Beam Radiosurgery History
Stephen B. Tatter, M.D., Ph.D.
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.
Bragg-peak Proton Radiosurgery
Experience with Pituitary 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 used.
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
Kjellberg Risk Prediction Curve
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.
of Imaging and Treatment Planning Techniques
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,
of Beam Delivery and Patient Positioning
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.
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
WE, Ogilvy CS, Chapman PH, Verhy L , Zervas NT. "Stereotactic
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Baseline and Trends, ed. L. Steiner. 85-91. New York: Raven
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.
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.
JC: The integrated logistic formula and predictions of complications
from radiosurgery. Int J Radiat Oncol Biol Phys 23:879-85,
KP, Verhey LJ, Wagner M: Computer-assisted positioning of radiotherapy
patients using implanted radiopaque fiducials. Medical Physics
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.
RN, Shintani A, Frantz AG, Kliman B: Proton-beam therapy in acromegaly.
New England Journal of Medicine 278:689-95, 1968.
B, Leksell L, Rexed B , et al: The high energy proton beam
as a neurosurgical tool. Nature 182:1222-3, 1958.
L: The stereotaxic method and radiosurgery of the brain. Acta
Chir Scand 102:316-19, 1951.
L: A note on the treatment of acoustic tumors. Acto Chir Scand
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,
CA, Lawrence JH, Born JL , et al: Pituitary irradiation
with high-energy proton beams. A preliminary report. Cancer
Res 18:121-34, 1958.
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
RR: Radiological use of fast protons. Radiology 47:487-91,