Professor of Neurosurgery and Director Radiosurgery and Stereotactic Surgery Stanford University School of Medicine, USA.
Surgery on the human body is almost as old as history. Evidence has been unearthed of surgery having been performed in ancient Egypt, Greece, India and China. Throughout the millennia surgical procedures have evolved into effective and precise therapeutic interventions. However, the history of the surgical experience for patients is marked by pain, blood, and risk to life and limb. The evolution of surgery may have been driven as much by the need to reduce its fearsome accompaniments as to improve the therapeutic outcome. Nevertheless, surgery is still widely viewed as both a powerful form of medicine and, because of the attendant suffering and risks, something of a last resort that should be reserved for the gravest of illnesses. Many of these deeply entrenched perceptions are being challenged by the rapidly growing scope of radiosurgery.
The concept of radiosurgery is attributable to the Swedish Neurosurgeon Lars Leksell, who described its basic elements in the 1950s. Simply put, radiosurgery precisely targets many cross-fired pencil beams of ionising (therapeutic) radiation to deliver large doses to destroy diseased tissue without injuring adjacent anatomy. In the 1960s and 70s, Leksell combined stereotactic frame-based targeting (using the frame he invented which was attached to the skull) with a specialised radioactive cobalt-charged apparatus and created Gamma Knife radiosurgery. Over the past 3 decades, the Gamma Knife and radiosurgical technologies developed since have literally transformed the treatment of brain disorders ranging from tumours to vascular malformations to facial pain. Despite the huge impact of the Gamma Knife on brain surgery, the biologic principles of radiosurgery are not inherently restricted to the head.
Although the frame-based design of first-generation technology restricted radiosurgery to lesions outside the cranium, if pathologic lesions could be targeted without stereotactic frames, extra cranial lesions might also be treated radiosurgically.
The CyberKnife was invented at Stanford University and Silicon Valley in the early 1990s grounded in the belief that radiosurgical ablation could significantly benefit many patients with extra cranial disorders if skeletally attached frames could be eliminated. The invention of computerised image guidance proved critical to achieving the objective of a universal targeting apparatus. The CyberKnife utilises a targeting technology developed specifically for this instrument called x-ray image-to-image correlation. This localisation method automatically compares live orthogonal x-ray images with digitally reconstructed radiographs (DRRs) made from the patient’s original CT scan. Because a rigidly fixed frame of reference is not required, the CyberKnife system is uniquely able to aim a beam of therapeutic radiation at virtually any anatomic site with radiosurgical precision.
The CyberKnife system also includes a robotic delivery mechanism, capable of flexibly and accurately targeting a compact LINAC source without a defined isocenter; all other radiation delivery systems are constrained to delivering radiation beams around and through a fixed point in space known as the isocenter. Taken together, these attributes make the CyberKnife system the first device to offer autonomous image-guided radiosurgery, a technology that was commercialised by Accuray Incorporated (Sunnyvale, CA, USA). The CyberKnife was awarded FDA clearance to treat tumours throughout the head and neck region in 1999. This clearance was expanded in 2001 to allow radiosurgery throughout the body.
Because many tumours in the chest and abdomen move with breathing a new system, the Synchrony™ Respiratory Tracking System (Accuray, Inc.), was added to the CyberKnife System in 2002. This technology correlates real time chest wall movements sensed by LED camera arrays on the patient’s chest with the position of gold seeds placed in or near the tumour and detected in orthogonal x-rays that are shot periodically during the procedure. The tumour position is calculated based on this correlation and fed back to the robot, which dynamically adjusts the aim of the radiation beam to compensate for the movement of the tumour. The constellation of technologies that make up a modern CyberKnife system enable radiosurgery to be delivered with sub-millimeter accuracy to static lesions and better than 2 mm accuracy to targets that move with respiration.
The CyberKnife was initially approved for brain applications, and treatment parameters were based largely on Gamma Knife experience. Since similar pathologies occur throughout the central nervous system, CyberKnife radiosurgery was rapidly expanded to include a broad range of lesions along the spinal axis. A growing body of medical literature now demonstrates the efficacy and safety of CyberKnife spinal radiosurgery for a range of intra and para-spinal tumours, and such treatment is entering the mainstream of clinical practice. Because no frame is required for accurate targeting, the CyberKnife permits a new approach to radiosurgery for certain brain lesions. For example, a multi-session approach (performed over 3-5 days) has been shown to result in higher rates of hearing preservation among patients with acoustic neuroma while a similar fractionated approach permits larger lesions and peri-optic tumours to be treated safely. Although such flexibility has greatly expanded the scope of neurosurgical diseases treated with radiosurgery, the impact of the CyberKnife has been even greater in other surgical disciplines.
In its initial years, most CyberKnife treatments were intracranial. However, thanks in part to an emerging group of participating surgical specialists, such as urologists, thoracic and general surgeons, an expanding percentage of CyberKnife treatments now target tumours within the chest, abdomen or pelvis. Moreover, there are a growing number of peer-reviewed outcome studies that document the effectiveness of such treatment for non-neurological neoplasms. For example, outpatient radiosurgery for unresectable pancreatic cancer achieves very high levels of local control and palliation; some of the more important endpoints compare favourably with much more invasive alternative therapies. In addition several published studies utilising less precise (than the CyberKnife) high dose irradiation to treat early-stage lung cancer patients now demonstrate long-term survival that mirrors open surgical resection.
Although the total number of prostate cancer patients treated with a 5-day course of CyberKnife radiosurgery to date is modestly small, recent preliminary data from Stanford University suggests that the incidence of side effects and tumour control as judged by prostate specific antigen (PSA) compare favourably with more invasive or lengthy procedures. The emergence of these new extra cranial procedures is gradually validating the CyberKnife’s original vision.
As the scope of practice expands, it is clear that the field of radiosurgery embodies dimensions of both surgery and radiation therapy. The aggressive application of anatomically precise ablative radiation against small early stage lesions has much in common with other forms of surgery. However, the basic use of therapeutic radiation, the frequent necessity to site CyberKnife systems in existing radiation departments, and the heavy focus on the management of cancer is more akin to the traditional domains of radiation therapy. Most of CyberKnife radiosurgery is practised as a multi-disciplinary procedure involving both surgical specialists and radiation oncologists, thereby reflecting its surgical and radiation therapy dimensions.
At present, more than 80 CyberKnife systems have been installed worldwide, with 24 of them in Asia, and something in excess of 20,000 patients have been treated. Moreover, more than 100 peer-reviewed publications have detailed both the performance of image-guided radiosurgery and clinical outcomes for a wide spectrum of disorders.
What is the future of the CyberKnife likely to encompass? Reminding oneself that the essence of radiosurgery is merely the non-invasive destruction of tissue with precision radiation, one can readily envision numerous technical improvements to the CyberKnife over the next decade that will facilitate this primary goal. Incremental improvements in targeting accuracy combined with ever better shaping of the field of radiation and appreciably faster treatment times will allow continued extension of radiosurgery into new clinical realms. For example, the more efficient treatment of metastatic disease may allow radiosurgery to effectively substitute for chemotherapy in patients with limited metastases, thereby precluding the complications of systemic treatments. Furthermore, clinical studies are being conducted that involve treating benign conditions ranging from painful facet syndrome (back pain) to atrial fibrillation with the CyberKnife. If only some of these studies demonstrate the utility of the CyberKnife, the field of radiosurgery could expand far beyond even the most ambitious of current expectations, and further challenge conventional notions about the nature of surgery.