ABOUT 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 to 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 beams coupled to the stereotactic frame. Leksell’s revolutionary concept preceded by decades the technology that could bring it to full fruition. Radiotherapy devices were of low energy, and imaging of the brain was limited to plain X-rays, and pneumo-encephalograms. Leksell continued to experiment with radiation sources during the next 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 Sophia Hemmet Hospital in Stockholm in 1968. The first treatment with this device was a gamma-thalamotomy for control of intractable pain in a cancer patient.

At the University of California Berkeley helium ions accelerated to very high energies by the cyclotron were used to treat human patients since the early 1950’s, relying on the Bragg peak effect.   This facility was founded by the late Dr. John Lawrence, brother of Dr. Ernest O. Lawrence, who received the Nobel Prize in Physics for the invention of the cyclotron. Lawrence commenced stereotactic radiosurgery with the treatment of pituitary disorders. Dr. Jacob Fabrikant continued this program with 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.

Thus all radiosurgery facilities in the early 1960's were charged particle based, and these early years saw broadening of the indications to include vascular malformations and intracranial tumors. Much of our current knowledge on the radiobiology of radiosurgery stems from this time frame. 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 was also the time frame for learning about 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.

The 1980's saw this approach pushing forward now with 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 good effect. Osvaldo Betti in Buenos Aires developed a linear accelerator approach, with the patient seated in a rotating chair, and a linear accelerator (linac) describing coronal non-coplanar arcs around the isocenter. Federico Colombo in Vincenza was another linac pioneer, whose first report of a multiple non-coplanar arc paradigm utilizing rotation of the linac couch was first published in 1984.

Wendell Lutz and Ken Winston working together in Boston added in 1986  their rectilinear linac phantom pointer system which was widely adopted as a method of mechanical calibration of the system’s accuracy. William Friedman and Frank Bova from the University of Florida created in 1988 a complete linac system 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 to radiosurgical treatment planning. This device was commercialized and marketed by Philips.

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.

In 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 conformality to target.

It was evident during the 1990's 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, putting together the time-proven 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, robotics, and radiation gating made practical the spread of stereotactic radiosurgery to other parts of the body. 

Technological advances are continuously transforming the time-honored 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 are also doing today frameless radiosurgery in the head, spine, lungs, liver and prostate.

The field of extracranial radiosurgery is rapidly increasing and it is clear that it will represent a revolution in the treatment of lung and prostate cancer as radiosurgery has been for the treatment of brain metastases. Small peripheral lung cancers, as well as small prostate cancers can be treated curatively via a stereotactic approach.
The treatment paradigm would not continue to be a legitimate approach if there was not ongoing evaluation of the process and outcome of these still novel methods.

A wealth of scientific information has evolved from the careful prospective monitoring of patients undergoing treatment with modern stereotactic techniques. A technique that expanded after the concept of evidence-based medicine was already well entrenched, radiosurgery is probably the best documented treatment technique in the field of the clinical neurosciences. Data for mid and long term results in large patient cohorts are already maturing and being reported.

As the only organization that gathers all the professionals and all the technologies in the field, the ISRS and its biennial Congress are the best forum for the interchange of experiences and the promotion of this ever evolving subspecialty.