Out-of-field dose equivalents delivered by proton therapy of prostate cancer

Measurements were performed to assess the dose equivalent outside a primary proton treatment field, using a silicon-on-insulator (SOI) microdosimeter. The SOI microdosimeter was placed on the surface of an anthropomorphic phantom and dose equivalents were determined as a function of lateral distance from a typical passively scattered and modulated prostate treatment field. Measurements were also completed within a polystyrene plate phantom as a function of depth for a distance of 5 cm from the field edge, as function of lateral distance from field edge at two different depths, and as a function of distance from the distal edge on the central beam axis. The dose equivalent at the surface of the anthropomorphic phantom decreases from 3.9 to 0.18 mSv/Gy when the lateral distance from the proton field edge increases from 2.5 to 60 cm. Measurements along the proton depth dose distribution at a constant distance of 5 cm from the primary field edge indicate a decrease in dose equivalent as a function of depth, with a 38% decrease relative to the surface dose at a depth of 5 cm in polystyrene. Measurements completed as a function of lateral distance from the primary field at two separate depths within polystyrene illustrate a convergence of the dose equivalent at approximately 20 cm from the primary field edge. Past the distal edge of the spread-out Bragg peak dose equivalents decrease exponentially for increasing distance, with an initial value of 1.6 mSv/Gy at 0.6 cm from the distal edge. Silicon microdosimetry measurements were also compared with published results obtained utilizing different measurement techniques. This study demonstrates the applicability of SOI microdosimetry in determining the dose equivalent outside proton treatment fields, and provides valuable information on the dose equivalent both at the surface and at depth experienced by prostate cancer patients treated with protons.     

Influence of dose engine accuracy on the optimum dose distribution in intensity-modulated proton therapy treatment plans

Analytical dose computation algorithms like pencil beam algorithms (PB) are presently used for clinical treatment planning in intensity-modulated proton therapy. PB offer fast computation times, but are based on substantial approximations. Monte Carlo algorithms (MC) offer better accuracy, but are slower. We present a comparison of optimized treatment plans for six patients computed either with PB or MC. Both PB and MC are used during optimization, plus MC is used to recompute PB results. PB is used with different accuracy settings that define the coarseness of approximation. We evaluate the errors of PB optimized treatment plans via comparison with MC optimized plans (convergence errors) and MC recomputed plans (systematic errors) occurring for different accuracy settings of the PB. The level of lateral heterogeneities, being one of the main sources of inaccuracies of the PB, is quantified by a formula. In geometries with high levels of lateral heterogeneities, the shortcomings of PB are most obvious. For these geometries, simple PB lead to clinically significant differences and more accurate PB settings have to be used to diminish the error. The most accurate PB settings lead however to longer computing times by approximately a factor of 2 to 4 compared to PB with simple settings. Although the errors can be diminished, they cannot be fully eliminated even with sophisticated PB. Further gain in accuracy can therefore only be reached with MC in optimization. The use of MC in optimization is technically feasible, the computing times are however about 25 to 50 times longer compared to PB with most accurate settings.     

Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy(-1). Sensitivity analysis revealed that E/D varied by +/-30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy(-1) in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy(-1) in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.     

A photon dose distribution model employing convolution calculations

A three-dimensional photon beam calculation is described which models the primary, first-scatter, and multiple-scatter dose components from first principles. Three key features of the model are (1) a multiple-scatter calculation based on diffusion theory, (2) the demonstration of the modulation transfer function of the radiation dose transport process, and (3) the use of the finite fast Fourier transform to perform the required convolutions. The results of calculations for cobalt-60 in a homogeneous phantom are used to verify the accuracy of the model.     

Electron dose rate and photon contamination in electron arc therapy

The electron dose rate at the depth of dose maximum dmax and the photon contamination are discussed as a function of several parameters of the rotational electron beam. A pseudoarc technique with an angular increment of 10 degrees and a constant number of monitor units per each stationary electron field was used in our experiments. The electron dose rate is defined as the electron dose at a given point in phantom divided by the number of monitor units given for any one stationary electron beam. For a given depth of isocenter di the electron dose rates at dmax are linearly dependent on the nominal field width w, while for a given w the dose rates are inversely proportional to di. The dose rates for rotational electron beams with different di are related through the inverse square law provided that the two beams have (di,w) combinations which give the same characteristic angle beta. The photon dose at the isocenter depends on the arc angle alpha, field width w, and isocenter depth di. For constant w and di the photon dose at isocenter is proportional to alpha, for constant alpha and w it is proportional to di, and for constant alpha and di it is inversely proportional to w. The w and di dependence implies that for the same alpha the photon dose at the isocenter is inversely proportional to the electron dose rate at dmax.     

Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.     

Fast range-corrected proton dose approximation method using prior dose distribution

For robust plan optimization and evaluation purposes, one needs a computationally efficient way to calculate dose distributions and dose-volume histograms (DVHs) under various changes in the variables associated with beam delivery and images. In this study, we report an approximate method for rapid calculation of dose when setup errors and anatomical changes occur during proton therapy. This fast dose approximation method calculates new dose distributions under various circumstances based on the prior knowledge of dose distribution from a reference setting. In order to validate the method, we calculated and compared the dose distributions from our approximation method to the dose distributions calculated from a clinically commissioned treatment planning system which was used as the ground truth. The overall accuracy of the proposed method was tested against varying degrees of setup error and anatomical deformation for selected patient cases. The setup error was simulated by rigid shifts of the patient; while the anatomical deformation was introduced using weekly acquired repeat CT data sets. We evaluated the agreement between the dose approximation method and full dose recalculation using a 3D gamma index and the root-mean-square (RMS) and maximum deviation of the cumulative dose volume histograms (cDVHs). The average passing rate of 3D gamma analysis under 3% dose and 3 mm distance-to-agreement criteria were 96% and 89% for setup errors and severe anatomy changes, respectively. The average of RMS and maximum deviation of the cDVHs under the setup error was 0.5% and 1.5%, respectively for all structures considered. Similarly, the average of RMS and maximum deviations under the weekly anatomical change were 0.6% and 2.7%, respectively. Our results show that the fast dose approximation method was able to account for the density variation of the patient due to the setup and anatomical changes with acceptable accuracy while significantly improving the computation time.     

QLX-2002前列腺增生光子治疗机的剂量分布研究

目的：研究QLX-2002前列腺增生光子治疗机在体内的剂量分布，特别是在前列腺位置垂直射线方向的剂量分布，方法：用不同厚度的有机玻璃代替组织的相对厚度，用电离室和胶片法测量：PDD、OAR和等剂量分布曲线。结论：治疗头的开口窗尺寸应缩小。     

Analytic estimates of secondary neutron dose in proton therapy

Proton beam losses in various components of a treatment nozzle generate secondary neutrons, which bring unwanted out of field dose during treatments. The purpose of this study was to develop an analytic method for estimating neutron dose to a distant organ at risk during proton therapy. Based on radiation shielding calculation methods proposed by Sullivan, we developed an analytical model for converting the proton beam losses in the nozzle components and in the treatment volume into the secondary neutron dose at a point of interest. Using the MCNPx Monte Carlo code, we benchmarked the neutron dose rates generated by the proton beam stopped at various media. The Monte Carlo calculations confirmed the validity of the analytical model for simple beam stop geometry. The analytical model was then applied to neutron dose equivalent measurements performed on double scattering and uniform scanning nozzles at the Midwest Proton Radiotherapy Institute (MPRI). Good agreement was obtained between the model predictions and the data measured at MPRI. This work provides a method for estimating analytically the neutron dose equivalent to a distant organ at risk. This method can be used as a tool for optimizing dose delivery techniques in proton therapy.     

Investigation of dose perturbations and the radiographic visibility of potential fiducials for proton radiation therapy of the prostate

Image guidance using implanted fiducial markers is commonly used to ensure accurate and reproducible target positioning in radiation therapy for prostate cancer. The ideal fiducial marker is clearly visible in kV imaging, does not perturb the therapeutic dose in the target volume and does not cause any artifacts on the CT images used for treatment planning. As yet, ideal markers that fully meet all three of these criteria have not been reported. In this study, 12 fiducial markers were evaluated for their potential clinical utility in proton radiation therapy for prostate cancer. In order to identify the good candidates, each fiducial was imaged using a CT scanner as well as a kV imaging system. Additionally, the dose perturbation caused by each fiducial was quantified using radiochromic film and a clinical proton beam. Based on the results, three fiducials were identified as good candidates for use in proton radiotherapy of prostate cancer.     

Maximum likelihood estimation of proton irradiated field and deposited dose distribution

In proton therapy, it is important to evaluate the field irradiated with protons and the deposited dose distribution in a patient's body. Positron emitters generated through fragmentation reactions of target nuclei can be used for this purpose. By detecting the annihilation gamma rays from the positron emitters, the annihilation gamma ray distribution can be obtained which has information about the quantities essential to proton therapy. In this study, we performed irradiation experiments with mono-energetic proton beams of 160 MeV and the spread-out Bragg peak beams to three kinds of targets. The annihilation events were detected with a positron camera for 500 s after the irradiation and the annihilation gamma ray distributions were obtained. In order to evaluate the range and the position of distal and proximal edges of the SOBP, the maximum likelihood estimation (MLE) method was applied to the detected distributions. The evaluated values with the MLE method were compared with those estimated from the measured dose distributions. As a result, the ranges were determined with the difference between the MLE range and the experimental range less than 1.0 mm for all targets. For the SOBP beams, the positions of distal edges were determined with the difference less than 1.0 mm. On the other hand, the difference amounted to 7.9 mm for proximal edges.     

质子点扫描技术与光子Tomotherapy在前列腺癌应用中的剂量学比较

目的:比较前列腺癌质子点扫描技术（SSS-PT）与光子螺旋断层放射治疗（HT）两者之间的剂量学特点,其数据将为临床提供一定的参考。方法:选取12例既往前列腺癌患者作为研究对象,定位后,将CT图像分别传至Raystation和HT计划系统进行放疗计划设计。处方剂量为69 Gy/25 F。比较分析两种放疗计划的靶区适形度指数（CI）、均匀性指数（HI）、靶区和危及器官剂量学参数。结果:靶区的均匀性方面,SSS-PT优于HT（P=0.001）;直肠平均剂量SSS-PT［（21.92±4.00） Gy］低于HT［（31.97±2.60） Gy］（P=0.000）;膀胱平均剂量SSS-PT［（17.62±3.15） Gy］低于HT［（30.52±3.94） Gy］（P=0.000）;对于直肠和膀胱的保护,SSS-PT在低、中剂量区总是优于HT。结论:SSS-PT和HT两种治疗方式在靶区剂量分布均可满足临床需求,在同样靶区覆盖条件下,SSS-PT相较于HT能够更好地保护直肠和膀胱,尤其是在低、中剂量区。     

Targeted therapy in prostate cancer

The therapeutic approach to advanced prostate cancer has seen greater changes in the last 7 years than it did in the preceding 70. Although only one of the newly approved agents that improve overall survival is a targeted agent, it is a validation of the method of pathway analysis and drug design in delivering novel, clinically usable agents. As our knowledge of the molecular circuitry of tumour invasion, metastases and treatment resistance has become more refined, the number of new, potentially useful, targets has grown exponentially. This is reflected in the vast array of diverse targeted agents that are currently being evaluated in human trials. In this review, we briefly describe some of the key pathways that are involved in the evolution of the prostate cancer 'lethal phenotype', and review the clinical activity of some of the newly approved targeted therapies or those in advanced phases of clinical development.     

Sensitivity of different dose scoring methods on organ-specific neutron dose calculations in proton therapy

Scattered doses, e.g. neutron doses in proton therapy, are of concern in radiation therapy. Although measured data are the gold standard, Monte Carlo simulations allow a more realistic consideration of patient anatomy via whole-body phantoms. When calculating neutron doses with Monte Carlo techniques, the dose can be scored in different ways because neutrons deposit dose indirectly. The purpose of this study was to assess the differences in neutron dose predictions when using different dose scoring methods. Two methods were tested. In the first method, the organ dose was calculated by accumulating dose from each individual dose deposition event with a particle-specific radiation weighting factor applied. Alternatively, we applied a method where the calculation was done by averaging the dose over the total number of events irrespective of particle type and applying average neutron radiation weighting factors. In addition, we assessed the sensitivity of different neutron quality factor assignments based on two recommendations by the International Commission on Radiological Protection (ICRP). We found that the scoring procedure can lead to differences in the organ equivalent dose of about 25%. As to the ICRP definition of neutron quality factors, the most recent recommendation results in about 10% higher organ doses.     

Monte Carlo dose calculations for spot scanned proton therapy

Density heterogeneities can have a profound effect on dose distributions for proton therapy. Although analytical calculations in homogeneous media are relatively straightforward, the modelling of the propagation of the beam through density heterogeneities can be more problematical. At the Paul Scherrer Institute, an in-house dedicated Monte Carlo (MC) code has been used for over a decade to assess the possible deficiencies of the analytical calculations in patient geometries. The MC code has been optimized for speed, and as such traces primary protons only through the treatment nozzle and patient's CT. Contributions from nuclear interactions are modelled analytically with no tracing of secondary particles. The MC code has been verified against measured data in water and experimental proton radiographs through a heterogeneous anthropomorphic phantom. In comparison to the analytical calculation, the MC code has been applied to both spot scanned and intensity modulated proton therapy plans, and to a number of cases containing titanium metal implants. In summary, MC-based dose calculations could provide an invaluable tool for independently verifying the calculated dose distribution within a patient geometry as part of a comprehensive quality assurance protocol for proton treatment plans.     

A Monte Carlo dose calculation algorithm for proton therapy

A Monte Carlo (MC) code (VMCpro) for treatment planning in proton beam therapy of cancer is introduced. It is based on ideas of the Voxel Monte Carlo algorithm for photons and electrons and is applicable to human tissue for clinical proton energies. In the present paper the implementation of electromagnetic and nuclear interactions is described. They are modeled by a Class II condensed history algorithm with continuous energy loss, ionization, multiple scattering, range straggling, delta-electron transport, nuclear elastic proton nucleus scattering and inelastic proton nucleus reactions. VMCpro is faster than the general purpose MC codes FLUKA by a factor of 13 and GEANT4 by a factor of 35 for simulations in a phantom with inhomogeneities. For dose calculations in patients the speed improvement is larger, because VMCpro has only a weak dependency on the heterogeneity of the calculation grid. Dose distributions produced with VMCpro are in agreement with GEANT4 results. Integrated or broad beam depth dose curves show maximum deviations not larger than 1% or 0.5 mm in regions with large dose gradients for the examples presented here.     

Comparative study of alkaline phosphatase and prostate specific antigen in prostate cancer

The study comprised between healthy and benign controls and proven 62 cases of prostate cancer at different clinical stages. The mean value of increasing level of PSA in group III was found to be highly significant when compared with group I. Whereas, the mean value of elevated levels of ALP in stage III and IV from group III was found to be highly significant when compared with group I. Though the mean value of ALP was increased in stage I and II from group III when compared with group I, it was not found highly significant. Hence the elevated levels of ALP were significantly correlated with advanced stages of prostate cancer. Whereas, increased levels of PSA contribute to the diagnosis of potentially increased volume of the prostate cancer.     

Estimate of the uncertainties in the relative risk of secondary malignant neoplasms following proton therapy and intensity-modulated photon therapy

Theoretical calculations have shown that proton therapy can reduce the incidence of radiation-induced secondary malignant neoplasms (SMN) compared with photon therapy for patients with prostate cancer. However, the uncertainties associated with calculations of SMN risk had not been assessed. The objective of this study was to quantify the uncertainties in projected risks of secondary cancer following contemporary proton and photon radiotherapies for prostate cancer. We performed a rigorous propagation of errors and several sensitivity tests to estimate the uncertainty in the ratio of relative risk (RRR) due to the largest contributors to the uncertainty: the radiation weighting factor for neutrons, the dose-response model for radiation carcinogenesis and interpatient variations in absorbed dose. The interval of values for the radiation weighting factor for neutrons and the dose-response model were derived from the literature, while interpatient variations in absorbed dose were taken from actual patient data. The influence of each parameter on a baseline RRR value was quantified. Our analysis revealed that the calculated RRR was insensitive to the largest contributors to the uncertainty. Uncertainties in the radiation weighting factor for neutrons, the shape of the dose-risk model and interpatient variations in therapeutic and stray doses introduced a total uncertainty of 33% to the baseline RRR calculation.