電腦刀放射外科如何在 1-5天有效治療良性和惡性疾病How CyberKnife Radiosurgery Effectively Treat Malignant and Benign Diseases in One to Five Fractions

陳光耀Kuang Y. Chen, M.D., Ph.D. （醫師、博士）Consultant, Cancer Center, Taipei Veterans General HospitalConsultant, CyberKnife Center, Tri-Service General Hospital

For nearly one hundred years, 2 Gy per day is the norm of fractionation in radiotherapy for human epithelial cancers, the whole course of treatment generally last 6 to 8 weeks with 30-40 fractions. Because of normal tissue reactions, attempt to shorten the treatment course by increasing the daily dose or daily number of fraction is very difficult to achieve. On the other extreme, Lars Leksell, a neurosurgeon of Sweden, used one fraction of large dose of gamma rays to treat the intracranial lesion successfully in 1967 opened a new discipline of medicine called Gamma Knife radiosurgery. For the past forty years, hundred of Gamma Knives have been practicing in medical centers and hospitals where no less than 350,000 patients had been treated for their intracranial benign and malignant lesions. The radiosurgical equipment extends from Gamma Knife to X Knife to nowaday, CyberKnife. In the matter of fact, hypofractionated radiotherapy appears in brachytherapy, teleradiotherapy with oral, vaginal and rectal cones, intraoperative radiotherapy, proton and heavy ion treatment. Why conventional radiotherapy needs 35 fractions of 2 Gy and radiosurgery can deliver 25-60 Gy in one to five fractions to treat biologically similar epithelial tumors? For trigeminal neuralgia, radiosurgeons even give 70-80 Gy in one fraction and the treatment is still safe and effective. The answer of this mark difference in fraction size and number are targeting accuracy and diversification of incoming treatment beams. Any attempt to adopt the radiosurgical principles to treat extracranial lesions without adequate patient fixation, reliably tackle the target movement becomes an extremely risky practice.

Take malignant tumor as an example, target movement can

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be day to day, hour to hour, minute to minute and second to second. Examples of day to day target movement are patient setup errors, urinary bladder and rectal filling and tumor pushing, tumor shrinkage, weight loss and skin moving etc. Hour to hour and minute to minute target movements are bladder and rectal filling and tumor pushing, position changes due to unnoticed muscle flexion and relaxation. Second to Second target movements are tumor moves along with respiration, heartbeat, peristalsis, cough and sudden pain etc. IGRT (image-guided radiotherapy) at its best is only partially responded to day to day target movement. There seems no radiotherapeutic system response to intrafractional target movement satisfactory except CyberKnife.

With its submillimeter targeting accuracy for stationary tumor treatment and 1.5 mm accuracy of dynamic treatment for tumors move along with respiration under natural breathing, CyberKnife is able to treat lesions of different parts in the body by 1-5 fractions, on the average 2-3 fractions in many hospitals. This is a truly hypofractionated radiotherapy, even though many people call it radiosurgery. The CyberKnife technique to overcome the target movement is a pairs of ceiling mounted X-ray tubes which 45°diagonally expose the target for patient setup and intrafractional target movement detection, any 6D translational and rotational movement can be real-time automatically detected and corrected either by automatic readjustment of the 6D couch position or by automatically moving the 6 MV X-ray source to a new position and angulation as to compensate any deviation from digitally reconstructed radiograph derived from treatment planning CT images. Synchrony is the system that the CyberKnife uses to setup 4D irradiation for thoracic and abdominal tumors moving along with respiration. The principle of Synchrony is relatively simple. Under natural respiration, one set of three cameras receive the red-light moving signals which emitted from the chest wall as the external movement track, another set of multiple X-ray exposures at different time points of a respiratory cycle of the tumor or golden markers around the tumor construct the internal target movement, couple the external and internal movement information into a mathematical model, the robotic arm as well as

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the X-ray treatment beams can follow the respiratory rhythm to do the 4D dynamic irradiation.

There are good reasons in physics and biology that hypofractionated radiosurgery can effectively treat variety of benign and malignant diseases, at least in the CyberKnife system, namely: diversification of treatment beams, accuracy of beam delivery and overcome target movement physically; newly concept of cell survival models, therapeutic ratio gain and other rationales of hypofractionation radiobiologically. Therefore philosophically, hypofractionation is a hundred years old technique in medical history of radiotherapy and radiosurgery, the safety and efficacy are ever better in the well-designed equipment such as CyberKnife, the indication of treatment are becoming wider, the therapeutic course is much shorter and simpler, only waiting for clinicians to accept.

In summary, using its 150 Kg linear accelerator and robotic arm, as well as in-room X-ray imaging equipment and Synchrony system to track the real-time position of the target and then to tackle the inter- and intrafractional target movement, CyberKnife is able to deliver variable diameter (5-60mm) 6 MV X-ray beams accurately from 1,500 solid angles toward the target, the dose distribution is highly conformal and homogenous, the rapid fall off of the marginal dose around the tumor render the surrounding normal tissue well protected. Only under these circumstances the CyberKnife is able to treat variety of benign and malignant lesions in the hypofractionated schemes as presented during the meeting and in the newly published monograph named ”CyberKnife Radiosurgery Treatment Guidelines” in Chinese by the same author of this abstract. If more cases and longer follow-up repeatedly indicated that CyberKnife stereotactic radiosurgery is more effective and safer than conventional fractionated radiotherapy and, I assume that CyberKnife hypofractionation is the future of radiotherapy, and may be the future of certain parts of surgical oncology too !

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