PTCOG Gastrointestinal Subcommittee Lower Gastrointestinal Tract Malignancies Consensus Statement.

Purpose: Radiotherapy delivery in the definitive management of lower gastrointestinal (LGI) tract malignancies is associated with substantial risk of acute and late gastrointestinal (GI), genitourinary, dermatologic, and hematologic toxicities. Advanced radiation therapy techniques such as proton beam therapy (PBT) offer optimal dosimetric sparing of critical organs at risk, achieving a more favorable therapeutic ratio compared with photon therapy. Materials and Methods: The international Particle Therapy Cooperative Group GI Subcommittee conducted a systematic literature review, from which consensus recommendations were developed on the application of PBT for LGI malignancies. Results: Eleven recommendations on clinical indications for which PBT should be considered are presented with supporting literature, and each recommendation was assessed for level of evidence and strength of recommendation. Detailed technical guidelines pertaining to simulation, treatment planning and delivery, and image guidance are also provided. Conclusion: PBT may be of significant value in select patients with LGI malignancies. Additional clinical data are needed to further elucidate the potential benefits of PBT for patients with anal cancer and rectal cancer.

Knowledge-based quality assurance of a comprehensive set of organ at risk contours for head and neck radiotherapy.

Introduction: Manual review of organ at risk (OAR) contours is crucial for creating safe radiotherapy plans but can be time-consuming and error prone. Statistical and deep learning models show the potential to automatically detect improper contours by identifying outliers using large sets of acceptable data (knowledge-based outlier detection) and may be able to assist human reviewers during review of OAR contours. Methods: This study developed an automated knowledge-based outlier detection method and assessed its ability to detect erroneous contours for all common head and neck (HN) OAR types used clinically at our institution. We utilized 490 accurate CT-based HN structure sets from unique patients, each with forty-two HN OAR contours when anatomically present. The structure sets were distributed as 80% for training, 10% for validation, and 10% for testing. In addition, 190 and 37 simulated contours containing errors were added to the validation and test sets, respectively. Single-contour features, including location, shape, orientation, volume, and CT number, were used to train three single-contour feature models (z-score, Mahalanobis distance [MD], and autoencoder [AE]). Additionally, a novel contour-to-contour relationship (CCR) model was trained using the minimum distance and volumetric overlap between pairs of OAR contours to quantify overlap and separation. Inferences from single-contour feature models were combined with the CCR model inferences and inferences evaluating the number of disconnected parts in a single contour and then compared. Results: In the test dataset, before combination with the CCR model, the area under the curve values were 0.922/0.939/0.939 for the z-score, MD, and AE models respectively for all contours. After combination with CCR model inferences, the z-score, MD, and AE had sensitivities of 0.838/0.892/0.865, specificities of 0.922/0.907/0.887, and balanced accuracies (BA) of 0.880/0.900/0.876 respectively. In the validation dataset, with similar overall performance and no signs of overfitting, model performance for individual OAR types was assessed. The combined AE model demonstrated minimum, median, and maximum BAs of 0.729, 0.908, and 0.980 across OAR types. Discussion: Our novel knowledge-based method combines models utilizing single-contour and CCR features to effectively detect erroneous OAR contours across a comprehensive set of 42 clinically used OAR types for HN radiotherapy.

Validation of clinical acceptability of deep-learning-based automated segmentation of organs-at-risk for head-and-neck radiotherapy treatment planning.

Introduction: Organ-at-risk segmentation for head and neck cancer radiation therapy is a complex and time-consuming process (requiring up to 42 individual structure, and may delay start of treatment or even limit access to function-preserving care. Feasibility of using a deep learning (DL) based autosegmentation model to reduce contouring time without compromising contour accuracy is assessed through a blinded randomized trial of radiation oncologists (ROs) using retrospective, de-identified patient data. Methods: Two head and neck expert ROs used dedicated time to create gold standard (GS) contours on computed tomography (CT) images. 445 CTs were used to train a custom 3D U-Net DL model covering 42 organs-at-risk, with an additional 20 CTs were held out for the randomized trial. For each held-out patient dataset, one of the eight participant ROs was randomly allocated to review and revise the contours produced by the DL model, while another reviewed contours produced by a medical dosimetry assistant (MDA), both blinded to their origin. Time required for MDAs and ROs to contour was recorded, and the unrevised DL contours, as well as the RO-revised contours by the MDAs and DL model were compared to the GS for that patient. Results: Mean time for initial MDA contouring was 2.3 hours (range 1.6-3.8 hours) and RO-revision took 1.1 hours (range, 0.4-4.4 hours), compared to 0.7 hours (range 0.1-2.0 hours) for the RO-revisions to DL contours. Total time reduced by 76% (95%-Confidence Interval: 65%-88%) and RO-revision time reduced by 35% (95%-CI,-39%-91%). All geometric and dosimetric metrics computed, agreement with GS was equivalent or significantly greater (p<0.05) for RO-revised DL contours compared to the RO-revised MDA contours, including volumetric Dice similarity coefficient (VDSC), surface DSC, added path length, and the 95%-Hausdorff distance. 32 OARs (76%) had mean VDSC greater than 0.8 for the RO-revised DL contours, compared to 20 (48%) for RO-revised MDA contours, and 34 (81%) for the unrevised DL OARs. Conclusion: DL autosegmentation demonstrated significant time-savings for organ-at-risk contouring while improving agreement with the institutional GS, indicating comparable accuracy of DL model. Integration into the clinical practice with a prospective evaluation is currently underway.

A Prospective Study of Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer Patients.

PURPOSE: Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus-related oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: From March 2016 through May 2019, patients were enrolled in this institutional review board-approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. RESULTS: There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis-free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P < .02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation = 12.5 Gy). CONCLUSIONS: Mucosal sparing radiation is well tolerated in select resected human papillomavirus-related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events.

The Importance of Verification CT-QA Scans in Patients Treated with IMPT for Head and Neck Cancers.

PURPOSE: To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice. PATIENTS AND METHODS: We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs). P < .05 was considered statistically significant. RESULTS: Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82, P = .04; MVA: HR, 3.64, P = .03), advanced stage disease (UVA: HR, 4.68, P < .01; MVA: HR, 3.10, P < .05), dose > 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99, P < .01; MVA: HR, 2.20, P < .01), primary disease (UVA: HR, 2.00 versus recurrent, P = .01; MVA: HR, 2.46, P = .01), concurrent chemotherapy (UVA: HR, 2.05, P < .01; MVA: not statistically significant [NS]), definitive intent treatment (UVA: HR, 1.70 versus adjuvant, P < .02; MVA: NS), bilateral neck treatment (UVA: HR, 2.07, P = .03; MVA: NS), and greater number of beams (5 beam UVA: HR, 5.55 versus 1 or 2 beams, P < .02; MVA: NS). Maximal weight change from baseline was associated with higher odds of a replan (≥3 kg: OR, 1.97, P = .04; ≥ 5 kg: OR, 2.13, P = .02). CONCLUSIONS: Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.

Radiation biology considerations of proton therapy for gastrointestinal cancers.

Clinical enthusiasm for proton therapy (PT) is high, with an exponential increase in the number of centers offering treatment. Attraction for this charged particle therapy modality stems from the favorable proton dose distribution, with low radiation dose absorption on entry and maximum radiation deposition at the Bragg peak. The current clinical convention is to use a fixed relative biological effectiveness (RBE) value of 1.1 in order to correct the physical dose relative to photon therapy (i.e., proton radiation is 10% more biologically effective then photon radiation). In recent years, concerns about the potential side effects of PT have emerged. Various studies and review articles have sought to better quantify the RBE of PT and shine some light on the complexity of this problem. Reduction in biologic hot spots of non-target tissue is paramount in proton radiation therapy (RT) planning as the primary benefit of proton RT is a reduction in organ at risk (OAR) irradiation. New and emerging clinical data is in support of variable proton biological effectiveness and demonstrate late toxicity, presumably associated with high biological dose, to OAR. Overall, PT has promise to treat many cancer sites with similar efficacy as conventional RT but with fewer acute and late toxicities. However, further knowledge of biologic effective dose and its impact on both cancer and adjacent OAR is paramount for effective and safe treatment of patients with PT.

Individual Field Simultaneous Optimization (IFSO) in spot scanning proton therapy of head and neck cancers.

In order to better spare organs at risk in the head and neck, the application of proton beam therapy is of great interest. In this study we report the clinical utilization of a novel and robust scanning proton beam therapy treatment planning method called Individual Field Simultaneous Optimization (IFSO) that incorporates the advantages of field patching technique integrated with simultaneous optimization of multiple fields. A treatment planning intercomparison between a conventional Intensity Modulated Proton Therapy Treatment Plan with single target volume vs a split target volume utilizing IFSO method demonstrates superiority of IFSO with regards to sparing of organs at risk and plan robustness.

Hydrogel Nanosensors for Colorimetric Detection and Dosimetry in Proton Beam Radiotherapy.

Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristic of protons, which results in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Currently available dosimeters are intrinsic, complex, and expensive and are not routinely used to determine the dose delivered to the tumor. Here, we report a hydrogel-based plasmonic nanosensor for detecting clinical doses used in conventional and hyperfractionated proton beam radiotherapy. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during proton treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime, and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy.

Use of a radial projection to reduce the statistical uncertainty of spot lateral profiles generated by Monte Carlo simulation.

Monte Carlo (MC) simulation has been used to generate commissioning data for the beam modeling of treatment planning system (TPS). We have developed a method called radial projection (RP) for postprocessing of MC-simulation-generated data. We used the RP method to reduce the statistical uncertainty of the lateral profile of proton pencil beams with axial symmetry. The RP method takes advantage of the axial symmetry of dose distribution to use the mean value of multiple independent scores as the representative score. Using the mean as the representative value rather than any individual score results in substantial reduction in statistical uncertainty. Herein, we present the concept and step-by-step implementation of the RP method, as well as show the advantage of the RP method over conventional measurement methods for generating lateral profile. Lateral profiles generated by both methods were compared to demonstrate the uncertainty reduction qualitatively, and standard error comparison was performed to demonstrate the reduction quantitatively. The comparisons showed that statistical uncertainty was reduced substantially by the RP method. Using the RP method to postprocess MC data, the corresponding MC simulation time was reduced by a factor of 10 without quality reduction in the generated result from the MC data. We concluded that the RP method is an effective technique to increase MC simulation efficiency for generating lateral profiles for axially symmetric pencil beams.

Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know.

Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution.

An efficient method to determine double Gaussian fluence parameters in the eclipse™ proton pencil beam model.

PURPOSE: To find an efficient method to configure the proton fluence for a commercial proton pencil beam scanning (PBS) treatment planning system (TPS). METHODS: An in-water dose kernel was developed to mimic the dose kernel of the pencil beam convolution superposition algorithm, which is part of the commercial proton beam therapy planning software, eclipse™ (Varian Medical Systems, Palo Alto, CA). The field size factor (FSF) was calculated based on the spot profile reconstructed by the in-house dose kernel. The workflow of using FSFs to find the desirable proton fluence is presented. The in-house derived spot profile and FSF were validated by a direct comparison with those calculated by the eclipse TPS. The validation included 420 comparisons of the FSFs from 14 proton energies, various field sizes from 2 to 20 cm and various depths from 20% to 80% of proton range. RESULTS: The relative in-water lateral profiles between the in-house calculation and the eclipse TPS agree very well even at the level of 10-4. The FSFs between the in-house calculation and the eclipse TPS also agree well. The maximum deviation is within 0.5%, and the standard deviation is less than 0.1%. CONCLUSIONS: The authors' method significantly reduced the time to find the desirable proton fluences of the clinical energies. The method is extensively validated and can be applied to any proton centers using PBS and the eclipse TPS.

Scanning proton beam therapy reduces normal tissue exposure in pelvic radiotherapy for anal cancer.

An inter-comparison planning study between photon beam therapy (IMRT) and scanning proton beam therapy (SPBT) for squamous cell carcinoma of the anus (SCCA) is presented. SPBT plans offer significant reduction (>50%, P=0.008) in doses to small bowel, and bone marrow thereby offering the potential to reduce bowel and hemotoxicities.

Impact of range shifter material on proton pencil beam spot characteristics.

PURPOSE: To quantitatively investigate the effect of range shifter materials on single-spot characteristics of a proton pencil beam. METHODS: An analytic approximation for multiple Coulomb scattering ("differential Moliere" formula) was adopted to calculate spot sizes of proton spot scanning beams impinging on a range shifter. The calculations cover a range of delivery parameters: six range shifter materials (acrylonitrile butadiene styrene, Lexan, Lucite, polyethylene, polystyrene, and wax) and water as reference material, proton beam energies ranging from 75 to 200 MeV, range shifter thicknesses of 4.5 and 7.0 g/cm(2), and range shifter positions from 5 to 50 cm. The analytic method was validated by comparing calculation results with the measurements reported in the literature. RESULTS: Relative to a water-equivalent reference, the spot size distal to a wax or polyethylene range shifter is 15% smaller, while the spot size distal to a range shifter made of Lexan or Lucite is about 6% smaller. The relative spot size variations are nearly independent of beam energy and range shifter thickness and decrease with smaller air gaps. CONCLUSIONS: Among the six material investigated, wax and polyethylene are desirable range shifter materials when the spot size is kept small. Lexan and Lucite are the desirable range shifter materials when the scattering power is kept similar to water.

Impact of respiratory motion on worst-case scenario optimized intensity modulated proton therapy for lung cancers.

PURPOSE: We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. METHODS AND MATERIALS: For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests. RESULTS: Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035]). CONCLUSIONS: Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.

Proton beam therapy for locally advanced lung cancer: A review.

Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.

The use of computed radiography plates to determine light and radiation field coincidence.

PURPOSE: Photo-stimulable phosphor computed radiography (CR) has characteristics that allow the output to be manipulated by both radiation and optical light. The authors have developed a method that uses these characteristics to carry out radiation field and light field coincidence quality assurance on linear accelerators. METHODS: CR detectors from Kodak were used outside their cassettes to measure both radiation and light field edges from a Varian linear accelerator. The CR detector was first exposed to a radiation field and then to a slightly smaller light field. The light impinged on the detector's latent image, removing to an extent the portion exposed to the light field. The detector was then digitally scanned. A MATLAB-based algorithm was developed to automatically analyze the images and determine the edges of the light and radiation fields, the vector between the field centers, and the crosshair center. Radiographic film was also used as a control to confirm the radiation field size. RESULTS: Analysis showed a high degree of repeatability with the proposed method. Results between the proposed method and radiographic film showed excellent agreement of the radiation field. The effect of varying monitor units and light exposure time was tested and found to be very small. Radiation and light field sizes were determined with an uncertainty of less than 1 mm, and light and crosshair centers were determined within 0.1 mm. CONCLUSIONS: A new method was developed to digitally determine the radiation and light field size using CR photo-stimulable phosphor plates. The method is quick and reproducible, allowing for the streamlined and robust assessment of light and radiation field coincidence, with no observer interpretation needed.

Beyond Gaussians: a study of single-spot modeling for scanning proton dose calculation.

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field size effects on dose output. In this study, we developed a pencil beam algorithm for scanning proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy.

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.

Parameterization of multiple Bragg curves for scanning proton beams using simultaneous fitting of multiple curves.

Although Bortfeld's analytical formula is useful for describing Bragg curves, measured data can deviate from the values predicted by the model. Thus, we sought to determine the parameters of a closed analytical expression of multiple Bragg curves for scanning proton pencil beams using a simultaneous optimization algorithm and to determine the minimum number of energies that need to be measured in treatment planning so that complete Bragg curves required by the treatment planning system (TPS) can be accurately predicted. We modified Bortfeld's original analytical expression of Bragg curves to accurately describe the dose deposition resulting from secondary particles. The parameters of the modified analytical expression were expressed as the parabolic cylinder function of the ranges of the proton pencil beams in water. Thirty-nine discrete Bragg curves were measured in our center using a PTW Bragg Peak chamber during acceptance and commission of the scanning beam proton delivery system. The coefficients of parabolic function were fitted by applying a simultaneous optimization algorithm to seven measured curves. The required Bragg curves for 45 energies in the TPS were calculated using our parameterized analytical expression. Finally, the 10 cm width of spread-out Bragg peaks (SOBPs) of beams with maximum energies of 221.8 and 121.2 MeV were then calculated in the TPS and compared with measured data. Compared with Bortfeld's original formula, our modified formula improved fitting of the measured depth dose curves at depths around three-quarters of the maximum range and in the beam entrance region. The parabolic function described the relationship between the parameters of the analytic expression of different energies. The predicted Bragg curves based on the parameters fitted using the seven measured curves accurately described the Bragg curves of proton pencil beams of 45 energies configured in our TPS. When we used the calculated Bragg curves as the input to TPS, the standard deviations of the measured and calculated data points along the 10 cm SOBPs created with proton pencil beams with maximum energies of 221.8 and 121.2 MeV were 1.19% and 1.18%, respectively, using curves predicted by the algorithm generated from the seven measured curves. Our method would be a valuable tool to analyze measured Bragg curves without the need for time-consuming measurements and correctly describe multiple Bragg curves using a closed analytical expression.

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.