Dragan Mirkovic

The risk of developing a second cancer after receiving craniospinal proton irradiation

The purpose of this work was to compare the risk of developing a second cancer after craniospinal irradiation using photon versus proton radiotherapy by means of simulation studies designed to account for the effects of neutron exposures. Craniospinal irradiation of a male phantom was calculated for passively-scattered and scanned-beam proton treatment units. Organ doses were estimated from treatment plans; for the proton treatments, the amount of stray radiation was calculated separately using the Monte Carlo method. The organ doses were converted to risk of cancer incidence using a standard formalism developed for radiation protection purposes. The total lifetime risk of second cancer due exclusively to stray radiation was 1.5% for the passively scattered treatment versus 0.8% for the scanned proton beam treatment. Taking into account the therapeutic and stray radiation fields, the risk of second cancer from intensity-modulated radiation therapy and conventional radiotherapy photon treatments were 7 and 12 times higher than the risk associated with scanned-beam proton therapy, respectively, and 6 and 11 times higher than with passively scattered proton therapy, respectively. Simulations revealed that both passively scattered and scanned-beam proton therapies confer significantly lower risks of second cancers than 6 MV conventional and intensity-modulated photon therapies.

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 patients 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.

An evaluation of three commercially available metal artifact reduction methods for CT imaging

Three commercial metal artifact reduction methods were evaluated for use in computed tomography (CT) imaging in the presence of clinically realistic metal implants: Philips O-MAR, GEs monochromatic gemstone spectral imaging (GSI) using dual-energy CT, and GSI monochromatic imaging with metal artifact reduction software applied (MARs). Each method was evaluated according to CT number accuracy, metal size accuracy, and streak artifact severity reduction by using several phantoms, including three anthropomorphic phantoms containing metal implants (hip prosthesis, dental fillings and spinal fixation rods). All three methods showed varying degrees of success for the hip prosthesis and spinal fixation rod cases, while none were particularly beneficial for dental artifacts. Limitations of the methods were also observed. MARs underestimated the size of metal implants and introduced new artifacts in imaging planes beyond the metal implant when applied to dental artifacts, and both the O-MAR and MARs algorithms induced artifacts for spinal fixation rods in a thoracic phantom. Our findings suggest that all three artifact mitigation methods may benefit patients with metal implants, though they should be used with caution in certain scenarios.

Determination of patient-specific internal gross tumor volumes for lung cancer using four-dimensional computed tomography

BackgroundTo determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers.MethodsWe analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (1) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches.ResultsThe IGTVMIP and IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified also matched the best with IGTVAllPhases.ConclusionIGTVMIP and IGTV2Phases underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation in lung cancer.

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.

Monte Carlo simulations of neutron spectral fluence, radiation weighting factor and ambient dose equivalent for a passively scattered proton therapy unit

Stray neutron exposures pose a potential risk for the development of secondary cancer in patients receiving proton therapy. However, the behavior of the ambient dose equivalent is not fully understood, including dependences on neutron spectral fluence, radiation weighting factor and proton treatment beam characteristics. The objective of this work, therefore, was to estimate neutron exposures resulting from the use of a passively scattered proton treatment unit. In particular, we studied the characteristics of the neutron spectral fluence, radiation weighting factor and ambient dose equivalent with Monte Carlo simulations. The neutron spectral fluence contained two pronounced peaks, one a low-energy peak with a mode around 1 MeV and one a high-energy peak that ranged from about 10 MeV up to the proton energy. The mean radiation weighting factors varied only slightly, from 8.8 to 10.3, with proton energy and location for a closed-aperture configuration. For unmodulated proton beams stopped in a closed aperture, the ambient dose equivalent from neutrons per therapeutic absorbed dose (H*(10)/D) calculated free-in-air ranged from about 0.3 mSv/Gy for a small scattered field of 100 MeV proton energy to 19 mSv/Gy for a large scattered field of 250 MeV proton energy, revealing strong dependences on proton energy and field size. Comparisons of in-air calculations with in-phantom calculations indicated that the in-air method yielded a conservative estimation of stray neutron radiation exposure for a prostate cancer patient.

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 patients 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.

Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy

The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.

Can megavoltage computed tomography reduce proton range uncertainties in treatment plans for patients with large metal implants

Treatment planning calculations for proton therapy require an accurate knowledge of radiological path length, or range, to the distal edge of the target volume. In most cases, the range may be calculated with sufficient accuracy using kilovoltage (kV) computed tomography (CT) images. However, metal implants such as hip prostheses can cause severe streak artifacts that lead to large uncertainties in proton range. The purposes of this study were to quantify streak-related range errors and to determine if they could be avoided by using artifact-free megavoltage (MV) CT images in treatment planning. Proton treatment plans were prepared for a rigid, heterogeneous phantom and for a prostate cancer patient with a metal hip prosthesis using corrected and uncorrected kVCT images alone, uncorrected MVCT images and a combination of registered MVCT and kVCT images (the hybrid approach). Streak-induced range errors of 5-12 mm were present in the uncorrected kVCT-based patient plan. Correcting the streaks by manually assigning estimated true Hounsfield units improved the range accuracy. In a rigid heterogeneous phantom, the implant-related range uncertainty was estimated at <3 mm for both the corrected kVCT-based plan and the uncorrected MVCT-based plan. The hybrid planning approach yielded the best overall result. In this approach, the kVCT images provided good delineation of soft tissues due to high-contrast resolution, and the streak-free MVCT images provided smaller range uncertainties because they did not require artifact correction.

Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation

The purpose of this study was to compare the predicted risks of second malignant neoplasm (SMN) incidence and mortality from secondary neutrons for a 9-year-old girl and a 10-year-old boy who received proton craniospinal irradiation (CSI). SMN incidence and mortality from neutrons were predicted from equivalent doses to radiosensitive organs for cranial, spinal and intracranial boost fields. Therapeutic proton absorbed dose and equivalent dose from neutrons were calculated using Monte Carlo simulations. Risks of SMN incidence and mortality in most organs and tissues were predicted by applying risks models from the National Research Council of the National Academies to the equivalent dose from neutrons; for non-melanoma skin cancer, risk models from the International Commission on Radiological Protection were applied. The lifetime absolute risks of SMN incidence due to neutrons were 14.8% and 8.5%, for the girl and boy, respectively. The risks of a fatal SMN were 5.3% and 3.4% for the girl and boy, respectively. The girl had a greater risk for any SMN except colon and liver cancers, indicating that the girls higher risks were not attributable solely to greater susceptibility to breast cancer. Lung cancer predominated the risk of SMN mortality for both patients. This study suggests that the risks of SMN incidence and mortality from neutrons may be greater for girls than for boys treated with proton CSI.