A comparison of two methodologies for radiotherapy treatment plan optimization and QA for clinical trials.

BACKGROUND AND PURPOSE: The efficacy of clinical trials and the outcome of patient treatment are dependent on the quality assurance (QA) of radiation therapy (RT) plans. There are two widely utilized approaches that include plan optimization guidance created based on patient-specific anatomy. This study examined these two techniques for dose-volume histogram predictions, RT plan optimizations, and prospective QA processes, namely the knowledge-based planning (KBP) technique and another first principle (FP) technique. METHODS: This analysis included 60, 44, and 10 RT plans from three Radiation Therapy Oncology Group (RTOG) multi-institutional trials: RTOG 0631 (Spine SRS), RTOG 1308 (NSCLC), and RTOG 0522 (H&N), respectively. Both approaches were compared in terms of dose prediction and plan optimization. The dose predictions were also compared to the original plan submitted to the trials for the QA procedure. RESULTS: For the RTOG 0631 (Spine SRS) and RTOG 0522 (H&N) plans, the dose predictions from both techniques have correlation coefficients of >0.9. The RT plans that were re-optimized based on the predictions from both techniques showed similar quality, with no statistically significant differences in target coverage or organ-at-risk sparing. The predictions of mean lung and heart doses from both methods for RTOG1308 patients, on the other hand, have a discrepancy of up to 14 Gy. CONCLUSIONS: Both methods are valuable tools for optimization guidance of RT plans for Spine SRS and Head and Neck cases, as well as for QA purposes. On the other hand, the findings suggest that KBP may be more feasible in the case of inoperable lung cancer patients who are treated with IMRT plans that have spatially unevenly distributed beam angles.

Characterization of a new physical phantom for testing rigid and deformable image registration.

The purpose of this study was to describe a new user-friendly, low-cost phantom that was developed to test the accuracy of rigid and deformable image registration (DIR) systems and to demonstrate the functional efficacy of the new phantom. The phantom was constructed out of acrylic and includes a variety of inserts that simulate different tissue shapes and properties. It can simulate deformations and location changes in patient anatomy by changing the rotations of both the phantom and the inserts. CT scans of this phantom were obtained and used to test the rigid and deformable registration accuracy of the Velocity software. Eight rotation and translation scenarios were used to test the rigid registration accuracy, and 11 deformation scenarios were used to test the DIR accuracy. The mean rotation accuracies in the X-Y (axial) and X-Z (coronal) planes were 0.50° and 0.13°, respectively. The mean translation accuracy was 1 mm in both the X and Y direction and was tested in soft tissue and bone. The DIR accuracies for soft tissue and bone were 0.93 (mean Dice similarity coefficient), 8.3 and 4.5 mm (mean Hausdouff distance), 0.95 and 0.79 mm (mean distance), and 1.13 and 1.12 (mean volume ratio) for soft tissue content (DTE oil) and bone, respectively. The new phantom has a simple design and can be constructed at a low cost. This phantom will allow DIR systems to be effectively and efficiently verified to ensure system performance.

Spot scanning proton therapy minimizes neutron dose in the setting of radiation therapy administered during pregnancy.

This is a real case study to minimize the neutron dose equivalent (H) to a fetus using spot scanning proton beams with favorable beam energies and angles. Minimum neutron dose exposure to the fetus was achieved with iterative planning under the guidance of neutron H measurement. Two highly conformal treatment plans, each with three spot scanning beams, were planned to treat a 25-year-old pregnant female with aggressive recurrent chordoma of the base of skull who elected not to proceed with termination. Each plan was scheduled for delivery every other day for robust target coverage. Neutron H to the fetus was measured using a REM500 neutron survey meter placed at the fetus position of a patient simulating phantom. 4.1 and 44.1 µSv/fraction were measured for the two initial plans. A vertex beam with higher energy and the fetal position closer to its central axis was the cause for the plan that produced an order higher neutron H. Replacing the vertex beam with a lateral beam reduced neutron H to be comparable with the other plan. For a prescription of 70 Gy in 35 fractions, the total neutron H to the fetus was estimated to be 0.35 mSv based on final measurement in single fraction. In comparison, the passive scattering proton plan and photon plan had an estimation of 26 and 70 mSv, respectively, for this case. While radiation therapy in pregnant patients should be avoided if at all possible, our work demonstrated spot scanning beam limited the total neutron H to the fetus an order lower than the suggested 5 mSv regulation threshold. It is far superior than passive scattering beam and careful beam selection with lower energy and keeping fetus further away from beam axis are essential in minimizing the fetus neutron exposure.

A six-year review of more than 13,000 patient-specific IMRT QA results from 13 different treatment sites.

Due to a lack of information regarding the current clinical experience of IMRT QA for a large and varied plan population, we reviewed our patient-specific IMRT quality assurance (QA) results for 13,003 treatment plans from 13 distinct treatment sites from a six-year period. QA records were reviewed for dose difference (single point with ion chamber measurement; ± 3% agreement criteria) and percentage of pixels passing relative dose gamma analysis (film measurement; 90% passing 5%(global)/3 mm agreement criteria) from 2005 through 2011. Plan records were analyzed for trends with measurement date and treatment site. Plans failing to meet QA tolerance criteria were evaluated for follow-up clinical action (i.e., if repeat measurements were performed). The mean difference (± SD) between ion chamber point measurements and calculated doses was -0.29% ± 1.64% (calculated values being slightly higher) and, regarding planar dose evaluations, the mean percentage of pixels passing the gamma criteria of 5%(global)/3 mm was 97.7% (lower 95th percentile: 92.2%). 97.7% and 99.3% of plans passed the point dose and planar dose verification, respectively. We observed statistically significant differences (p< 0.05) in both point dose and planar dose verification measurements as a function of treatment site (particularly for stereotactic spine and mesothelioma sites) and measurement date (average agreement improved with time). However, despite improved dosimetric agreement, the percentage of failing plans has remained nearly constant at 2.3%.

Relative stopping power measurements to aid in the design of anthropomorphic phantoms for proton radiotherapy.

The delivery of accurate proton dose for clinical trials requires that the appropriate conversion function from Hounsfield unit (HU) to relative linear stopping power (RLSP) be used in proton treatment planning systems (TPS). One way of verifying that the TPS is calculating the correct dose is an end-to-end test using an anthropomorphic phantom containing tissue equivalent materials and dosimeters. Many of the phantoms in use for such end-to-end tests were originally designed using tissue-equivalent materials that had physical characteristics to match patient tissues when irradiated with megavoltage photon beams. The aim of this study was to measure the RLSP of materials used in the phantoms, as well as alternative materials to enable modifying phantoms for use at proton therapy centers. Samples of materials used and projected for use in the phantoms were measured and compared to the HU assigned by the treatment planning system. A percent difference in RLSP of 5% was used as the cutoff for materials deemed acceptable for use in proton therapy (i.e., proton equivalent). Until proper tissue-substitute materials are identified and incorporated, institutions that conduct end-to-end tests with the phantoms are instructed to override the TPS with the measured stopping powers we provide. To date, the RLSPs of 18 materials have been measured using a water phantom and/or multilayer ion chamber (MLIC). Nine materials were identified as acceptable for use in anthropomorphic phantoms. Some of the failing tissue substitute materials are still used in the current phantoms. Further investigation for additional appropriate tissue substitute materials in proton beams is ongoing. Until all anthropomorphic phantoms are constructed of appropriate materials, a unique HU-RLSP phantom has been developed to be used during site visits to verify the proton facility's treatment planning HU-RLSP calibration curve.

Development of a modified head and neck quality assurance phantom for use in stereotactic radiosurgery trials.

An anthropomorphic head phantom, constructed from a water-equivalent plastic shell with only a spherical target, was modified to include a nonspherical target (pituitary) and an adjacent organ at risk (OAR) (optic chiasm), within 2 mm, simulating the anatomy encountered when treating acromegaly. The target and OAR spatial proximity provided a more realistic treatment planning and dose delivery exercise. A separate dosimetry insert contained two TLD for absolute dosimetry and radiochromic film, in the sagittal and coronal planes, for relative dosimetry. The prescription was 25 Gy to 90% of the GTV, with ≤ 10% of the OAR volume receiving ≥ 8 Gy for the phantom trial. The modified phantom was used to test the rigor of the treatment planning process and phantom reproducibility using a Gamma Knife, CyberKnife, and linear accelerator (linac)-based radiosurgery system. Delivery reproducibility was tested by repeating each irradiation three times. TLD results from three irradiations on a CyberKnife and Gamma Knife agreed with the calculated target dose to within ± 4% with a maximum coefficient of variation of ± 2.1%. Gamma analysis in the coronal and sagittal film planes showed an average passing rate of 99.4% and 99.5% using ± 5%/3 mm criteria, respectively. Results from the linac irradiation were within ± 6.2% for TLD with a coefficient of variation of ± 0.1%. Distance to agreement was calculated to be 1.2 mm and 1.3mm along the inferior and superior edges of the target in the sagittal film plane, and 1.2 mm for both superior and inferior edges in the coronal film plane. A modified, anatomically realistic SRS phantom was developed that provided a realistic clinical planning and delivery challenge that can be used to credential institutions wanting to participate in NCI-funded clinical trials.

Dynamically accumulated dose and 4D accumulated dose for moving tumors.

PURPOSE: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. METHODS: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a "pulsed beam"; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a "continuous beam." A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. RESULTS: The numerical simulations confirmed that the number of deliveries for each phase converges to K∕N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and∕or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. CONCLUSIONS: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and∕or total deliver time was also established.

A procedure to determine the planar integral spot dose values of proton pencil beam spots.

PURPOSE: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. METHODS: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeV energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D(0)) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D(0). The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD(RBPC). The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD(full). The calculated values of PISD(RBPC) obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD(full)∕PISD(RBPC) at different depths for PPBSs of different energies. RESULTS: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD(RBPC) values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD(full) values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. CONCLUSIONS: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

BACKGROUND: The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. METHODS: Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. RESULTS: Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. CONCLUSIONS: Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC.

Early findings on toxicity of proton beam therapy with concurrent chemotherapy for nonsmall cell lung cancer.

BACKGROUND: Concurrent chemoradiation therapy, the standard of care for locally advanced nonsmall cell lung cancer (NSCLC), can cause life-threatening pneumonitis and esophagitis. X-ray (photon)-based radiation therapy (RT) often cannot be given at tumoricidal doses without toxicity to proximal normal tissues. We hypothesized that proton beam therapy for most patients with NSCLC could permit higher tumor doses with less normal-tissue toxicity than photon RT delivered as 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: We compared the toxicity of proton therapy+concurrent chemotherapy in 62 patients with NSCLC (treatment period 2006-2008) with toxicity for patients with similar disease given 3D-CRT+chemotherapy (n = 74; treatment period 2001-2003) or IMRT+chemotherapy (n = 66; treatment period 2003-2005). Proton therapy to the gross tumor volume was given with weekly intravenous paclitaxel (50 mg/m²) and carboplatin (area under the curve 2 mg/mL/min). The primary endpoint was toxicity (Common Terminology Criteria for Adverse Events version 3.0). RESULTS: Median follow-up times were 15.2 months (proton), 17.9 months (3D-CRT), and 17.4 months (IMRT). Median total radiation dose was 74 Gy(RBE) for the proton group versus 63 Gy for the other groups. Rates of severe (grade ≥ 3) pneumonitis and esophagitis in the proton group (2% and 5%) were lower despite the higher radiation dose (3D-CRT, 30% and 18%; IMRT, 9% and 44%; P<.001 for all). CONCLUSIONS: We found that higher doses of proton radiation could be delivered to lung tumors with a lower risk of esophagitis and pneumonitis. A randomized comparison of IMRT versus proton therapy is underway.

Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy.

PURPOSE: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. METHODS: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. RESULTS: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 +/- 35 patients. CONCLUSIONS: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Toward a better understanding of the gamma index: Investigation of parameters with a surface-based distance method.

PURPOSE: The purpose of this work was to clarify the interactions between the parameters used in the γ index with the surface-based distance method, which itself can be viewed as a generalized version of the γ index. The examined parameters included the distance to agreement (DTA)/dose difference (DD) criteria, the percentage used as a passing criterion, and the passing percentage for given DTA/DD criteria. The specific aims of our work were (1) to understand the relationships between the parameters used in the γ index, (2) to determine the detection limit, or the minimum detectable error, of the γ index with a given set of parameters, and (3) to establish a procedure to determine parameters that are consistent with the capacity of an IMRT QA system. METHODS: The surface-based distance technique with dose gradient factor was derived, and then the relationship between surface-based distance and γ index was established. The dose gradient factor for plans and measurements of 10 IMRT patients, 10 spine stereotactic radiosurgery (SRS) patients, and 3 Radiological Physics Center (RPC) head and neck phantom were calculated and evaluated. The detection limits of the surface-based distance and γ index methods were examined by introducing known shifts to the 10 IMRT plans. RESULTS: The means of the dose gradient factors were 0.434 mm/% and 0.956 mm/% for the SRS and IMRT plans, respectively. Key quantities (including the mean and 90th and 99th percentiles of the distance distribution) of the surface-based distance distribution between two dose distributions were linearly proportional to the actual shifts. However, the passing percentage of the γ index for a given set of DTA/DD criteria was not associated with the actual shift. For IMRT, using the standard quality assurance criteria of 3 mm/3% DTA/DD and a 90% passing rate, we found that the detection limit of the γ index in terms of global shift was 4.07 mm/4.07 % without noise. CONCLUSIONS: Surface-based distance is a direct measure of the difference between two dose distributions and can be used to evaluate or determine parameters for use in calculating the γ index. The dose gradient factor represents the weighting between spatial and dose shift and should be determined before DTA/DD criteria are set. The authors also present a procedure to determine γ index parameters from measurements.

Neutron-induced electronic failures around a high-energy linear accelerator.

PURPOSE: After a new in-vault CT-on-rails system repeatedly malfunctioned following use of a high-energy radiotherapy beam, we investigated the presence and impact of neutron radiation on this electronic system, as well as neutron shielding options. METHODS: We first determined the CT scanner's failure rate as a function of the number of 18 MV monitor units (MUs) delivered. We then re-examined the failure rate with both 2.7-cm-thick and 7.6-cm-thick borated polyethylene (BPE) covering the linac head for neutron shielding. To further examine shielding options, as well as to explore which neutrons were relevant to the scanner failure, Monte Carlo simulations were used to calculate the neutron fluence and spectrum in the bore of the CT scanner. Simulations included BPE covering the CT scanner itself as well as covering the linac head. RESULTS: We found that the CT scanner had a 57% chance of failure after the delivery of 200 MUs. While the addition of neutron shielding to the accelerator head reduced this risk of failure, the benefit was minimal and even 7.6 cm of BPE was still associated with a 29% chance of failure after the delivery of 200 MU. This shielding benefit was achieved regardless of whether the linac head or CT scanner was shielded. Additionally, it was determined that fast neutrons were primarily responsible for the electronic failures. CONCLUSIONS: As illustrated by the CT-on-rails system in the current study, physicists should be aware that electronic systems may be highly sensitive to neutron radiation. Medical physicists should therefore monitor electronic systems that have not been evaluated for potential neutron sensitivity. This is particularly relevant as electronics are increasingly common in the therapy vault and newer electronic systems may exhibit increased sensitivity.

Verification of patient-specific dose distributions in proton therapy using a commercial two-dimensional ion chamber array.

PURPOSE: The purpose of this study was to determine whether a two-dimensional (2D) ion chamber array detector quickly and accurately measures patient-specific dose distributions in treatment with passively scattered and spot scanning proton beams. METHODS: The 2D ion chamber array detector MatriXX was used to measure the dose distributions in plastic water phantom from passively scattered and spot scanning proton beam fields planned for patient treatment. Planar dose distributions were measured using MatriXX, and the distributions were compared to those calculated using a treatment-planning system. The dose distributions generated by the treatment-planning system and a film dosimetry system were similarly compared. RESULTS: For passively scattered proton beams, the gamma index for the dose-distribution comparison for treatment fields for three patients with prostate cancer and for one patient with lung cancer was less than 1.0 for 99% and 100% of pixels for a 3% dose tolerance and 3 mm distance-to-dose agreement, respectively. For spot scanning beams, the mean (+/- standard deviation) percentages of pixels with gamma indices meeting the passing criteria were 97.1% +/- 1.4% and 98.8% +/- 1.4% for MatriXX and film dosimetry, respectively, for 20 fields used to treat patients with prostate cancer. CONCLUSIONS: Unlike film dosimetry, MatriXX provides not only 2D dose-distribution information but also absolute dosimetry in fractions of minutes with acceptable accuracy. The results of this study indicate that MatriXX can be used to verify patient-field specific dose distributions in proton therapy.

Energy dependence and dose response of Gafchromic EBT2 film over a wide range of photon, electron, and proton beam energies.

PURPOSE: Since the Gafchromic film EBT has been recently replaced by the newer model EBT2, its characterization, especially energy dependence, has become critically important. The energy dependence of the dose response of Gafchromic EBT2 film is evaluated for a broad range of energies from different radiation sources used in radiation therapy. METHODS: The beams used for this study comprised of kilovoltage x rays (75, 125, and 250 kVp), 137Cs gamma (662 KeV), 60Co gamma (1.17-1.33 MeV), megavoltage x rays (6 and 18 MV), electron beams (6 and 20 MeV), and proton beams (100 and 250 MeV). The film's response to each of the above energies was measured over the dose range of 0.4-10 Gy, which corresponds to optical densities ranging from 0.05 to 0.74 for the film reader used. RESULTS: The energy dependence of EBT2 was found to be relatively small within measurement uncertainties (1 sigma = +/- 4.5%) for all energies and modalities. CONCLUSION: For relative and absolute dosimetry of radiation therapy beams, the weak energy dependence of the EBT2 makes it most suitable for clinical use compared to other films.

An MCNPX Monte Carlo model of a discrete spot scanning proton beam therapy nozzle.

PURPOSE: The purposes of this study were to validate a discrete spot scanning proton beam nozzle using the Monte Carlo (MC) code MCNPX and use the MC validated model to investigate the effects of a low-dose envelope, which surrounds the beam's central axis, on measurements of integral depth dose (IDD) profiles. METHODS: An accurate model of the discrete spot scanning beam nozzle from The University of Texas M. D. Anderson Cancer Center (Houston, Texas) was developed on the basis of blueprints provided by the manufacturer of the nozzle. The authors performed simulations of single proton pencil beams of various energies using the standard multiple Coulomb scattering (MCS) algorithm within the MCNPX source code and a new MCS algorithm, which was implemented in the MCNPX source code. The MC models were validated by comparing calculated in-air and in-water lateral profiles and percentage depth dose profiles for single pencil beams with their corresponding measured values. The models were then further tested by comparing the calculated and measured three-dimensional (3-D) dose distributions. Finally, an IDD profile was calculated with different scoring radii to determine the limitations on the use of commercially available plane-parallel ionization chambers to measure IDD. RESULTS: The distance to agreement, defined as the distance between the nearest positions of two equivalent distributions with the same value of dose, between measured and simulated ranges was within 0.13 cm for both MCS algorithms. For low and intermediate pencil beam energies, the MC simulations using the standard MCS algorithm were in better agreement with measurements. Conversely, the new MCS algorithm produced better results for high-energy single pencil beams. The IDD profile calculated with cylindrical tallies with an area equivalent to the area of the largest commercially available ionization chamber showed up to 7.8% underestimation of the integral dose in certain depths of the IDD profile. CONCLUSIONS: The authors conclude that a combination of MCS algorithms is required to accurately reproduce experimental data of single pencil beams and 3-D dose distributions for the scanning beam nozzle. In addition, the MC simulations showed that because of the low-dose envelope, ionization chambers with radii as large as 4.08 cm are insufficient to accurately measure IDD profiles for a 221.8 MeV pencil beam in the scanning beam nozzle.

Commissioning of the discrete spot scanning proton beam delivery system at the University of Texas M.D. Anderson Cancer Center, Proton Therapy Center, Houston.

PURPOSE: To describe a summary of the clinical commissioning of the discrete spot scanning proton beam at the Proton Therapy Center, Houston (PTC-H). METHODS: Discrete spot scanning system is composed of a delivery system (Hitachi ProBeat), an electronic medical record (Mosaiq V 1.5), and a treatment planning system (TPS) (Eclipse V 8.1). Discrete proton pencil beams (spots) are used to deposit dose spot by spot and layer by layer for the proton distal ranges spanning from 4.0 to 30.6 g/cm2 and over a maximum scan area at the isocenter of 30 x 30 cm2. An arbitrarily chosen reference calibration condition has been selected to define the monitor units (MUs). Using radiochromic film and ion chambers, the authors have measured spot positions, the spot sizes in air, depth dose curves, and profiles for proton beams with various energies in water, and studied the linearity of the dose monitors. In addition to dosimetric measurements and TPS modeling, significant efforts were spent in testing information flow and recovery of the delivery system from treatment interruptions. RESULTS: The main dose monitors have been adjusted such that a specific amount of charge is collected in the monitor chamber corresponding to a single MU, following the IAEA TRS 398 protocol under a specific reference condition. The dose monitor calibration method is based on the absolute dose per MU, which is equivalent to the absolute dose per particle, the approach used by other scanning beam institutions. The full width at half maximum for the spot size in air varies from approximately 1.2 cm for 221.8 MeV to 3.4 cm for 72.5 MeV. The measured versus requested 90% depth dose in water agrees to within 1 mm over ranges of 4.0-30.6 cm. The beam delivery interlocks perform as expected, guarantying the safe and accurate delivery of the planned dose. CONCLUSIONS: The dosimetric parameters of the discrete spot scanning proton beam have been measured as part of the clinical commissioning program, and the machine is found to function in a safe manner, making it suitable for patient treatment.

Monte Carlo Simulations of Neutron Ambient Dose Equivalent in a Novel Proton Therapy Facility Design.

PURPOSE: The neutron shielding properties of the concrete structures of a proposed proton therapy facility were evaluated with help of the Monte Carlo technique. The planned facility's design omits the typical maze-structured entrances to the treatment rooms to facilitate more efficient access and, instead, proposes the use of massive concrete/steel doors. Furthermore, straight conduits in the treatment room walls were used in the design of the facility, necessitating a detailed investigation of the neutron radiation outside the rooms to determine if the design can be applied without violating existing radiation protection regulations. This study was performed to investigate whether the operation of a proton therapy unit using such a facility design will be in compliance with radiation protection requirements. METHODS: A detailed model of the planned proton therapy expansion project of the University of Texas, M. D. Anderson Cancer Center in Houston, Texas, was produced to simulate secondary neutron production from clinical proton beams using the MCNPX Monte Carlo radiation transport code. Neutron spectral fluences were collected at locations of interest and converted to ambient dose equivalents using an in-house code based on fluence to dose-conversion factors provided by the International Commission on Radiological Protection. RESULTS AND CONCLUSIONS: At all investigated locations of interest, the ambient dose equivalent values were below the occupational dose limits and the dose limits for individual members of the public. The impact of straight conduits was negligible because their location and orientation were such that no line of sight to the neutron sources (ie, the isocenter locations) was established. Finally, the treatment room doors were specially designed to provide spatial efficiency and, compared with traditional maze designs, showed that while it would be possible to achieve a lower neutron ambient dose equivalent with a maze, the increased spatial (and financial) requirements may offset this advantage.

Evaluation of the high definition field of view option of a large-bore computed tomography scanner for radiation therapy simulation.

BACKGROUND AND PURPOSE: Computed tomography (CT) scanning is the basis for radiation treatment planning, but the 50-cm standard scanning field of view (sFOV) may be too small for imaging larger patients. We evaluated the 65-cm high-definition (HD) FOV of a large-bore CT scanner for CT number accuracy, geometric distortion, image quality degradation, and dosimetric accuracy of photon treatment plans. MATERIALS AND METHODS: CT number accuracy was tested by placing two 16-cm acrylic phantoms on either side of a 40-cm phantom to simulate a large patient extending beyond the 50-cm-diameter standard scanning FOV. Dosimetric accuracy was tested using anthropomorphic pelvis and thorax phantoms, with additional acrylic body parts on either side of the phantoms. Two volumetric modulated arc therapy beams (a 15-MV and a 6-MV) were used to cover the planning target volumes. Two-dimensional dose distributions were evaluated with GAFChromic film and point dose accuracy was checked with multiple thermoluminescent dosimeter (TLD) capsules placed in the phantoms. Image quality was tested by placing an American College of Radiology accreditation phantom inside the 40-cm phantom. RESULTS: The HD FOV showed substantial changes in CT numbers, with differences of 314 HU-725 HU at different density levels. The volume of the body parts extending into the HD FOV was distorted. However, TLD-reported doses for all PTVs agreed within ± 3%. Dose agreement in organs at risk were within the passing criteria, and the gamma index pass rate was >97%. Image quality was degraded. CONCLUSIONS: The HD FOV option is adequate for RT simulation and met accreditation standards, although care should be taken during contouring because of reduced image quality.

Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question-Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head: A Phase II Randomized Clinical Trial.

PURPOSE: NRG/RTOG 0848 was designed to determine whether adjuvant radiation with fluoropyrimidine sensitization improved survival following gemcitabine-based adjuvant chemotherapy for patients with resected pancreatic head adenocarcinoma. In step 1 of this protocol, patients were randomized to adjuvant gemcitabine versus the combination of gemcitabine and erlotinib. This manuscript reports the final analysis of these step 1 data. METHODS: Eligibility-within 10 weeks of curative intent pancreaticoduodenectomy with postoperative CA19-9<180. Gemcitabine arm-6 cycles of gemcitabine. Gemcitabine+erlotinib arm-gemcitabine and erlotinib 100 mg/d. Two hundred deaths provided 90% power (1-sided α=0.15) to detect the hypothesized OS signal (hazard ratio=0.72) in favor of the arm 2. RESULTS: From November 17, 2009 to February 28, 2014, 163 patients were randomized and evaluable for arm 1 and 159 for arm 2. Median age was 63 (39 to 86) years. CA19-9 ≤90 in 93%. Arm 1: 32 patients (20%) grade 4 and 2 (1%) grade 5 adverse events; arm 2, 27 (17%) grade 4 and 3 (2%) grade 5. GI adverse events, arm 1: 22% grade ≥3 and arm 2: 28%, (P=0.22). The median follow-up (surviving patients) was 42.5 months (min-max: <1 to 75). With 203 deaths, the median and 3-year OS (95% confidence interval) are 29.9 months (21.7, 33.4) and 39% (30, 45) for arm 1 and 28.1 months (20.7, 30.9) and 39% (31, 47) for arm 2 (log-rank P=0.62). Hazard ratio (95% confidence interval) comparing OS of arm 2 to arm 1 is 1.04 (0.79, 1.38). CONCLUSIONS: The addition of adjuvant erlotinib to gemcitabine did not provide a signal for increased OS in this trial.