- Email: [email protected]
Frameless image-guided intracranial and extracranial radiosurgery using the Cyberknife™ robotic system
Cancer/Radiothérapie 10 (2006) 283–287 http://france.elsevier.com/direct/CANRAD/
Mise au point
Frameless image-guided intracranial and extracranial radiosurgery using the Cyberknife™ robotic system Radiothérapie intra- et extracrânienne guidée par l’imagerie par système robotisé Cyberknife™ I.C. Gibbs Stanford University, 875 Blake Wilbur Drive, Room G222A, Stanford, CA 94305-5847, USA Received 11 March 2006; accepted 31 May 2006 Available online 21 July 2006
Abstract The Cyberknife™ is an image-guided robotic radiosurgery system. The image guidance system includes a kilovoltage X-ray imaging source and amorphous silica detectors. The radiation delivery device is a mobile X-band linear accelerator mounted onto a robotic arm. Through a highly complex interplay between the image guidance system, an automated couch, and the high-speed linear accelerator, near real-time tracking of the target is achieved. The Cyberknife™ gained Federal Drug Administration clearance in the United States in 2001 for treatment of tumors “anywhere in the body where radiation treatment is indicated.” Because the Cyberknife™ system does not rely on rigid fixation of a stereotactic frame, tumors outside of the intracranial compartment, even those tumors that move with respiration can be treated with a similar degree of ease as intracranial targets. A description of the Cyberknife™ technology and a review of some of the current intracranial and extracranial applications are detailed herein. © 2006 Elsevier Masson SAS. All rights reserved. Résumé Le Cyberknife™ est un système de la radiochirurgie robotisée guidée par l’image. Le système de guidage par l’image inclut une source d’imagerie RX de basse énergie et des détecteurs en silicium amorphe. L’appareil utilisé pour la réalisation d’irradiation est un accélérateur linéaire mobile monté sur un bras robotisé. Grâce à une interaction de haute technologie entre le système de guidage par imagerie, la table de traitement automatisée et un accélérateur linéaire de grande vitesse, un repérage et une poursuite de la cible en temps réel sont obtenus. Le Cyberknife™ a obtenu l’autorisation de la FDA aux États-Unis en 2001 pour traiter différents types des tumeurs pour lesquels une irradiation est justifiée. Le système Cyberknife™ ne nécessite pas un système de fixation stéréotaxique rigide, les tumeurs extracrâniennes, même celles qui sont en mouvements à cause de la respiration, peuvent être traitées aussi aisément que les tumeurs intracrâniennes. Une description de la technologie Cyberknife™ et une revue des certaines applications cliniques intra- et extracrâniennes est réalisée dans cet article. © 2006 Elsevier Masson SAS. All rights reserved. Keywords: Robotic radiosurgery; Cyberknife; Spinal radiosurgery; Non-CNS extracranial radiosurgery Mots clés : Radiochirurgie robotisée ; Cyberknife ; Radiochirurgie spinale ; Radiochirurgie extracrânienne
E-mail address: [email protected] (I.C. Gibbs). 1278-3218/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.canrad.2006.05.013
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I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
1. Introduction The Cyberknife™ image-guided robotic radiosurgery system emerged as a tool to counter the limitations of traditional radiosurgery systems whose accuracy rely on rigid fixation. Like traditional radiosurgery such as Gammaknife™, the Cyberknife™ is capable of delivering highly precise crossfired radiation beams that yield conformal radiation dose distributions with rapid fall off of dose at the perimeter of the target lesion. Unlike traditional radiosurgery, however, the Cyberknife™ uses near real-time imaging to achieve accurate target localization and high-speed robotics to achieve accurate dose delivery. Dr. John Adler of neurosurgery at Stanford University worked with physicists and robotics experts to create the concept of the Cyberknife™. After several years of development, the prototype Cyberknife™, (Neurotron 1000) was installed in 1994. In the decade since the first patient was treated on the Stanford Cyberknife™, radiosurgery has been redefined to include the highly accurate treatment of not only brain tumors, but also extracranial tumors that move with respiration. In 2001, the Stanford clinical experience confirmed the accuracy of the Cyberknife™ and helped to gain the United States FDA approval of the device for treatment of tumors “anywhere in the body where radiation treatment is indicated.” Since then, the Cyberknife™ technology has been adopted by university hospitals, private hospitals, and free-standing radiation facilities across the United States, Asia, and Europe to treat tumors and lesions of the brain, spine, thorax, abdomen, and pelvis. 2. Cyberknife™ The Cyberknife™ is an integrated image-guided, frameless radiosurgery system. The physical components include a compact 6 MV X-band linear accelerator mounted to the mobile arm of a robotic manipulator and a real-time imaging system connected to a remote image registration console (Fig. 1). The X-ray imaging system acquires high-resolution digital images
onto paired orthogonal amorphous silica flat panel detectors. These images are processed and projected onto monitors at the console. The images are then registered to treatment planning digital reconstructed radiographs (DRR) where differences in the three translational and three rotational axes between the X-ray image and DRR are measured. The robotic manipulator compensates for these differences, and retargets the radiation beam to the new position, thus maintaining spatial precision. The position of the treatment volume is defined with respect to radiographic features such as skeletal anatomy or implanted fiducial rather than a stereotactic frame. The complete process of image acquisition, processing, registration, and retargeting is automatic and fast enough to be performed repeatedly during treatment. Shifting the beam rather than relying on rigid target fixation compensates changes in patient position. In addition to the standard components of the Cyberknife™ system described above, the XSight™ spinal tracking system allows spinal tumors to be treated without fiducial placement and the Sychrony™ system allows for treatment of thoracic, abdominal, and pelvic lesions with respiratory tracking. The XSight™ system (Fig. 2) relies on non-rigid deformation modeling of bony spinal anatomy and a hierarchical mesh tracking system to achieve sub millimeter accuracy for spinal and paraspinal lesions. This system eliminates the need for metal fiducial tracking in the spine. The Synchrony™ is a continuous respiratory tracking system. Unlike respiratory gating, the Synchrony delivers radiation throughout the respiratory cycle during normal active breathing. Coupling the image-guidance of internal fiducials with chest wall respiratory excursion ensures the accuracy of radiation dose delivery. Light emitting diode (LED) detectors are placed onto the chest wall of the patient to estimate patterns of the respiratory cycle while implanted internal fiducials in the vicinity of the target tumor are tracked by a separate imageguidance system and correlated with the movement of the chest wall. The relative relationship between these patterns of movement is assessed to create a predictive model, which is continuously updated throughout the treatment delivery process. 3. Spinal radiosurgery
Fig. 1. The Cyberknife™, illustrating (a) the X-band LINAC, (b) the robotic manipulator, (c) the treatment couch, (d) the diagnostic imaging detectors, and (e) the X-ray sources.
Cyberknife™ image-guided robotic radiosurgery delivery allows for real-time radiation delivery to spinal lesions with 1-mm spatial accuracy [1,3,4]. Spinal lesions are an ideal target for this system since the changes in position of the spine are less dependent on respiration, particularly when the patient is in the supine position [11]. The frameless platform of the Cyberknife™ system permits the radiation to be delivered as a single session or as a hypo-fractionated course. Hypofractionation may be preferred for intramedullary tumors or those in exquisite proximity to the spinal cord. Multiple reports of Cyberknife™ radiosurgery for spinal metastases have shown these approaches to be feasible and efficacious methods of palliation of spinal metastases [2,4,5]. The ability to generate
I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
285
Fig. 2. The XSight™ spinal tracking system (a) synthetic images (DRR’s) depicted in the first column of images, (b) Real-time camera images depicted in the second column of images, (c) overlay of synthetic and real-time images depicted in the third column of images and in the larger image on the right. Estimates of displacements that place both image sets in alignment are displayed as “Couch Corrections” for translational and rotational degrees of freedom.
Fig. 3. Examples of single fraction (A) and hypo-fractionated (B) plans for spinal radiosurgery. Target lesions are outlined in red with yellow points; the prescription doses are outlined in green (A) T12 metastatic lung cancer in a previously irradiated patient treated to 18 Gy in a single session; (B) C2-3 intramedullary metastatic breast cancer treated to 21 Gy in three sessions.
treatment plans that effectively limit the dose to the spinal cord is particularly crucial for spinal metastases since most of the patients presented in these reports had already received previous spinal irradiation. Fig. 3 below shows examples of single session and hypo-fractionated radiosurgery treatments. From 1994 to 2006, over 300 benign and malignant spinal lesions were treated on an IRB-approved registry protocol at Stanford University. These lesions consisted of meningiomas, nerve sheath tumors, metastatic tumors, chordomas, arteriovenous malformations, hemangioblastomas, and other lesions. We have determined that image-guided radiosurgery for spinal tumors and lesions is feasible and relatively safe overall. Our results along with emerging data from other institutions will add to the understanding of the radiation response of the spinal cord and which factors may augment that response. In our experience, four patients developed myelopathy; among these
patients, two had prior radiation and two were exposed to antivascular agents. Interestingly, however, within the cohort of patients with intramedullary spinal cord AVM’s which were treated with quite aggressive courses of hypo-fractionated radiosurgery, no myelopathy developed. Since many of these lesions were small, < 1 cm3, these findings might also suggest a dose–volume response of the spinal cord. We await longer follow-up and more detailed analyses to confirm these assertions. 4. Non-CNS extracranial radiosurgery Using the Synchrony respiratory tracking system, tumors of the pancreas, liver, and lung have been accurately treated. Several phase one and phase two clinical trials for these tumors have been conducted using the Cyberknife™. In the first
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I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
phase 1 dose escalation trial of pancreatic cancer, a respiratory breath-holding technique was used and not only showed that image-guided robotic radiosurgery is accurate, feasible, and safe, but also that a single dose of 25 Gy achieved 100% local control [7]. When 25 Gy Cyberknife™ radiosurgery was delivered as boost within 1 month of 45 Gy locoregional IMRT, local control was achieved in 94% of patients, although overall survival was not impacted [8]. The findings of these studies together prompted the authors to conclude that local control alone will not likely impact the overall outcome in pancreatic cancer until better systemic therapies are developed. In the phase 2 trial, more acute toxicities and late duodenal ulcers were seen. Therefore, the current practice is to “sandwich” Cyberknife™ radiosurgery between cycles of chemotherapy, eliminating the IMRT. As Cyberknife™ was beneficial in terms of local control and palliation, the benefit of this approach is to shorten the overall course of radiation while introducing systemic therapy earlier into the treatment course. Below is an example of a typical treatment plan for pancreatic cancer where care is taken to protect the medial wall of the duodenum (Fig. 4).
Fig. 4. Head of pancreas cancer, outlined in red with yellow points. A prescription dose of 25 Gy is shown by the green isodose curve.
Fig. 5. Primary non-small cell lung cancer (outlined in red). The prescription isodose of 30 Gy is shown by the light green curve. The lungs are contoured in dark green. Axial (A), sagittal (B), and coronal (C) projections are shown.
Fig. 6. Images showing 3 mm length and 1.2 mm diameter fiducials (A), and digital reconstructions of the implanted fiducials (B), (C) that are used for image guidance to treat a prostate tumor.
I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
Highly conformal fields and hypo-fractionated radiotherapy schedules are increasingly being used as a means to achieve biologic dose escalation for early stage lung cancer. Single fraction radiosurgery represents the ultimate in these hypofractionated schedules [10]. Starting at a single dose of 15 Gy and increasing dose in 5–10 Gy increments, over 30 patients with primary and metastatic tumors up to 5 cm in largest dimension have been treated using Cyberknife™ at Stanford. A representative treatment plan of a primary lung tumor treated to 30 Gy in a single fraction is shown below (Fig. 5). Early clinical results of 19 patients have been reported [9,12]. There were 11 primary early stage lung cancers and eight metastatic tumors. After a mean follow-up of 8 months, there were four local relapses; all in the group who received the lowest tumor dose of 15 Gy. In addition to abdominal and thoracic tumors, pelvic tumors such as prostate cancer and select rectal tumors have been treated with Cyberknife image guided radiosurgery. A dose response appears to exist in prostate cancer for both tumor control and normal tissue late effects. Additionally there is sufficient data to support that the prostate cancer may be sensitive to a higher dose per fraction, and characterized by a much lower α/β ratio than previously appreciated [6]. Since 2003, 25 prostate cancers have been treated at our institution. Using implanted gold fiducials, a hypo-fractionated course of 36.75 Gy is delivered in five fractions over 10 days on protocol (Fig. 6). There have been no severe complications of treatment. Long-term results are awaited to confirm the efficacy of this approach.
287
References [1] Adler Jr. JR, Murphy MJ, Chang SD, Hancock SL. Image-guided robotic radiosurgery. Neurosurgery 1999;44:1299–306 (discussion 1306-1297). [2] Degen JW, Gagnon GJ, Voyadzis JM, McRae DA, Lunsden M, Dieterich S, et al. CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine 2005;2:540–9. [3] Gerszten PCOC, Burton ST, Kalnicki S, Welch WC. Feasibility of frameless single-fraction stereotactic radiosurgery for spinal lesions. Neurosurg Focus 2002;13 (Article 2). [4] Gerszten PC, Ozhasoglu C, Burton SA, et al. CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery 2004;55:89–98 (discussion 98-89). [5] Gerszten PC, Welch WC. Cyberknife radiosurgery for metastatic spine tumors. Neurosurg Clin N Am 2004;15:491–501. [6] King CR, Lehmann J, Adler JR, Hai J. Cyberknife Radiotherapy for Localized Prostate Cancer: Rationale and Technical Feasibility. Technol Cancer Res Treat 2003;2:25–30. [7] Koong AC, Le Q-T, Ho A, Fong B, Fisher GA, Cho C, et al. Phase I Trial of Stereotactic Radiosurgery in Patients with Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2004;58:1017–21. [8] Koong AC, Christofferson E, Le Q-T, Goodman KA, Ho A, Kuo T, et al. Phase II Study to Assess the Efficacy of Conventionally Fractionated Radiotherapy followed by a Stereotactic Radiosurgery Boost in Patients with Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2005;63:320–3. [9] Le QT, Ho A, Cotrutz C, Wakelee H, Kee ST, Donnington J, et al. Single fraction Stereotactic Radiosurgery (SFSR) for Lung Tumors- a Phase I Dose Escalation Trial. J Clin Oncol 2004;22:7231. [10] Le QT, Petrik DW. Nonsurgical Therapy for Stages I and II Non-Small Cell Lung Cancer. Hematol Oncol Clin N Am 2005;19:237–61. [11] Murphy MJ, Chang SD, Gibbs IC, Le QT, Hai J, Kim D, et al. Patterns of patient movement during frameless image-guided radiosurgery. Int J Radiat Oncol Biol Phys 2003;55:1400–8. [12] Whyte RI, Crownover R, Murphy MJ. Stereotactic Radiosurgery for Lung Tumors: preliminary report of a Phase I Trial. Ann Thorac Surg 2003;75:1097–101.
Mise au point
Frameless image-guided intracranial and extracranial radiosurgery using the Cyberknife™ robotic system Radiothérapie intra- et extracrânienne guidée par l’imagerie par système robotisé Cyberknife™ I.C. Gibbs Stanford University, 875 Blake Wilbur Drive, Room G222A, Stanford, CA 94305-5847, USA Received 11 March 2006; accepted 31 May 2006 Available online 21 July 2006
Abstract The Cyberknife™ is an image-guided robotic radiosurgery system. The image guidance system includes a kilovoltage X-ray imaging source and amorphous silica detectors. The radiation delivery device is a mobile X-band linear accelerator mounted onto a robotic arm. Through a highly complex interplay between the image guidance system, an automated couch, and the high-speed linear accelerator, near real-time tracking of the target is achieved. The Cyberknife™ gained Federal Drug Administration clearance in the United States in 2001 for treatment of tumors “anywhere in the body where radiation treatment is indicated.” Because the Cyberknife™ system does not rely on rigid fixation of a stereotactic frame, tumors outside of the intracranial compartment, even those tumors that move with respiration can be treated with a similar degree of ease as intracranial targets. A description of the Cyberknife™ technology and a review of some of the current intracranial and extracranial applications are detailed herein. © 2006 Elsevier Masson SAS. All rights reserved. Résumé Le Cyberknife™ est un système de la radiochirurgie robotisée guidée par l’image. Le système de guidage par l’image inclut une source d’imagerie RX de basse énergie et des détecteurs en silicium amorphe. L’appareil utilisé pour la réalisation d’irradiation est un accélérateur linéaire mobile monté sur un bras robotisé. Grâce à une interaction de haute technologie entre le système de guidage par imagerie, la table de traitement automatisée et un accélérateur linéaire de grande vitesse, un repérage et une poursuite de la cible en temps réel sont obtenus. Le Cyberknife™ a obtenu l’autorisation de la FDA aux États-Unis en 2001 pour traiter différents types des tumeurs pour lesquels une irradiation est justifiée. Le système Cyberknife™ ne nécessite pas un système de fixation stéréotaxique rigide, les tumeurs extracrâniennes, même celles qui sont en mouvements à cause de la respiration, peuvent être traitées aussi aisément que les tumeurs intracrâniennes. Une description de la technologie Cyberknife™ et une revue des certaines applications cliniques intra- et extracrâniennes est réalisée dans cet article. © 2006 Elsevier Masson SAS. All rights reserved. Keywords: Robotic radiosurgery; Cyberknife; Spinal radiosurgery; Non-CNS extracranial radiosurgery Mots clés : Radiochirurgie robotisée ; Cyberknife ; Radiochirurgie spinale ; Radiochirurgie extracrânienne
E-mail address: [email protected] (I.C. Gibbs). 1278-3218/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.canrad.2006.05.013
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I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
1. Introduction The Cyberknife™ image-guided robotic radiosurgery system emerged as a tool to counter the limitations of traditional radiosurgery systems whose accuracy rely on rigid fixation. Like traditional radiosurgery such as Gammaknife™, the Cyberknife™ is capable of delivering highly precise crossfired radiation beams that yield conformal radiation dose distributions with rapid fall off of dose at the perimeter of the target lesion. Unlike traditional radiosurgery, however, the Cyberknife™ uses near real-time imaging to achieve accurate target localization and high-speed robotics to achieve accurate dose delivery. Dr. John Adler of neurosurgery at Stanford University worked with physicists and robotics experts to create the concept of the Cyberknife™. After several years of development, the prototype Cyberknife™, (Neurotron 1000) was installed in 1994. In the decade since the first patient was treated on the Stanford Cyberknife™, radiosurgery has been redefined to include the highly accurate treatment of not only brain tumors, but also extracranial tumors that move with respiration. In 2001, the Stanford clinical experience confirmed the accuracy of the Cyberknife™ and helped to gain the United States FDA approval of the device for treatment of tumors “anywhere in the body where radiation treatment is indicated.” Since then, the Cyberknife™ technology has been adopted by university hospitals, private hospitals, and free-standing radiation facilities across the United States, Asia, and Europe to treat tumors and lesions of the brain, spine, thorax, abdomen, and pelvis. 2. Cyberknife™ The Cyberknife™ is an integrated image-guided, frameless radiosurgery system. The physical components include a compact 6 MV X-band linear accelerator mounted to the mobile arm of a robotic manipulator and a real-time imaging system connected to a remote image registration console (Fig. 1). The X-ray imaging system acquires high-resolution digital images
onto paired orthogonal amorphous silica flat panel detectors. These images are processed and projected onto monitors at the console. The images are then registered to treatment planning digital reconstructed radiographs (DRR) where differences in the three translational and three rotational axes between the X-ray image and DRR are measured. The robotic manipulator compensates for these differences, and retargets the radiation beam to the new position, thus maintaining spatial precision. The position of the treatment volume is defined with respect to radiographic features such as skeletal anatomy or implanted fiducial rather than a stereotactic frame. The complete process of image acquisition, processing, registration, and retargeting is automatic and fast enough to be performed repeatedly during treatment. Shifting the beam rather than relying on rigid target fixation compensates changes in patient position. In addition to the standard components of the Cyberknife™ system described above, the XSight™ spinal tracking system allows spinal tumors to be treated without fiducial placement and the Sychrony™ system allows for treatment of thoracic, abdominal, and pelvic lesions with respiratory tracking. The XSight™ system (Fig. 2) relies on non-rigid deformation modeling of bony spinal anatomy and a hierarchical mesh tracking system to achieve sub millimeter accuracy for spinal and paraspinal lesions. This system eliminates the need for metal fiducial tracking in the spine. The Synchrony™ is a continuous respiratory tracking system. Unlike respiratory gating, the Synchrony delivers radiation throughout the respiratory cycle during normal active breathing. Coupling the image-guidance of internal fiducials with chest wall respiratory excursion ensures the accuracy of radiation dose delivery. Light emitting diode (LED) detectors are placed onto the chest wall of the patient to estimate patterns of the respiratory cycle while implanted internal fiducials in the vicinity of the target tumor are tracked by a separate imageguidance system and correlated with the movement of the chest wall. The relative relationship between these patterns of movement is assessed to create a predictive model, which is continuously updated throughout the treatment delivery process. 3. Spinal radiosurgery
Fig. 1. The Cyberknife™, illustrating (a) the X-band LINAC, (b) the robotic manipulator, (c) the treatment couch, (d) the diagnostic imaging detectors, and (e) the X-ray sources.
Cyberknife™ image-guided robotic radiosurgery delivery allows for real-time radiation delivery to spinal lesions with 1-mm spatial accuracy [1,3,4]. Spinal lesions are an ideal target for this system since the changes in position of the spine are less dependent on respiration, particularly when the patient is in the supine position [11]. The frameless platform of the Cyberknife™ system permits the radiation to be delivered as a single session or as a hypo-fractionated course. Hypofractionation may be preferred for intramedullary tumors or those in exquisite proximity to the spinal cord. Multiple reports of Cyberknife™ radiosurgery for spinal metastases have shown these approaches to be feasible and efficacious methods of palliation of spinal metastases [2,4,5]. The ability to generate
I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
285
Fig. 2. The XSight™ spinal tracking system (a) synthetic images (DRR’s) depicted in the first column of images, (b) Real-time camera images depicted in the second column of images, (c) overlay of synthetic and real-time images depicted in the third column of images and in the larger image on the right. Estimates of displacements that place both image sets in alignment are displayed as “Couch Corrections” for translational and rotational degrees of freedom.
Fig. 3. Examples of single fraction (A) and hypo-fractionated (B) plans for spinal radiosurgery. Target lesions are outlined in red with yellow points; the prescription doses are outlined in green (A) T12 metastatic lung cancer in a previously irradiated patient treated to 18 Gy in a single session; (B) C2-3 intramedullary metastatic breast cancer treated to 21 Gy in three sessions.
treatment plans that effectively limit the dose to the spinal cord is particularly crucial for spinal metastases since most of the patients presented in these reports had already received previous spinal irradiation. Fig. 3 below shows examples of single session and hypo-fractionated radiosurgery treatments. From 1994 to 2006, over 300 benign and malignant spinal lesions were treated on an IRB-approved registry protocol at Stanford University. These lesions consisted of meningiomas, nerve sheath tumors, metastatic tumors, chordomas, arteriovenous malformations, hemangioblastomas, and other lesions. We have determined that image-guided radiosurgery for spinal tumors and lesions is feasible and relatively safe overall. Our results along with emerging data from other institutions will add to the understanding of the radiation response of the spinal cord and which factors may augment that response. In our experience, four patients developed myelopathy; among these
patients, two had prior radiation and two were exposed to antivascular agents. Interestingly, however, within the cohort of patients with intramedullary spinal cord AVM’s which were treated with quite aggressive courses of hypo-fractionated radiosurgery, no myelopathy developed. Since many of these lesions were small, < 1 cm3, these findings might also suggest a dose–volume response of the spinal cord. We await longer follow-up and more detailed analyses to confirm these assertions. 4. Non-CNS extracranial radiosurgery Using the Synchrony respiratory tracking system, tumors of the pancreas, liver, and lung have been accurately treated. Several phase one and phase two clinical trials for these tumors have been conducted using the Cyberknife™. In the first
286
I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
phase 1 dose escalation trial of pancreatic cancer, a respiratory breath-holding technique was used and not only showed that image-guided robotic radiosurgery is accurate, feasible, and safe, but also that a single dose of 25 Gy achieved 100% local control [7]. When 25 Gy Cyberknife™ radiosurgery was delivered as boost within 1 month of 45 Gy locoregional IMRT, local control was achieved in 94% of patients, although overall survival was not impacted [8]. The findings of these studies together prompted the authors to conclude that local control alone will not likely impact the overall outcome in pancreatic cancer until better systemic therapies are developed. In the phase 2 trial, more acute toxicities and late duodenal ulcers were seen. Therefore, the current practice is to “sandwich” Cyberknife™ radiosurgery between cycles of chemotherapy, eliminating the IMRT. As Cyberknife™ was beneficial in terms of local control and palliation, the benefit of this approach is to shorten the overall course of radiation while introducing systemic therapy earlier into the treatment course. Below is an example of a typical treatment plan for pancreatic cancer where care is taken to protect the medial wall of the duodenum (Fig. 4).
Fig. 4. Head of pancreas cancer, outlined in red with yellow points. A prescription dose of 25 Gy is shown by the green isodose curve.
Fig. 5. Primary non-small cell lung cancer (outlined in red). The prescription isodose of 30 Gy is shown by the light green curve. The lungs are contoured in dark green. Axial (A), sagittal (B), and coronal (C) projections are shown.
Fig. 6. Images showing 3 mm length and 1.2 mm diameter fiducials (A), and digital reconstructions of the implanted fiducials (B), (C) that are used for image guidance to treat a prostate tumor.
I.C. Gibbs / Cancer/Radiothérapie 10 (2006) 283–287
Highly conformal fields and hypo-fractionated radiotherapy schedules are increasingly being used as a means to achieve biologic dose escalation for early stage lung cancer. Single fraction radiosurgery represents the ultimate in these hypofractionated schedules [10]. Starting at a single dose of 15 Gy and increasing dose in 5–10 Gy increments, over 30 patients with primary and metastatic tumors up to 5 cm in largest dimension have been treated using Cyberknife™ at Stanford. A representative treatment plan of a primary lung tumor treated to 30 Gy in a single fraction is shown below (Fig. 5). Early clinical results of 19 patients have been reported [9,12]. There were 11 primary early stage lung cancers and eight metastatic tumors. After a mean follow-up of 8 months, there were four local relapses; all in the group who received the lowest tumor dose of 15 Gy. In addition to abdominal and thoracic tumors, pelvic tumors such as prostate cancer and select rectal tumors have been treated with Cyberknife image guided radiosurgery. A dose response appears to exist in prostate cancer for both tumor control and normal tissue late effects. Additionally there is sufficient data to support that the prostate cancer may be sensitive to a higher dose per fraction, and characterized by a much lower α/β ratio than previously appreciated [6]. Since 2003, 25 prostate cancers have been treated at our institution. Using implanted gold fiducials, a hypo-fractionated course of 36.75 Gy is delivered in five fractions over 10 days on protocol (Fig. 6). There have been no severe complications of treatment. Long-term results are awaited to confirm the efficacy of this approach.
287
References [1] Adler Jr. JR, Murphy MJ, Chang SD, Hancock SL. Image-guided robotic radiosurgery. Neurosurgery 1999;44:1299–306 (discussion 1306-1297). [2] Degen JW, Gagnon GJ, Voyadzis JM, McRae DA, Lunsden M, Dieterich S, et al. CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine 2005;2:540–9. [3] Gerszten PCOC, Burton ST, Kalnicki S, Welch WC. Feasibility of frameless single-fraction stereotactic radiosurgery for spinal lesions. Neurosurg Focus 2002;13 (Article 2). [4] Gerszten PC, Ozhasoglu C, Burton SA, et al. CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery 2004;55:89–98 (discussion 98-89). [5] Gerszten PC, Welch WC. Cyberknife radiosurgery for metastatic spine tumors. Neurosurg Clin N Am 2004;15:491–501. [6] King CR, Lehmann J, Adler JR, Hai J. Cyberknife Radiotherapy for Localized Prostate Cancer: Rationale and Technical Feasibility. Technol Cancer Res Treat 2003;2:25–30. [7] Koong AC, Le Q-T, Ho A, Fong B, Fisher GA, Cho C, et al. Phase I Trial of Stereotactic Radiosurgery in Patients with Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2004;58:1017–21. [8] Koong AC, Christofferson E, Le Q-T, Goodman KA, Ho A, Kuo T, et al. Phase II Study to Assess the Efficacy of Conventionally Fractionated Radiotherapy followed by a Stereotactic Radiosurgery Boost in Patients with Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2005;63:320–3. [9] Le QT, Ho A, Cotrutz C, Wakelee H, Kee ST, Donnington J, et al. Single fraction Stereotactic Radiosurgery (SFSR) for Lung Tumors- a Phase I Dose Escalation Trial. J Clin Oncol 2004;22:7231. [10] Le QT, Petrik DW. Nonsurgical Therapy for Stages I and II Non-Small Cell Lung Cancer. Hematol Oncol Clin N Am 2005;19:237–61. [11] Murphy MJ, Chang SD, Gibbs IC, Le QT, Hai J, Kim D, et al. Patterns of patient movement during frameless image-guided radiosurgery. Int J Radiat Oncol Biol Phys 2003;55:1400–8. [12] Whyte RI, Crownover R, Murphy MJ. Stereotactic Radiosurgery for Lung Tumors: preliminary report of a Phase I Trial. Ann Thorac Surg 2003;75:1097–101.