Risk of Secondary Malignant Neoplasms From Proton Therapy and Intensity-Modulated X-Ray Therapy for Early-Stage Prostate Cancer

Purpose: To assess the risk of a secondary malignant neoplasm (SMN) from proton therapy relative to intensity-modulated radiation therapy (IMRT) using X-rays, taking into account contributions from both primary and secondary sources of radiation, for prostate cancer. Methods and Materials: A proton therapy plan and a 6-MV IMRT plan were constructed for 3 patients with early-stage adenocarcinoma of the prostate. Doses from the primary fields delivered to organs at risk of developing an SMN were determined from treatment plans. Secondary doses from the proton therapy and IMRT were determined from Monte Carlo simulations and available measured data, respectively. The risk of an SMN was estimated from primary and secondary doses on an organ-by-organ basis by use of risk models from the Committee on the Biological Effects of Ionizing Radiation. Results: Proton therapy reduced the risk of an SMN by 26% to 39% compared with IMRT. The risk of an SMN for both modalities was greatest in the in-field organs. However, the risks from the in-field organs were considerably lower with the proton therapy plan than with the IMRT plan. This reduction was attributed to the substantial sparing of the rectum and bladder from exposure to the therapeutic beam by the proton therapy plan. Conclusions: When considering exposure to primary and secondary radiation, proton therapy can reduce the risk of an SMN in prostate patients compared with contemporary IMRT. © 2009 Elsevier Inc. All rights reserved

Dose perturbations from implanted helical gold markers in proton therapy of prostate cancer

Implanted gold fiducial markers are widely used in radiation therapy to improve targeting accuracy. Recent investigations have revealed that metallic fiducial markers can cause severe perturbations in dose distributions for proton therapy, suggesting smaller markers should be considered. The objective of this study was to estimate the dosimetric impact of small gold markers in patients receiving proton therapy for prostate cancer. Small, medium, and large helical wire markers with lengths of 10 mm and helix diameters of 0.35 mm, 0.75 mm, and 1.15 mm, respectively, were implanted in an anthropomorphic phantom. Radiographic visibility was confirmed using a kilovoltage x-ray imaging system, and dose perturbations were predicted from Monte Carlo simulations and confirmed by measurements. Monte Carlo simulations indicated that size of dose perturbation depended on marker size, orientation, and distance from the beam\u27s end of range. Specifically, the perturbation of proton dose for the lateral-opposed-pair treatment technique was 31% for large markers and 23% for medium markers in a typical oblique orientation. Results for perpendicular and parallel orientations were respectively lower and higher. Consequently, these markers are not well suited for use in patients receiving proton therapy for prostate cancer. Dose perturbation was not observed for the small markers, but these markers were deemed too fragile for transrectal implantation in the prostate

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. © 2010 Institute of Physics and Engineering in Medicine

Ambient dose equivalent versus effective dose for quantifying stray radiation exposures to a patient receiving proton therapy for prostate cancer

The purpose of this study was to evaluate the suitability of the quantity ambient dose equivalent H*(10) as a conservative estimate of effective dose E for estimating stray radiation exposures to patients receiving passively scattered proton radiotherapy for cancer of the prostate. H*(10), which is determined from fluence free-in-air, is potentially useful because it is simpler to measure or calculate because it avoids the complexities associated with phantoms or patient anatomy. However, the suitability of H*(10) as a surrogate for E has not been demonstrated for exposures to high-energy neutrons emanating from radiation treatments with proton beams. The suitability was tested by calculating H*(10) and E for a proton treatment using a Monte Carlo model of a double-scattering treatment machine and a computerized anthropomorphic phantom. The calculated E for the simulated treatment was 5.5 mSv/Gy, while the calculated H*(10) at the isocenter was 10 mSv/Gy. A sensitivity analysis revealed that H*(10) conservatively estimated E for the interval of treatment parameters common in proton therapy for prostate cancer. However, sensitivity analysis of a broader interval of parameters suggested that H*(10) may underestimate E for treatments of other sites, particularly those that require large field sizes. Simulations revealed that while E was predominated by neutrons generated in the nozzle, neutrons produced in the patient contributed up to 40% to dose equivalent in near-field organs

Advantages of MCNPX-based lattice tally over mesh tally in high-speed Monte Carlo dose reconstruction for proton radiotherapy

Monte Carlo simulations are increasingly used to reconstruct dose distributions in radiotherapy research studies. Many studies have used the MCNPX Monte Carlo code with a mesh tally for dose reconstructions. However, when the number of voxels in the simulated patient anatomy is large, the computation time for a mesh tally can become prohibitively long. The purpose of this work was to test the feasibility of using lattice tally instead of mesh tally for whole-body dose reconstructions. We did this by comparing the dosimetric accuracy and computation time of lattice tallies with those of mesh tallies for craniospinal proton irradiation. The two tally methods generated nearly identical dosimetric results, within 1% in dose and within 1 mm distance-to-agreementfor 99% of the voxels. For a typical craniospinal proton treatment field, simulation speed was 4 to 17 times faster using the lattice tally than using the mesh tally, depending on the numbers of proton histories and voxels. We conclude that the lattice tally is an acceptable substitute for the mesh tally in dose reconstruction, making it a suitable potential candidate for clinical treatment planning

An analytic model of neutron ambient dose equivalent and equivalent dose for proton radiotherapy

Stray neutrons generated in passively scattered proton therapy are of concern because they increase the risk that a patient will develop a second cancer. Several investigations characterized stray neutrons in proton therapy using experimental measurements and Monte Carlo simulations, but capabilities of analytical methods to predict neutron exposures are less well developed. The goal of this study was to develop a new analytical model to calculate neutron ambient dose equivalent in air and equivalent dose in phantom based on Monte Carlo modeling of a passively scattered proton therapy unit. The accuracy of the new analytical model is superior to a previous analytical model and comparable to the accuracy of typical Monte Carlo simulations and measurements. Predictions from the new analytical model agreed reasonably well with corresponding values predicted by a Monte Carlo code using an anthropomorphic phantom. © 2010 Institute of Physics and Engineering in Medicine

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\u27s 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. © 2008 Institute of Physics and Engineering in Medicine

Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams

Proton beam radiotherapy unavoidably 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\u27s risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients. © 2009 Institute of Physics and Engineering in Medicine

Benchmark measurements and simulations of dose perturbations due to metallic spheres in proton beams

Monte Carlo simulations are increasingly used for dose calculations in proton therapy due to its inherent accuracy. However, dosimetric deviations have been found using Monte Carlo code when high density materials are present in the proton beamline. The purpose of this work was to quantify the magnitude of dose perturbation caused by metal objects. We did this by comparing measurements and Monte Carlo predictions of dose perturbations caused by the presence of small metal spheres in several clinical proton therapy beams as functions of proton beam range and drift space. Monte Carlo codes MCNPX, GEANT4 and Fast Dose Calculator (FDC) were used. Generally good agreement was found between measurements and Monte Carlo predictions, with the average difference within 5% and maximum difference within 17%. The modification of multiple Coulomb scattering model in MCNPX code yielded improvement in accuracy and provided the best overall agreement with measurements. Our results confirmed that Monte Carlo codes are well suited for predicting multiple Coulomb scattering in proton therapy beams when short drift spaces are involved. © 2013 Elsevier Ltd. All rights reserved