CyberKnife radiosurgery for stage I lung cancer: results at 36 months

PURPOSE: The aims of this study were to determine if image-guided robotic stereotactic radiosurgery by CyberKnife Radiosurgery System using ablative radiation doses achieves acceptable local control in medically inoperable patients with early non-small-cell lung cancer (NSCLC) and to evaluate disease-free survival, toxicity, and failure. CyberKnife can deliver the prescribed dose by using many different angles converging on the target, with real-time target tracking through a combined orthogonal radiograph imaging and optic motion tracking system (Synchrony). MATERIALS AND METHODS: A review of treatment details and outcomes for 59 patients, ranging in age from 51 years to 96 years, with 61 tumors with histologically proven cancers treated by image-guided robotic stereotactic radiosurgery at the CyberKnife Center of Miami between March 2004 and March 2007 is presented. Target localization and respiratory movement compensation were accomplished using a single fiducial marker placed within the tumor, and the X-Sight and Synchrony systems. Total doses ranged from 15 Gy to 67.5 Gy delivered in 1-5 fractions with an equivalent dose range of 24-110 Gy normalized treatment dose in 2 Gy fractions (alpha/beta = 20 Gy). RESULTS: Four patients with stage 1A NSCLC and 2 patients with stage 1B NSCLC had persistent or recurrent disease. All patients tolerated the radiosurgery well, fatigue being the main side effect. Of the 59 patients treated, 51 (86%) were still alive at 1-33-month follow-up. Eight patients have died, 2 of diseases other than cancer progression. CONCLUSION: The results indicate that the delivery of precisely targeted ablative radiation doses with surgical precision to limited treatment volumes of lung tumors in a hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of lung tumors with CyberKnife(R) achieves excellent rates of local disease control with limited toxicity to surrounding tissues and, in many cases, might be curative for patients for whom surgery is not an option.     

Organ deformation and dose coverage in robotic respiratory-tracking radiotherapy

PURPOSE: Respiratory motion presents a significant challenge in stereotactic body radiosurgery. Respiratory tracking that follows the translational movement of the internal fiducials minimizes the uncertainties in dose delivery. However, the effect of deformation, defined as any changes in the body and organs relative to the center of fiducials, remains unanswered. This study investigated this problem and a possible solution. METHODS AND MATERIALS: Dose delivery using a robotic respiratory-tracking system was studied with clinical data. Each treatment plan was designed with the computed tomography scan in the end-expiration phase. The planned beams were applied to the computed tomography scan in end-inspiration following the shift of the fiducials. The dose coverage was compared with the initial plan, and the uncertainty due to the deformation was estimated. A necessary margin from the clinical target volume to the planning target volume was determined to account for this and other sources of uncertainty. RESULTS: We studied 12 lung and 5 upper abdomen lesions. Our results demonstrated that for lung patients with properly implanted fiducials a 3-mm margin is required to compensate for the deformation and a 5-mm margin is required to compensate for all uncertainties. Our results for the upper abdomen tumors were still preliminary but indicated a similar result, although a larger margin might be required. CONCLUSION: The effect of body deformation was studied. We found that adequate dose coverage for lung tumors can be ensured with proper fiducial placement and a 5-mm planning target volume margin. This approach is more practical and effective than a recent proposal to combine four-dimensional planning with respiratory tracking.     

Real-time 4-D radiotherapy for lung cancer

Respiratory motion considerably influences dose distribution, and thus clinical outcomes in radiotherapy for lung cancer. Breath holding, breath coaching, respiratory gating with external surrogates, and mathematical predicting models all have inevitable uncertainty due to the unpredictable variations of internal tumor motion. The amplitude of the same tumor can vary with standard deviations > 5 mm occurring in 23% of T1-2N0M0 non-small cell lung cancers. Residual motion varied 1-6 mm (95th percentile) for the 40% duty cycle of respiratory gating with external surrogates. The 4-D computed tomography is vulnerable to problems relating to the external surrogates. Real-time 4-D radiotherapy (4DRT), where the temporal changes in anatomy during the delivery of radiotherapy are explicitly considered in real time, is emerging as a new method to reduce these known sources of uncertainty. Fluoroscopic, real-time tumor-tracking technology using internal fiducial markers near the tumor has ± 2 mm accuracy, and has achieved promising clinical results when used with X-ray therapy. Instantaneous irradiation based on real-time verification of internal fiducial markers is considered the minimal requisite for real-time 4DRT of lung cancers at present. Real-time tracking radiotherapy using gamma rays from positron emitters in tumors is in the preclinical research stage, but has been successful in experiments in small animals. Real-time tumor tracking via spot-scanning proton beam therapy has the capability to cure large lung cancers in motion, and is expected to be the next-generation real-time 4DRT.     

Intrafractional tumor motion: lung and liver

Three-dimensional (3D) dose distribution has been improved by 3D conformation and intensity modulation in external radiotherapy. Interfractional uncertainty has been reduced by image-guided setup techniques. Reduction of ambiguity because of intrafractional target motion is the next step forward. Respiratory organ motion is known to be the largest intrafractional organ motion. Radiotherapy techniques controlling, gating, or tracking respiratory motion are under investigation to use smaller safety margins and higher doses for moving tumors. However, data on intrafractional tumor motion are sparse. We developed a fluoroscopic real-time tracking system and implantation techniques of fiducial markers for moving organs and have been accumulating knowledge about internal tumor motion. We also found the importance of 4-dimensional treatment planning to account for tumor motion in precision radiotherapy. This article reviews the current basic knowledge on respiratory physiology and summarizes the accumulating knowledge on internal motion of lung and liver tumors.     

Electromagnetic Transponder Based Tracking and Gating in the Radiotherapeutic Treatment of Thoracic Malignancies

PurposeThis report details our institutional workflow and technique for use of the Calypso electromagnetic transponder system with respiratory gating for localization and tracking of lung tumors during stereotactic radiation therapy for early stage thoracic malignancies.Methods and MaterialsSixteen patients underwent bronchoscopic fiducial placement of 3 transponders in small airways in proximity to the primary tumor. Transponders were placed <19 cm from the most anterior skin location of the patient for appropriate tracking functionality. Patients underwent simulation with 4-dimensional assessment and were treated with transponder based positional gating if tumors moved >5 mm in any direction. Tumor motion <5 mm was not gated and treated using an internal target volume approach. A 5 mm uniform planning target volume was used. Before treatment, fiducial placement and tumor location were verified by daily kilovoltage (kV) and cone beam computed tomography image guidance. Tracking limits were placed based on the movement of the transponders from the centroid of the structures on the maximum intensity projection image. The Calypso treatment system paused treatment automatically if beacons shifted beyond the predefined tracking limits.ResultsAll 16 patients underwent successful implantation of the electromagnetic transponders. Eight patients exhibited tumor motion sufficient to require respiratory gating, and the other 8 patients were treated using a free breathing internal target volume technique. Difficulty with transponder sensing was experienced in 3 patients as a result of anatomic interference with the placement of the sensing arrays; each of these cases was successfully treated after making setup modifications. Triggered imaging of fiducials during treatment was consistent with real-time positioning determined by the Calypso tracking system.ConclusionsRespiratory gated electromagnetic based transponder guided stereotactic body radiation therapy using the workflow described is feasible and well tolerated in selected patients with early stage lung malignancies.     

Quantitative measurement of CyberKnife robotic arm steering

Respiratory motion is a significant and challenging problem for radiation medicine. Without adequate compensation for respiratory motion, it is impossible to deliver highly conformal doses to tumors in the thorax and abdomen. The CyberKnife frameless stereotactic radiosurgery system with Synchrony provides respiratory motion adaptation by monitoring skin motion and dynamically steering the beam to follow the moving tumor. This study quantitatively evaluated this beam steering technology using optical tracking of both the linear accelerator and a ball-cube target. Respiratory motion of the target was simulated using a robotic motion platform and movement patterns recorded from previous CyberKnife patients. Our results show that Synchrony respiratory tracking can achieve sub-millimeter precision when following a moving object.     

Analyse de la toxicité précoce des traitements par Cyberknife des cancers pulmonaires et résultats préliminaires

PurposeHigh-dose robotic stereotactic irradiation can be achieved with high precision using the Cyberknife^®M system equipped with the Synchrony^® respiratory tracking device. Cyberknife^® irradiation can overcome some limitations of conventional radiotherapy including errors due to breathing motion and patient setup. High dose levels are of interest for tumours that have shown a dose-response relationship including lung tumours. We reviewed the treatments and outcomes for the first French patients with lung tumours treated at the Cyberknife^® centre of Nice.Patients and methodsThirty four patients were treated between November 2006 and November 2007 at the Cyberknife^® centre of Nice, Centre Lacassagne, France. Thirty had untreated primary lung cancer, 4 had colorectal metastasis to the lung. We evaluated the feasibility and reliability of fiducial placement, toxicity and early outcomes. Objective tumour response was assessed on thoracic CT scan every three months.ResultsThere was no grade 3–4 toxicity. Toxicity (11%) mainly consisted of grade 1–2 asthenia. Crude overall tumour response rate was 96% for all assessable patients and 91% at 3 and 6 months, respectively. The use of one fiducial ensured minimal toxicity (no grade III pneumothorax) while allowing reliable tumour tracking as shown by the low infield failure rate (no geographic miss). Diagnostic procedure was performed during fiducial placement when required.ConclusionEarly toxicity and tumour control rates from this population suggest that the use of a unique fiducial for a Cyberknife treatment was safe and effective for the treatment of selected primary and secondary lung tumours. This strategy is corroborated by similar control rates in the literature. Longer follow-up are awaited.     

射波刀在早期非小细胞肺癌的应用及影响疗效的因素

早期非小细胞肺癌(NSCLC)主要治疗方法是外科切除,放疗是不能耐受或拒绝手术NSCLC患者的另一选择。射波刀是近年来新出现的一种立体定向放射治疗技术,兼具放射外科和放射治疗两种功能。采用实时图像引导系统以及呼吸追踪系统,以其大剂量、高精度和周围受照射的正常组织或重要器官的范围小等优点,在治疗早期非小细胞肺癌(NSCLC)方面取得了与手术相似的疗效。但是对于早期NSCLC,尽管射波刀实施了有效的生物剂量,实时靶区追踪,但局部失效仍会发生。本文就射波刀在早期NSCLC治疗中的应用进行综述并进一步探讨相关的影响因素。     

Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience

To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac® X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac® Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within ±1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.     

An Overview of CyberKnife Radiosurgery

Stereotactic radiosurgery is a non-invasive procedure that utilizes precisely targeted radiation as an ablative surgical tool. Conventional radiosurgery devices, such as the Gamma Knife, rely upon skeletally attached Stereotactic frames to immobilize the patient and precisely determine the 3D spatial position of a tumor. A relatively new instrument, the CyberKnife (Accuray, Inc., Sunnyvale, CA), makes it possible to administer radiosurgery without a frame. The CyberKnife localizes clinical targets using a very accurate image-to-image correlation algorithm, and precisely cross-fires high-energy radiation from a lightweight linear accelerator by means of a highly manipulable robotic arm. CyberKnife radiosurgery is an effective alternative to conventional surgery or radiation therapy for a range of tumors and some non-neoplastic disorders. This report will describe CyberKnife technology and oncologic applications in neurosurgery and throughout the body.     

Intercepting radiotherapy using a real-time tumor-tracking radiotherapy system for highly selected patients with hepatocellular carcinoma unresectable with other modalities

PURPOSE: To assess the clinical outcome of intercepting radiotherapy, in which radiotherapy is delivered only when a tumor in motion enters a target area, using a real-time tumor-tracking radiotherapy (RTRT) system for patients with hepatocellular carcinoma who were untreatable with other modalities because the tumors were adjacent to crucial organs or located too deep beneath the skin surface. METHODS AND MATERIALS: Eighteen tumors, with a mean diameter of 36 mm, were studied in 15 patients. All tumors were treated on a hypofractionated schedule with a tight margin for setup and organ motion using a 2.0-mm fiducial marker in the liver and the RTRT system. The most commonly used dose of radiotherapy was 48 Gy in 8 fractions. Sixteen lesions were treated with a BED(10) of 60 Gy or more (median, 76.8 Gy). RESULTS: With a mean follow-up period of 20 months (range, 3-57 months), the overall survival rate was 39% at 2 years after RTRT. The 2-year local control rate was 83% for initial RTRT but was 92% after allowance for reirradiation using RTRT, with a Grade 3 transient gastric ulcer in 1 patient and Grade 3 transient increases of aspartate amino transaminase in 2 patients. CONCLUSIONS: Intercepting radiotherapy using RTRT provided effective focal high doses to liver tumors. Because the fiducial markers for RTRT need not be implanted into the tumor itself, RTRT can be applied to hepatocellular carcinoma in patients who are not candidates for other surgical or nonsurgical treatments.     

Development of a streamlined, non-invasive robotic radiosurgery method for treatment of uveal melanoma

To analyze the feasibility and safety of frameless, image-guided robotic radiosurgery against uveal melanoma, we developed a streamlined procedure that is completed within 3 hours under retrobulbar anesthesia without immobilization. Twenty patients (10 men and 10 women) with medium (3-5-mm prominence) and large (>5-mm prominence) unilateral uveal melanomas were treated with a frameless robotic radiosurgery system. Median age was 61 years (range 32-78 years). All patients underwent a single-session procedure beginning with retrobulbar anaesthesia, followed by computerized tomography (CT) scanning that was used in the generation of a treatment plan, and then the delivery of a radiosurgical tumor dose between 18 and 22 Gy to the 70% isodose line. Three-dimensional treatment planning was aimed at securing the optical lens and the optic disc as much as possible. Follow-up occurred at 3, 6, 12, and 18 months after the radiosurgery with clinical, ultrasound, and CT studies. We were able to treat all patients in the frameless setup within 3 hours. In five patients with lateral and dorsal tumors, the dose to the optic lens could be kept below 2 Gy. The clinical response was evaluated for the first seven patients treated with a follow-up of at least 6 months. No local recurrences occurred with any of the clinically evaluated patients for a mean 13-month follow-up (range 6-22 months). Maximum median apical tumor height according to standardized A-scan ultrasound evaluations decreased from 7.7 to 5.6 mm (p < 0.1). The median reflectivity increased from 41% to 70% (p < 0.01). None of the patients developed a secondary glaucoma during the short-term follow-up period. Frameless, single-session, image-guided robotic radiosurgery is a feasible, safe and comfortable treatment option for patients with uveal melanoma. Longer follow-up and analysis of a larger patient series is required for definitive clinical recommendations.     

Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy

BACKGROUND: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. METHODS AND MATERIALS: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. RESULTS: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. CONCLUSION: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology.     

Frameless single-session robotic radiosurgery of liver metastases in colorectal cancer patients

IntroductionDue to advanced chemotherapy regimens, patients presenting with residual liver metastases of colorectal cancer (CRC) has increased. Surgery of residual metastases enhances overall survival, but surgical resection is often limited. Less invasive techniques have been invented to enhance local disease control. We investigated in a selected patient cohort local control of liver metastasis from CRC using robotic radiosurgery.Methods and materialsIn this study patients with colorectal liver metastases were prospectively followed after having been treated with single-session radiosurgery using a robotic image-guided device and real-time tumour tracking. The primary end-point was local control (LC); secondary end-points were toxicity, progression-free survival (PFS) and overall survival (OS). Extrahepatic metastases were excluded using a whole body (PET-CT: positron emission tomography computed tomography). Follow up was done by liver MRI every 3 months post-treatment.ResultsFourteen patients (median age 65 years), with a total of 19 colorectal liver metastases were treated with 24 Gy in one fraction. Median follow up was 16.8 months. A one-year LC rate of 87% and a median PFS of 9.2 months were reached.DiscussionFrameless robotic image-guided radiosurgery with real-time tumour tracking as an effective treatment for patients with colorectal liver metastases. This technique enhances the possibilities of multidisciplinary oncological concepts.     

Radiosurgery using the Cyberknife for benign spinal tumors: Korea Cancer Center Hospital experience

This study evaluated clinical outcome and safety of radiosurgery using the Cyberknife for treatment of benign spinal tumors. The authors treated 30 benign spinal tumors in 20 patients with the Cyberknife (Accuray, Inc., Sunnyvale, CA, USA) from 2002 to 2008. Among these there were 20 neurogenic tumors, eight hemangioblastomas, and two meningiomas. Four patients with neurofibromatosis (NF) type 2 and four patients with Von Hippel Lindau disease were also included. Radiosurgery was done as primary treatment for 22 lesions, for postoperative residual tumor control for four lesions, and for the remaining four lesions with image-based progression after initial subtotal resection. The distribution of lesions was cervical (18 tumors), thoracic (six), and cauda equina level (six). Follow-up data included imaging studies, clinical findings, and radiotherapy data. Tumor volume ranged from 0.04 to 33.65 cm³ (mean, 4.52 cm³). A 14–33 Gy marginal dose was delivered in 1–5 fractions. The mean follow-up period was 35.6 months (range, 12–84 months). On follow-up, most lesions decreased in size (57%) or remained unchanged (33%). Two lesions initially decreased, then increased later. One lesion increased without response. With regard to clinical aspects, radicular pain and myelopathic pain improved after radiosurgery in most cases (94%). Motor weakness recovered in two out of five patients and recovery of sensory change occurred in four out of ten patients. In two patients, symptoms were aggravated by tumor enlargement and the occurrence of new lesion. Mean spinal cord volumes receiving more than 10 and 8 Gy were 0.40 ± 0.4 and 0.81 ± 0.7 cm³, respectively. Stereotactic radiosurgery (SRS) using the Cyberknife showed the ability to control benign spinal tumors without complication in most cases.     

Use of motion tracking in stereotactic body radiotherapy: Evaluation of uncertainty in off-target dose distribution and optimization strategies

Spatial accuracy in extracranial radiosurgery is affected by organ motion. Motion tracking systems may be able to avoid PTV enlargement while preserving treatment times, however special attention is needed when fiducial markers are used to identify the target can move with respect to organs at risk (OARs). Ten patients treated by means of the Synchrony system were taken into account. Sparing of irradiated volume and of complication probability were estimated by calculating treatment plans with a motion tracking system (Cyberknife Synchrony, Sunnyvale, CA, USA) and a PTV-enlargement strategy for ten patients. Six patients were also evaluated for possible inaccuracy of estimation of dose to OARs due to relative movement between PTV and OAR during respiration. Dose volume histograms (DVH) and Equivalent Uniform Dose (EUD) were calculated for the organs at risk. In the cases for which the target moved closer to the OAR (three cases of six), a small but significant increase was detected in the DVH and EUD of the OAR. In three other cases no significant variation was detected. Mean reduction in PTV volume was 38% for liver cases, 44% for lung cases and 8.5% for pancreas cases. NTCP for liver reduced from 23.1 to 14.5% on average, for lung it reduced from 2.5 to 0.1% on average. Significant uncertainty may arise from the use of a motion-tracking device in determination of dose to organs at risk due to the relative motion between PTV and OAR. However, it is possible to limit this uncertainty. The breathing phase in which the OAR is closer to the PTV should be selected for planning. A full understanding of the dose distribution would only be possible by means of a complete 4D-CT representation.     

射波刀在非小细胞肺癌治疗中的应用

肺癌是癌症死亡的首要原因。放疗是治疗肺癌的主要手段之一,与手术、化疗同等重要。射波刀是近年来新出现的一种立体定向放射治疗技术,兼具放射外科和放射治疗两种功能。采用实时图像引导系统以及呼吸追踪系统,以其大剂量、高精度和周围受照射的正常组织或重要器官的范围小等优点,在治疗非小细胞肺癌（ＮＳＣＬＣ）方面取得了显著的效果。本文就射波刀在ＮＳＣＬＣ治疗中的应用进行综述,并探讨其局限性。