W Newhauser

Assessing the risk of second malignancies after modern radiotherapy

Recent advances in radiotherapy have enabled the use of different types of particles, such as protons and heavy ions, as well as refinements to the treatment of tumours with standard sources (photons). However, the risk of second cancers arising in long-term survivors continues to be a problem. The long-term risks from treatments such as particle therapy have not yet been determined and are unlikely to become apparent for many years. Therefore, there is a need to develop risk assessments based on our current knowledge of radiation-induced carcinogenesis.

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.

Calculations of neutron dose equivalent exposures from range-modulated proton therapy beams

Passive beam spreading techniques have been used for most proton therapy treatments worldwide. This delivery method employs static scattering foils to spread the beam laterally and a range modulating wheel or ridge filter to spread the high dose region in depth to provide a uniform radiation dose to the treatment volume. Neutrons produced by interactions of the treatment beam with nozzle components, such as the range modulation wheel, can account for a large portion of the secondary dose delivered to healthy tissue outside the treatment volume. Despite this fact, little is known about the effects of range modulation on the secondary neutron exposures around passively scattered proton treatment nozzles. In this work, the neutron dose equivalent spectra per incident proton (H(E)/p) and total neutron dose equivalent per therapeutic absorbed dose (H/D) were studied using Monte Carlo techniques for various values of range modulation at 54 locations around a passive scattering proton therapy treatment nozzle. As the range modulator wheel step thickness increased from 1.0 to 11.5 cm, the peak values of H(E)/p decreased from approximately 1 x 10(-17) mSv Gy(-1) to approximately 2 x 10(-18) mSv Gy(-1) at 50 cm from isocentre along the beams central axis. In general, H/D increased with increasing range modulation at all locations studied, and the maximum H/D exposures shifted away from isocentre.

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.

Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer.

PURPOSE To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. METHODS AND MATERIALS The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. RESULTS Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. CONCLUSIONS Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.

The physics of proton therapy

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.

Monte Carlo simulations of a nozzle for the treatment of ocular tumours with high-energy proton beams.

By the end of 2002, 33 398 patients worldwide had been treated with proton radiotherapy, 10 829 for eye diseases. The dose prediction algorithms used today for ocular proton therapy treatment planning rely on parameterizations of measured proton dose distributions, i.e., broad-beam and pencil-beam techniques, whose predictive capabilities are inherently limited by severe approximations and simplifications in modelling the radiation transport physics. In contrast, the Monte Carlo radiation transport technique can, in principle, provide accurate predictions of the proton treatment beams by taking into account all the physical processes involved, including coulombic energy loss, energy straggling, multiple Coulomb scattering, elastic and nonelastic nuclear interactions, and the transport of secondary particles. It has not been shown, however, whether it is possible to commission a proton treatment planning system by using data exclusively from Monte Carlo simulations of the treatment apparatus and a phantom. In this work, we made benchmark comparisons between Monte Carlo predictions and measurements of an ocular proton treatment beamline. The maximum differences between absorbed dose profiles from simulations and measurements were 6% and 0.6 mm, while typical differences were less than 2% and 0.2 mm. The computation time for the entire virtual commissioning process is less than one day. The study revealed that, after a significant development effort, a Monte Carlo model of a proton therapy apparatus is sufficiently accurate and fast for commissioning a treatment planning system.