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History of Stereotactic Radiosurgery

Tatter, M.D., Ph.D.

     Crossfire Proton-beam Treatments

          In 1946, Wilson first proposed the clincial use of
          charged-particle beams because of their unique characteristics.14
          Lars Leksell adressed the theoretical and many practical aspects
          of stereotactic radiosurgery in 1951.9 Using the Uppsala
          University cyclotron Leksell and Borje Larsson, a radiobiologist,
          used a cross fired proton beam in intial experiments in animals
          and in the first treatments of human patients.8 These treatments
          used the plataeu ionization portion of the beam's energy rather
          than the focal Bragg peak at its end.

     Early Bragg-peak Proton Radiosurgery

          In 1954, John Lawrence began to use the Berkely cyclotron's Bragg
          peak to irradiate the pituitaries of patients with metastatic
          breast cancer for hormonal suppression.12 The first thirty
          patients were treated with protons and thereafter helium ions were

          In 1961 Raymond Kjellberg began treating patients using the Bragg
          peak of protons from the Harvard Cyclotron Laboratory.7 This was
          soon followed by similar efforts led by V.S. Koroshkov in Moscow.

     Early Experience with Pituitary Radiosurgery

          Pituitary lesioning and subsequently treatment of adenomas were
          the first successful applications of radiosurgery because of the
          ability to localize the sella turcica on plane radiographs. The
          main risks of such treatment was injury to the cranial nerves.13
          Late hypopituitarism is also confirmed as an expected result of
          successful control of secretory and non-functioning adenomas.

     The Kjellberg Risk Prediction Curve

          Ateriovenous malformations were the first parenchymal lesions on
          which radiosurgery was extensively evaluated. Development of
          single-dose radiation for this type of lesion required
          determination of the tolerance of normal brain and of the brain
          surrounding AVMs to radiosurgical doses. Using a combination of
          clinical and experimental observations, Kjellberg proposed the
          standard dose effect curves for radiation necrosis in proton
          therapy of the brain.6 It is of particular note that Kjellberg's
          one percent dose-diameter line for radiation necrosis also serves
          as the basis for gamma knife and linear accelerator dosimetry.4,

     Evolution of Imaging and Treatment Planning Techniques

          Initial attempts at proton radiosurgery were limited by
          neuroradiologic techniques which prevented successful three
          dimensional treatment planning. These limitations were first
          overcome for proton radiosurgery of the pituitary because of its
          midline symmetry and because of the presence of reliable bony
          landmarks visible on conventional radiographs. Stereotactic
          treatment of arteriovenous malformations began in 1963 and was
          based on a stereotactic guidance device and angiograms.6 Some
          tumors including skull base lesions could be adequately localized
          by pneumoencephelography. Leksell performed the first such
          treatment, radiating a vestibular schwannoma in 1969.10 Treatment
          of the majority of intracranial tumors required the ability to
          image three dimensionally and awaited the widespread availability
          of computed tomography and magnetic resonance imaging.

     Evolution of Beam Delivery and Patient Positioning

          Intital efforts at beam delivery used conventional radiographs and
          stereotactic immobilization to identify targets. Three-dimensional
          stereotactic techniques were then applied to radiosurgery, but
          required continuous immobilization of the patient in the
          sterotactic apparatus from the time of imaging to the completion
          of the treatment. Transposition of three-dimensional imaging
          information to conventional X-ray stereotactic space was possible
          but somewhat inconvenient and occassionally inaccurate.3 More
          recently, implanted skull fiducials have been employed to allow
          reproducible correlation of conventional radiographs with
          three-dimensional imaging.1, 5 This makes fractionated proton
          therapy practicle and may allow a further increase in the
          risk-to-benefit ratio of particle beam radiosurgery.

          Beam scanning is another technique under development to allow
          optimization of delivery. Current proposals involve using
          electromagnetic beam modulators to move the single Bragg peak
          through the entire treament volume rather than using a fixed
          number of static beams.

          A patient positioning system known as STAR (stereotactic alignment
          for radiosurgery) is currently in use at the Harvard Cyclotron.2
          It uses the target-centered principle, allowing complete
          rotational freedom once the linear coordinates of the target have
          been defined. It is compatible with any orthogonal or radial
          stereotactic coordinate system and accepts targets obtained
          directly from computed tomography, magnetic resonance imaging, and
          angiography. This arrangement is required to allow the
          implementation of line-of-sight treament planning because the
          Harvard beam is limited to the horizontal position. Another
          solution to this challenge used by some new medically-dedicated
          particle beams are designs that allow protons to be delivery from
          arbitrary angles rather than from a horizontal beam.


   * Butler WE, Ogilvy CS, Chapman PH, Verhy L , Zervas NT. "Stereotactic
     alignment for Bragg peak radiosurgery." In Radiosurgery: Baseline and
     Trends, ed. L. Steiner. 85-91. New York: Raven Press, 1992.
   * Chapman PH, Ogilvy CS , Butler WE. "A new stereotactic alignment system
     for charged-particle radiosurgery at the Harvard Cyclotron Laboratory,
     Boston." In Stereotactic Radiosurgery, ed. Eben Alexander III, Jay S.
     Loeffler, and L. Dade Lunsford. 105-108. New York: McGraw-Hill, 1993.
   * De Salles AA, Asfora WT, Abe M, Kjellberg RN: Transposition of target
     information from the magnetic resonance and computed tomography scan
     images to conventional X-ray stereotactic space. Applied
     Neurophysiology 50:23-32, 1987.
   * Flickinger JC: The integrated logistic formula and predictions of
     complications from radiosurgery. Int J Radiat Oncol Biol Phys
     23:879-85, 1989.
   * Gall KP, Verhey LJ, Wagner M: Computer-assisted positioning of
     radiotherapy patients using implanted radiopaque fiducials. Medical
     Physics 20:1153-9, 1993.
   * Kjellberg RN, Hanamura T, Davis KR, Lyons SL , Adams RD: Bragg-peak
     proton-beam therapy for arteriovenous malformations of the brain. New
     England Journal of Medicine 309:269-74, 1983.
   * Kjellberg RN, Shintani A, Frantz AG, Kliman B: Proton-beam therapy in
     acromegaly. New England Journal of Medicine 278:689-95, 1968.
   * Larsson B, Leksell L, Rexed B , et al: The high energy proton beam as a
     neurosurgical tool. Nature 182:1222-3, 1958.
   * Leksell L: The stereotaxic method and radiosurgery of the brain. Acta
     Chir Scand 102:316-19, 1951.
   * Leksell L: A note on the treatment of acoustic tumors. Acto Chir Scand
     137:763-5, 1969.
   * Saunders WM, Winston KR, Siddon RL , et al: Radiosurgery for
     arteriovenous malformations of the brain using a standard linear
     accelerator. Rationale and technique. Int J Radiat Biol Phys 15:441-7,
   * Tobias CA, Lawrence JH, Born JL , et al: Pituitary irradiation with
     high-energy proton beams. A preliminary report. Cancer Res 18:121-34,
   * Urie MM, Fullerton B, Tatsuzaki H, Birnbaum S, Suit HD, Convery K,
     Skates , Goitein M: A dose response analysis of injury to cranial
     nerves and/or nuclei following proton beam radiation therapy.
     International Journal of Radiation Oncology, Biology, Physics 23:27-39,
   * Wilson RR: Radiological use of fast protons. Radiology 47:487-91, 1946.

by MGH Neurosurgical Service 1998