Human Bone Marrow Cell Extracts Mitigate Radiation Injury to Salivary Gland.

Mitigation of irradiation injury to salivary glands was previously reported using a cell-free extract from mouse bone marrow. However, to bring this potential therapy a step closer to clinical application, a human bone marrow cell extract (BMCE) needs to be tested. Here, we report that irradiation-induced injury of salivary glands in immunocompetent mice treated with human BMCE secreted 50% more saliva than saline-injected mice, and BMCE did not cause additional acute inflammatory reaction. In addition, to identify the cell fraction in BMCE with the most therapeutic activity, we sorted human bone marrow into 3 cell fractions (mononuclear, granulocyte, and red blood cells) and tested their respective cell extracts. We identified that the mononuclear cell extract (MCE) provided the best therapeutic efficacy. It increased salivary flow 50% to 73% for 16 wk, preserved salivary parenchymal and stromal cells, and doubled cell proliferation rates while producing less inflammatory response. In contrast, the cell extract of granulocytes was of shorter efficacy and induced an acute inflammatory response, while that from red blood cells was not therapeutically effective for salivary function. Several proangiogenic (MMP-8, MMP-9, VEGF, uPA) and antiangiogenic factors (TSP-1, PF4, TIMP-1, PAI-1) were identified in MCE. Added advantages of BMCE and MCE for potential clinical use were that cell extracts from both male and female donors were comparably bioactive and that cell extracts could be stored and transported much more conveniently than cells. These findings suggest human BMCE, specifically the MCE fraction, is a promising therapy against irradiation-induced salivary hypofunction.

Calibration of MTT assay in proton beams using radiochromic films.

PURPOSE: This study provides methodology of calibrating as well as controlling the output for an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay irradiated in a low energy proton beam using EBT3-model GAFCHROMICTM film, without correcting for quenching effect. METHODS: A calibrated Markus ionization chamber was used to measure the depth dose and beam output for 26.5 MeV protons produced by a CS30 cyclotron. A time-controlled aluminum cylinder was added in front of the horizontal beam-exit serving as a radiation shutter. Following the TRS-398 reference dosimetry protocol for proton beams, the output was calibrated in water at a reference depth of 3 mm. EBT3 film was calibrated for doses up to 8 Gy at the same depth. To verify the dose distribution for each 96-well MTT assay plate, EBT3 film was placed at the reference depth during irradiation and cell doses were scaled by measured percent depth dose (PDD) data. RESULTS: The radiochromic film dosimetry system in this study provides dose measurements with an uncertainty better than 3.3% for doses higher than 1 Gy. From a single exposure and utilizing the Gaussian shape of the beam, multiple dose points can be obtained within different wells of the same plate ranging from 6.9 Gy (sigma ∼4%) in the central well, and 2 Gy (sigma ∼8%) for wells positioned closer to the periphery. CONCLUSIONS: We described a methodology for radiochromic film-based dose monitoring system, using low-energy protons, which can be used for the MTT assay in any proton beam, except within Bragg peak region.

Determination of consensus k Q values for megavoltage photon beams for the update of IAEA TRS-398.

The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.

Labial Stem Cell Extract Mitigates Injury to Irradiated Salivary Glands.

Stem cell-based therapies could provide a permanent treatment for salivary gland (SG) hypofunction caused by ionizing radiation (IR) injury. However, current challenges for SG stem cells to reach the clinic include surgical invasiveness, amount of tissue needed, cell delivery, and storage methods. The objective of this study was to develop a clinically less invasive method to isolate and expand human SG stem cells and then to obtain a cell-free extract to be used as a therapy for IR-injured SGs. Human labial glands were biopsied, and labial stem cells (LSCs) were expanded by explant culture. The LSC extract (LSCE) was obtained by releasing the cellular components after 3 freeze-thaw cycles and 17,000g force centrifugation. LSCE was injected intravenously into mice that had their SGs injured with 13-Gy IR. Positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Three pieces of labial glands (0.1 g weight) could expand 1 to 2 million cells. LSCs had a doubling time of 18.8 h; could differentiate into osteocytes, adipocytes, and chondrocytes; and were positive for mesenchymal stem cell markers. Both angiogenic (FGF-1, FGF-2, KGF, angiopoietin, uPA, VEGF) and antiangiogenic factors (PAI-1, TIMP-1, TSP-1, CD26) were detected in LSCE. In addition, some angiogenic factors (PEDF, PTX3, VEGF) possessed neurotrophic functions. Mice treated with LSCE had 50% to 60% higher salivary flow rate than saline-treated mice at 8 and 12 wk post-IR. Saliva lag time measurements also confirmed that LSCE restored SG function. Histologic analyses of parotids and submandibular glands reported comparable numbers of acinar cells, blood vessels, and parasympathetic nerves and cell proliferation rates in sham IR and LSCE-treated mice, though significantly lower in saline-treated mice. An explant culture method can harvest a large number of LSCs from small pieces of labial glands. LSCE showed clinical potential to mitigate IR-injured SGs.

Absorbed dose calorimetry.

This article reviews the development and summarizes the state-of-the-art in absorbed dose calorimetry for all the common clinical beam modalities covered in reference dosimetry codes of practice, as well as for small and nonstandard fields, and brachytherapy. It focuses primarily on work performed in the last ten years by national laboratories and research institutions and is not restricted to primary standard instruments. The most recent absorbed dose calorimetry review article was published over twenty years ago by Ross and Klassen (1996 Phys. Med. Biol. 41 1-29), and even then, its scope was limited to water calorimeters. Since the application of calorimetry to the measurement of radiation has a long and often overlooked history, a brief introduction into its origins is provided, along with a summary of some of the landmark research that have shaped the current landscape of absorbed dose calorimeters. Technical descriptions of water and graphite calorimetry are kept general, as these have been detailed extensively in relatively recent review articles (e.g. McEwen and DuSautoy (2009 Metrologia 46 S59-79) and Seuntjens and Duane (2009 Metrologia 46 S39-58). The review categorizes calorimeters by the radiation type for which they are applied; from the widely established standards for Co-60 and high-energy x-rays, to the prototype calorimeters used in high-energy electrons and hadron therapy. In each case, focus is placed on the issues and constraints affecting dose measurement in that beam type, and the innovations developed to meet these requirements. For photons, electrons, proton and carbon ion beams, a summary of the ionization chamber beam quality conversion factors (k Q ) determined using said calorimeters is also provided. The article closes with a look forward to some of the most promising new techniques and areas of research and speculates about the future clinical role of absorbed dose calorimetry.

Lyophilized bone marrow cell extract functionally restores irradiation-injured salivary glands.

OBJECTIVE: Bone marrow cell extract (BMCE) was previously reported to restore salivary gland hypofunction caused by irradiation injury. Proteins were shown to be the main active factors in BMCE. However, BMCE therapy requires multiple injections and protein denaturation is a concern during BMCE storage. This study aimed to preserve, by lyophilization (freeze-drying), the bioactive factors in BMCE. METHODS: We developed a method to freeze-dry BMCE and then to analyze its ingredients and functions in vivo. Freeze-dried (FD) BMCE, freshly prepared BMCE (positive control), or saline (vehicle control) was injected into the tail vein of mice that had received irradiation to damage their salivary glands. RESULTS: Results demonstrated that the presence of angiogenesis-related factors and cytokines in FD-BMCE remained comparable to those found in fresh BMCE. Both fresh and FD-BMCE restored comparably saliva secretion, increased cell proliferation, upregulated regenerative/repair genes, protected salivary acinar cells, parasympathetic nerves, and blood vessels from irradiation-damaged salivary glands. CONCLUSION: Lyophilization of BMCE maintained its bioactivity and therapeutic effect on irradiation-injured salivary glands. The advantages of freeze-drying BMCE are its storage and transport at ambient temperature.

Development and application of a water calorimeter for the absolute dosimetry of short-range particle beams.

In this work, we describe a new design of water calorimeter built to measure absorbed dose in non-standard radiation fields with reference depths in the range of 6-20 mm, and its initial testing in clinical electron and proton beams. A functioning calorimeter prototype with a total water equivalent thickness of less than 30 mm was constructed in-house and used to obtain measurements in clinical accelerator-based 6 MeV and 8 MeV electron beams and cyclotron-based 60 MeV monoenergetic and modulated proton beams. Corrections for the conductive heat transfer due to dose gradients and non-water materials was also accounted for using a commercial finite element method software package. Absorbed dose to water was measured with an associated type A standard uncertainty of approximately 0.4% and 0.2% for the electron and proton beam experiments, respectively. In terms of thermal stability, drifts were on the order of a couple of hundred µK min-1, with a short-term variation of 5-10 µK. Heat transfer correction factors ranged between 1.021 and 1.049. The overall combined standard uncertainty on the absorbed dose to water was estimated to be 0.6% for the 6 MeV and 8 MeV electron beams, as well as for the 60 MeV monoenergetic protons, and 0.7% for the modulated 60 MeV proton beam. This study establishes the feasibility of developing an absorbed dose transfer standard for short-range clinical electrons and protons and forms the basis for a transportable dose standard for direct calibration of ionization chambers in the user's beam. The largest contributions to the combined standard uncertainty were the positioning (⩽0.5%) and the correction due to conductive heat transfer (⩽0.4%). This is the first time that water calorimetry has been used in such a low energy proton beam.

Direct reconstruction of the source intensity distribution of a clinical linear accelerator using a maximum likelihood expectation maximization algorithm.

Direct determination of the source intensity distribution of clinical linear accelerators is still a challenging problem for small field beam modeling. Current techniques most often involve special equipment and are difficult to implement in the clinic. In this work we present a maximum-likelihood expectation-maximization (MLEM) approach to the source reconstruction problem utilizing small fields and a simple experimental set-up. The MLEM algorithm iteratively ray-traces photons from the source plane to the exit plane and extracts corrections based on photon fluence profile measurements. The photon fluence profiles were determined by dose profile film measurements in air using a high density thin foil as build-up material and an appropriate point spread function (PSF). The effect of other beam parameters and scatter sources was minimized by using the smallest field size ([Formula: see text] cm(2)). The source occlusion effect was reproduced by estimating the position of the collimating jaws during this process. The method was first benchmarked against simulations for a range of typical accelerator source sizes. The sources were reconstructed with an accuracy better than 0.12 mm in the full width at half maximum (FWHM) to the respective electron sources incident on the target. The estimated jaw positions agreed within 0.2 mm with the expected values. The reconstruction technique was also tested against measurements on a Varian Novalis Tx linear accelerator and compared to a previously commissioned Monte Carlo model. The reconstructed FWHM of the source agreed within 0.03 mm and 0.11 mm to the commissioned electron source in the crossplane and inplane orientations respectively. The impact of the jaw positioning, experimental and PSF uncertainties on the reconstructed source distribution was evaluated with the former presenting the dominant effect.

Patient-specific compensation for Co-60 TBI treatments based on Monte Carlo design: A feasibility study.

PURPOSE: To develop an AP-PA treatment technique for the delivery of total body irradiation (TBI) at extended SSD using a modified Co-60 unit equipped with flattening filter and patient-specific compensators supported by Monte Carlo (MC) simulations and measurements. METHODS: An existing Eldorado-78 Co-60 teletherapy unit was stripped of its original collimator and equipped with two beam-defining cerrobend blocks. An acrylic flattening filter was numerically designed based on detailed mapping of the dose distribution of the large open field at a 10 cm depth in water using a primary radiation attenuation calculation. An EGSnrc/BEAMnrc MC model of the resulting unit was developed and experimentally validated and was used to calculate MC dose distributions in whole-body supine and prone CT images of a patient. AP-PA patient-specific compensators were designed based on the supine and prone mid-plane dose distributions. RESULTS: The designed flattening filter flattens the beam to within ±2% over a 200 cm × 70 cm area at 10 cm depth in water. Experimental validation of the calculated dose profiles in the open and flattened beams shows agreement of better than 2% and 1%, respectively. Patient MC dose calculations in the flattened, uncompensated beam showed dose deviations from prescription dose most notably in lung, neck and extremities ranging from -5% to +25%. The use of patient-specific compensators reduced inhomogeneities to within -5% to +10%. CONCLUSIONS: This work demonstrates that a Co-60 TBI setup upgraded with patient-specific compensators, numerically designed using MC patient dose calculations, is feasible and considerably improves the dose homogeneity.

On the correction, perturbation and modification of small field detectors in relative dosimetry.

The purpose of this study was to derive a complete set of correction and perturbation factors for output factors (OF) and dose profiles. Modern small field detectors were investigated including a plastic scintillator (Exradin W1, SI), a liquid ionization chamber (microLion 31018, PTW), an unshielded diode (Exradin D1V, SI) and a synthetic diamond (microDiamond 60019, PTW). A Monte Carlo (MC) beam model was commissioned for use in small fields following two commissioning procedures: (1) using intermediate and moderately small fields (down to 2 × 2 cm(2)) and (2) using only small fields (0.5 × 0.5 cm(2) -2 × 2 cm(2)). In the latter case the detectors were explicitly modelled in the dose calculation. The commissioned model was used to derive the correction and perturbation factors with respect to a small point in water as suggested by the Alfonso formalism. In MC calculations the design of two detectors was modified in order to minimize or eliminate the corrections needed. The results of this study indicate that a commissioning process using large fields does not lead to an accurate estimation of the source size, even if a 2 × 2 cm(2) field is included. Furthermore, the detector should be explicitly modelled in the calculations. On the output factors, the scintillator W1 needed the smallest correction (+0.6%), followed by the microDiamond (+1.3%). Larger corrections were observed for the microLion (+2.4%) and diode D1V (-2.4%). On the profiles, significant corrections were observed out of the field on the gradient and tail regions. The scintillator needed the smallest corrections (-4%), followed by the microDiamond (-11%), diode D1V (+13%) and microLion (-15%). The major perturbations reported were due to volume averaging and high density materials that surround the active volumes. These effects presented opposite trends in both OF and profiles. By decreasing the radius of the microLion to 0.85 mm we could modify the volume averaging effect in order to achieve a discrepancy less than 1% for OF and 5% for profiles compared to water. Similar results were observed for the diode D1V if the radius was increased to 1 mm.

Delivery validation of an automated modulated electron radiotherapy plan.

PURPOSE: Modulated electron radiation therapy (MERT) represents an active area of interest that offers the potential to improve healthy tissue sparing in treatment of certain cancer cases. Challenges remain however in accurate beamlet dose calculation, plan optimization, collimation method, and delivery accuracy. In this work, the authors investigate the accuracy and efficiency of an end-to-end MERT plan and automated delivery method. METHODS: Treatment planning was initiated on a previously treated whole breast irradiation case including an electron boost. All dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. RESULTS: The automated delivery, which covered four electron energies, 196 subfields, and 6183 total MU was completed in 25.8 min, including 6.2 min of beam-on time. The remainder of the delivery time was spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. Comparison of the planned and delivered film dose gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9, 12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was also performed with a MapCHECK device and resulted in 3%/3 mm gamma pass rates of 88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies, respectively. CONCLUSIONS: Results of the authors' study showed that an accurate delivery utilizing an add-on tertiary electron collimator is possible using Monte Carlo calculated plans and inverse optimization, which brings MERT closer to becoming a viable option for physicians in treating superficial malignancies.

Design and validation of novel scattering foils for modulated electron radiation therapy.

Modulated Electron Radiation Therapy (MERT) continues to be an area of interest to various groups, however, the scattering foils used in beam flattening have not been optimized for this modality. In this work, the feasibility of novel scattering foils specifically designed for MERT is investigated using Monte Carlo methods. Different designs based on foil material, shape and thickness were analyzed. It was shown that low atomic number materials such as aluminum were optimal, while shaped foils such as those employed in current dual foil designs were not necessary. Aluminum foil thickness between 0.36 mm and 1.50 mm were capable of sufficiently broadening beams with energies between 12 MeV and 20 MeV respectively, with beams of lower energies receiving sufficient scatter from the treatment head components and air scatter. Finally, custom foils were manufactured based upon previously simulated designs and were placed into the beamline of a 2100 EX accelerator, and showed excellent agreement between the simulated and measured PDDs and profiles. Custom foils achieved higher dose rates on the central axis compared to the clinical foils by factors of 5.4, 4.9 and 4.5 for 12 MeV, 16 MeV and 20 MeV, respectively.

Improving the energy response of external beam therapy (EBT) GafChromicTM dosimetry films at low energies (≤ 100 keV).

PURPOSE: Purpose of this work is to investigate the effects of varying the active layer composition of external beam therapy (EBT) GafChromic(TM) films on the energy dependence of the film, as well as try to develop a new prototype with more uniform energy response at low photon energies (⩽ 100 keV). METHODS: First, the overall energy response (S(AD, W)(Q)) of different commercial EBT type film models that represent the three different generations produced to date, i.e., EBT, EBT2, and EBT3, was investigated. Pieces of each film model were irradiated to a fixed dose of 2 Gy to water for a wide range of beam qualities and the corresponding S(AD, W)(Q) was measured using a flatbed document scanner. Furthermore, the DOSRZnrc Monte Carlo code was used to determine the absorbed dose to water energy dependence of the film, f(Q). Moreover, the intrinsic energy dependence, kbq(Q), for each film model was evaluated using the corresponding S(AD, W)(Q) and f(Q). In the second part of this study, the authors investigated the effects of changing the chemical composition of the active layer on SAD, W(Q). Finally, based on these results, the film manufacturer fabricated several film prototypes and the authors evaluated their S(AD, W)(Q). RESULTS: The commercial EBT film model shows an under response at all energies below 100 keV reaching 39% ± 4% at about 20 keV. The commercial EBT2 and EBT3 film models show an under response of about 27% ± 4% at 20 keV and an over response of about 16% ± 4% at 40 keV.S(AD, W)(Q) of the three commercial film models at low energies show strong correlation with the corresponding f(-) (1)(Q) curves. The commercial EBT3 model with 4% Cl in the active layer shows under response of 22% ± 4% at 20 keV and 6% ± 4% at about 40 keV. However, increasing the mass percent of chlorine makes the film more hygroscopic which may affect the stability of the film's readout. The EBT3 film prototype with 7.5% Si shows a significant improvement in the energy response at very low energies compared to the commercial EBT3 films with 4% Cl. It shows under response of 15% ± 5% at about 20 keV to 2% ± 5% at about 40 keV. However, according to the manufacturer, the addition of 7.5% Si as SiO2 adversely affected the viscosity of the active fluid and therefore affected the potential use in commercial machine coating. The latest commercial EBT3 film model with 7% Al as Al2O3 shows an overall improvement in SAD, W(Q) compared to previous commercial EBT3 films. It shows under response at all energies <100 keV, varying from 20% ± 4% at 20 keV to 6% ± 4% at 40 keV. CONCLUSIONS: The energy response of films in the energy range <100 keV can be improved by adjusting the active layer chemical composition. Removing bromine eliminated the over response at about 40 keV. The under response at energies ≤ 30 keV is improved by adding 7% Al to the active layer in the latest commercial EBT3 film models.

An experimental feasibility study on the use of scattering foil free beams for modulated electron radiotherapy.

The potential benefit of using scattering foil free beams for delivery of modulated electron radiotherapy is investigated in this work. Removal of the scattering foil from the beamline showed a measured bremsstrahlung tail dose reduction just beyond R(p) by a factor of 12.2, 6.9, 7.4, 7.4 and 8.3 for 6, 9, 12, 16 and 20 MeV beams respectively for 2 × 2 cm(2) fields defined on-axis when compared to the clinical beamline. Monte Carlo simulations were matched to measured data through careful tuning of source parameters and the modification of certain accelerator components beyond the manufacturer's specifications. An accelerator model based on the clinical beamline and one with the scattering foil removed were imported into a Monte Carlo-based treatment planning system (McGill Monte Carlo Treatment Planning). A treatment planning study was conducted on a test phantom consisting of a PTV and two distal organs at risk (OAR) by comparing a plan using the clinical beamline to a plan using a scattering foil free beamline. A DVH comparison revealed that for quasi-identical target coverage, the volume of each OAR receiving a given dose was reduced, thus reducing the dose deposited in healthy tissue.

Sci-Thur AM: Planning - 07: A fast and accurate source model for energy and intensity modulated electron beams.

The purpose of this study is to develop a highly accurate and fast method for calculating electron beam dose distributions in Modulated Electron Radiation Therapy (MERT). An algorithm has been developed for creating phase-space files at the exit of a linear accelerator for any arbitrary intensity and energy electron beam without the need of full Monte Carlo simulations. The model assigns each particle to one of the 3 following sources: primary, secondary collimator and electron collimator scatter. The primary component is derived by fast MC transport in air. The scatter components are derived by the use of MC pre-calculated leaf kernels. Each kernel includes the fluence distribution, energy distribution and scatter probability of generating an electron from a leaf. The original position is sampled from tunable Gaussian or uniform distributions. The direction is estimated by geometrical means. According to the projection of the direction a particle is rejected if it is expected to suffer a leaf-hit. A leaf-hit counter is used to calculate the output of scatter particles based on the pre-calculated scatter probabilities. To account for multiple coulomb scattering in air a MC-corrected version of the Fermi-Eyges scattering theory was implemented. Depth and profile dose distributions were derived for the largest and smallest square field sizes, as well as for irregular and off-axis fields. The model agreed with full MC dose distributions within 3 % in all cases. Output at the depth of maximum dose exhibited discrepancies less than 2.6 % in all cases. The model was 16-22 times faster in generating a phase-space file than a full MC simulation with the BEAMnrc code.

Sci-Thur PM: YIS - 09: Development of a graphite probe calorimeter for absolute clinical dosimetry: Numerical design optimization, prototyping and experimental proof-of-concept.

In this work, the feasibility of absolute dose to water measurements using a small-scale graphite probe calorimeter (GPC) in a clinical environment is established. A numerical design optimization study was conducted by simulating the heat transfer in the GPC resulting from irradiation using a finite element method software package. The choice of device shape, dimensions and materials was made to minimize the heat loss in the sensitive volume of the GPC. The resulting design, which incorporates a novel aerogel-based thermal insulator, was built in-house. Absorbed dose to water measurements were made under standard conditions in a 6 MV 1000 MU/min photon beam and subsequently compared against TG-51 derived values. The average measured dose to water was 95.7 ±1.4 cGy/100 MU, as compared to an expected value of 96.6 cGy/100 MU. The Monte Carlo-calculated graphite to water dose conversion factor was 1.099, while the derived heat loss correction factors varied between 1.005 and 1.013. The most significant sources of uncertainty were the repeatability (type A, 1.4%) and thermistor calibration (type B, 2.1%). The contribution of these factors to the overall uncertainty is expected to decrease significantly upon the implementation of active thermal stabilization provided by a temperature controller and direct electrical calibration, respectively. This work demonstrates the feasibility of using the GPC as a practical clinical absolute photon dosimeter and will serve as the basis for a miniaturized version applicable to small and composite fields.

Sci-Thur PM: YIS - 01: Inverse treatment planning for modulated electrons and mixed photon and electron radiotherapy.

Modulated electron radiotherapy (MERT) takes advantage of the low distal dose of electrons to reduce dose to healthy tissue. The dosimetric advantage of MERT is clear when compared against single-field electron irradiation where MERT demonstrates superior target homogeneity and sparing; however the dosimetric advantage is unclear when comparing MERT with photon intensity-modulated radiotherapy (IMRT) where MERT techniques struggle to match the IMRT target homogeneity but with less total energy delivered to healthy tissues. In an effort to improve dosimetric benefits of MERT, this study investigated an inverse planning technique for the creation of hybrid MERT-IMRT mixed beam radiotherapy (MBRT) plans. The optimization process decouples the photon and electron beamlets for combined modality optimization. The input to the optimization algorithm was a series of patient-specific 3D dose distributions for the corresponding electron and photon beamlets, while the output was a list of weights that satisfied the optimization constraints. A photon IMRT Eclipse (Varian, Palo Alto, CA) plan and a MERT plan were created for a patient-specific sarcoma irradiation. The MERT plan was competitive in its ability to reduce dose to organs at risk and total-body dose; however, the plan suffered from poorer target conformity compared with the IMRT plan. The MBRT plan was created by adding two photon fields, divided into beamlets, to the electron beamlets of the MERT plan for reoptimization. The MBRT plan improved MERT target coverage with only minimal cost to healthy tissue dose. The MBRT plan provided clear dosimetric advantages over the IMRT and MERT plan.

Sci-Thur AM: Planning - 08: Validation of a commercial Monte Carlo code used for stereotactic radiosurgery and stereotactic body radiation therapy.

Our project consisted of validating the BrainLab iPlan Monte Carlo algorithm, used in conjunction with the stereotactic radiosurgery (SRS) mode of the Varian Novalis TX linear accelerator, for clinical use. Our approach was to "benchmark" the iPlan algorithm by comparing dose distributions with those obtained using a BEAMnrc model of the Novalis SRS mode. The BEAMnrc model was obtained by modifying an existing accelerator model to include the SRS flattening filter and source characteristics of the Novalis TX, and by reprogramming a component module to model the high definition 120-leaf multi-leaf collimator. The free parameters of interleaf air gap and leaf density were adjusted by matching to interleaf leakage profiles measured with EBT2 film. The BEAMnrc model was used to perform comparisons of depth dose curves and planar distributions for fields in homogeneous and heterogeneous slab phantoms between both MC codes and film. The source parameters of electron beam energy, size and angular spread were determined to be 6.6 MeV, 0.7 mm and 0.8 mm (cross and in-plane), and 1.27°, respectively. Comparisons between iPlan and EGSnrc MC codes show agreement within 2% for PDD curves, and a high pass rate (>98%) on gamma analysis (3%/3mm) for planar distributions, when the scored quantity is dose to medium. Discrepancies between both MC codes and film measurements were seen near bone inhomogeneities, where the film trend agrees somewhat with iPlan MC reporting dose-to-water. Further work is being performed to understand these differences and how film is used to measure dose near bone.

Poster - Thur Eve - 73: Prediction of risks of cardiac mortality and secondary cancers after radiotherapy for Hodgkin's lymphoma, non-Hodgkin's lymphoma, and breast cancer.

PURPOSE: To predict the risks of late, radiation-induced effects for young patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), or breast cancer (BC) if treated with intensity modulated proton therapy (IMPT) compared to 3D conformal photon radiotherapy (3D-CRT). Late effects considered were cardiac mortality and secondary cancer in the lungs and breasts (for female patients). METHODS: Patient data were acquired for twenty-six patients (ages 12-29) who were treated with 3D-CRT for HL, NHL, or BC in 2010. Original CT simulation images were used to re-plan the patients with IMPT using commercially-available treatment planning software. The contours of the organs at risk were reviewed by a single physician and modified for consistency. The dose-volume data of the 3D-CRT plans and the new IMPT plans were analyzed to model the risks of late effects. The relative seriality model was used to predict excess risk of cardiac mortality at fifteen years post-irradiation. A modified linear quadratic model was used to predict the Excess Absolute Risk (EAR) for induction of lung cancer and breast cancer at thirty years post-irradiation. RESULTS: For 3D-CRT and IMPT respectively, the mean excess risks of cardiac mortality were 0.9% and 0.5%. Mean EARs for lung cancer were 17.5 cases per 10,000 persons per year (PY) and 10.1 PY. Mean EARs for breast cancer were 8.2 PY and 2.8 PY. CONCLUSIONS: IMPT may significantly reduce the risks of radiation-induced cardiac mortality and secondary cancer in the lungs and breasts of young patients receiving radiotherapy for HL, NHL, or breast cancer.