Jonas D. Fontenot

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.

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.

Monte Carlo study of neutron dose equivalent during passive scattering proton therapy

Stray radiation exposures are of concern for patients receiving proton radiotherapy and vary strongly with several treatment factors. The purposes of this study were to conservatively estimate neutron exposures for a contemporary passive scattering proton therapy system and to understand how they vary with treatment factors. We studied the neutron dose equivalent per therapeutic absorbed dose (H/D) as a function of treatment factors including proton energy, location in the treatment room, treatment field size, spread-out Bragg peak (SOBP) width and snout position using both Monte Carlo simulations and analytical modeling. The H/D value at the isocenter for a 250 MeV medium field size option was estimated to be 20 mSv Gy(-1). H/D values generally increased with the energy or penetration range, fell off sharply with distance from the treatment unit, decreased modestly with the aperture size, increased with the SOBP width and decreased with the snout distance from the isocenter. The H/D values from Monte Carlo simulations agreed well with experimental results from the literature. The analytical model predicted H/D values within 28% of those obtained in simulations; this value is within typical neutron measurement uncertainties.

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.

Monte Carlo simulations for configuring and testing an analytical proton dose-calculation algorithm

Contemporary treatment planning systems for proton radiotherapy typically use analytical pencil-beam algorithms - which require a comprehensive set of configuration data - to predict the absorbed dose distributions in the patient. In order to reduce the time required to prepare a new proton treatment planning system for clinical use, it was desirable to configure the planning system before measured beam data were available. However, it was not known if the Monte Carlo simulation method was a practical alternative to measuring beam profiles. The purpose of this study was to develop a model of a passively scattered proton therapy unit, to simulate the properties of the proton fields using the Monte Carlo technique and to configure an analytical treatment planning system using the simulated beam data. Additional simulations and treatment plans were calculated in order to validate the pencil-beam predictions against the Monte Carlo simulations using realistic treatment beams. Comparison of dose distributions in a water phantom revealed small dose difference and distances to agreement under the validation conditions. The total simulation time for generating the 768 beam configuration profiles was approximately 6 weeks using 30 nodes in a parallel processing cluster. The results of this study show that it is possible to configure and test a proton treatment planning system prior to the availability of measured proton beam data. The model presented here provided a means to reduce by several months the time required to prepare an analytical treatment planning system for patient treatments.

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.

Monte Carlo simulations of the dosimetric impact of radiopaque fiducial markers for proton radiotherapy of the prostate

Many clinical studies have demonstrated that implanted radiopaque fiducial markers improve targeting accuracy in external-beam radiotherapy, but little is known about the dose perturbations these markers may cause in patients receiving proton radiotherapy. The objective of this study was to determine what types of implantable markers are visible in setup radiographs and, at the same time, perturb the therapeutic proton dose to the prostate by less than 10%. The radiographic visibility of the markers was assessed by visual inspection of lateral setup radiographs of a pelvic phantom using a kilovoltage x-ray imaging system. The fiducial-induced perturbations in the proton dose were estimated with Monte Carlo simulations. The influence of marker material, size, placement depth and orientation within the pelvis was examined. The radiographic tests confirmed that gold and stainless steel markers were clearly visible and that titanium markers were not. The Monte Carlo simulations revealed that titanium and stainless steel markers minimally perturbed the proton beam, but gold markers cast unacceptably large dose shadows. A 0.9 mm diameter, 3.1 mm long cylindrical stainless steel marker provides good radiographic visibility yet perturbs the proton dose distribution in the prostate by less than 8% when using a parallel opposed lateral beam arrangement.

Dosimetric impact of tantalum markers used in the treatment of uveal melanoma with proton beam therapy

Metallic fiducial markers are frequently implanted in patients prior to external-beam radiation therapy to facilitate tumor localization. There is little information in the literature, however, about the perturbations in proton absorbed-dose distribution these objects cause. The aim of this study was to assess the dosimetric impact of perturbations caused by 2.5 mm diameter by 0.2 mm thick tantalum fiducial markers when used in proton therapy for treating uveal melanoma. Absorbed dose perturbations were measured using radiochromic film and confirmed by Monte Carlo simulations of the experiment. Additional Monte Carlo simulations were performed to study the effects of range modulation and fiducial placement location on the magnitude of the dose shadow for a representative uveal melanoma treatment. The simulations revealed that the fiducials caused perturbations in the absorbed-dose distribution, including absorbed-dose shadows of 22% to 82% in a typical proton beam for treating uveal melanoma, depending on the marker depth and orientation. The clinical implication of this study is that implanted fiducials may, in certain circumstances, cause dose shadows that could lower the tumor dose and theoretically compromise local tumor control. To avoid this situation, fiducials should be positioned laterally or distally with respect to the target volume.