- Email: [email protected]
A Perspective on Radiosurgery: Creativity, Elegance, Simplicity, and Flexibility to Change
Perspectives
Jason Sheehan, M.D., Ph.D. Vice Chair and Alumni Professor of Neurological Surgery Department of Neurological Surgery University of Virginia School of Medicine
A Perspective on Radiosurgery: Creativity, Elegance, Simplicity, and Flexibility to Change Jason Sheehan and Ladislau Steiner
R
adiosurgery is a minimally invasive technique designed by Lars Leksell to deliver a destructive amount of radiation to intracranial lesions that may be inaccessible or unsuitable for open surgery. Undoubtedly, the experiences of delivering ether anesthesia to neurosurgical patients for Dr. Olivecrona motivated Leksell to develop a technique with fewer complications than open surgery. A passage from Leksell’s autobiography proved the idea of a minimally invasive neurosurgical approach as on his mind for some time. At the first Scandinavian neurosurgical meeting held in Oslo, Leksell left the conference room during a less-than-exciting presentation and decided to walk in a garden. While on this walk, Leksell met Sir Hugh Cairns. Leksell confessed to Cairns his doubts concerning the state of neurosurgical techniques available at the time and was convinced that something new had to be developed. He explained his plans to mechanically direct a probe into the brain using perhaps the brain’s own electrical activity and ablate pain pathways. He also mused about the idea of using narrow-beam X-ray or ultrasound as the physical agent and doing away with the probe entirely. His enthusiasm and ideas were given a warm reception by Cairns, and the encouraged young Leksell began work that led to the development of an “arc-radius” type stereotactic system. Leksell wrote, “I was born under the sign of the ‘archer’ and looked forward to sharpshoot into the brain” (39).
Leksell first built upon the principles of a target-centered semicircular stereotactic arc. In the early 1950s, he replaced electrodes with ionizing radiation via the use of X-rays. Building on the work of radiation therapists who were treating pituitary adenomas with a greater dose and fewer fraction protocols, Leksell postulated that a single fraction of radiation could be even more beneficial for intracranial pathology. In the 10 years that followed, Leksell made considerable progress in the treatment of deep brain structures with a single heavy dose of radiation. He collaborated with physicists Kurt Liden and Borje Larsson to use a proton beam for radiosurgery (14, 15, 25).
Key words Creativity - Gamma knife - Leksell - Radiosurgery - Simplicity -
Abbreviations and Acronyms APS: Automatic positioning systems MRI: Magnetic resonance imaging
WORLD NEUROSURGERY 80 [1/2]: 83-86, JULY/AUGUST 2013
The first stereotactic proton beam operation was performed at the Gustaf Werner Institute in Uppsala in 1960. Leksell found the synchrotron too awkward and expensive for widespread use and, as such, developed a similar technique based upon the linear accelerator. The linear accelerator, however, lacked the precision and simplicity needed to be handled by the neurosurgeon. Leksell also tried focused-beam ultrasound, but this too lacked the precision and required a cranial defect be made before its use. The next logical step was to look for another radiation source. Leksell turned to cobalt-60. The first stereotactic Gamma Knife unit was installed in Sophiahemmet Hospital in 1968 (17). The unit was originally intended for functional neurosurgery (16). However, the applications were quickly expanded to include arteriovenous malformations and certain brain tumors (18, 38). The first Gamma Knife yielded fairly promising results, and an improved second Gamma Knife unit was built and installed at the Karolinska Institute in 1974. This unit proved to be both reliable and easy to use. Leksell wrote that “[M]aybe the most important lesson learnt at the Karolinska is that the simplicity of using the Gamma Unit makes this integration possible and that the same individual can be a competent microsurgeon and also a stereotactic radiosurgeon. Someone competent in both techniques is best fitted to decide where the boundaries between the two methods should lie” (17). With every major innovation, a creative leap must occur. The conceptualization of radiosurgery, and the subsequent design and development of the Gamma Knife, was no exception to this rule. In 1951, Dr. Leksell demonstrated his initial creativity in radiosurgery (19): the invention of the Gamma Knife was a truly creative act. During the 40 years that followed, other neurosurgeons, medical physicists, and radiation oncologists have built upon this creative leap. Many of the accomplishments of others who followed Leksell and refined the technique of and expanded the indications for radiosurgery represent works of excellence.
Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA To whom correspondence should be addressed: Jason Sheehan, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2013) 80, 1/2:83-86. http://dx.doi.org/10.1016/j.wneu.2013.03.074
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Innovative work in the field of radiosurgery via the use of heavy particles from cyclotrons has been conducted by Raymond Kjellberg, Jay Loeffler, and Jacob Fabrikant.
6. You need to be prepared to start over again. 7. You need to use concepts. 8. You may need to break things down into smaller units.
In 1983 at a hospital in Buenos Aires, Betti and Derechinsky introduced the concept of a modified linear accelerator for radiosurgery (1, 2). This system relied upon a 10-MV linear accelerator and used a chair based Talairach stereotactic frame (29). Other innovative developments in linear accelerator based radiosurgical devices quickly followed from Hartmann and Sturm in Heidelberg (9), Barcia-Salorio et al. (1, 2) in Valencia, Colombo et al. (3) in Vincenza, and Podgorsak et al. in Canada (32). Such interval improvements upon this fundamental concept through intensive research have been essential to major advances in clinical medicine. Although we do not wish to diminish the work of those that followed, Leksell was the one to demonstrate a true creative leap. The Gamma Knife is no exception to Leksell’s creativity and design. In fact, virtually all of the instruments that Leksell designed were beautiful, simple, and elegant. For instance, Leksell wrote that in one of the art galleries in Stockholm, “I took my stereotactic instrument and showed it to the owner of the gallery. ‘I would like to display it,’ he said” (20). Similarly, he designed a rongeur for removal of shell splinters situated in or near the spinal cord. When the Swedish instrument maker Stille advertised this instrument, they featured the instrument in the foreground and a ballerina in the background. The words across the add stated “form and balance are essential.to artistic achievement” (20). Leksell’s designs were beautiful, and the artistic influences upon his life presumably helped to influence his creativity and drive. We are not proposing that technological advances are wrong. A Luddite fear of technology would have prevented technological advances (e.g., bipolar cautery, the operating microscope, ultrasound) in neurosurgery that are critical to the way it is currently practiced. However, the assimilation and application of new technologies into the field of neurosurgery are oftentimes best accomplished when these advances are simple, elegant, and precise. Simplicity and elegance are themes that are frequently observed together in other fields too. In computer science, the present-day embrace of the Linux operating system over Windows and Mac OS is a testament to simplicity and elegance. In architecture, Frank Lloyd Wright used simple Euclidean geometry in his critically acclaimed designs and even wrote that “[S]implicity and repose are the qualities that measure the true value of any work of art.” In art, who cannot help but marvel over the superiority of simple yet beautiful paintings created by the brushes of masters such as Leonardo da Vinci or Michelangelo compared with “perfect” computer-generated art graphics. Edward de Bono wrote a book entitled Simplicity (1990; Penguin Books). In it, de Bono outlined 10 rules on the subject of simplicity, and they are as follow: 1. You need to put a very high value on simplicity. 2. You must be determined to seek simplicity. 3. You need to understand the matter very well. 4. You need to design alternatives and possibilities. 5. You need to challenge and discard existing elements.
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9. You need to be prepared to trade off other things for simplicity. 10. You need to know for whose sake the simplicity is being designed. Elegance and simplicity of design are critical elements of any good design and do not happen by shear happenstance. In fact, simplicity is often one of the first elements to succumb to the effects of ad hoc design changes or advancements of a technology. A degree of flexibility must be exercised in any field, and radiosurgery is no exception. Flexibility in design and philosophy prevents obsolescence. Flexible solutions must always be considered as an alternative and adopted so as to keep in mind future possibilities. In so doing, simplicity and elegance are not compromised by a flexible design solution. The nature of simple and elegant solutions is constantly under assault from ad hoc designs. A flexible solution that maintains and respects the principles of elegance and simplicity can still allow for advancement in a field. For example, a device that enables greater range of control or application yet still respects simplicity and elegance will normally lead to progress in the field and serve as a platform for future development. Nearly 40 years ago, few would have believed that Leksell’s Gamma Knife would have had such profound effects upon the field of neurosurgery. In 1989, the fifth Gamma Knife in the world and the second in the United States was installed at the University of Virginia. At that time, Elekta AB representatives (Stockholm Sweden), makers of the Gamma Knife, thought that two or three units would more than serve the needs of the United States. Now, nearly 200 Gamma Knife centers have treated more than 250,000 patients throughout the world. The success of the original model U Gamma Knife and subsequent models is largely to the result of Leksell’s creative leap and the simplicity and elegance of the Gamma Knife’s design. With the advent of computed tomography and magnetic resonance imaging (MRI), neurosurgeons performing stereotactic radiosurgery no longer had to rely solely upon planar X-rays, pneumoencephalography, and angiograms (21, 22). In fact, Leksell embraced the new neuroimaging technologies and wrote “NMRimaging appears to be a valuable tool for clarifying some of the still unsolved problems connected with the use of the gamma unit and will make stereotactic radiosurgery still safer and more effective” (23). He also spent time adapting his frame and other surgical devices so as to make them compatible with these newer imaging technologies (24, 27). Leksell embraced these new imaging modalities as an opportunity to improve radiosurgery. Design changes were made to accommodate computed tomography and later MRI into Gamma Knife surgery, but the simplicity and elegance of the overall unit was never compromised. The addition of MRI to orthogonal angiography in dose planning has led to a more accurate assessment of the overall nidus volume in the treatment of arteriovenous malformation. However, highly conformal radiosurgical plans for brain metastases or high-grade gliomas based upon MRI may at times translate into worse tumor
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PERSPECTIVES
control results. The apparent discreteness of malignant lesions on MRI is seldom the case in reality. In microsurgery, a margin is often necessary to achieve the best results, and, in radiosurgery, a margin may be prudent too. Improved conformality, however, may lessen the complication rate associated with radiosurgery (4, 7). Often, a creative leap results in an initially primitive design. For example, in 1903, the Wright brothers developed and flew the first airplane. This was a crude device, and, at the time, few would have dreamed that this airplane would lead to other planes that now permit transcontinental or even transglobal flight. Similarly, in 1974, Raymond Damadian developed a primitive device that relied upon static and dynamic magnetic fields either to determine chemical composition of a tissue or be transformed into pictures. His MRI was exceedingly crude (Figure 1). Through refinements in the original design, MRI has gone on to forever improve the field of medicine. Leksell’s original Gamma Knife was similarly primitive, and it required refinements. Those refinements represent works of excellence, whereas the original design is a work of creativity. Creative ideas revolutionize the thinking in a particular field. Advances in the Gamma Knife technology over the years have led to the development of the models B, B2, and C and to changes in the planning software from KULA to Gamma Plan. The most significant changes in the Gamma Knife to date have been in the planning software and the introduction of the automatic positioning systems (APS). The Gamma Plan software represents a much more user-friendly interface over KULA and its algorithms for dose calculations are more robust particularly when treating multiple lesions in the same session (e.g. multiple brain metastases). The APS system has led to an improvement in the conformality index and to a decrease in overall treatment time (12, 13, 34). The latter has led to improved patient satisfaction at our center. Plans using the APS frequently require more isocenters and increased total radiation time to achieve the improvements in conformality index and overall treatment time (34). The APS eliminates the concern for coordinate slippage and may prevent Gamma Knife misadministrations (6, 8). Building upon the foundations of Leksell and his Gamma Knife, many new devices have been built to delivery intracranial and extracranial radiosurgery. Devices such as the Cyberknife
Figure 1. (A) Dr. Damadian (left) with postdoctoral fellows L. Minoff and M. Goldsmith (right) standing in front of the first magnetic resonance imaging (MRI) unit, named “Indomitable.” (B) An illustration of the original MRI as depicted in the 1974 patent application.
WORLD NEUROSURGERY 80 [1/2]: 83-86, JULY/AUGUST 2013
(Accuray, Sunnyvale, California, USA), developed by Dr. Adler of Stanford University, Synergy S (Elekta Instruments, Norcross, Georgia, USA), Novalis (Brain Lab, Munich, Germany), and Tomotherapy (Tomotherapy, Inc., Madison, Wisconsin, USA) are just a few of the units currently available. Still others are reevaluating Leksell’s original idea of focused ultrasound and exploring its possibilities for instantaneous cell death rather than the delayed effects afford by radiation (28). A device coupling focused ultrasound and MRI guidance is currently being tested for the detection of intracranial lesions (ExAblate, InSightec Inc., Tel Aviv, Israel). All of these units resemble to some degree the Gamma Knife and rely upon the biological lessons learned from it. More are likely on the way in what is a fast-moving, technologically driven field. However, many of these devices lack the simplicity and elegance of Leksell’s original design and, as a result, may not stand the test of time. The Gamma Knife, with its very limited number of moving parts, is not troubled with the isocenter verification issues encountered by most linear accelerator based radiosurgical systems (29). It remains to be seen how much of an improvement in tumor control and a decrease in morbidity these changes in hardware and software will actually afford. For instance, one of the earliest Gamma Knife series reported arteriovenous malformation obliteration rates of approximately 80% in optimal treated lesions (39). That series largely relied upon angiographic imaging alone and relatively primitive dose planning. Despite the incorporation of stereotactic MRI, computerized algorithms, robotics, and multiple isocenter plans, the outcomes in modern radiosurgical series for patients with arteriovenous malformations remain essential the same (5, 10, 11, 26, 31, 33, 36, 37). In the modern era, complication rates associated with the radiosurgery of vestibular schwannomas have decreased. However, rather than being a result of hardware or software development, this appears to be a function of refined dose selection from the original margin dose of 25e35 Gy prescribed by Leksell to 12e13 Gy currently given by most centers (4, 18, 30, 35). Will the outcomes of the modern era of radiosurgery be remarkably better than those in its beginning? If so, do any observed improvements in results arise from technological advances or simply more appropriate dose selection? Should neurosurgeons continue to focus on robotics, new preoperative or intraoperative neuroimaging modalities and more sophisticated computer planning software as a means of improving radiosurgical outcomes? Alternately, should neurosurgeons look to other energy sources (e.g., focused ultrasound) as the next creative leap in neurosurgical doctrine? Rigorous comparison and analysis of early and modern results will help to answer this question and may shed light on ways to further improve radiosurgery. The more disconcerting change has been that the added sophistication of these devices has threatened the leadership of neurosurgeons in the application of radiosurgery to central nervous system pathology. Leksell maintained that the neurosurgeon was the best at selecting, treating, and managing radiosurgical patients. Neurosurgeons are uniquely trained to understand neuroanatomy in the setting of neuropathology and the behavior, clinical symptoms, and alternative treatments of central nervous system lesions. Neurosurgeons are best able to administer radiosurgery and to care for the patient before, during, and after the procedure.
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As the field of radiosurgery evolves, neurosurgeons should look to the past for creative inspiration. The principles of simplicity and elegance that Leksell held so dear should be steadfastly protected. The best pathway for future progress will be a design
REFERENCES 1. Betti O, Derechinsky V: Multiple-beam stereotaxic irradiation [in French]. Neurochirurgie 29: 295-298, 1983. 2. Betti OO: History of radiosurgery [in French]. Cancer Radiother 2:101-104, 1998. 3. Colombo F, Benedetti A, Pozza F, Avanzo RC, Marchetti C, Chierego G, Zanardo A: External stereotactic irradiation by linear accelerator. Neurosurgery 16:154-160, 1985. 4. Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD: Results of acoustic neuroma radiosurgery: an analysis of 5 years’ experience using current methods. J Neurosurg 94:1-6, 2001. 5. Flickinger JC, Pollock BE, Kondziolka D, Lunsford LD: A dose-response analysis of arteriovenous malformation obliteration after radiosurgery. Int J Radiat Oncol Biol Phys 36:873-879, 1996. 6. Foote RL, Pollock BE, Link MJ, Garces YI, Kline RW: Leksell Gamma Knife coordinate setting slippage: how often, how much? J Neurosurg 101:590-593, 2004. 7. Friedman WA, Bova FJ, Bollampally S, Bradshaw P: Analysis of factors predictive of success or complications in arteriovenous malformation radiosurgery. Neurosurgery 52:296-307, 2003:discussion 307-298. 8. Goetsch SJ: Risk analysis of Leksell Gamma Knife Model C with automatic positioning system. Int J Radiat Oncol Biol Phys 52:869-877, 2002. 9. Hartmann GH, Schlegel W, Sturm V, Kober B, Pastyr O, Lorenz WJ: Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. Int J Radiat Oncol Biol Phys 11: 1185-1192, 1985. 10. Izawa M, Hayashi M, Chernov M, Nakaya K, Ochiai T, Murata N, Takasu Y, Kubo O, Hori T, Takakura K: Long-term complications after gamma knife surgery for arteriovenous malformations. J Neurosurg 102(Suppl):34-37, 2005. 11. Karlsson B, Lindquist C, Steiner L: Effect of Gamma Knife surgery on the risk of rupture prior to AVM obliteration. Minim Invasive Neurosurg 39:21-27, 1996. 12. Kondziolka D, Maitz AH, Niranjan A, Flickinger JC, Lunsford LD: An evaluation of the Model C gamma knife with automatic patient positioning. Neurosurgery 50:429-431, 2002:discussion 431-422. 13. Kuo JS, Yu C, Giannotta SL, Petrovich Z, Apuzzo ML: The Leksell gamma knife Model U versus Model C: a quantitative comparison of radiosurgical treatment parameters. Neurosurgery 55:168-172, 2004:discussion 172-163.
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that incorporates flexible change yet still adheres to simplicity and elegance. Moreover, for the sake of the patients, neurosurgeons must continue to play a leadership role in the field of radiosurgery.
14. Larsson B, Leksell L, Rexed B, Sourander P: Effect of high energy protons on the spinal cord. Acta Radiol 51:52-64, 1959.
30. Noren G: Stereotactic Radiosurgery in Acoustic Neurinomas. A New Therapeutic Approach. Stockholm: Karolinska Institute; 1982.
15. Larsson B, Leksell L, Rexed B, Sourander P, Mair W, Andersson B: The high-energy proton beam as a neurosurgical tool. Nature 182:1222-1223, 1958.
31. Pedroso AG, De Salles AA, Tajik K, Golish R, Smith Z, Frighetto L, Solberg T, CabatanAwang C, Selch MT: Novalis shaped beam radiosurgery of arteriovenous malformations. J Neurosurg 101(Suppl 3):425-434, 2004.
16. Larsson B, Liden K, Sarby B: Irradiation of small structures through the intact skull. Acta Radiol 13: 512-534, 1974. 17. Leksell L: Stereotactic radiosurgery. J Neurol Neurosurg Psychiatry 46:797-803, 1983. 18. Leksell L: A note on the treatment of acoustic tumours. Acta Chir Scand 137:763-765, 1971. 19. Leksell L: The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102:316-319, 1951. 20. Leksell L: Brain arragments. In: Steiner L, Forster D, Backlund E-O, eds. Radiosurgery: Baseline and Trends. New York: Raven Press; 1992:263-292. 21. Leksell L: Stereotaxis and Radiosurgery: An Operative System. Springfield, IL: Charles C. Thomas; 1971. 22. Leksell L: Echoencephalography. II. Midline echo from the pineal body as an index of pineal displacement. Acta Chir Scand 115:255-259, 1958. 23. Leksell L, Herner T, Leksell D, Persson B, Lindquist C: Visualisation of stereotactic radiolesions by nuclear magnetic resonance. J J Neurol Neurosurg Psychiatry 48:19-20, 1985. 24. Leksell L, Jernberg B: Stereotaxis and tomography. A technical note. Acta Neurochir (Wien) 52:1-7, 1980. 25. Leksell L, Larsson B, Andersson B, Rexed B, Sourander P, Mair W: Lesions in the depth of the brain produced by a beam of high energy protons. Acta Radiol 54:251-264, 1960. 26. Lindqvist M, Karlsson B, Guo WY, Kihlstrom L, Lippitz B, Yamamoto M: Angiographic long-term follow-up data for arteriovenous malformations previously proven to be obliterated after gamma knife radiosurgery. Neurosurgery 46:803-808, 2000:discussion 809-810. 27. Lunsford LD, Leksell L, Jernberg B: Probe holder for stereotactic surgery in the CT scanner. A technical note. Acta Neurochir (Wien) 69:297-304, 1983. 28. McDannold N, Moss M, Killiany R, Rosene DL, King RL, Jolesz FA, Hynynen K: MRI-guided focused ultrasound surgery in the brain: tests in a primate model. Magn Res Med 49:1188-1191, 2003.
32. Podgorsak EB, Olivier A, Pla M, Hazel J, de Lotbiniere A, Pike B: Physical aspects of dynamic stereotactic radiosurgery. Appl Neurophysiol 50: 263-268, 1987. 33. Pollock BE, Gorman DA, Coffey RJ: Patient outcomes after arteriovenous malformation radiosurgical management: results based on a 5- to 14year follow-up study. Neurosurgery 52:1291-1296, 2003:discussion 1296-1297. 34. Regis J, Hayashi M, Porcheron D, Delsanti C, Muracciole X, Peragut JC: Impact of the model C and Automatic Positioning System on gamma knife radiosurgery: an evaluation in vestibular schwannomas. J Neurosurg 97(5 Suppl):588-591, 2002. 35. Rowe JG, Radatz MW, Walton L, Hampshire A, Seaman S, Kemeny AA: Gamma knife stereotactic radiosurgery for unilateral acoustic neuromas. J Neurol Neurosurg Psychiatry 74:1536-1542, 2003. 36. Schlienger M, Atlan D, Lefkopoulos D, Merienne L, Touboul E, Missir O, Nataf F, Mammar H, Platoni K, Grandjean P, Foulquier JN, Huart J, Oppenheim C, Meder JF, Houdart E, Merland JJ: Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients. Int J Radiat Oncol Biol Phys 46:1135-1142, 2000. 37. Shin M, Maruyama K, Kurita H, Kawamoto S, Tago M, Terahara A, Morita A, Ueki K, Takakura K, Kirino T: Analysis of nidus obliteration rates after gamma knife surgery for arteriovenous malformations based on long-term follow-up data: the University of Tokyo experience. J Neurosurg 101:18-24, 2004. 38. Steiner L, Leksell L, Greitz T, Forster DM, Backlund EO: Stereotaxic radiosurgery for cerebral arteriovenous malformations. Report of a case. Acta Chir Scand 138:459-464, 1972. 39. Steiner L, Prasad D, Lindquist C, Karlsson B, Steiner M: Gamma Knife surgery in vascular, neoplastic, and functional disorders of the nervous system. In: Schidek HH, Sweet WH, eds. Operative Neurosurgical Techniques. 3rd ed., Vol 1. Philadelphia: WB Saunders; 1995:667. Citation: World Neurosurg. (2013) 80, 1/2:83-86. http://dx.doi.org/10.1016/j.wneu.2013.03.074 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
29. Mehta MP: The physical, biologic, and clinical basis of radiosurgery. Curr Probl Cancer 19: 265-329, 1995.
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WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.03.074
Jason Sheehan, M.D., Ph.D. Vice Chair and Alumni Professor of Neurological Surgery Department of Neurological Surgery University of Virginia School of Medicine
A Perspective on Radiosurgery: Creativity, Elegance, Simplicity, and Flexibility to Change Jason Sheehan and Ladislau Steiner
R
adiosurgery is a minimally invasive technique designed by Lars Leksell to deliver a destructive amount of radiation to intracranial lesions that may be inaccessible or unsuitable for open surgery. Undoubtedly, the experiences of delivering ether anesthesia to neurosurgical patients for Dr. Olivecrona motivated Leksell to develop a technique with fewer complications than open surgery. A passage from Leksell’s autobiography proved the idea of a minimally invasive neurosurgical approach as on his mind for some time. At the first Scandinavian neurosurgical meeting held in Oslo, Leksell left the conference room during a less-than-exciting presentation and decided to walk in a garden. While on this walk, Leksell met Sir Hugh Cairns. Leksell confessed to Cairns his doubts concerning the state of neurosurgical techniques available at the time and was convinced that something new had to be developed. He explained his plans to mechanically direct a probe into the brain using perhaps the brain’s own electrical activity and ablate pain pathways. He also mused about the idea of using narrow-beam X-ray or ultrasound as the physical agent and doing away with the probe entirely. His enthusiasm and ideas were given a warm reception by Cairns, and the encouraged young Leksell began work that led to the development of an “arc-radius” type stereotactic system. Leksell wrote, “I was born under the sign of the ‘archer’ and looked forward to sharpshoot into the brain” (39).
Leksell first built upon the principles of a target-centered semicircular stereotactic arc. In the early 1950s, he replaced electrodes with ionizing radiation via the use of X-rays. Building on the work of radiation therapists who were treating pituitary adenomas with a greater dose and fewer fraction protocols, Leksell postulated that a single fraction of radiation could be even more beneficial for intracranial pathology. In the 10 years that followed, Leksell made considerable progress in the treatment of deep brain structures with a single heavy dose of radiation. He collaborated with physicists Kurt Liden and Borje Larsson to use a proton beam for radiosurgery (14, 15, 25).
Key words Creativity - Gamma knife - Leksell - Radiosurgery - Simplicity -
Abbreviations and Acronyms APS: Automatic positioning systems MRI: Magnetic resonance imaging
WORLD NEUROSURGERY 80 [1/2]: 83-86, JULY/AUGUST 2013
The first stereotactic proton beam operation was performed at the Gustaf Werner Institute in Uppsala in 1960. Leksell found the synchrotron too awkward and expensive for widespread use and, as such, developed a similar technique based upon the linear accelerator. The linear accelerator, however, lacked the precision and simplicity needed to be handled by the neurosurgeon. Leksell also tried focused-beam ultrasound, but this too lacked the precision and required a cranial defect be made before its use. The next logical step was to look for another radiation source. Leksell turned to cobalt-60. The first stereotactic Gamma Knife unit was installed in Sophiahemmet Hospital in 1968 (17). The unit was originally intended for functional neurosurgery (16). However, the applications were quickly expanded to include arteriovenous malformations and certain brain tumors (18, 38). The first Gamma Knife yielded fairly promising results, and an improved second Gamma Knife unit was built and installed at the Karolinska Institute in 1974. This unit proved to be both reliable and easy to use. Leksell wrote that “[M]aybe the most important lesson learnt at the Karolinska is that the simplicity of using the Gamma Unit makes this integration possible and that the same individual can be a competent microsurgeon and also a stereotactic radiosurgeon. Someone competent in both techniques is best fitted to decide where the boundaries between the two methods should lie” (17). With every major innovation, a creative leap must occur. The conceptualization of radiosurgery, and the subsequent design and development of the Gamma Knife, was no exception to this rule. In 1951, Dr. Leksell demonstrated his initial creativity in radiosurgery (19): the invention of the Gamma Knife was a truly creative act. During the 40 years that followed, other neurosurgeons, medical physicists, and radiation oncologists have built upon this creative leap. Many of the accomplishments of others who followed Leksell and refined the technique of and expanded the indications for radiosurgery represent works of excellence.
Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA To whom correspondence should be addressed: Jason Sheehan, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2013) 80, 1/2:83-86. http://dx.doi.org/10.1016/j.wneu.2013.03.074
www.WORLDNEUROSURGERY.org
83
PERSPECTIVES
Innovative work in the field of radiosurgery via the use of heavy particles from cyclotrons has been conducted by Raymond Kjellberg, Jay Loeffler, and Jacob Fabrikant.
6. You need to be prepared to start over again. 7. You need to use concepts. 8. You may need to break things down into smaller units.
In 1983 at a hospital in Buenos Aires, Betti and Derechinsky introduced the concept of a modified linear accelerator for radiosurgery (1, 2). This system relied upon a 10-MV linear accelerator and used a chair based Talairach stereotactic frame (29). Other innovative developments in linear accelerator based radiosurgical devices quickly followed from Hartmann and Sturm in Heidelberg (9), Barcia-Salorio et al. (1, 2) in Valencia, Colombo et al. (3) in Vincenza, and Podgorsak et al. in Canada (32). Such interval improvements upon this fundamental concept through intensive research have been essential to major advances in clinical medicine. Although we do not wish to diminish the work of those that followed, Leksell was the one to demonstrate a true creative leap. The Gamma Knife is no exception to Leksell’s creativity and design. In fact, virtually all of the instruments that Leksell designed were beautiful, simple, and elegant. For instance, Leksell wrote that in one of the art galleries in Stockholm, “I took my stereotactic instrument and showed it to the owner of the gallery. ‘I would like to display it,’ he said” (20). Similarly, he designed a rongeur for removal of shell splinters situated in or near the spinal cord. When the Swedish instrument maker Stille advertised this instrument, they featured the instrument in the foreground and a ballerina in the background. The words across the add stated “form and balance are essential.to artistic achievement” (20). Leksell’s designs were beautiful, and the artistic influences upon his life presumably helped to influence his creativity and drive. We are not proposing that technological advances are wrong. A Luddite fear of technology would have prevented technological advances (e.g., bipolar cautery, the operating microscope, ultrasound) in neurosurgery that are critical to the way it is currently practiced. However, the assimilation and application of new technologies into the field of neurosurgery are oftentimes best accomplished when these advances are simple, elegant, and precise. Simplicity and elegance are themes that are frequently observed together in other fields too. In computer science, the present-day embrace of the Linux operating system over Windows and Mac OS is a testament to simplicity and elegance. In architecture, Frank Lloyd Wright used simple Euclidean geometry in his critically acclaimed designs and even wrote that “[S]implicity and repose are the qualities that measure the true value of any work of art.” In art, who cannot help but marvel over the superiority of simple yet beautiful paintings created by the brushes of masters such as Leonardo da Vinci or Michelangelo compared with “perfect” computer-generated art graphics. Edward de Bono wrote a book entitled Simplicity (1990; Penguin Books). In it, de Bono outlined 10 rules on the subject of simplicity, and they are as follow: 1. You need to put a very high value on simplicity. 2. You must be determined to seek simplicity. 3. You need to understand the matter very well. 4. You need to design alternatives and possibilities. 5. You need to challenge and discard existing elements.
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9. You need to be prepared to trade off other things for simplicity. 10. You need to know for whose sake the simplicity is being designed. Elegance and simplicity of design are critical elements of any good design and do not happen by shear happenstance. In fact, simplicity is often one of the first elements to succumb to the effects of ad hoc design changes or advancements of a technology. A degree of flexibility must be exercised in any field, and radiosurgery is no exception. Flexibility in design and philosophy prevents obsolescence. Flexible solutions must always be considered as an alternative and adopted so as to keep in mind future possibilities. In so doing, simplicity and elegance are not compromised by a flexible design solution. The nature of simple and elegant solutions is constantly under assault from ad hoc designs. A flexible solution that maintains and respects the principles of elegance and simplicity can still allow for advancement in a field. For example, a device that enables greater range of control or application yet still respects simplicity and elegance will normally lead to progress in the field and serve as a platform for future development. Nearly 40 years ago, few would have believed that Leksell’s Gamma Knife would have had such profound effects upon the field of neurosurgery. In 1989, the fifth Gamma Knife in the world and the second in the United States was installed at the University of Virginia. At that time, Elekta AB representatives (Stockholm Sweden), makers of the Gamma Knife, thought that two or three units would more than serve the needs of the United States. Now, nearly 200 Gamma Knife centers have treated more than 250,000 patients throughout the world. The success of the original model U Gamma Knife and subsequent models is largely to the result of Leksell’s creative leap and the simplicity and elegance of the Gamma Knife’s design. With the advent of computed tomography and magnetic resonance imaging (MRI), neurosurgeons performing stereotactic radiosurgery no longer had to rely solely upon planar X-rays, pneumoencephalography, and angiograms (21, 22). In fact, Leksell embraced the new neuroimaging technologies and wrote “NMRimaging appears to be a valuable tool for clarifying some of the still unsolved problems connected with the use of the gamma unit and will make stereotactic radiosurgery still safer and more effective” (23). He also spent time adapting his frame and other surgical devices so as to make them compatible with these newer imaging technologies (24, 27). Leksell embraced these new imaging modalities as an opportunity to improve radiosurgery. Design changes were made to accommodate computed tomography and later MRI into Gamma Knife surgery, but the simplicity and elegance of the overall unit was never compromised. The addition of MRI to orthogonal angiography in dose planning has led to a more accurate assessment of the overall nidus volume in the treatment of arteriovenous malformation. However, highly conformal radiosurgical plans for brain metastases or high-grade gliomas based upon MRI may at times translate into worse tumor
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control results. The apparent discreteness of malignant lesions on MRI is seldom the case in reality. In microsurgery, a margin is often necessary to achieve the best results, and, in radiosurgery, a margin may be prudent too. Improved conformality, however, may lessen the complication rate associated with radiosurgery (4, 7). Often, a creative leap results in an initially primitive design. For example, in 1903, the Wright brothers developed and flew the first airplane. This was a crude device, and, at the time, few would have dreamed that this airplane would lead to other planes that now permit transcontinental or even transglobal flight. Similarly, in 1974, Raymond Damadian developed a primitive device that relied upon static and dynamic magnetic fields either to determine chemical composition of a tissue or be transformed into pictures. His MRI was exceedingly crude (Figure 1). Through refinements in the original design, MRI has gone on to forever improve the field of medicine. Leksell’s original Gamma Knife was similarly primitive, and it required refinements. Those refinements represent works of excellence, whereas the original design is a work of creativity. Creative ideas revolutionize the thinking in a particular field. Advances in the Gamma Knife technology over the years have led to the development of the models B, B2, and C and to changes in the planning software from KULA to Gamma Plan. The most significant changes in the Gamma Knife to date have been in the planning software and the introduction of the automatic positioning systems (APS). The Gamma Plan software represents a much more user-friendly interface over KULA and its algorithms for dose calculations are more robust particularly when treating multiple lesions in the same session (e.g. multiple brain metastases). The APS system has led to an improvement in the conformality index and to a decrease in overall treatment time (12, 13, 34). The latter has led to improved patient satisfaction at our center. Plans using the APS frequently require more isocenters and increased total radiation time to achieve the improvements in conformality index and overall treatment time (34). The APS eliminates the concern for coordinate slippage and may prevent Gamma Knife misadministrations (6, 8). Building upon the foundations of Leksell and his Gamma Knife, many new devices have been built to delivery intracranial and extracranial radiosurgery. Devices such as the Cyberknife
Figure 1. (A) Dr. Damadian (left) with postdoctoral fellows L. Minoff and M. Goldsmith (right) standing in front of the first magnetic resonance imaging (MRI) unit, named “Indomitable.” (B) An illustration of the original MRI as depicted in the 1974 patent application.
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(Accuray, Sunnyvale, California, USA), developed by Dr. Adler of Stanford University, Synergy S (Elekta Instruments, Norcross, Georgia, USA), Novalis (Brain Lab, Munich, Germany), and Tomotherapy (Tomotherapy, Inc., Madison, Wisconsin, USA) are just a few of the units currently available. Still others are reevaluating Leksell’s original idea of focused ultrasound and exploring its possibilities for instantaneous cell death rather than the delayed effects afford by radiation (28). A device coupling focused ultrasound and MRI guidance is currently being tested for the detection of intracranial lesions (ExAblate, InSightec Inc., Tel Aviv, Israel). All of these units resemble to some degree the Gamma Knife and rely upon the biological lessons learned from it. More are likely on the way in what is a fast-moving, technologically driven field. However, many of these devices lack the simplicity and elegance of Leksell’s original design and, as a result, may not stand the test of time. The Gamma Knife, with its very limited number of moving parts, is not troubled with the isocenter verification issues encountered by most linear accelerator based radiosurgical systems (29). It remains to be seen how much of an improvement in tumor control and a decrease in morbidity these changes in hardware and software will actually afford. For instance, one of the earliest Gamma Knife series reported arteriovenous malformation obliteration rates of approximately 80% in optimal treated lesions (39). That series largely relied upon angiographic imaging alone and relatively primitive dose planning. Despite the incorporation of stereotactic MRI, computerized algorithms, robotics, and multiple isocenter plans, the outcomes in modern radiosurgical series for patients with arteriovenous malformations remain essential the same (5, 10, 11, 26, 31, 33, 36, 37). In the modern era, complication rates associated with the radiosurgery of vestibular schwannomas have decreased. However, rather than being a result of hardware or software development, this appears to be a function of refined dose selection from the original margin dose of 25e35 Gy prescribed by Leksell to 12e13 Gy currently given by most centers (4, 18, 30, 35). Will the outcomes of the modern era of radiosurgery be remarkably better than those in its beginning? If so, do any observed improvements in results arise from technological advances or simply more appropriate dose selection? Should neurosurgeons continue to focus on robotics, new preoperative or intraoperative neuroimaging modalities and more sophisticated computer planning software as a means of improving radiosurgical outcomes? Alternately, should neurosurgeons look to other energy sources (e.g., focused ultrasound) as the next creative leap in neurosurgical doctrine? Rigorous comparison and analysis of early and modern results will help to answer this question and may shed light on ways to further improve radiosurgery. The more disconcerting change has been that the added sophistication of these devices has threatened the leadership of neurosurgeons in the application of radiosurgery to central nervous system pathology. Leksell maintained that the neurosurgeon was the best at selecting, treating, and managing radiosurgical patients. Neurosurgeons are uniquely trained to understand neuroanatomy in the setting of neuropathology and the behavior, clinical symptoms, and alternative treatments of central nervous system lesions. Neurosurgeons are best able to administer radiosurgery and to care for the patient before, during, and after the procedure.
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As the field of radiosurgery evolves, neurosurgeons should look to the past for creative inspiration. The principles of simplicity and elegance that Leksell held so dear should be steadfastly protected. The best pathway for future progress will be a design
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that incorporates flexible change yet still adheres to simplicity and elegance. Moreover, for the sake of the patients, neurosurgeons must continue to play a leadership role in the field of radiosurgery.
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