Verification of dosimetric accuracy on the TrueBeam STx: rounded leaf effect of the high definition MLC.

PURPOSE: The dosimetric leaf gap (DLG) in the Varian Eclipse treatment planning system is determined during commissioning and is used to model the effect of the rounded leaf-end of the multileaf collimator (MLC). This parameter attempts to model the physical difference between the radiation and light field and account for inherent leakage between leaf tips. With the increased use of single fraction high dose treatments requiring larger monitor units comes an enhanced concern in the accuracy of leakage calculations, as it accounts for much of the patient dose. This study serves to verify the dosimetric accuracy of the algorithm used to model the rounded leaf effect for the TrueBeam STx, and describes a methodology for determining best-practice parameter values, given the novel capabilities of the linear accelerator such as flattening filter free (FFF) treatments and a high definition MLC (HDMLC). METHODS: During commissioning, the nominal MLC position was verified and the DLG parameter was determined using MLC-defined field sizes and moving gap tests, as is common in clinical testing. Treatment plans were created, and the DLG was optimized to achieve less than 1% difference between measured and calculated dose. The DLG value found was tested on treatment plans for all energies (6 MV, 10 MV, 15 MV, 6 MV FFF, 10 MV FFF) and modalities (3D conventional, IMRT, conformal arc, VMAT) available on the TrueBeam STx. RESULTS: The DLG parameter found during the initial MLC testing did not match the leaf gap modeling parameter that provided the most accurate dose delivery in clinical treatment plans. Using the physical leaf gap size as the DLG for the HDMLC can lead to 5% differences in measured and calculated doses. CONCLUSIONS: Separate optimization of the DLG parameter using end-to-end tests must be performed to ensure dosimetric accuracy in the modeling of the rounded leaf ends for the Eclipse treatment planning system. The difference in leaf gap modeling versus physical leaf gap dimensions is more pronounced in the more recent versions of Eclipse for both the HDMLC and the Millennium MLC. Once properly commissioned and tested using a methodology based on treatment plan verification, Eclipse is able to accurately model radiation dose delivered for SBRT treatments using the TrueBeam STx.

Clinical development of a failure detection-based online repositioning strategy for prostate IMRT--experiments, simulation, and dosimetry study.

PURPOSE: To implement and evaluate clinic-ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as-needed use of on-board kV. METHODS: The authors examine the two-step decision-making strategy: (1) Use cine-MV imaging and online-updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV-kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field-by-field based motion correction for present-day linacs and (2) instantaneous repositioning for new-generation linacs with capabilities of simultaneous MV-kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients. RESULTS: Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the marker's projected position on the MV imager, the field-by-field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV-kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage (approximation 2/fraction), the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to < 2%) if the MLC blockage problem were relieved. The information acquired for repositioning using combined MV-kV images was found to have submillimeter accuracy. CONCLUSIONS: This work demonstrated with a current clinical setup that substantial reduction of adverse targeting effects of intrafraction prostate motion can be realized. The proposed adaptive imaging strategy incurs minimal imaging dose to the patient as compared to other stereoscopic imaging techniques.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

A study of image-guided intensity-modulated radiotherapy with fiducials for localized prostate cancer including pelvic lymph nodes.

PURPOSE: To study the impact on nodal coverage and dose to fixed organs at risk when using daily fiducial localization of the prostate to deliver intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Five patients with prostate cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied. Dose was prescribed such that 95% of the prostate planning target volume (PTV) and 90% of the nodal PTV were covered. Random and systematic prostate displacements in the anterior-posterior, superior-inferior, and left-right directions were simulated to shift the original isocenter of the IMRT plan. The composite dose during the course of treatment was calculated. RESULTS: Compared with a static setup, simulating random shifts reduced dose by less than 1.5% for nodal hotspot (i.e., dose to 1 cm(3)), by less than 1% for the 90% nodal PTV coverage, and by less than 0.5% for the nodal mean dose. Bowel and femoral head hotspots were reduced by less than 1.5% and 2%, respectively. A 10-mm systematic offset reduced nodal coverage by up to 10%. CONCLUSION: The use of prostate fiducials for daily localization during IMRT treatment results in negligible changes in dose coverage of pelvic nodes or normal tissue sparing in the absence of a significant systematic offset. This offers a simple and practical solution to the problem of image-guided radiotherapy for prostate cancer when including pelvic nodes.

Quantification of motion of different thoracic locations using four-dimensional computed tomography: implications for radiotherapy planning.

PURPOSE: To assess the respiratory motion of different thoracic nodal locations and its dependence on the presence of enlarged nodes; to assess the respiratory motion of different parenchymal tumor locations; and to determine the appropriate margins to cover the respiratory motion of targets at these locations. METHODS AND MATERIALS: We reviewed the four-dimensional computed tomography scans of 20 patients with thoracic tumors treated at our institution. The motion of four central thoracic locations (aortic arch, carina, and bilateral hila), parenchymal tumor locations (upper vs. lower, and anterior vs. middle vs. posterior thorax), and bilateral diaphragmatic domes was measured. RESULTS: For the central thoracic locations, the largest motion was in the superoinferior (SI) dimension (>5 mm for bilateral hila and carina, but <4 mm for aortic arch). No significant difference was found in the motion of these locations in the absence or presence of enlarged nodes. For parenchymal tumors, upper tumors exhibited smaller SI motion than did lower tumors (3.7 vs. 10.4 mm, p = 0.029). Similarly, anterior tumors exhibited smaller motion than did posterior tumors in both the SI (4.0 vs. 8.0 mm, p = 0.013) and lateral (2.8 vs. 4.6 mm, p = 0.045) directions. The margins that would be needed to encompass the respiratory motion of each of the evaluated locations in 95% of patients were tabulated and range from 3.4 to 37.2 mm, depending on the location and direction. CONCLUSIONS: The results of our study have provided data for appropriate site-specific internal target volume expansion that could be useful in the absence of four-dimensional computed tomography-based treatment planning. However, generalizing the results from a small patient population requires discretion.

Investigation of linac-based image-guided hypofractionated prostate radiotherapy.

A hypofractionation treatment protocol for prostate cancer was initiated in our department in December 2003. The treatment regimen consists of a total dose of 36.25 Gy delivered at 7.25 Gy per fraction over 10 days. We discuss the rationale for such a prostate hypofractionation protocol and the need for frequent prostate imaging during treatment. The CyberKnife (Accuray Inc., Sunnyvale, CA), a linear accelerator mounted on a robotic arm, is currently being used as the radiation delivery device for this protocol, due to its incorporation of near real-time kV imaging of the prostate via 3 gold fiducial seeds. Recently introduced conventional linac kV imaging with intensity modulated planning and delivery may add a new option for these hypofractionated treatments. The purpose of this work is to investigate the use of intensity modulated radiotherapy (IMRT) and the Varian Trilogy Accelerator with on-board kV imaging (Varian Medical Systems Inc., Palo Alto, CA) for treatment of our hypofractionated prostate patients. The dose-volume histograms and dose statistics of 2 patients previously treated on the CyberKnife were compared to 7-field IMRT plans. A process of acquiring images to observe intrafraction prostate motion was achieved in an average time of about 1 minute and 40 seconds, and IMRT beam delivery takes about 40 seconds per field. A complete 7-field IMRT plan can therefore be imaged and delivered in 10 to 17 minutes. The Varian Trilogy Accelerator with on-board imaging and IMRT is well suited for image-guided hypofractionated prostate treatments. During this study, we have also uncovered opportunities for improvement of the on-board imaging hardware/software implementation that would further enhance performance in this regard.

A quality assurance program for the on-board imagers.

To develop a quality assurance (QA) program for the On-Board Imager (OBI) system and to summarize the results of these QA tests over extended periods from multiple institutions. Both the radiographic and cone-beam computed tomography (CBCT) mode of operation have been evaluated. The QA programs from four institutions have been combined to generate a series of tests for evaluating the performance of the On-Board Imager. The combined QA program consists of three parts: (1) safety and functionality, (2) geometry, and (3) image quality. Safety and functionality tests evaluate the functionality of safety features and the clinical operation of the entire system during the tube warm-up. Geometry QA verifies the geometric accuracy and stability of the OBI/CBCT hardware/software. Image quality QA monitors spatial resolution and contrast sensitivity of the radiographic images. Image quality QA for CBCT includes tests for Hounsfield Unit (HU) linearity, HU uniformity, spatial linearity, and scan slice geometry, in addition. All safety and functionality tests passed on a daily basis. The average accuracy of the OBI isocenter was better than 1.5 mm with a range of variation of less than 1 mm over 8 months. The average accuracy of arm positions in the mechanical geometry QA was better than 1 mm, with a range of variation of less than 1 mm over 8 months. Measurements of other geometry QA tests showed stable results within tolerance throughout the test periods. Radiographic contrast sensitivity ranged between 2.2% and 3.2% and spatial resolution ranged between 1.25 and 1.6 lp/mm. Over four months the CBCT images showed stable spatial linearity, scan slice geometry, contrast resolution (1%; <7 mm disk) and spatial resolution (>6 lp/cm). The HU linearity was within +/-40 HU for all measurements. By combining test methods from multiple institutions, we have developed a comprehensive, yet practical, set of QA tests for the OBI system. Use of the tests over extended periods show that the OBI system has reliable mechanical accuracy and stable image quality. Nevertheless, the tests have been useful in detecting performance deficits in the OBI system that needed recalibration. It is important that all tests are performed on a regular basis.

Overview of image-guided radiation therapy.

Radiation therapy has gone through a series of revolutions in the last few decades and it is now possible to produce highly conformal radiation dose distribution by using techniques such as intensity-modulated radiation therapy (IMRT). The improved dose conformity and steep dose gradients have necessitated enhanced patient localization and beam targeting techniques for radiotherapy treatments. Components affecting the reproducibility of target position during and between subsequent fractions of radiation therapy include the displacement of internal organs between fractions and internal organ motion within a fraction. Image-guided radiation therapy (IGRT) uses advanced imaging technology to better define the tumor target and is the key to reducing and ultimately eliminating the uncertainties. The purpose of this article is to summarize recent advancements in IGRT and discussed various practical issues related to the implementation of the new imaging techniques available to radiation oncology community. We introduce various new IGRT concepts and approaches, and hope to provide the reader with a comprehensive understanding of the emerging clinical IGRT technologies. Some important research topics will also be addressed.

Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord.

A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.

Predictors of toxicity associated with stereotactic body radiation therapy to the central hepatobiliary tract.

PURPOSE: To identify dosimetric predictors of hepatobiliary (HB) toxicity associated with stereotactic body radiation therapy (SBRT) for liver tumors. METHODS AND MATERIALS: We retrospectively reviewed 96 patients treated with SBRT for primary (53%) or metastatic (47%) liver tumors between March 2006 and November 2013. The central HB tract (cHBT) was defined by a 15-mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. Patients were censored for toxicity upon local progression or additional liver-directed therapy. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. To compare different SBRT fractionations, doses were converted to biologically effective doses (BED) by using the standard linear quadratic model α/ß = 10 (BED10). RESULTS: Median follow-up was 12.7 months after SBRT. Median BED10 was 85.5 Gy (range: 37.5-151.2). The median number of fractions was 5 (range: 1-5), with 51 patients (53.1%) receiving 5 fractions and 29 patients (30.2%) receiving 3 fractions. In total, there were 23 (24.0%) grade 2+ and 18 (18.8%) grade 3+ HB toxicities. Nondosimetric factors predictive of grade 3+ HB toxicity included cholangiocarcinoma (CCA) histology (P<.0001), primary liver tumor (P=.0087), and biliary stent (P<.0001). Dosimetric parameters most predictive of grade 3+ HB toxicity were volume receiving above BED10 of 72 Gy (VBED1072) ≥ 21 cm(3) (relative risk [RR]: 11.6, P<.0001), VBED1066 ≥ 24 cm(3) (RR: 10.5, P<.0001), and mean BED10 (DmeanBED10) cHBT ≥14 Gy (RR: 9.2, P<.0001), with VBED1072 and VBED1066 corresponding to V40 and V37.7 for 5 fractions and V33.8 and V32.0 for 3 fractions, respectively. VBED1072 ≥ 21 cm(3), VBED1066 ≥ 24 cm(3), and DmeanBED10 cHBT ≥14 Gy were consistently predictive of grade 3+ toxicity on multivariate analysis. CONCLUSIONS: VBED1072, VBED1066, and DmeanBED10 to cHBT are associated with HB toxicity. We suggest VBED1072 < 21 cm(3) (5-fraction: V40 < 21 cm(3); 3-fraction: V33.8 < 21 cm(3)), VBED1066 < 24 cm(3) (5-fraction: V37.7 < 24 cm(3); 3-fraction: V32 < 24 cm(3)) as potential dose constraints for the cHBT when clinically indicated.

Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate.

INTRODUCTION: Intensity-modulated radiotherapy (IMRT) has introduced novel dosimetry that often features increased dose heterogeneity to target and normal structures. This raises questions of the biologic effects of IMRT compared to conventional treatment. We compared dosimetry and radiobiologic model predictions of tumor control probability (TCP) and normal tissue complication probability (NTCP) for prostate cancer patients planned for IMRT as opposed to standardized three-dimensional conformal radiotherapy (3DCRT). METHODS AND MATERIALS: Segmented multileaf collimator IMRT treatment plans for 32 prostate cancer patients were compared to 3DCRT plans for the same patients. Twenty-two received local-field irradiation (LFI), and 10 received extended-field irradiation (EFI) that included pelvic lymph nodes. For LFI, IMRT was planned for delivery of 2 Gy minimum dose to the prostate (> or =99% volume coverage) for 35 fractions. The 3DCRT plans, characterized by more homogenous dose to the target, were designed according to a different protocol to deliver 2 Gy to the center of the prostate for 37 fractions. Mean total dose from 35 fractions of IMRT was equal to mean total dose from 37 fractions of 3DCRT. For EFI, both IMRT and 3DCRT were planned for 2 Gy per fraction to a total dose of 50 Gy to prostate and pelvic lymph nodes, followed by 2 Gy per fraction to 20 Gy to the prostate alone. Treatment dose for EFI-IMRT was defined as minimum dose to the target, whereas for EFI-3DCRT, it was defined as dose to the center of the prostate. TCP was calculated for the prostate in the linear-quadratic model for two choices of alpha/beta. NTCP was calculated with the Lyman model for organs at risk, using Kutcher-Burman dose-volume histogram reduction with Emami parameters. RESULTS AND CONCLUSIONS: Dose to the prostate, expressed as mean +/- standard deviation, was 74.7 +/- 1.1 Gy for IMRT vs. 74.6 +/- 0.3 Gy for 3D for the LFI plans, and 74.8 +/- 0.6 Gy for IMRT vs. 71.5 +/- 0.6 Gy for 3D for the EFI plans. For the studied protocols, TCP was greater for IMRT than for 3D across the full range of target sensitivity, for both localized- and extended-field irradiation. For LFI, this was due to the smaller number of fractions (35 vs. 37) used for IMRT, and for EFI, this was due to the greater mean dose for IMRT, compared to 3D. For all organs, mean NTCP tended to be lower for IMRT than for 3D, although NTCP values were very small for both 3D and IMRT. Differences were statistically significant for rectum (LFI and EFI), bladder (EFI), and bowel (EFI). For both LFI and EFI, the calculated NTCPs qualitatively agreed with early published clinical data comparing genitourinary and gastrointestinal complications of IMRT and 3D. Present calculations support the hypothesis that accurately delivered IMRT for prostate cancer can limit dose to normal tissue by reducing treatment margins relative to conventional 3D planning, to allow a reduction in complication rate spanning several sensitive structures while maintaining or increasing tumor control probability.

Lens dose in MLC-based IMRT treatments of the head and neck.

PURPOSE: The objectives of this work are: (1) to determine typical dose to the lens during step-and-shoot intensity modulated radiotherapy (IMRT) treatments of the head and neck, and (2) to report on the dose calculation accuracy of a commercial inverse planning system in predicting lens dose. METHODS AND MATERIALS: The Corvus inverse treatment planning system (Nomos, Cranberry Township, PA) was used to plan IMRT treatments for patients with head-and-neck cancers in our clinic. Patients were treated on Varian C-series linacs (Varian, Palo Alto, CA) with 4-MV or 6-MV X-rays. A Rando phantom (Alderson Laboratories, Stamford, CT) was specially modified to accommodate 1 x 1 x 1 mm(3) thermoluminescent dosimeters at the position of the lens. The IMRT treatment plans were then delivered to the modified Rando phantom. The thermoluminescent dosimeter measurements were converted to dose and taken as an estimate of the lens dose. A total of 20 cases were used in this study (15 cases with 4 MV and 5 cases with 6 MV). RESULTS: Expressed as a percentage of the prescription dose, the mean dose to the left and right lens for all 4-MV cases was 9.1% (range, 2.0% to 61.3%). For the 6-MV cases, the mean dose to the left and right lens was 12.8% (range, 3.6% to 41.3%). For both the 4-MV and 6-MV cases, the case of maximum dose occurred when the IMRT treatment target included volumes superior to the level of the lens. The field size and number of monitor units did not correlate with the measured lens dose. The only factor of significance affecting lens dose was the inferior-to-superior distance of the target to the lens. For target-lens distance >/=6 mm, the maximum measured lens doses were 5.9% and 9.0% relative to the prescribed dose for the 4-MV and 6-MV beams, respectively. These data are similar to those observed in conventional head-and-neck treatments. For all cases, the difference between the dose measured and that predicted by Corvus was less than 2% and 4% of the dose prescribed to the gross tumor volume for the 4-MV and 6-MV cases, respectively. CONCLUSION: In IMRT, factors such as leaf leakage and number of monitor units play a secondary role and are not more significant than what is observed in conventional head-and-neck treatment when the lens is shielded by the collimator jaws. The target-lens distance is the parameter that affects the lens dose most strongly. For cases where the tumor is at or above the level of the lens, the lens dose can amount to an appreciable fraction of the prescription dose. To keep the lens dose to a minimum, noncoplanar beams that enter or exit into the lens should not be used.

Independent dosimetric calculation with inclusion of head scatter and MLC transmission for IMRT.

Independent verification of the MU settings and dose calculation of IMRT treatment plans is an important step in the IMRT quality assurance (QA) procedure. At present, the verification is mainly based on experimental measurements, which are time consuming and labor intensive. Although a few simplified algorithms have recently been proposed for the independent dose (or MU) calculation, head scatter has not been precisely taken into account in all these investigations and the dose validation has mainly been limited to the central axis. In this work we developed an effective computer algorithm for IMRT MU and dose validation. The technique is superior to the currently available computer-based MU check systems in that (1) it takes full consideration of the head scatter and leaf transmission effects; and (2) it allows a precise dose calculation at an arbitrary spatial point instead of merely a point on the central axis. In the algorithm the dose at an arbitrary spatial point is expressed as a summation of the contributions of primary and scatter radiation from all beamlets. Each beamlet is modulated by a dynamic modulation factor (DMF), which is determined by the MLC leaf trajectories, the head scatter, the jaw positions, and the MLC leaf transmission. A three-source model was used to calculate the head scatter distribution for irregular segments shaped by MLC and the scatter dose contributions were computed using a modified Clarkson method. The system reads in MLC leaf sequence files (or RTP files) generated by the Corvus (NOMOS Corporation, Sewickley, PA) inverse planning system and then computes the doses at the desired points. The algorithm was applied to study the dose distributions of several testing intensity modulated fields and two multifield Corvus plans and the results were compared with Corvus plans and experimental measurements. The final dose calculations at most spatial points agreed with the experimental measurements to within 3% for both the specially designed testing fields and the clinical intensity modulated field. Furthermore, excellent agreement (mostly within +/- 3.0%) was also found between our independent calculation and the ion chamber measurements at both central axis and off-axis positions for the multifield Corvus IMRT plans. These results indicate that the approach is robust and valuable for routine clinical IMRT plan validation.

Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modulated radiation therapy.

PURPOSE: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. METHODS AND MATERIALS: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. RESULTS: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

Fidelity of dose delivery at high dose rate of volumetric modulated arc therapy in a truebeam linac with flattening filter free beams.

The purpose of this study is to assess fidelity of radiation delivery between high and low dose rates of the flattening filter free (FFF) modes of a new all-digital design medical linear accelerator (Varian TrueBeam™), particularly for plans optimized for volumetric modulated arc therapy (VMAT). Measurements were made for the two energies of flattening filter free photon beams with a Varian TrueBeam™ linac: 6 MV (6 XFFF) at 400 and 1400 MU/min, and 10 MV (10 XFFF) at 400 and 2400 MU/min. Data acquisition and analysis was performed with both ionization chambers and diode detector system Delta(4), for square radiation fields and for 8 VMAT treatment plans optimized for SBRT treatment of lung tumors. For the square fields, a percent dose difference between high and low dose rate of the order of 0.3-0.4% for both photon energies was seen with the ionization chambers, while the contribution to the difference from ion recombination was found to be negligible. For both the VMAT and square-field deliveries, the Delta(4) showed the same average percent dose difference between the two dose rates of ~0.8% and ~0.6% for 10 MV and 6 MV, respectively, with the lower dose rate values giving the greater measured dose compared to the high dose rate. Thus, the VMAT deliveries introduced negligible dose differences between high and low dose rate. Finally, reproducibility of dose measurements was good for both energies.

Normal tissue complication probability modeling of acute hematologic toxicity in patients treated with intensity-modulated radiation therapy for squamous cell carcinoma of the anal canal.

PURPOSE: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade ≥3 HT (HT3+) and hematologic event (HE), defined as any grade ≥2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. RESULTS: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD(50) = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose ≥30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. CONCLUSIONS: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

Normal tissue complication probability estimation by the Lyman-Kutcher-Burman method does not accurately predict spinal cord tolerance to stereotactic radiosurgery.

PURPOSE: To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for α/ß, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/ß and n. RESULTS: In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/ß and n yielded better predictions (0.7 complications), with n = 0.023 and α/ß = 17.8 Gy. CONCLUSIONS: The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/ß value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

Dose verification for respiratory-gated volumetric modulated arc therapy.

A novel commercial medical linac system (TrueBeam™, Varian Medical Systems, Palo Alto, CA) allows respiratory-gated volumetric modulated arc therapy (VMAT), a new modality for treating moving tumors with high precision and improved accuracy by allowing for regular motion associated with a patient's breathing during VMAT delivery. The purpose of this work is to adapt a previously-developed dose reconstruction technique to evaluate the fidelity of VMAT treatment during gated delivery under clinic-relevant periodic motion related to patient breathing. A Varian TrueBeam system was used in this study. VMAT plans were created for three patients with lung or pancreas tumors. Conventional 6 and 15 MV beams with flattening filter and high-dose-rate 10 MV beams with no flattening filter were used in these plans. Each patient plan was delivered to a phantom first without gating and then with gating for three simulated respiratory periods (3, 4.5 and 6 s). Using the adapted log-file-based dose reconstruction procedure supplemented with ion chamber array (Seven29™, PTW, Freiburg, Germany) measurements, the delivered dose was used to evaluate the fidelity of gated VMAT delivery. Comparison of Seven29 measurements with and without gating showed good agreement with gamma-index passing rates above 99% for 1%/1 mm dose accuracy/distance-to-agreement criteria. With original plans as reference, gamma-index passing rates were 100% for the reconstituted plans (1%/1 mm criteria) and 93.5-100% for gated Seven29 measurements (3%/3 mm criteria). In the presence of leaf error deliberately introduced into the gated delivery of a pancreas patient plan, both dose reconstruction and Seven29 measurement consistently indicated substantial dosimetric differences from the original plan. In summary, a dose reconstruction procedure was demonstrated for evaluating the accuracy of respiratory-gated VMAT delivery. This technique showed that under clinical operation, the TrueBeam system faithfully realized treatment plans with gated delivery. This methodology affords a useful tool for machine- and patient-specific quality assurance of the newly available respiratory-gated VMAT.

Stereotactic radiosurgery yields long-term control for benign intradural, extramedullary spinal tumors.

BACKGROUND: The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors. OBJECTIVE: To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors. METHODS: From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm). RESULTS: After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ≥ 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up. CONCLUSION: As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.