J. Xue

Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy

Almost 20 years ago, Emami et al. presented a comprehensive set of dose tolerance limits for normal tissue organs to therapeutic radiation, which has proven essential to the field of radiation oncology. The paradigm of stereotactic body radiotherapy (SBRT) has dramatically different dosing schemes but, to date, there has still been no comprehensive set of SBRT normal organ dose tolerance limits. As an initial step toward that goal, we performed an extensive review of the literature to compare dose limits utilized and reported in existing publications. The impact on dose tolerance limits of some key aspects of the methods and materials of the various authors is discussed. We have organized a table of 500 dose tolerance limits of normal structures for SBRT. We still observed several dose limits that are unknown or not validated. Data for SBRT dose tolerance limits are still preliminary and further clinical trials and validation are required. This manuscript presents an extensive collection of normal organ dose tolerance limits to facilitate both clinical application and further research. PACS numbers: 87.53.Ly, 87.55.dk

A quality assurance method with submillimeter accuracy for stereotactic linear accelerators

The Stereotactic Alignment for Linear Accelerator (S. A. Linac) system is developed to conveniently improve the alignment accuracy of a conventional linac equipped with stereotactic cones. From the Winston‐Lutz test, the SAlinac system performs three‐dimensional (3D) reconstruction of the quality assurance (QA) ball coordinates with respect to the radiation isocenter, and combines this information with digital images of the laser target to determine the absolute position of the room lasers. A handheld device provides near‐real‐time repositioning advice to enable the user to align the QA ball and room lasers to within 0.25 mm of the centroid of the radiation isocenter. The results of 37 Winston‐Lutz tests over 68 days showed that the median 3D QA ball alignment error was 0.09 mm, and 97% of the time the 3D error was ≤0.25 mm. All 3D isocentric errors in the study were 0.3 mm or less. The median x and y laser alignment coordinate error was 0.09 mm, and 94% of the time the x and y laser error was ≤0.25 mm. A phantom test showed that the system can make submillimeter end‐to‐end accuracy achievable, making a conventional linac a “Submillimeter Knife”. PACS numbers: 87.53.Ly, 87.55.Qr

Dosimetric investigation of accelerated partial breast irradiation (APBI) using CyberKnife

PURPOSE To investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife. METHODS Fourteen previously treated patients with early-stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo. RESULTS For all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39∕RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%-97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V(50%) and mean V(100%) to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V(5%) and mean V(30%) to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V(5%) to the heart was 0.2 ± 0.5% for right-sided tumors and 9.4 ± 10.1% for left-sided tumors. Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V(20%) to V(100%) of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V(5%) for the lung and heart in CyberKnife planning was slightly higher. CONCLUSIONS The dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39∕RTOG 0413 protocol. With advanced real-time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment.

Low toxicity for lung tumors near the mediastinum treated with stereotactic body radiation therapy.

PURPOSE To report the local control, survival, and low toxicity observed at the Cooper University Hospital CyberKnife Center post stereotactic body radiation therapy (SBRT) in the treatment of lung tumors near the mediastinum. METHODS AND MATERIALS Twenty-four medically inoperable lung cancer patients with tumors near the mediastinum were treated using the Accuray CyberKnife system (Accuray, Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in 3-5 fractions. For conventional fractionation schemes, Emami et al(1) organized the dose tolerance limits into a unified format for clinical utility and partitioned them into 2 risk levels (5% and 50%) with preset volumes for most critical structures throughout the body. In contrast, statistical SBRT dose tolerance limits for mediastinal structures have not been established yet. We have sufficient experience at least to begin organizing a unified format with low-risk and high-risk partitions and preset volumes for 1-5 fractions exposing mediastinal structures. With the help of the (dose-volume histogram) DVH Evaluator, a software tool developed by our senior author, each treatment plan was assessed for safety and feasibility prior to treatment. The DVH Evaluator was also used to analyze the follow-up data and to create graphs of risk, called DVH Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance limits. RESULTS It was not feasible to prescribe the doses of peripheral lung lesions for all tumors near the mediastinum because of known toxicity. The crude local tumor control rate achieved in our series was 92%. Median survival was 26.8 months for the primary lung cases and 9.6 months for the metastatic cases. No patients experienced grade 3 or higher toxicities. CONCLUSIONS We affirm that SBRT is feasible in the treatment of centrally located lung cancers when the dose tolerance limits of critical structures are diligently respected. The low adverse event rates that we have experienced, combined with a good local tumor control rate, are encouraging.

Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy

Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation.

Introduction and Clinical Overview of the DVH Risk Map

Radiation oncologists need reliable estimates of risk for various fractionation schemes for all critical anatomical structures throughout the body, in a clinically convenient format. Reliable estimation theory can become fairly complex, however, and estimates of risk continue to evolve as the literature matures. To navigate through this efficiently, a dose-volume histogram (DVH) Risk Map was created, which provides a comparison of radiation tolerance limits as a function of dose, fractionation, volume, and risk level. The graphical portion of the DVH Risk Map helps clinicians to easily visualize the trends, whereas the tabular portion provides quantitative precision for clinical implementation. The DVH Risk Map for rib tolerance from stereotactic ablative body radiotherapy (SABR) and stereotactic body radiation therapy (SBRT) is used as an example in this overview; the 5% and 50% risk levels for 1-5 fractions for 5 different volumes are given. Other articles throughout this issue of Seminars in Radiation Oncology present analysis of new clinical datasets including the DVH Risk Maps for other anatomical structures throughout the body.

SU‐E‐T‐246: Preliminary Normal Tissue Complication Probability (NTCP) Analysis for Radiation Pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT)

PURPOSE NTCP analysis was performed with Lyman model to study the dose tolerance limits for radiation-induced pneumonitis (RP) in hypofractionated SBRT. Since SBRT is increasingly being applied for the treatment of large and central tumors, it is important from a clinical point of view to determine the dose tolerance limits for specific risk of toxicity. METHODS Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc) for lung tumors exceeding 80cc were assessed. The evaluation of toxicity was scored using Common Toxicity Criteria AE4.0. Median follow-up time was 12.8 months. Clinical outcomes have been published, and we performed an NTCP analysis to determine the complication rate in relation to statistical dose tolerance limits. The dose volume histogram (DVH) reduction techniques of the total lung V20Gy, V15Gy, V10Gy, V5Gy and mean lung dose (MLD) were each analyzed, as well as the ipsilateral lung V5Gy and the contralateral lung V5Gy. The framework of the Lyman Model was used except that each DVH reduction method was analyzed independently instead of using the power-law relationship for volume dependence. Model parameters were fitted using the Maximum Likelihood technique. RESULTS RP was reported in 5 patients (CTC Grade 2 in 3, and Grade 3 in 2). Total lung V5Gy and contralateral lung V5Gy were the best predictors of RP (p < 0.0001 for both). For V5Gy, the 10% risk level for Grade 2-3 RP was 28.4% for total lung and 21.6% for contralateral lung. CONCLUSIONS Analysis of RP endpoints has identified total lung V5Gy and contralateral lung V5Gy as the best predictors of RP following RapidArc. These findings are based on limited clinical data, and longer follow-up in larger patient cohorts is required in order to determine more accurate dose tolerance limits. Dr. Grimm developed the DVH Evaluator, described at www.DiversiLabs.com and distributed by www.LifeLineSoftware.com. The analysis presented here is part of that software. Dr. Senans department has received research funding from Varian Medical Systems, and Dr. Senan has received speakers honoraria from Varian.

SU‐E‐T‐436: Lung Material Phantom for Small Field Monte Carlo Dose Validation

PURPOSE Commissioning Monte Carlo beam data for clinical use within a treatment planning system (TPS) for Stereotactic Body Radiation Therapy (SBRT) should require validation both in homogeneous and in heterogeneous phantom materials. Compounding this task is the difficulty in accurately measuring small field sizes. This work outlines the use of a new lung phantom in conjunction with a new scintillation detector designed for small field measurement to verify the dose calculated in the TPS. METHODS The measurements were performed on a CyberKnife VSI. The Stereotactic Dose Verification Phantom (SDVP) from Standard Imaging (SI) was fitted with a newly designed 12cm lung material insert with a mass density of 0.28 g/cc. The scintillating detector was placed in a 1.5 cm diameter water-equivalent insert, simulating the central dose measurement of a small tumor, which was then placed in the SDVP lung phantom and CT scanned. The new SI W1 pinpoint scintillator is nearly water equivalent but the 1mm diameter by 3mm long scintillating fiber was visible and was contoured in the MultiPlan TPS. After dose cross-calibration with the SI A19 ion chamber in the basic SDVP water equivalent phantom, measurements were taken with the 5, 7.5, 10, 12.5, 15, 20, 30, and 60mm cones. For cross-calibration to known larger field conditions, the SI A16 ion chamber was used to remeasure the 20, 30, and 60mm cones. RESULTS The measured dose matched the Monte Carlo dose within 2% for the three collimator sizes that were used with the A16. All measurements with the W1 matched Monte Carlo dose as well, with the exception of the 30mm cone, which was 3.18% deviant. CONCLUSION The SDVP lung material inserts combined with the W1 scintillator Result in clinically acceptable correlation to the Monte Carlo dose calculated in the TPS for all CyberKnife fixed collimator sizes. Dr. Grimm received a consulting fee from Standard Imaging for guiding the research.

SU‐E‐T‐883: Clinical Application of Monte Carlo for SBRT: Mediastinal Lung

Purpose: Treatment planning systems have provided Monte Carlo dose calculations for several years but many physicians are still hesitant to use them clinically due to lack of data. Therefore we recalculated 200 Ray Tracing treatment plans using Monte Carlo with heterogeneity corrections and compared to SBRT dose tolerance limits. Methods: From among these 200 CyberKnife cases, 25 mediastinal lung cases are presented in this study. An extensive literature review obtained 105 published SBRT dose tolerance limits for the mediastinal critical structures aorta, bronchi, esophagus, heart, and trachea. These limits were partitioned into high‐risk and low‐risk categories. The DVH Evaluator software tool was used to generate DVH Risk Maps for these critical structures, which superimpose a) published dose tolerance limits b) unified high‐risk and low‐risk trends and c) published adverse event doses, onto Monte Carlo patient data to assess risk of adverse events. Results: Recalculated treatment plan data is within the expected range of published SBRT dose tolerance limits, providing optimism for clinical use. None of the patients experienced any Grade 3 or higher adverse events. The low‐risk dose tolerance limits were exceeded 22 times in these cases with no severe adverse event, thus helping to validate their safety. Conclusions: The range of doses calculated by Monte Carlo for our historical patient data is compatible with published SBRT dose tolerance limits. SBRT dose tolerance limits should be fine‐tuned by Monte Carlo dose calculations in long‐term statistical followup studies. Disclosure: The first author has developed the DVH Evaluator software.

MO‐D‐BRB‐07: Phantom Validation and Clinical Application of Monte Carlo for Small Field SBRT

Purpose: Small field dosimetry is challenging in homogeneous medium and extremely difficult in an inhomogeneous medium. Monte Carlo dose calculation algorithms are considered as the most accurate for treatment planning. We present our validation of the Monte Carlo algorithm in the Accuray Multiplan system using measurements in a cork phantom. We also recalculated Ray Tracing treatment plans with the Monte Carlo algorithm and compared to SBRT dose tolerance limits. Methods: In our validation measurements with a cork phantom, an Exradin A16 ion chamber was used for collimators from 60mm to 20mm on a CyberKnife, and a PTW 60012 stereotactic diode for collimators from 60mm to 5mm. A literature review of more than 500 published SBRT dose tolerance limits was partitioned into high‐risk and low‐risk categories. Two hundred CyberKnife treatment plans were recalculated using Monte Carlo and compared to the dose limits. The DVH Evaluator software tool was used to generate DVH Risk Maps for 25 critical structures throughout the body, which superimpose a) published dose tolerance limits b) unified high‐risk and low‐risk trends and c) published adverse event doses, onto Monte Carlo patient doses to assess risk of adverse events. Results: The Monte Carlo calculations matched the Exradin A16 measurements to within 2.5% for field sizes down to 20mm, and matched the PTW 60012 measurements to within 2.5% for all field sizes down to 5mm. Recalculated treatment plan data is within the expected range of published SBRT dose tolerance limits, providing optimism for clinical use. Conclusions: The Accuray MultiPlan Monte Carlo algorithm is accurate even for small fields in heterogeneous media. The range of doses calculated by Monte Carlo for our patient data is compatible with published SBRT dose tolerance limits. SBRT dose tolerance limits should be fine‐tuned by Monte Carlo dose calculations in long‐term statistical followup studies. Disclosure: The first author has developed the DVH Evaluator software.