X. Ronald Zhu

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.

Comprehensive analysis of proton range uncertainties related to patient stopping-power-ratio estimation using the stoichiometric calibration

The purpose of this study was to analyze factors affecting proton stopping-power-ratio (SPR) estimations and range uncertainties in proton therapy planning using the standard stoichiometric calibration. The SPR uncertainties were grouped into five categories according to their origins and then estimated based on previously published reports or measurements. For the first time, the impact of tissue composition variations on SPR estimation was assessed and the uncertainty estimates of each category were determined for low-density (lung), soft, and high-density (bone) tissues. A composite, 95th percentile water-equivalent-thickness uncertainty was calculated from multiple beam directions in 15 patients with various types of cancer undergoing proton therapy. The SPR uncertainties (1σ) were quite different (ranging from 1.6% to 5.0%) in different tissue groups, although the final combined uncertainty (95th percentile) for different treatment sites was fairly consistent at 3.0-3.4%, primarily because soft tissue is the dominant tissue type in the human body. The dominant contributing factor for uncertainties in soft tissues was the degeneracy of Hounsfield numbers in the presence of tissue composition variations. To reduce the overall uncertainties in SPR estimation, the use of dual-energy computed tomography is suggested. The values recommended in this study based on typical treatment sites and a small group of patients roughly agree with the commonly referenced value (3.5%) used for margin design. By using tissue-specific range uncertainties, one could estimate the beam-specific range margin by accounting for different types and amounts of tissues along a beam, which may allow for customization of range uncertainty for each beam direction.

Four‐dimensional cone beam CT with adaptive gantry rotation and adaptive data sampling

We have developed a new four-dimensional cone beam CT (4D-CBCT) on a Varian image-guided radiation therapy system, which has radiation therapy treatment and cone beam CT imaging capabilities. We adapted the speed of gantry rotation time of the CBCT to the average breath cycle of the patient to maintain the same level of image quality and adjusted the data sampling frequency to keep a similar level of radiation exposure to the patient. Our design utilized the real-time positioning and monitoring system to record the respiratory signal of the patient during the acquisition of the CBCT data. We used the full-fan bowtie filter during data acquisition, acquired the projection data over 200 deg of gantry rotation, and reconstructed the images with a half-scan cone beam reconstruction. The scan time for a 200-deg gantry rotation per patient ranged from 3.3 to 6.6 min for the average breath cycle of 3-6 s. The radiation dose of the 4D-CBCT was about 1-2 times the radiation dose of the 4D-CT on a multislice CT scanner. We evaluated the 4D-CBCT in scanning, data processing and image quality with phantom studies. We demonstrated the clinical applicability of the 4D-CBCT and compared the 4D-CBCT and the 4D-CT scans in four patient studies. The contrast-to-noise ratio of the 4D-CT was 2.8-3.5 times of the contrast-to-noise ratio of the 4D-CBCT in the four patient studies.

Comparison of 2D radiographic images and 3D cone beam computed tomography for positioning head-and-neck radiotherapy patients.

PURPOSE To assess the positioning accuracy using two-dimensional kilovoltage (2DkV) imaging and three-dimensional cone beam CT (CBCT) in patients with head and neck (H&N) cancer receiving radiation therapy. To assess the benefit of patient-specific headrest. MATERIALS AND METHODS All 21 patients studied were immobilized using thermoplastic masks with either a patient-specific vacuum bag (11 of 21, IMA) or standard clear plastic (10 of 21, IMB) headrests. Each patient was imaged with a pair of orthogonal 2DkV images in treatment position using onboard imaging before the CBCT procedure. The 2DkV and CBCT images were acquired weekly during the same session. The 2DkV images were reviewed by oncologists and also analyzed by a software tool based on mutual information (MI). RESULTS Ninety-eight pairs of assessable 2DkV-CBCT alignment sets were obtained. Systematic and random errors were <1.6 mm for both 2DkV and CBCT alignments. When we compared shifts determined by CBCT and 2DkV for the same patient setup, statistically significant correlations were observed in all three major directions. Among all CBCT couch shifts, 4.1% > or = 0.5 cm and 18.7% > or = 0.3 cm, whereas among all 2DkV (MI) shifts, 1.7% > or = 0.5 cm and 11.2% > or = 0.3 cm. Statistically significant difference was found on anteroposterior direction between IMA and IMB with the CBCT alignment only. CONCLUSIONS The differences between 2D and 3D alignments were mainly caused by the relative flexibility of certain H&N structures and possibly by rotation. Better immobilization of the flexible neck is required to further reduce the setup errors for H&N patients receiving radiotherapy.

The M. D. Anderson proton therapy system

PURPOSE The purpose of this study is to describe the University of Texas M. D. Anderson proton therapy system (PTC-H) including the accelerator, beam transport, and treatment delivery systems, the functionality and clinical parameters for passive scattering and pencil beam scanning treatment modes, and the results of acceptance tests. METHODS The PTC-H has a synchrotron (70-250 MeV) and four treatment rooms. An overall control system manages the treatment, physics, and service modes of operation. An independent safety system ensures the safety of patients, staff, and equipment. Three treatment rooms have isocentric gantries and one room has two fixed horizontal beamlines, which include a large-field treatment nozzle, used primarily for prostate treatments, and a small-field treatment nozzle for ocular treatments. Two gantry treatment rooms and the fixed-beam treatment room have passive scattering nozzles. The third gantry has a pencil beam scanning nozzle for the delivery of intensity modulated proton treatments (IMPT) and single field uniform dose (SFUD) treatments. The PTC-H also has an experimental room with a fixed horizontal beamline and a passive scattering nozzle. The equipment described above was provided by Hitachi, Ltd. Treatment planning is performed using the Eclipse system from Varian Medical Systems and data management is handled by the MOSAIQ system from IMPAC Medical Systems, Inc. The large-field passive scattering nozzles use double scattering systems in which the first scatterers are physically integrated with the range modulation wheels. The proton beam is gated on the rotating range modulation wheels at gating angles designed to produce spread-out-Bragg peaks ranging in size from 2 to 16 g/cm2. Field sizes of up to 25 x 25 cm2 can be achieved with the double scattering system. The IMPT delivery technique is discrete spot scanning, which has a maximum field size of 30 x 30 cm2. Depth scanning is achieved by changing the energy extracted from the synchrotron (energy can be changed pulse to pulse). The PTC-H is fully integrated with DICOM-RT ION interfaces for imaging, treatment planning, data management, and treatment control functions. RESULTS The proton therapy system passed all acceptance tests for both passive scattering and pencil beam scanning. Treatments with passive scattering began in May 2006 and treatments with the scanning system began in May 2008. The PTC-H was the first commercial system to demonstrate capabilities for IMPT treatments and the first in the United States to treat using SFUD techniques. The facility has been in clinical operation since May 2006 with up-time of approximately 98%. CONCLUSIONS As with most projects for which a considerable amount of new technology is developed and which have duration spanning several years, at project completion it was determined that several upgrades would improve the overall system performance. Some possible upgrades are discussed. Overall, the system has been very robust, accurate, reproducible, and reliable. The authors found the pencil beam scanning system to be particularly satisfactory; prostate treatments can be delivered on the scanning nozzle in less time than is required on the passive scattering nozzle.

A beam-specific planning target volume (PTV) design for proton therapy to account for setup and range uncertainties

PURPOSE To report a method for explicitly designing a planning target volume (PTV) for treatment planning and evaluation in heterogeneous media for passively scattered proton therapy and scanning beam proton therapy using single-field optimization (SFO). METHODS AND MATERIALS A beam-specific PTV (bsPTV) for proton beams was derived by ray-tracing and shifting ray lines to account for tissue misalignment in the presence of setup error or organ motion. Range uncertainties resulting from inaccuracies in computed tomography-based range estimation were calculated for proximal and distal surfaces of the target in the beam direction. The bsPTV was then constructed based on local heterogeneity. The bsPTV thus can be used directly as a planning target as if it were in photon therapy. To test the robustness of the bsPTV, we generated a single-field proton plan in a virtual phantom. Intentional setup and range errors were introduced. Dose coverage to the clinical target volume (CTV) under various simulation conditions was compared between plans designed based on the bsPTV and a conventional PTV. RESULTS The simulated treatment using the bsPTV design performed significantly better than the plan using the conventional PTV in maintaining dose coverage to the CTV. With conventional PTV plans, the minimum coverage to the CTV dropped from 99% to 67% in the presence of setup error, internal motion, and range uncertainty. However, plans using the bsPTV showed minimal drop of target coverage from 99% to 94%. CONCLUSIONS The conventional geometry-based PTV concept used in photon therapy does not work well for proton therapy. We investigated and validated a beam-specific PTV method for designing and evaluating proton plans.

Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

PURPOSE We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. PATIENTS AND METHODS Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. RESULTS Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). CONCLUSIONS Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution.

Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

PURPOSE Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. METHODS AND MATERIALS Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. RESULTS IMPT produced lower mean lung dose (MLD), lung V5 and V20, heart V40, and esophageal V60 than did IMRT (P<.05) and lower MLD, lung V20, and esophageal V60 than did passive scattering proton therapy (PSPT) (P<.05). D5 to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the γ index. Adaptive replanning was used for 9 patients (26.5%). CONCLUSIONS IMPT using 4D CT-based planning, motion management, and optimization was implemented successfully and met our quality assurance parameters for treating challenging thoracic cancers.

Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers

PURPOSE Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H&N) cancer patients. METHODS Two sets of IMPT plans were generated for 14 H&N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests. RESULTS CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D95%), improved dose homogeneity (i.e., smaller D5% - D95%), and lower or equivalent dose to organs at risk. CONCLUSIONS CTV-based robust optimization provided significantly more robust dose distributions to targets and organs than PTV-based conventional optimization in H&N using IMPT. Eliminating the use of PTV and planning directly based on CTV provided better or equivalent normal tissue sparing.

Scatter kernel estimation with an edge-spread function method for cone-beam computed tomography imaging

The clinical applications of kilovoltage x-ray cone-beam computed tomography (CBCT) have been compromised by the limited quality of CBCT images, which typically is due to a substantial scatter component in the projection data. In this paper, we describe an experimental method of deriving the scatter kernel of a CBCT imaging system. The estimated scatter kernel can be used to remove the scatter component from the CBCT projection images, thus improving the quality of the reconstructed image. The scattered radiation was approximated as depth-dependent, pencil-beam kernels, which were derived using an edge-spread function (ESF) method. The ESF geometry was achieved with a half-beam block created by a 3 mm thick lead sheet placed on a stack of slab solid-water phantoms. Measurements for ten water-equivalent thicknesses (WET) ranging from 0 cm to 41 cm were taken with (half-blocked) and without (unblocked) the lead sheet, and corresponding pencil-beam scatter kernels or point-spread functions (PSFs) were then derived without assuming any empirical trial function. The derived scatter kernels were verified with phantom studies. Scatter correction was then incorporated into the reconstruction process to improve image quality. For a 32 cm diameter cylinder phantom, the flatness of the reconstructed image was improved from 22% to 5%. When the method was applied to CBCT images for patients undergoing image-guided therapy of the pelvis and lung, the variation in selected regions of interest (ROIs) was reduced from >300 HU to <100 HU. We conclude that the scatter reduction technique utilizing the scatter kernel effectively suppresses the artifact caused by scatter in CBCT.