Extracranial Stereotactic Radiosurgery Research Articles

Stereotactic radiotherapy for spinal meningiomas and neurinomas

Over the past decades, stereotactic conformal radiotherapy of intracranial meningiomas and schwannomas has been recognized as an effective and safe procedure. Due to the wide use of the CyberKnife system and the procedure of extracranial stereotactic radiotherapy and radiosurgery, the positive experience can be used to treat spinal tumors. This study assessed the effectiveness of stereotactic radiaotherapy of spinal meningiomas and neurinomas using the CyberKnife system. 46 patients (34 females and 12 males) received treatment between November 2009 and December 2013 (65 tumor nodules). The median age of patients receiving radiotherapy was 49 years (range: 20 to 82 years). Twenty neoplasms were subjected to surgical treatment. In 11 patients, formation of the recurrent tumor foci following treatment was observed along with the systemic disease, neurofibromatosis. Six patients had multiple meningiomas. The median total dose of radiation therapy of neurinomas was 13.6 Gy (12.1-14.1 Gy) per fraction; up to 18.2 Gy (16.0-21.1 Gy) per three fractions; and up to 25.6 Gy (24.8-27.6 Gy) per five fractions. Higher doses were used for meningiomas: 15.9 Gy (14.1-16.2 Gy) per fraction; 20.9 Gy (19.5-21.1 Gy) per three fractions; and 27.5 Gy (25.0-29.9 Gy) per five fractions. The load to 0.15 cm3 of the spinal cord was no higher than the maximum permissible load of 12 Gy per fraction. The mean catamnestic follow-up was 18.1 (4-52) months: 21,1 (4-52) months for neurinomas and 18 (4-31) months for meningiomas. We have not observed complete tumor elimination (i.e., complete response to radiation therapy) in our series. Partial response was observed in 9 (13.8%) cases; stabilization was achieved in 54 (83.1%) cases; and tumor continued to grow in 2 (3.1%) cases. The patients' status was evaluated using the Frankel, the Karnofsky, and the VAS scales. Our findings clearly demonstrate the short-term benefits of using CyberKnife radiotherapy for benign spinal cord tumors. The catamnestic follow-up needs to be extended to elaborate recommendations for radiation. The progress in this therapy type will considerably improve the quality of medical care provided to this cohort of patients.

SP-0007 THE DNA DAMAGE RESPONSE FOLLOWING IRRADIATION AND ITS IMPORTANCE

not received SP-0010 EXTRACRANIAL STEREOTACTIC RADIOSURGERY FOR SPINAL AND PARASPINAL METASTASIS D. Rades 1 1 University of Lubeck, Radiation Oncology, Lubeck, Germany Single-fraction stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) are all well established for treatment of brain

MO-SAM-BRB-04: Use of Volumetric Modulated Arc Therapy for Intra and Extra Cranial Stereotactic Radiosurgery

Volumetric modulated arc therapy (VMAT, aka. volumetric IMRT) burst upon the scene two years ago as a practical means of deliveringIMRT as the gantry arcs continuously around the patient. The approach leads to shorter treatment times, fewer total MUs and may facilitate reducing normal tissuedoses. The technology has come into ever wider use in clinics as the software for treatment planning has become further refined and supported in multiple treatment planning systems and accelerators. During that period, the literature detailing novel use of volumetric IMRT, clinical implementation and experience with outcome has also grown. As a planning and treatment approach, VMAT is well on its way to becoming standard of care for many anatomic sites. During this period, wider use of hypo‐fractionated dose protocols for carrying out stereotactic radiation therapy/surgery for intra cranial lesions and for extra‐cranial lesions in the lung, liver and spine have come into wider use. The concurrence of this trend with the emergence of the technology has quickly led to use of VMAT for stereotactic radiosurgery(SRS) in some centers. The aim of this lecture is to facilitate understanding the differences and similarities with conventional techniques and the potential implications for radiobiology, patient positioning equipment and QA issues. Effective treatment planning approaches for intra and extra cranial SRS targets will be presented along with normal tissue constraints used. Implications of reduced treatment time enabled by VMAT on radiobiological response of tumors and normal tissues will be discussed. Speakers have been selected to present information on a diverse set of equipment and clinical practices. Learning Objectives: 1. Able to compare and contrast dose distributions for conventional vs. VMAT techniques 2. Understand technical and potential radio‐biological implications of using VMAT for SRS 3. Understand implications of single isocenter treatments of multi‐focal targets.

SU-FF-T-611: Intensity-Modulated Radiation Therapy (IMRT) Versus Stereotactic Radiosurgery (SRS) in Spinal Tumors - a Head to Head Comparison Between the Most Advanced Planning Techniques

Background:Radiation treatment of spinal and paraspinal tumors has been limited by the tolerance of the spinal cord. With new treatment technologies, like IMRT and extracranial SRS, higher radiationdose can be delivered to the target with the capability of sparing sensitive normal structure. This study is comparing the most advanced radiation techniques (IMRT and SBRT) for spinal tumortreatment.Methods: 12 patients were treated for 13 spinal lesions; the treated lesions included metastases and primary spinal tumors in all spinal segments. Treatment indications were tumor control and pain palliation. All patients had been treated with SRS. We retrospectively compared the SRS and IMRTtreatment plan. SRS was planned using the 3Dline, (ERGO++, Elekta) for direct treatment planning. For IMRT planning we used CMS Xio software (CMS, St. Louis, MO). A dose‐volume histogram for the peripheral tissue and organ at risk around the target generated and evaluate. The IMRT plan had to meet the same tumor coverage as the srs. The SRS plan were transferred to the XiO planning system and recomputed in order to eliminate algorithm accuracy performance difference. Results: The median target volume was 8.1 cc (4.1–12.5cc). The SRS plan showed lower median target dose (5.3%, range 3–31%) and lower median dose (27.9%, range 6.6–27.2%) to critical structures (spinal cord, kidneys). The IMRT plan showed higher peripheral dose volume exposure for of 30.3%, 49.4% and 62.7% for the 10%, 20% and 30%, respectively, of overall exposed tissue volume. The planning and quality assurance duration for SRS was on average 75 minutes and for the IMRT plan 480 minutes. Conclusion:SRS technique showed a higher and faster gradient fall off reflected by a more conformal tumor coverage and less exposure to normal tissue.SRS was less time consuming for planning and quality assurance compared to the IMRT.

Image Guided Radiation Therapy Using Cone-Beam Computed Tomography in Stereotactic Radiosurgery for Lung Tumor

Extracranial stereotactic radiosurgery (SRS) is a high-precision radiotherapy for small size tumor, especially in lung tumor. Setup accuracy and exact tumor position are most important for successful SRS. This study evaluated the usefulness of kilo-voltage cone beam computed tomography (KV CBCT, Varian) for assessing setup accuracy and tumor position during SRS in lung tumor.

MO‐E‐M100F‐06: Intra‐Fraction and Inter‐Fraction Real‐Time Tumor Motion Prediction Using Multiple External Surrogates

Purpose: To determine the feasibility of predicting real‐time tumor positions using multiple external surrogates and Partial‐Least‐Squares (PLS) regression. Methods: Nine patients with lung tumors underwent extracranial stereotactic radiosurgery comprising 3 fractions with the Cyberknife Synchrony™ system. Three LED markers were placed on the patient's abdomen and in close contact with the skin. Synchronous LED marker and tumor marker coordinates were measured periodically using an LED camera and stereoscopic x‐ray images, respectively. PLS performs regression on a small number of latent variables (LVs), which represent the underlying factors responsible for the variation in the output response. They are linear combinations of the original independent variables. The number of LVs in the PLS model was determined by performing a cross‐validation using a training data set and minimizing the error. The LV coefficients were then extracted from the cross‐correlation of input and output variables. Tumor position prediction errors were evaluated for the following scenarios: (1) tumor/external surrogate relationship for a given fraction, (2) predictive model developed in one fraction and applied to other fractions. Prediction errors were compared with standard multiple linear regression (MLR). Results: The mean tumor motion displacement was 7.3 mm for the patient data investigated. The average error for intra‐fraction tumor position prediction based on external markers was 1.47±0.90 mm for PLS and 3.07±1.67 mm for MLR when data from a single fraction was used. When the predictive model from one fraction was applied to the remaining two fractions, the average real‐time inter‐fraction error was 1.48±0.57 mm for PLS and 6.69±3.58 mm for MLR. Conclusion: PLS can predict the tumor position using external surrogates with errors of < 2mm and with superior accuracy compared with MLR. Intra‐ and inter‐fraction prediction errors were statistically similar.

Reducing Set-up Uncertainty in the Elekta Stereotactic Body Frame Using Stealthstation Software

The Elekta Stereotactic Body Frame (SBF) is a device which allows extracranial targets to be localized and irradiated in a stereotactic coordinate system. Errors of positioning of the body relative to the frame are indirectly estimated by image fusion of multiple CT scans. A novel repositioning methodology, based on neurosurgical Stealth technology, is presented whereby accurate patient repositioning is directly confirmed before treatment delivery. Repositioning was performed on four extracranial stereotactic radiosurgery patients and a radiotherapy simulation phantom. The setup error was quantitatively measured by fiducial localization. A confirmatory CT scan was performed and the resulting image set registered to the initial scan to quantify shifts in the GTV isocenter. Alignment confirmation using Stealth took between 5 and 10 minutes. For the phantom studies, a reproducibly of 0.6 mm accuracy of phantom-to-SBF alignment was measured. The results on four actual patients showed setup errors of 1.5 mm or less. Using the Stealth Station process, rapid confirmation of alignment on the treatment table is possible.

Intracranial and extracranial stereotactic radiosurgery and radiotherapy

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are both flourishing, potent, noninvasive methods of precise high-dose RT for localized benign and malignant tumor in cranial or extracranial locations (stereotactic body radiotherapy [SBRT]). Both have in common the use of image guidance and related treatment delivery technology for escalating the radiation dose to the tumor with as little radiation dose to the surrounding normal tissue as possible. The advent and implementation of SRT and SBRT are novel, but they are a natural progression of the clinical implementation of SRS technologies that has occurred during the previous decades.

Intracranial and extracranial stereotactic radiotherapy and radiosurgery

Intracranial and extracranial stereotactic radiotherapy and radiosurgery

WE-D-224C-02: High Dose Rate Mode Linear Accelerator Based Stereotactic Radiosurgery and Image Guided Radiation Therapy

Introduction: In order to improve the standard linear accelerator's ability to address the demands of intracranial and extracranial stereotactic radiosurgery as well as for image‐guided and intensity modulated radiotherapy, a high dose rate output accelerator was developed. The objective of this study was to assess the device performance and compare it to standard accelerators. Materials and Methods: The 6 MV x‐ray beam of a Siemens Oncor linac was modified by removing the flattening filter, enabling dose rates to reach 1000 MU per minute. Ion chambers, diodes, and film dosimeters were used to assess monitor chamber behavior, energy, and dose profile characteristics. Treatment time required for radiosurgerytreatments in 40 patients was measured. Results: Even at this high dose rate, the linacdosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Measurements at incrementally reduced dose rates (1000 to 300 in 100 MU increments) showed the output calibration to fall from 1.000 cGy/MU to 0.994 cGy/MU, with an average value of 0.997 cGy/MU. Over this range of dose rates the beam energy held consistent, with the ratio of percent depth dose values within 0.5%. Dose profiles for larger field sizes are not flat, but they are radially symmetric and as such able to be modeled by a treatment planning system. Radiosurgerytreatment times, computed here as the beginning of x‐ray delivery until the end of treatment, were reduced to an average of 2 minutes and 18 seconds per arc, or 11 minutes 27 seconds per isocenter. Conclusions: Even at this high dose rate, the linacdosimetry system remains robust. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high dose rate design should be pursued.

SU-FF-T-199: Dosimetry Validation for Spinal Cord Irradiation In Extracranial Stereotactic Radiosurgery

Purpose: A single large dose in the range of 16 to 20 Gray at 90% isodose line can be safely delivered to solitary or multiple metastases in the vertebral column via extracranial stereotactic radiosurgery. However, the spinal cord dose is usually limited to 10 Gy within the treatment segment. Thus, the dosimetry validation for the spinal cord is critical for this procedure and for further dose escalation. Methods and Materials: Bearing the challenges of the great dose gradient and irregular shape of the target around the cord, we have designed an experiment to measure the absolute dose to the cord using a farm chamber placed at the location of the spine cord inside the solid water phantom. The air‐cavity of the chamber is precisely delineated in the iPlan system (BrainLAB) and dose volume histogram for the air cavity was used for calculating the effective dose in the treatment plan. This can then be compared with measured doses by the chamber. Isodose distributions in two coronal planes through the center of tumor and through the cord are also measured with EDR2 films and compared with the planned dose distributions. Results: Our tests demonstrated that this dosimetry measurement is reliable with high accuracy and precision of < 3% deviation in such difficult dosimetry verification. Results from five spinal SRS cases show that the cord doses with IMRS plans are within 5 % from those of the treatment planned doses. Importantly, the isodose distributions at the cord and near the target volume are consistent with the planed dose distributions. Conclusions: The small discrepancies (up to 5%) for the absolute dose measurement show no gross errors in the dose delivery and dose calculation using a pencil beam algorithm in the planning system.

1423 POSTER Preliminary evaluation of tolerance and local effectiveness of extracranial stereotactic radiosurgery and radioablation in patients with lung tumors

Metastatic medulloblastoma has a poorer prognosis than localised disease in part due to inherent properties of the tumour. 1H magnetic resonance spectroscopy (MRS) provides a powerful method for investigating tumour metabolism in vivo.Magnetic resonance imaging and short echo time (Te 30 ms) single voxel MRS were performed on the primary tumour of 16 children with medulloblastoma prior to surgical resection. Tumour volumes were calculated using a segmentation technique and the MRS was analysed using LCModel™.Patients with metastatic disease had primary tumours which were smaller (p = 0.01), had higher levels of total choline (p = 0.03) and lower levels of mobile lipids (p = 0.04).Metastatic medulloblastomas have metabolite profiles indicative of increased cell growth and decreased cell death compared with localised tumours reflecting intrinsic differences in underlying biology. Localised tumours with an MRS metabolite profile similar to those with metastatic disease may be at increased risk of metastatic relapse.

Repeat Stereotactic Radiosurgery for Spinal Tumors: Lessons Learned

Purpose/Objective: To evaluate the feasibility, efficacy, and potential toxicity of repeat frameless extracranial stereotactic radiosurgery (SRS) using a single-fraction technique for the treatment of patients with spinal tumors.

TU-C-T-617-06: Importance of Pre-Fraction Helical CT Isocenter Verification in Extracranial Stereotactic Radiosurgery

Purpose: To quantify the impact of pre-fraction helical CT isocenter verification vs. setup based on planning CT in fractionated extracranial stereotactic radiosurgery. Method and Materials: Treatment plans (Elekta PrecisePlan) and pre-fraction isocenter verification helical CT scans for 12 patients (40 fractions) were recovered from treatment plan archives. All structures were contoured by a single physician at the time of treatment. Each plan was imported into a customizable treatment plan analysis suite (CERR). Using CERR, pre-fraction isocenter verification CT scans were fused with the original treatment plan using the external body frame as a reference. The original planned dose distribution was then translated from original treatment plan isocenter to pre-fraction verification isocenters in each fraction. Dose and volume parameters for pertinent structures were automatically extracted using both registration methods (planned or pre-fraction scans) for the original treatment plan and for all subsequent fractions. All patients were treated using the pre-fraction verified isocenter rather than pre-calculated body frame fiducials as per our institutional policies. Results: GTV volumes on pre-fraction CTs varied from original planned GTV volume (64%–203%, mean=101.8+/−26.5%) largely due to helical sampling of a mobile target. Using the external body frame as the only setup reference would have resulted in geographic misses (<80% coverage of 95% of GTV) in 7/40 (17.5%) fractions. Pre-fraction isocenter verification resulted in improved D95 GTV coverage (88–102%, mean=99.3% +/−2.4%) with no geographic misses. Conclusion: The current RTOG protocol (0236) evaluating extracranial stereotactic radiosurgery does not require pre-fraction CT tumor position verification. Our institutional policy is to verify isocenter/tumor position prior to each fraction via CT. Although helical scanning artifacts are present, pre-fraction CT-based isocenter verification may provide more consistent tumor coverage than setup to planned body frame fiducials. Conflict of Interest: Support for this research was provided in part by Elekta, Inc.

SU‐FF‐J‐120: Patient Motion During Extracranial Stereotactic Radiosurgery

Purpose: Advances in image‐guided treatments have made frameless stereotactic radiosurgery (SRS) feasible. Extracranial SRS treatments are highly conformal, and technical delivery precision on phantoms has been shown to be less than 1 mm. The human component of error, i.e. voluntary and involuntary motions during the treatment, plays an increasing role in the determination of PTV margins. The residual motion between imaging intervals during image‐guided treatments constitutes the treatment uncertainty and needs to be compensated by the application of a PTV margin. Method and Materials: During Cyberknife extracranial SRS, the patient position is verified by orthogonal x‐ray images every 80 seconds on average. Data of 90 extracranial SRS patients have been analyzed. The extent of patient motion has been studied during the whole treatment, the first 5 minutes and first 15 minutes of each treatment. Motion patterns of anatomical sub‐sites were studied. Results: The maximum frequency of all translational patient motions was in the range of 0.02–0.2 mm, with 90% of all motions below 1 mm. No differences between the three translational directions have been observed. The maximum frequency of rotational patient motions was between 0.1–0.2 degrees, with a wider distribution in the degree of roll. The average patient motion for cervical spine was 0.47 mm, thoracic spine 0.34 mm, and lumbar spine 0.29 mm. In the 214 fractions analyzed, patients moved on average 1 mm away from their original setup position after 5 minutes of treatment. No statistically significant difference exists for the range of patient motion during the first 5 or 15 minutes as compared to the whole treatment. Conclusion: For image‐guided treatments, PTV margins of 1.0 mm include 90% of observed patients motions for static lesions. Larger margins may be necessary if the treatment field is not rotationally symmetric around the isocenter.

Extending the linear–quadratic model for large fraction doses pertinent to stereotactic radiotherapy

Ongoing clinical trials designed to explore the use of extracranial stereotactic radiosurgery (ESR) for different tumour sites use large doses per fraction (15, 20, 30 Gy or even larger). The question of whether the linear–quadratic (LQ) model is appropriate to describe radiation response for such large fraction doses has been raised and has not been answered definitively. It has been proposed that mechanism-based models, such as the lethal–potentially lethal (LPL) model, could be more appropriate for such large fraction/acute doses. However, such models are not well characterized with clinical data and they are generally not easy to use. The purpose of this work is to modify the LQ model to more accurately describe radiation response for high fraction/acute doses. A new parameter is introduced in the modified LQ (MLQ) model. The new parameter introduced is characterized based both on in vitro cell survival data of several human tumour cell lines and in vivo animal iso-effect curves. The MLQ model produces a better fit to the iso-effect data than the LQ model. For a high single dose irradiation, the prediction of the MLQ is consistent with that from the LPL model. Unlike the LPL model, the MLQ model retains the simplicity of the LQ model and uses the well-characterized α and β parameters. This work indicates that the standard LQ model can lead to erroneous results when used to calculate iso-effects with large fraction doses, such as those used for ESR. We present a solution to this problem.

Extracranial frameless stereotactic radiosurgery with multi-modal imaging and opto-electronic position verification

The purpose of the present work is to investigate the feasibility and develop the methods for a clinical protocol of frameless extracranial stereotactic hypo-fractioned radiotherapy and radiosurgery, for the treatment of small secondary tumours. The main concept relies on the exploitation of opto-electronic technologies and multi-modal imaging to increase the target localization accuracy in treatment planning and dose delivery. Preliminary results show that the combined use of PET/CT imaging and opto-electronic respiratory gating is a promising technique for the reduction of localization uncertainties in extracranial stereotactic irradiation. The application of moderate deep inspiration breath-hold manoeuvres, guided by an opto-electronic localizer, can provide an effective improvement in localization accuracy.

Malignant spinal cord compression.

Malignant spinal cord compression is one of the most dreaded complications of cancer. If untreated, it can lead to worsening neurologic function culminating in paralysis and sphincter incontinence. The most challenging aspect in the management of this complication is early diagnosis because the single most important factor determining outcome is the level of neurologic function at initiation of therapy. Magnetic resonance imaging is the diagnostic modality of choice. Steroids have a proven role in the treatment. Radiation therapy has been the standard of care, with surgery reserved for special cases. A recent randomized trial has proven that in appropriately selected patients initial surgery, followed by radiation, provides better functional and neurologic outcome compared to radiation alone and will likely become the standard of care in the future. Newer modalities, such as transarterial embolization and extracranial stereotactic radiosurgery, are emerging and may be considered in appropriate cases if available.

Retrospective clinicopathologic correlation of gross tumor size of hepatocellular carcinoma: implications for extracranial stereotactic radiosurgery

Purpose/Objective: Extracranial stereotactic radiosurgery is a new radiation technique for the treatment of localized hepatocellular carcinoma (HCC). Accurate assessment of tumor size by imaging is of utmost importance because minimal treatment planning margins are added to the gross tumor. Thus, it is important that the size of the lesion on CT or MRI accurately estimates the true gross pathologic size. The purpose of the present analysis is to compare the size of HCC on gross pathologic examination with the size on preoperative CT or MRI scan.

Analysis of extracranial stereotactic radiosurgery via equivalent uniform dose and tumor control probability: practical ramifications and translational implications

Purpose/Objective: Extracranial stereotactic radiosurgery (ESR) is being widely investigated, and encouraging tumor control rates have been observed. However, variations in dose prescriptions between institutions and inherent inter-patient variability render it difficult to construct accurate dose-response relationships. These limitations could impede efforts to conduct multi-center clinical trials. Equivalent uniform dose (EUD) formalism was applied to describe the differences in biologic effect among clinically applied methods of ESR. Additionally, since the typical dose per fraction in ESR is much higher than conventional radiotherapy and most cells of average radiosensitivity will be killed, the implications of observed tumor control rates with respect to the fraction of highly resistant cells are explored by analyzing tumor control probability (TCP).