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History - Brain radiosurgery

The concept, the first applications and even the denomination “Radiosurgery” were all defined by the Swedish neurosurgeon Lars Leksell in a seminal article published in 1951. Three years before that Leksell had created one of the first stereotactic apparatus intended for human use. Stereotaxis enables the accurate targeting of any point within the skull and inserting an electrode or needle with high precision into that point.

Leksell, in his lifetime search for less invasive means to treat intracranial disease, conceived the concept of replacing the electrode with a source of ionizing radiation coupled to the stereotactic frame. Leksell’s revolutionary concept preceded by decades the technology that would bring it to full fruition. Radiotherapy devices were low energy, and imaging of the brain was limited to plain X-rays, angiography and pneumo-encephalograms.

Leksell continued to experiment with radiation sources over the following 15 years using particle beams generated by the Uppsala cyclotron. The first clinically efficient radiosurgical device, the 179 source Cobalt 60 Gamma Knife prototype, was designed by Leksell and his associate Borje Larsson and installed in the Sophiahemmet Hospital in Stockholm in 1968. The first treatment after installation of this device was a gamma-thalamotomy for control of intractable pain in a cancer patient.

Helium ions accelerated to very high energies by means of the cyclotron were employed at the University of California Berkeley to treat human patients since the early 1950’s, relying on the Bragg peak effect. The facility was founded by the late Dr. John Lawrence, brother of Dr. Ernest O. Lawrence, who was awarded the Nobel Prize in Physics for the invention of the cyclotron. Lawrence commenced stereotactic radiosurgery by treating pituitary disorders. Dr. Jacob Fabrikant went on to launch a highly successful program for the treatment of intracranial arteriovenous malformations (AVMs) and pituitary adenomas.
The Boston-based neurosurgeon Dr. Ray Kjellberg, after visiting Dr. Leksell in Stockholm, initiated stereotactic irradiation with protons from the Harvard cyclotron in the late 1950's, again utilizing the Bragg peak effect. Dr. Kjellberg published extensively on his experience with AVMs and pituitary tumors.

All radiosurgery facilities in the early 1960's were charged-particle based, and those early years saw a broadening of the indications to include vascular malformations and intracranial tumors. Much of our current knowledge on the radiobiology of radiosurgery stems from this timeframe. It became apparent that vascular obliteration of AVMs, and control of pituitary adenomas, with hormonal reduction or normalization for the functioning tumors, was achievable. This period was also marked by important findings in terms of normal tissue reactions, with Kjellberg's 1% dose volume isoeffect line for radiation necrosis being reported. Borje Larsson developed radiobiological models in animals, the end point being necrosis demonstrating the interconnection between dose and volume.

In the 1980's this approach made giant strides thanks to better and more patient friendly stereotactic devices. Barcia-Salorio in Madrid used a fixed cobalt device rotating around the patient's head to treat a carotid cavernous fistula with a positive outcome. Osvaldo Betti in Buenos Aires developed a linear accelerator approach, whereby the patient was sitting on a rotating chair, while a linear accelerator (linac) described coronal non-coplanar arcs around the isocenter. Federico Colombo in Vicenza was another linac pioneer, whose first report on a multiple non-coplanar arc paradigm, with rotation of the linac couch, was first published in 1984.
In 1986  Wendell Lutz and Ken Winston, who collaborated in Boston, introduced their rectilinear linac phantom pointer system, which was widely adopted as a method of mechanical calibration of the system’s accuracy. In 1988 William Friedman and Frank Bova from the University of Florida created a complete linac system, thus achieving excellent mechanical accuracy by means of a floor mount ring holder and a collimator holder uncoupled from the linac head. Their system was also the first one to introduce high-end 3D computer graphics and dosimetry in radiosurgical treatment planning. This device was marketed by Philips. 

The first Gamma Knife built by Drs. Leksell and Larsson was donated to the University of California in Los Angeles (UCLA) and treated patients in that institution by Dr. Robert Rand in the early 1980’s.

In 1987 the first 201 source Gamma Knife (Model U) in the United States was installed at the University of Pittsburgh under the direction of Dade Lunsford. This installation and the wealth of clinical data that began to be reported by the Pittsburgh group, represented a pivotal point in the recognition of radiosurgery as an important therapeutic tool.

Over the last 20 years we have seen a virtual explosion of facilities around the world capable of providing this treatment approach. Concurrently the indications for radiosurgery have expanded to a host of benign and malignant tumors, and functional applications such as trigeminal neuralgia, focal epilepsy, movement and mood disorders.  
The computer revolution and the increasing sophistication of brain imaging have been instrumental to increase both the reach and the quality of radiosurgery. MRI fusion software enabled much better definition of the lesions to be treated, and normal structures to be avoided. All treatment approaches developed more sophisticated delivery capabilities and treatment delivery verification now became feasible including the use of more accurate dosimetric algorithms.
Strictly conformal radiation delivery became an achievable goal with powerful computers. The Gamma Knife evolution to automatic positioning system, or APS, (1999) made the use of more isocenters a reasonable undertaking. The introduction of the first micro multileaf collimator in 1997 (Brainlab’s M3) stirred the linac systems into a completely different paradigm of single isocenter conformal beams and later conformal dynamic rotation for the achievement of radiation conformity to target, having the first completely dedicated linear accelerator device installed at UCLA that year by Drs. Antonio De Salles and Timothy Solberg.

During the 1990's it was proposed that there were certain intracranial lesions that because of site or size were not appropriately treated in a single session, and thus the field of fractionated stereotactic radiation (FSR) was born, aiming to use the biological advantages of fractionated radiation, with the increased accuracy of stereotactic localization. FSR was first done with relocatable stereotactic devices and more recently with frameless methods (frameless radiosurgery), due to the availability of real time imaging and matching techniques.  
These technologies, including robotics spearheaded by the Dr. John Adler and his team at Stanford University in California, and radiation gating made practical the spread of stereotactic radiosurgery to other parts of the body. 

Technological advances are continuously transforming the time-honoured tools for radiosurgery, enhancing and extending their capabilities.

The Gamma-knife, the archetypical photon beam radiosurgery device has been progressively transformed in a completely automated system by means of robotic automatic positioning of the isocenter and lately, dynamic change of collimator openings. Particle beams continue to be used although their cost and complicated setup have limited their availability. Specialized linacs such as the Tomotherapy system deliver radiosurgery with a non-isocentric gating paradigm from a rotating gantry that enables real time imaging and treatment of several lesions simultaneously.
The Cyberknife is another example of a non-isocentric linac radiosurgery system mounted on an industrial robot and coupled with on-line imaging. The system can readily address lesions in the spine and extra neural organs using frameless technology.
Similar technologies (online imaging and robotic positioning) have been applied to the more classical linac radiosurgery systems. Dedicated linacs such as the Novalis and Truebeam are also performing today frameless radiosurgery.