Anthony Ho

Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors.

Background: The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy (RT) in patients with inoperable lung tumors. Methods: Eligible patients included those with inoperable T1-2N0 non-small cell lung cancer (NSCLC) or solitary lung metastases. Treatments were delivered by means of the CyberKnife. All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting. Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction. A minimal 3-month period was required between each dose level to monitor toxicity. Results: Thirty-two patients (21 NSCLC and 11 metastatic tumors) were enrolled. At 25 Gy, pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc; therefore, dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc. Ten patients received doses less than 20 Gy, 20 received 25 Gy, and two received 30 Gy. RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis, one pleural effusion, and three possible treatment-related deaths. The 1-year freedom from local progression was 91% for dose greater than 20 Gy and 54% for dose less than 20 Gy in NSCLC (p = 0.03). NSCLC patients had significantly better freedom from relapse (p = 0.003) and borderline higher survival than those with metastatic tumors (p = 0.07). Conclusions: Single-fraction stereotactic RT is feasible for selected patients with lung tumors. For those with prior thoracic RT, 25 Gy may be too toxic. Higher dose was associated with improved local control. Longer follow-up is necessary to determine the treatment efficacy and toxicity.

A Study of the Accuracy of CyberKnife Spinal Radiosurgery Using Skeletal Structure Tracking

OBJECTIVE New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance. METHODS Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery. RESULTS The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm. CONCLUSION The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

Evaluation of Intensity-Based 2D-3D Spine Image Registration Using Clinical Gold-Standard Data

In this paper, we evaluate the accuracy and robustness of intensity-based 2D-3D registration for six image similarity measures using clinical gold-standard spine image data from four patients. The gold-standard transformations are obtained using four bone-implanted fiducial markers. The three best similarity measures are mutual information, cross correlation, and gradient correlation. The mean target registration errors for these three measures range from 1.3 to 1.5 mm. We believe this is the first reported evaluation using clinical gold-standard data.

The Use of TLD and Gafchromic Film to Assure Submillimeter Accuracy for Image-Guided Radiosurgery

The Cyberknife is an image-guided radiosurgical system. It uses a compact X-band 6-MV linear accelerator mounted on a robotic arm to deliver radiosurgical doses. While routine quality assurance (QA) is essential for any radiosurgery system, QA plays an even more vital role for the Cyberknife system, due to the complexity of the system and the wide range of applications. This paper presents a technique for performing quality assurance using thermoluminescence detectors (TLDs) and Gafchromic films that is intended to be specific for the Cyberknife. However, with minor modification, the proposed method can also be used for QA of other radiosurgery systems. Our initial QA procedure for the CyberKnife utilized a 30 x 30 x 11-cm solid water phantom containing a planar array of slots for 1x 1 x 1-mm TLDs on a 2-mm grid. With the objective of significantly simplifying CyberKnife QA, a new procedure for verification was developed, which uses much fewer TLDs than the prior solid water phantom technique. This new method requires only that the system target dose to the center of a cluster of 7 TLDs. In a prior study with Gafchromic films, conducted at 3 different Cyberknife facilities, the mean clinically relevant error was demonstrated to be 0.7 mm. A similar Gafchromic film analysis replicated these error measurements as part of the present investigation. It cannot be emphasized enough the importance of implementing routine QA to verify the accuracy of any radiosurgery system. Our quality assurance procedure tests the treatment planning system, as well as the entire treatment delivery including the image targeting system and the robot system. Either TLDs or Gafchromic films may be used for QA test of a radiosurgery system. Using both methods for measurement has the advantage independently verifying the accuracy of the system. This approach, which is routinely in used at our institution, has repeatedly confirmed the submillimeter targeting accuracy of our Cyberknife.

Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery☆☆☆

Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

Trigeminal neuralgia treatment dosimetry of the Cyberknife

There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patients right, whereas the second is on the patients left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

SU‐GG‐T‐442: Dose Verification of SRS Monte Carlo Plan with a Moving Anthropomorphic Phantom

Purpose: Dose verification of Stereotactic Radiosurgery plan using Monte Carlo for tissue heterogeneity correction with a moving anthropomorphic phantom Method and Materials: An anthropomorphic lung phantom has gold fiducials, TLD capsules and GAFChromic films imbedded in a target in the left lung,TLD capsules are also inserted in heart and cord structures. The phantom was scanned, CT images were sent to Cyberknife Multiplan for planning. Target and critical structures were contoured. A SRS treatment plan with no tissue heterogeneity correction was generated to give 6Gy to 95% of the target, 5.4Gy to 99% of the target, no point > 2cm from target > 3.5Gy, conformai index < 1.2, cord < 1.8Gy, heart < 3Gy, 10% of whole lung < 2Gy. The plan was recalculated with Monte Carlo with 2% uncertainty for tissue heterogeneity correction for dose delivery. During delivery the phantom moved in superior/inferior and anterior/posterior direction, Cyberknife Synchrony tracking system took orthogonal x‐ray images of the phantom while infra‐red camera tracked LED diodes placed on the phantom to track phantom motion in real time. After the fiducials were identified by the tracking program and correlated with the motion of LED diodes, a motion model of the target was built; radiation started with the Cyberknife robot following the predicted target motion and adjusted its position during irradiation. Throughout delivery, the motion model was updated and adjusted with new x‐ray images of the fiducials. Results: Target TLD was 98.3% of Monte Carlodose;heart and cord TLD were within 7% acceptability. Profiles from 3 orthogonal films were displaced L/R 0mm/3mm, P/A 1mm/5mm and I/S 1mm/2mm from treatment plan profiles, within 5mm acceptability. Conclusion: Cyberknife Multiplan with Monte Carlo accurately predicts dose in heterogeneous tissue; Cyberknife Synchrony tracking system delivers dose accurately to a target in a moving phantom.

SU‐GG‐T‐527: Patient Specific Delivery Quality Assurance for Robotic Stereotactic Radiosurgery of Functional Targets

Purpose: Develop and implement a patient‐specific delivery QA (DQA) procedure for small functional targets treated with radiosurgery using a Cyberknife. The procedure verifies both the dose and targeting accuracy. Method and Materials: Cyberknife treatment plans (Multiplan v3.5) for functional targets were created. Phantom overlay plans were created using a head and neck phantom with the BallCubeII insert to a maximum dose of 6Gy. Specially cut EBT2 GaFchromic film was oriented orthogonally within the BallCubeII. The target dose distribution was placed such that high dose was on both pieces of film. The phantoms overlay plan was delivered and the film analyzed using FilmQA (3cognition) with an automatic detection component specific for the BallCubeII. A dose calibration curve was created using film from the same lot. The differences between the planned and delivered doses for each user defined ROI were determined, along with the distance to agreement (DTA) and gamma index (γ) values. Results: A number of different criteria were considered including γ (3%, 1mm), DTA (1mm) and dose difference (±5%, ±10%, ±15%). In general, all points (∼100%) within the ROI passed the DTA (1mm) and scored highly for γ index (3%, 1mm). Dose differences (Δdose ±5) for plans using 5mm and 7.5mm cones scored worse (20–50% passing) than those using 7.5mm cones and larger. For Δdose ±10%, the 5mm cone plans scored ∼80% pass rate. All plans passed Δdose ±15%. Conclusion: We have developed a patient‐specific delivery QA procedure using a phantom overlay plan delivered to EBT2 film in the BallCubeII insert and analyzed with FilmQA. Dose distributions and targeting accuracy were excellent. For small targets near an organ at risk, the dose discrepancy should be considered as well as the gamma index during patient specific delivery QA for small targets.