delineated primary tumors on a fractionated basis. In this paper we present the technique currently used in Montreal for the fractionated stereotactic radiotherapy of selected intracranial lesions. Methods and Materials: The regimen of six fractions given every other day has been in use for “fractionated stereotactic radiotherapy” in our center for the past 5 years. Our current irradiation technique, however, evolved from our initial method of using the stereotactic frame for target localization and first treatment, and a “halo-ring” with tattoo skin marks for the subsequent treatments. Recently, we developed a more precise irradiation technique, based on an in-house-built stereotactic frame which is left attached to the patient’s skull for the duration of the fractionated regimen. Patients are treated with the stereotactic dynamic rotation technique on a 10 MV linear accelerator (linac). Results: In preparation for the first treatment, the stereotactic frame is attached to the patient’s skull and the coordinates of the target center are determined. The dose distribution is then calculated, the target coordinates are marked onto a Lucite target localization box, and the patient is placed into the treatment position on the linac with the help of laser positioning devices. The Lucite target localization box is then removed, the target information is tattooed on the patient’s skin, and the patient is given the first treatment. The tattoo marks in conjunction with the target information on the Lucite target localization box are used for patient set-up on the linac for the subsequent 5 treatments. The location of the target center is marked with radio-opaque markers on the target localization box and verified with a computerized tomography scanner prior to the second treatment. The same verification is done prior to other treatments when the target center indicated by the target localization box disagrees with that indicated by the tattoo marks. The new position of the target center is then determined and used for treatment positioning. Conclusion: The in-house-built frame is inexpensive and easily left attached to the patient’s skull for the 12 day duration of the fractionated regimen. Positioning with the Lucite target localization box verified with tattoo marks ensures a high level of precision for individual fractionated treatments. Radiosurgery, Fractionated stereotactic radiotherapy, Small beam irradiation, Stereotactic frame, Brain irradiation.
INTRODUmION
radiosurgery. This has led to a gradual shift from the treatment of vascular brain diseases to the treatment of solitary metastatic tumors or well delineated primary tumors ( 11, 18) together with a move from dose delivery in a single session to fractionated dose regimens (4, 15, 17). Delivery of dose with stereotactic techniques in a single session continues to be referred to as stereotactic radiosurgery, while the fractionated regimens are referred to as
The recent introduction of radiosurgery to radiotherapy departments through linear accelerator-based techniques such as multiple converging arcs ( 1, 3, 9) or dynamic rotation (13, 14) has brought radiosurgery into the mainstream of radiotherapy. It also has stimulated attempts to broaden the range of intracranial disorders treated with
Presented at the 34th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), San Diego, CA, 9-13 November 1992. Reprint requests to: Ervin B. Podgorsak, Ph.D., Department of Medical Physics, Montreal General Hospital, 1650 Avenue Cedar, Montreal, Quebec H3G IA4 Canada.
Acknowledgements-This work was supported in part by a research grant MT-10830 from the Medical Research Council of Canada. Accepted for publication 16 June 1993.
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stereotactic radiotherapy. In the treatment of benign brain lesions such as arteriovenous malformations a single large dose of irradiation has been successfully used. However, for malignant intracranial tumors it is believed that the use of a fractionated regimen leads to an improved therapeutic ratio (7). Even small malignant tumors contain a proportion of hypoxic cells which are more resistant to killing by radiation. The use of multiple fractions increases the cellular depopulation of the tumor thereby improving the oxygenation of the hypoxic cells and making them more sensitive to the subsequent irradiation fractions. Moreover, because of the differences in shapes of the doseresponse curves between early responding normal and tumor tissues (rapidly proliferating) and late-responding normal tissues (slowly proliferating), fractionation reduces the damage to critical late-responding normal tissues (5, 7, 16). In 1987, in an attempt to improve the therapeutic ratio, we introduced a fractionated regimen using the dynamic radiosurgical technique for the treatment of selected tumors involving sensitive brain structures. Treatments are typically delivered in six sessions, every second day, resulting in a total treatment time of 12 days. In our original fractionated technique (2), the target localization was done with a stereotactic frame, which was then also used for the treatment set-up and patient immobilization during the first of the six treatments. After the first treatment, coordinates of the target center were marked on the patient’s skin with tattoos and the stereotactic frame was removed. Prior to the second treatment, 2 days later, a standard neurosurgical halo-ring was attached to the patient’s skull and used for patient set-up and immobilization during the 5 successive treatments. For these treatments the placement of the patient into the treatment position was achieved through the alignment of the tattoo marks on the skin with the laser positioning devices designating the linac isocenter in the treatment room. The halo-based fractionated treatment approach proved useful, yet somewhat cumbersome with regard to patient set-up on the treatment machine. In addition, the reliance on tattoo marks alone for patient placement into the linac isocenter was of some concern because of possible effects of tissue swelling on the position of tattoos relative to the target center which could adversely affect the accuracy of patient positioning. In the belief that the most reliable approach would be to treat all fractions with the help of the stereotactic frame, we developed a new technique in which an in-house-built stereotactic frame is left on the patient’s skull for the duration of treatments and all fractionated treatments are given with the stereotactic frame. In this note we describe
’Clinac- 18 linear accelerator, Varian Associates, Palo Alto, CA. * Leksell Stereotactic Frame, Model G, Electra Instrument AB, Stockholm, Sweden.
Volume 27, Number 5, 1993
our updated technique for the fractionated stereotactic treatments of well-defined solitary brain lesions with dimensions less than 4 cm. METHODS
AND MATERIALS
The stereotactic dynamic rotation treatments, which are characterized by simultaneous and continuous rotations of the gantry (300” from 30” to 330”) and couch (150” from 75’ to -75”) are given in our center with a 10 MV linear accelerator (linac)‘. Radiation fields are circular with diameters up to 4 cm. The dynamic stereotactic rotation technique has been described in detail elsewhere (13, 14). An in-house-built stereotactic frame, closely resembling the Leksell stereotactic frame,2 is used for the initial target localization procedure as well as for treatment set-up and patient immobilization during all 6 treatment procedures. The base of the in-house-built stereotactic frame is made of aluminum, the posts are made of plastic and the pins are made of aluminum with titanium tips. The frame is inexpensive, sturdy, weighs only 450 g, and is depicted in Figure 1. Since the frame is normally left attached to the patient for 12 days, our department has several of these frames so that we can have more than one patient on treatment at a given time. A commercial system3 is used for target localization in conjunction with computerized tomography (CT)- or magnetic resonance (MR) imaging procedures and the dose distributions are calculated with a treatment planning system developed locally and described in detail previously ( 12). For patients who require MR imaging we use a plastic in-house-built frame which is very similar to the aluminum frame. The coordinates of the target center are determined
Fig. 1. The in-house-built stereotactic frame with aluminum b&, plastic posts and aluminum screws.
3 Electra Instrument
AB, Stockholm, Sweden.
Stereotactic radiotherapy in the treatment of intracranial tumors 0 E. B. PODGORSAK
et al.
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with the standard procedure based on fiducial markers. The patient is positioned into the linac isocenter with the help of a Lucite target localization box containing the coordinates of the target center. Two different Lucite boxes, one with fiducial markers and the other with a target localization grid, may be used with the stereotactic frame, the former for target localization and the latter for treatment setup. However, to minimize the potential for errors, it is preferable to use only one box containing both the fiducial markers and the target localization grid. In Figure 2 we show the combined fiducial marker/ target localization box which we use in conjunction with the in-house-built stereotactic frame. The Cartesian coordinate system grids as well as fiducial marker lines are clearly visible on the right lateral side and the anterior side, as is a set of marks designating the location of a typical target. Similarly to our halo-based technique, tattoo marks are placed on the patient’s skin after the first treatment, but now they are only used for confirmation of the patient’s proper position during the subsequent treatments rather than for positioning itself. The positioning for all fractionated treatments is achieved with the Lucite target localization box, the stereotactic frame, and the laser positioning devices. Figure 3 shows the stereotactic frame affixed to a typical patient for the duration of the fractionated treatments. Although the frame is somewhat cumbersome for the patient during the 12 days of treatment, its use can be justified by several positive features. The frame enables an easy and fast patient set-up on the linac, it provides an excellent patient immobilization during the treatment, and, in conjunction with the target localization box, it gives an excellent reproducibility of treatments. Figure 4 shows the patient on the linac treatment couch in preparation for one of the fractionated treatments. The Lucite fiducial marker/target localization box, which is used to place the target center into the linac isocenter, is shown in the figure but is removed prior to treatment to decrease the interference of the stereotactic frame components with the radiation beam.
The experience with 49 patients who underwent fractionated treatments with the halo-ring in our center between 1987 and December 199 1 has shown that patients have no serious difficulty with the immobilization devices affixed to their skulls for the relatively short period of treatment time (2). Therefore, the switch from the haloring to the in-house-built stereotactic frame was justified easily, since the frame, even though slightly more inconvenient for the patient than the halo-ring, is affixed to the skull with exactly the same technique as was the haloring (local anaesthesia and 4 screws), yet it is much more practical and reliable for treatment setup and patient immobilization. Moreover, with the in-house frame the patient undergoes only one frame attachment procedure for all six treatments, while with the halo-ring there were 2; 1 to attach the stereotactic frame for the target localization
Fig. 2. The in-house-built stereotactic frame with the Lucite fiducial marker/target localization box attached. The location of a typical target is also shown.
Fig. 4. Patient set-up on the linac treatment couch, stereotactic frame fastened to the couch, the Lucite fiducial marker/target localization box attached to the stereo-tactic frame.
typical attachment of the stereotactic frame to patient’s skull. The frame remains attached to the patient for 12 days.
Fig. 3. A
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and first radiation treatment, and the other to attach the halo-ring for the subsequent 5 treatments. A concern could be raised that the simple in-housebuilt frame cannot be used to replace the sophisticated commercially available stereotactic frames. This is certainly true in the case of surgical procedures, such as stereotactic biopsies, and we would not advocate the use of the in-house-built frame for such procedures. In radiosurgery, however, it is the fiducial marker/target localization box that has to meet very stringent specifications; the base of the stereotactic frame is only of secondary importance. As long as the base of the frame meets the basic requirements, such as compatibility with imaging equipment, light weight, and sturdiness, it will be acceptable for radiosurgery. To ensure a high degree of accuracy in spatial dose delivery to the target for all 6 fractionated treatments, the target center points, as indicated by the 2 treatment room lateral lasers and by the vertical laser when the patient is in the proper treatment position, are tattooed onto the patient’s skin after the first treatment. During the 5 subsequent treatments, the 3 tattoo marks are used for confirmation of the treatment positions which are achieved with the help of the Lucite target localization box onto which the target information is marked, as shown in Figure 4. There are 2 possible causes for a discrepancy between the target information given by the Lucite target localization box and that given by the tattoo marks; either the frame has moved on the patient’s skull or the tattoo marks have shifted because of tissue swelling in the vicinity of the marks. The exact cause for the discrepancy can be determined easily with the CT-scanner through a repeat of the target localization procedure. To verify the reliability of the frame attachment to the patient’s skull during the 12 days of treatment, we tested the frame placement on the first 2 patients with 5 CTscanning procedures subsequent to the original one used for target localization. Thus, following the first treatment, a CT-target localization procedure was done before each of the 5 subsequent fractionated treatments. On the next 3 patients a CT-target localization procedure was done before the second, fourth, and last treatment. During each pretreatment scanning procedure, a series of transverse CT-slices is taken through the target volume and the position of the central slice is verified with the information that was calculated during the original target localization procedure and marked on the target localization box for all treatments. The verification of the central slice through the target confirms the axial coordinate of the target center. The other two coordinates lie in the transverse plane and are verified as follows: the horizontal (coronal) and vertical (sagittal) planes through the center of the target are defined on the Lucite target localization box with thin radio-opaque horizontal lines containing the target points as marked on the two lateral sides and the anterior side.
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The radio-opaque lines will appear as dots on the CT slice, similar to the fiducial marker dots obtained on transverse slices during the initial target localization procedure. In the target verification procedure, these dots on the central transverse slice show the position of the three target points on the target localization box, allowing us to verify the two coordinates of the target center in the transverse plane. In Figure 5 we show the results of the target verification procedure for the first patient. The patient was treated for an unresectable meningioma involving the right cavernous sinus. A central transverse CT-slice is shown for each of the 6 treatments. The slice for day 1 was used for the target localization procedure and the size of the tumor as well as the fiducial markers are clearly shown. Based on this information, the coordinates of the target center were determined and transferred to the Lucite target localization box to be used for patient set-up on the treatment machine for all six treatments. The other 5 slices (days 3, 5, 8, 10, 12) of Figure 5 represent the central slices obtained with the verification technique before each 1 of the 5 subsequent fractionated treatments, as described above. The 3 intercepts of the central slice with the radio-opaque lines defining the horizontal and vertical planes through the target center are clearly shown. On reconstruction, as indicated in Figure 5, the 2 coordinates of the target center in the transverse plane may be determined. For all 5 subsequent treatments, the pretreatment CT procedure resulted in target center coordinates within & 1 mm of the originally determined values and the tattoo marks agreed well with the target points marked on the target localization box. This result shows that for patient no. 1 during the 12-day duration of the treatment, neither of the 2 possibilities for error occurred, that is, the stereo-
Day 1
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Fig. 5. A series of transverse CT-scans through the center of the target volume. Scan on day 1 was used for the target localization procedure based on fiducial markers, the other scans were used for treatment set-up verification.
Stereotactic radiotherapy in the treatment of intracranial tumors 0 E. B.PODGORSAK etal.
tactic frame did not move relative to the skull, nor did the tattoo marks shift as a result of tissue swelling. All fractionated treatments were thus delivered with a high degree of reproducibility and precision. The results of the frame placement test for the second patient were also excellent, as were the results of the smaller scale tests performed on the next 3 patients. Based on these test results we concluded that the in-house-built stereotactic frame and the frame placement procedure are sufficiently reliable to allow us to reduce the routine use of pretreatment CT-scanning as a cost- and time-saving measure. Currently, target verification procedures are done on all patients prior to their second fractionated treatment, and for subsequent treatments only if the discrepancy between the target center indicated by the target localization box and the target center indicated by the tattoo marks exceeds 1 mm. New coordinates of the target center are then determined and used for subsequent treatments. To date, we have performed 48 fractionated treatments (8 patients) with in-house-built stereotactic frames, and only in 1 of the treatments observed a discrepancy between the target information given by the Lucite target localization box and that given by tattoo marks, necessitating the special target verification procedure to redefine the target center. The attachment of the stereotactic frame during the course of the fractionated regimen caused only minimal disturbances of patients’ daily activities or sleeping patterns and there were no acute complications, such as skin infection or hemorrhage. Fractionated stereotactic radiotherapy has also been used in other centers. The University of Miami (10, 15) has reported the use of a computer-controlled stereotactic radiotherapy system for fractionated treatments based on a halo-ring. Twenty-four patients underwent prolonged multifraction treatments (median number of fractions: 25.5) for benign or malignant brain lesions. Despite the long duration of the fractionated regimen (median duration: 40 days) no significant acute or chronic toxicity attributable to the stereotactic frame was observed. Others
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are advocating the use of noninvasive relocatable frames as a practical option for fractionated stereotactic radiotherapy (4, 6, 8). Noninvasive relocatable frames are certainly an elegant and practical solution for the discomfort caused by stereotactic frames left attached to patients’ skull for the duration of the fractionated regimens. Nevertheless, we believe that the inconvenience of the latter is outweighed by improved reliability and accuracy in the delivery of the fractionated treatment dose. Two promising new developments in dose delivery in radiotherapy are currently studied at various institutions and might prove useful in fractionated high precission radiotherapy. One, referred to as frameless radiosurgery, is based on a miniature megavoltage linac mounted on a robotic arm. The position of the radiation beam is controlled by on-line diagnostic x-ray images in conjunction with radiographs which were digitally reconstructed from CT axial images of the patient, obviating the need for a stereotactic frame in radiosurgery. The other approach uses intensity modulated radiation beams5 to obtain optimized dose distributions in irregular target volumes providing an excellent method for conformal radiotherapy on a fractionated basis. CONCLUSION The in-house-built stereotactic frame is simple to use, inexpensive, and yet it meets adequately the requirements for stereotactic frames used in radiosurgery. None of our patients had any serious difficulty with the frame attached to their skull during the 12 day duration of the fractionated treatments. For each patient, the combination of target information marked on the Lucite target localization box and target information provided by tattoo marks on patient’s skin gives a high degree of precision for all fractionated treatments. The stereotactic fractionated radiotherapy with the in-house-built stereotactic frame combines well the goals of the single fraction stereotactic radiosurgery with the aims of fractionation in the treatment of selected brain tumors.
REFERENCES Betti, 0. 0.; Derechinsky, V. E. Hyperselective encephalic irradiation with linear accel-erator. Acta Neurochirurgica 33 (Suppl.):385-390; 1984. Clark, B. G; Podgorsak, E. B; Souhami, L.; Olivier, A.; Sixel, K.; Caron, J.-L. A halo-ring technique for fractionated stereotactic radiotherapy. Br. J. Radio]. 66522-527; 1993. Colombo, F.; Benedetti, A.; Pozza, F.; Avanzo, R. C.; Marchetti, C.; Chierego, G.; Zanardo, A. External stereotactic irradiation by linear accelerator. Neurosurgery 16: 154- 160; 1985. Delannes, M.; Daly, N. J.; Bonnet, J.; Sabatier, J.; Tremoulet, M. Fractionated radio-therapy of small inoperable lesions of the brain using a noninvasive stereotactic frame. Int. J. Radiat. Oncol. Biol. Phys. 21:749-755; 1991. 4 Neurotron
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5. Fowler, J. F. What next in fractionated radiotherapy? Br. J. Cancer (Suppl.) 49:285-300; 1984. 6. Gill, S. S.; Thomas, D. G. T.; Warrington, A. P.; Brada, M. Relocatable frame for stereo-tactic external beam radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 20:599-603; 199 1. 7. Hall, E. J; Brenner, D. J. The radiobiology of radiosurgery: Rationale for different treatment regimens for AVMs and malignancies. Int. J. Radiat. Oncol. Biol. Phys. 25:381-385; 1993. 8. Harit, M. I.; Henriksson, R.; Lofroth, P.-O.; Laitinen, L.; Saberborg, N.-E. A noninvasive method for fractionated stereotactic irradiation of brain tumors with linear accelerator. Radioth. Oncol. 17:57-72; 1990. 9. Hartmann, G. H.; Schlegel, W.; Sturm, V.; Kober, B.; Pastyr, 5 Peacock System, Nomos Corp., Miami, FL.
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0.; Lorenz, W. J. Cerebral radiation surgery using moving field irradiation in a linear accelerator facility. Int. J. Radiat. Oncol. Biol. Phys. 1 I:1 185-l 192; 1985. IO. Houdek, P. V.; Schwade, J. G.; Serago, C. F.; Landy, H. J.; Pisciotta, V. J.; Wu, X.; Marboe, A.; Lewin, A. A.; Abitbol, A. A.; Bujnoski, J. L.; Marienberg, E. S.; Fiedler, J. A.; Ginsberg, M. S. Computer controlled stereotaxic radiotherapy system. Int. J. Radiat. Oncol. Biol. Phys. 22:175180; 1991. 11 McKenzie, M. R.; Souhami, L.; Podgorsak, E. B.; Olivier, A.; Caron, J.-L.; Villemure, J.-G. Photon beam radiosurgery; a clinical review. Can. J. Neurol. Sci. 19:212-221; 1992. 12. Pike, B.; Podgorsak, E. B.; Peters, T. M.; Pla, C. Dose distributions in dynamic stereotactic radiosurgery. Med. Phys. 14:780-789; 1987. 13. Podgorsak, E. B.; Olivier, A.; Pla, M.; Hazel, J.; de Lotbiniere, A.; Pike, G. B. Physical aspects ofdynamic stereotactic radiosurgery. Appl. Neurophysiol. 50:263-268; 1987.
Volume 27, Number 5, 1993 14. Podgorsak, E. B.; Olivier, A.; Pla, M.; Lefebvre, P. Y.; Hazel, J. Dynamic stereotactic radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 14:115-125; 1988. 15. Schwade, J. G.; Houdek, P. V.; Landy, H. J.; Bujnoski, J. L.; Lewin, A. A.; Abitbol, A. A.; Serago, C. F.; Pisciotta, V. J. Small field stereotactic external beam radiation therapy of intracranial lesions: Fractionated treatment with a fixed halo immobilization device. Radiology 176:563-565; 1990. 16. Sheline, G. E; Wara, W. M; Smith, V. Therapeutic irradiation and brain injury. Int. J. Radiat. Oncol. Biol. Phys. 6: 1215-1228, 1980. 17. Souhami, L.; Olivier, A.; Podgorsak, E. B.; Villemure, J.-G.; Pla, M.; Sadikot, A. Fractionated stereotactic radiation therapy for intracranial tumors. Cancer 68:2 10 1-2 108; 1990. 18. Souhami, L.; Podgorsak, E. B. Radiosurgery: A review of clinical aspects. In Benulic, T., Sersa, G., Kovac, V., eds. Advances in radiology and oncology. Ljubljana, Slovenia, Radiologia Iugoslavica; 1992: 15 l- 166.