Cyberknife

The CyberKnife is a frameless robotic radiosurgery system used for treating benign tumors, malignant tumors and other medical conditions.^[1][2] The system was invented by John R. Adler, a Stanford University Professor of Neurosurgery and Radiation Oncology, and Peter and Russell Schonberg of Schonberg Research Corporation. It is made by the Accuray company headquarterd in Sunnyvale, California.

The CyberKnife system is a method of delivering radiotherapy, with the intention of targeting treatment more accurately than standard radiotherapy.^[3] The two main elements of the CyberKnife are (1) the radiation produced from a small linear particle accelerator and (2) a robotic arm which allows the energy to be directed at any part of the body from any direction.

The main features of the CyberKnife system, shown on a Fanuc robot

Main features

Several generations of the CyberKnife system have been developed since its initial inception in 1990. There are two major features of the CyberKnife system that are different from other stereotactic therapy methods.

Robotic mounting

The first is that the radiation source is mounted on a general purpose industrial robot. The original CyberKnife used a Japanese Fanuc robot,^[4] however the more modern systems use a German KUKA KR 240.^[5] Mounted on the Robot is a compact X-band linac that produces 6MV X-ray radiation. The linac is capable of delivering approximately 600 cGy of radiation each minute - a new 800 cGy / minute model was announced at ASTRO^[6][7] 2007. The radiation is collimated using fixed tungsten collimators (also referred to as "cones") which produce circular radiation fields. At present the radiation field sizes are: 5, 7.5, 10, 12.5, 15, 20, 25, 30, 35, 40, 50 and 60 mm. ASTRO 2007 also saw the launch of the IRIS^[7] variable-aperture collimator which uses two offset banks of six prismatic tungsten segments to form a blurred regular dodecagon field of variable size which eliminates the need for changing the fixed collimators. Mounting the radiation source on the robot allows near-complete freedom to position the source within a space about the patient. The robotic mounting allows very fast repositioning of the source, which enables the system to deliver radiation from many different directions without the need to move both the patient and source as required by current gantry configurations.

Image guidance

The image guidance system is the other distinction of the CyberKnife system. X-ray imaging cameras are located on supports around the patient allowing instantaneous X-ray images to be obtained.

6D skull

The original (and still utilized) method is called 6D or skull based tracking. The X-ray camera images are compared to a library of computer generated images of the patient anatomy. Digitally Reconstructed Radiographs (or DRR's) and a computer algorithm determines what motion corrections have to be given to the robot because of patient movement. This imaging system allows the CyberKnife to deliver radiation with an accuracy of 0.5mm without using mechanical clamps attached to the patient's skull.^[8] The use of the image guided technique is referred to as frameless stereotactic radiosurgery. This method is referred to as 6D because corrections are made for the 3 translational motions (X,Y and Z) and three rotational motions. It should be noted that it is necessary to use some anatomical or artificial feature to orient the robot to deliver X-ray radiation, since the tumor is never sufficiently well defined (if visible at all) on the X-ray camera images.

6D Skull tracking

Xsight

Additional image guidance methods are available for spinal tumors and for tumors located in the lung. For a tumor located in the spine, a variant of the image guidance called Xsight-Spine^[9] is used. The major difference here is that instead of taking images of the skull, images of the spinal processes are used. Whereas the skull is effectively rigid and non-deforming, the spinal vertebrae can move relative to each other, this means that image warping algorithms must be used to correct for the distortion of the X-ray camera images.

A recent enhancement to Xsight is Xsight-Lung^[10] which allows tracking of some lung tumors without the need to implant fiducial markers.

Fiducial

For soft tissue tumors, a method known as fiducial tracking can be utilized.^[11] Small metal markers (fiducials) made out of gold for bio-compatibility and high density to give good contrast on X-ray images are surgically implanted in the patient. This is carried out by an interventional radiologist, or neurosurgeon. The placement of the fiducials is a critical step if the fiducial tracking is to be used. If the fiducials are too far from the location of the tumor, or are not sufficiently spread out from each other it will not be possible to accurately deliver the radiation. Once these markers have been placed, they are located on a CT scan and the image guidance system is programmed with their position. When X-ray camera images are taken, the location of the tumor relative to the fiducials is determined, and the radiation can be delivered to any part of the body. Thus the fiducial tracking does not require any bony anatomy to position the radiation. Fiducials are known however to migrate and this can limit the accuracy of the treatment if sufficient time is not allowed between implantation and treatment for the fiducials to stabilize.^[12][13]

Synchrony

The final technology of image guidance that the CyberKnife system can use is called the Synchrony system. The Synchrony system is utilized primarily for tumors that are in motion while being treated, such as lung tumors and pancreatic tumors.^[14]

The synchrony system uses a combination of surgically placed internal fiducials, and light emitting optical fibers (markers) mounted on the patient skin. Since the tumor is moving continuously, to continuously image its location using X-ray cameras would require prohibitive amounts of radiation to be delivered to the patients skin. The Synchrony system overcomes this by periodically taking images of the internal fiducials, and predicting their location at a future time using the motion of the markers that are located on the patient's skin. The light from the markers can be tracked continuously using a CCD camera, and are placed so that their motion is correlated with the motion of the tumor.

A computer algorithm creates a correlation model that represents how the internal fiducial markers are moving compared to the external markers. The Synchrony system is therefore continuously predicting the motion of the internal fiducials, and therefore the tumor, based on the motion of the markers. The correlation model can be updated at any time if the patient breathing becomes in any way irregular. The advantage of the Synchrony system is that no assumptions about the regularity or reproducibility of the patient breathing have to be made.

To function properly, the Synchrony system requires that for any given correlation model there is a functional relationship between the markers and the internal fiducials. The external marker placement is also important, and the markers are usually placed on the patient abdomen so that their motion will reflect the internal motion of the diaphragm and the lungs.

RoboCouch

A new robotic six degree of freedom patient treatment couch called RoboCouch^[15] has been added to the CyberKnife which provides the capability for significantly improving patient positioning options for treatment.

Frameless

The frameless nature of the CyberKnife also increases the clinical efficiency. In conventional frame-based radiosurgery, the accuracy of treatment delivery is determined solely by connecting a rigid frame to the patient which is anchored to the patient’s skull with invasive aluminum or titanium screws. The CyberKnife is the only radiosurgery device that does not require such a frame for precise targeting.^[16] Once the frame is connected, the relative position of the patient anatomy must be determined by making a CT or MRI scan. After the CT or MRI scan has been made, a radiation oncologist must plan the delivery of the radiation using a dedicated computer program, after which the treatment can be delivered, and the frame removed. The use of the frame therefore requires a linear sequence of events that must be carried out sequentially before another patient can be treated. Staged CyberKnife radiosurgery is of particular benefit to patients who have previously received large doses of conventional radiation therapy and patients with gliomas located near critical areas of the brain. Unlike whole brain radiotherapy, which must be administered daily over several weeks, radiosurgery treatment can usually be completed in 1-5 treatment sessions. Radiosurgery can be used alone to treat brain metastases, or in conjunction with surgery or whole brain radiotherapy, depending on the specific clinical circumstances.^[17]

By comparison, using a frameless system, a CT scan can be carried out on any day prior to treatment that is convenient. The treatment planning can also be carried out at any time prior to treatment. During the treatment the patient need only be positioned on a treatment table and the predetermined plan delivered. This allows the clinical staff to plan many patients at the same time, devoting as much time as is necessary for complicated cases without slowing down the treatment delivery. While a patient is being treated, another clinician can be considering treatment options and plans, and another can be conducting CT scans.

In addition, very young patients (pediatric cases) or patients with fragile heads because of prior brain surgery cannot be treated using a frame based system.^[18] Also, by being frameless the CyberKnife can efficiently re-treat the same patient without repeating the preparation steps that a frame-based system would require.

The delivery of a radiation treatment over several days or even weeks (referred to as fractionation) can also be beneficial from a therapeutic point of view. Tumor cells typically have poor repair mechanisms compared to healthy tissue, so by dividing the radiation dose into fractions the healthy tissue has time to repair itself between treatments.^[19] This can allow a larger dose to be delivered to the tumor compared to a single treatment.^[20]

Comparison with other stereotactic systems

Gamma Knife

One of the most widely known stereotactic radiosurgery systems is the Gamma Knife. The Gamma Knife was originally developed by Lars Leksell, remains the gold standard method for delivery of stereotactic radiosurgery to the brain, and is manufactured by Elekta. John Adler, the inventor of the CyberKnife system spent time training with Lars Leksell in Stockholm at the Karolinska Institute in 1985. The GammaKnife system typically uses 201 Cobalt-60 sources located in a ring around a central treatment point ("isocenter"). The Gamma Knife system is equipped with a series of 4 collimators of 4mm, 8mm, 14mm and 18mm diameter, and is capable of submillimeter accuracies. The Gamma Knife system does however require a head frame to be bolted onto the skull of the patient, and is only capable of treating cranial lesions. As a result of frame placement, treatment with Gamma Knife does not require real time imaging capability as the frame does not allow movement during treatment. Operators of the Gamma Knife system have argued that it is likely to be more accurate than CyberKnife for these reasons.^[21] The Cyberknife Society and Accuray maintain that there are no peer-reviewed published papers that establish Gamma Knife as being more accurate than CyberKnife.^[22][23]

Novalis

Another popular stereotactic system is the Novalis produced by Brainlab.^[24] The Novalis radiosurgery system utilizes a small computer-controlled micro Multi Leaf Collimator (mMLC) that can produce many complicated shapes. The maximum radiation field size that the Novalis can produce is 98 mm x 98 mm and the minimum is 3 mm x 3 mm, allowing a considerable range of tumors to be treated. The Novalis system also has X-ray imaging using amorphous silicon flat panel X-ray detectors. A 2D/3D image fusion of the patient setup X-rays with digitally reconstructed radiographs from a planning CT scan quickly determines a correction vector for the patient's position. Infrared fiducial markers attached to the patient then allow precise tracking of the correction vector's application to the patient's position via an infrared camera, and a couch that can move in all six dimensions enables the precise positioning of the patient. Patient immobilization can also be performed framelessly with ExacTrac Patient Positioning,^[25] which uses high-resolution stereoscopic X-Ray images to detect and visualize the patient's internal anatomy before or during treatment.^[26] Novalis has become a leading player in the world of neurosurgery.^[27]

Conventional linac

Conventional X-ray therapy linear accelerators can be utilized for radiosurgery, either by the use of additional blocking cones or by a removable or built in micro MLC system. Examples of removable micro MLC units are the Ergo from 3D line,^[28] the mMLC manufactured by Brainlab,^[29] and the AccuKnife produced by Direx.,^[30] or the Novalis TX

Clinical uses

Since August 2001, the CyberKnife system has FDA clearance for treatment of tumors in any location of the body.^[31] Some of the tumors treated include: pancreas,^[32][33] liver,^[34] prostate,^[35][36] spinal lesions,^[37] head and neck cancers,^[38] and benign tumors.^[39]

None of these studies have shown any general survival benefit over conventional treatment methods. By increasing the accuracy with which treatment is delivered there is a potential for dose escalation, and potentially a subsequent increase in effectiveness, particularly in local control rates. However the studies cited are so far limited in scope, and more extensive research will need to be completed in order to show any effects on survival.^[33]

In 2008 actor Patrick Swayze was among the people to be treated with CyberKnife radiosurgery.^[40]

Worldwide locations

CyberKnife systems have been installed in over 150 locations worldwide,^[41] including 100 hospitals in the United States.^[42]

Stanford University has treated over 2,500 patients using the Cyberknife system, and worldwide over 40,000 patients have been treated.^[43][44]

The Freemasons in London, UK, have paid for a CyberKnife to be placed in Barts Hospital, and it is available to all on the National Health Service. The Queen Elizabeth Hospital in Birmingham have recently bought a CyberKnife, the first NHS hospital outside of London to acquire one. The Royal Marsden NHS Foundation Trust has a CyberKnife at their Chelsea, London site.

Overlook Hospital in Summit, New Jersey was the first hospital in the New York metro area to offer the CyberKnife Stereotactic Radiosurgery System. Today, Overlook has performed the second most treatments of prostate cancer with the CyberKnife in the world.^[45]

There is a CyberKnife machine in Hong Kong Adventist Hospital (private service and expensive price) in Hong Kong.

The first next generation CyberKnife VSI in Asia at BLK CyberKnife in New Delhi India.

SRS Cyberknife is also available in Pakistan at Jinnah Post-Graduate Medical Centre Karachi, the only place where it is offered free of cost.

See also

• Horsley–Clarke apparatus
• Gamma knife
• Novalis radiosurgery
• Robotic surgery
• NCI-designated Cancer Centers in the United States

References

• Principles and Practice of Stereotactic Radiosurgery, Lawrence Chin, MD and William Regine, MD, Editors (2008)

External links

• Accuray - manufacturer of the CyberKnife
• CyberKnife patient Support
• iprostatecancer.com
• Wonky-eye.com Trigeminal Schwannoma controlled with CyberKnife Treatment (actual patient website)