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. 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 CyberKnife system is a method of delivering radiotherapy, with the intention of targeting treatment more accurately than standard radiotherapy.^[3]

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 essential features of the CyberKnife system that set it apart 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 essential item in 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 fiduciary 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 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, 12mm and 16mm 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. This is the reason that the Gamma Knife system is likely to be more accurate than Cyber Knife.^[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 3mm x 3mm 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 patients 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 using the patients internal anatomy as the frame of reference. An implanted marker based respiratory tracking option known as ExacTrac Gating is also an option. BrainLAB's Novalis has become a leading player in the world of neurosurgery.^[25]

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,^[26] the mMLC manufactured by Brainlab,^[24] and the AccuKnife produced by Direx.,^[27] 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.^[28] Some of the tumors treated include: pancreas,^[29][30] liver,^[31] prostate,^[32][33] Spinal Lesions,^[34] head and neck cancers,^[35] and benign tumors.^[36]

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.^[30]

In 2008 actor Patrick Swayze was among the people to be treated with Cyberknife radiotherapy.^[37]

Cyberknife worldwide locations

CyberKnife systems have been installed in over 150 locations worldwide,^[38] including 100 hospitals in the United States.^[39]

Stanford University has treated over 2,500 patients using the Cyberknife system, and worldwide over 40,000 patients have been treated.^[40][41]

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.^[42]

Accolades

The CyberKnife was recognized as an Innovative Medical Device in the 10th Annual Innovations in Healthcare^SM ABBY Awards event. These awards are given based on reducing the cost of quality healthcare. "...proven with their CyberKnife Robotic Radiosurgery System that medical technology can actually lower the cost of providing quality healthcare -- and at the same time produce a result that saves time for the patient, not to mention providing a 'scarless' result," Mimi Grant, president of the ABL Organization ^[43]

See also

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

References

1. ^ http://med.stanford.edu/neurosurgery/patient_care/radiosurgery.html Stanford Neurosurgery
2. ^ Robotic Whole Body Stereotactic Radiosurgery: Clinical Advantages of the CyberKnife Integrated System. . . . Reprinted by permission from The International Journal of Medical Robotics and Computer Assisted Surgery - Robotics Online
3. ^ Dr Nick Plowman, Senior Clinical Oncologist, London HCA - How CyberKnife Works
4. ^ Fanuc Robotics http://www.fanucrobotics.com/
5. ^ Kuka Roboter GmbH http://www.kuka.com/en/
6. ^ ASTRO annual meeting website
7. ^ ^{a b} Accuray announce 4 new products at ASTRO
8. ^ An Analysis of the Accuracy of the 6D Tracking With CyberKnife Inoue M, Sato K, Koike I International Journal of Radiation Oncology, Biology, Physics 01 November 2006 (Vol. 66, Issue 3 (Supplement), Page S611)
9. ^ Accuray::Xsight Spine Tracking System
10. ^ Accuray::Xsight Lung Tracking System
11. ^ CyberKnife Radiosurgery - Fiducial Overview
12. ^ Fuller CD, and Scarbrough TJ, MD Fiducial Markers in Image-guided Radiotherapy of the Prostate. U S ONCOLOGICAL DISEASE 2006 75-78
13. ^ Murphy MJ. Fiducial-based targeting accuracy for external-beam radiotherapy. Medical Physics March 2002 Volume 29, Issue 3, pp. 334–344
14. ^ Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, Ford J, Poen J, Gibbs IC, Mehta VK, Kee S, Trueblood W, Yang G, Bastidas JA International Journal of Radiation Oncology*Biology*Physics 15 March 2004 (Vol. 58, Issue 4, Pages 1017–1021)
15. ^ Accuray::RoboCouch Patient Positioning System
16. ^ Rocky Mountain CyberKnife Center - Brain Metastases
17. ^ Chang SD, Min W, Martin DP, Gibbs IC, Heilbrun MP. An analysis of the accuracy of the CyberKnife: A robotic frameless stereotactic radiosurgical system. Neurosurgery. 2003; 52: 140-147.
18. ^ http://biz.yahoo.com/bw/070115/20070115005165.html?.v=1
19. ^ Radiobiology for the Radiologist Eric J. Hall Lippincott Williams & Wilkins; 5th edition (2000)
20. ^ Comparisons between Gamma Knife, BrainLAB’s Novalis and Cyberknife
21. ^ Gamma Knife vs. CyberKnife :: Gamma Knife Center :: Wake Forest University Baptist Medical Center
22. ^ Radiosurgery CyberKnife Overview
23. ^ Yu, C, Main W, Taylor D, Kuduvalli G, Apuzzo M, Adler J, Wang M: An Anthropomorphic Phantom Study of the Accuracy of CyberKnife Spinal Radiosurgery. Neurosurgery, 55(5):1138–1149, 2004
24. ^ ^{a b} Brainlab http://www.brainlab.com/
25. ^ BBC news - Aug 2003 - Curing cancer with computers
26. ^ 3D line http://www.3dline.com/
27. ^ Direx http://www.direx.co.il/accu.htm
28. ^ "CyberKnife::Reimbursement Information." CyberKnife. Web. 10 Mar. 2010.<http://www.cyberknife.com/reimbursement-insurance/index.aspx>
29. ^ Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, Ford J, Poen J, Gibbs IC, Mehta VK, Kee S, Trueblood W, Yang G, Bastidas JA. International Journal of Radiation Oncology*Biology*Physics, 15 March 2004 (Vol. 58, Issue 4, Pages 1017–1021)
30. ^ ^{a b} Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Koong AC, Christofferson E, Le QT, Goodman KA, Ho A, Kuo T, Ford JM, Fisher GA, Greco R, Norton J, Yang GP. International Journal of Radiation Oncology*Biology*Physics, 01 October 2005 (Vol. 63, Issue 2, Pages 320-323)
31. ^ Phase I Dose Escalation Study of CyberKnife Stereotactic Radiosurgery for Liver Malignancies. Lieskovsky YC, Koong A, Fisher G, Yang G, Ho A, Nguyen M, Gibbs I, Goodman K.International Journal of Radiation Oncology*Biology*Physics, 01 October 2005 (Vol. 63, Issue (Supplement 1), Page S283)
32. ^ 2206: Hypofractionated Stereotactic Radiotherapy for Prostate Cancer: Early Results. Hara W, Patel D, Pawlicki T, Cotrutz C, Presti J, King C. International Journal of Radiation Oncology, Biology, Physics, 01 November 2006 (Vol. 66, Issue 3 (Supplement), Pages S324-S325)
33. ^ Wall street Journal - November 2008 - Is CyberKnife Ready for Prime Time in Prostate Cancer?
34. ^ Cyberknife frameless real-time image-guided stereotactic radiosurgery for the treatment of spinal lesions. Gerszten PC, Ozhasoglu C, Burton SA, Vogel WJ, Atkins BA, Kalnicki S, Welch WC. International Journal of Radiation Oncology*Biology*Physics, 01 October 2003 (Vol. 57, Issue 2 (Supplement), Pages S370-S371)
35. ^ CyberKnife Fractionated Stereotactic Radiosurgery for the Treatment of Primary and Recurrent Head and Neck Cancer. Liao JJ, Judson B, Davidson B, Amin A, Gagnon G, Harter K. International Journal of Radiation Oncology*Biology*Physics, 01 October 2005 (Vol. 63, Issue (Supplement 1), Page S381)
36. ^ Cyberknife frameless radiosurgery for the treatment of benign tumors. Bhatnagar AK, Gerzsten PC, Agarwal A, Ozhasoglu CW, Vogel WJ, Kalnicki S, Welch WC, Burton SA. International Journal of Radiation Oncology*Biology*Physics, September 2004 (Vol. 60, Issue 1 (Supplement), Page S548)
37. ^ Patrick-Swayze has Cyberknife radiotherapy
38. ^ Reuters -December 2008 - Accuray Achieves Milestone of 150th CyberKnife System Installed Worldwide
39. ^ Accuray Reaches 100th U.S. CyberKnife System Installation
40. ^ Cutland, Laura (25 September 2005). "Maverick in a mind field - Silicon Valley / San Jose Business Journal:". http://sanjose.bizjournals.com/sanjose/stories/2005/09/26/smallb1.html. 
41. ^ Accuray FAQ
42. ^ Atlantic Health
43. ^ "Innovations in Healthcare(SM) ABBY Award". http://www.redorbit.com/news/health/1364883/accuray_wins_innovations_in_healthcaresm_abby_award/index.html. 

• 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)