Vahagn Nazaryan

Variations in the RBE for Cell Killing Along the Depth-Dose Profile of a Modulated Proton Therapy Beam

Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D0.1 isoeffect dose RBE values (normalized against 60Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D0.1 isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D0.1 isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

Proton structure corrections to electronic and muonic hydrogen hyperfine splitting

We present a precise determination of the polarizability and other proton structure dependent contributions to the hydrogen hyperfine splitting, based heavily on the most recent published data on proton spin dependent structure functions from the EG1 experiment at the Jefferson Laboratory. As a result, the total calculated hyperfine splitting now has a standard deviation slightly under 1 part-per-million, and is about 1 standard deviation away from the measured value. We also present results for muonic hydrogen hyperfine splitting, taking care to ensure the compatibility of the recoil and polarizability terms.

Proton structure corrections to hyperfine splitting in muonic hydrogen

We present the derivation of the formulas for the proton structure-dependent terms in the hyperfine splitting of muonic hydrogen. We use compatible conventions throughout the calculations to derive a consistent set of formulas that reconcile differences between our results and some specific terms in earlier work. Convention conversion corrections are explicitly presented, which reduce the calculated hyperfine splitting by about 46 ppm. We also note that using only modern fits to the proton elastic form factors gives a smaller than historical spread of Zemach radii and leads to a reduced uncertainty in the hyperfine splitting. Additionally, hyperfine splittings have an impact on the muonic hydrogen Lamb shift/proton radius measurement, however the correction we advocate has a small effect there.

SU‐E‐T‐146: Uncertainty of Stopping Powers of Tissue Equivalent Materials in Uniformly Scanned Proton Beam

Purpose: To quantify uncertainties associated with the extraction of CT HU to stopping power conversion curve for tissue equivalent materials in uniformly scanned (US)proton beams. Methods and Materials: The Philips Gemini TF Big Bore PET/CT scanner at the Hampton University Proton Therapy Institute (HUPTI), was used to extract the HU numbers for several tissue equivalent materials in the CIRS M062 phantom. Protonstopping power for each material was extracted by measuring the range change with and without the material, in a USproton beam pristine Bragg peak, and comparing to its physical thickness. The in‐beam measurements were performed using a Multilayer Ionization Chamber device (IBA Dosimetry, Zebra). Data were analyzed using both IBA OmniPro Incline and an in‐house software analysis package. Several proton beam energies were used: 143 MeV, 175 MeV, and 210 MeV. For each material and energy the difference between measured and predicted value of the stopping power was quantified. Results: The difference between measured and calculated stopping power with proton energy was found to be within 1–2.5 percent. The upper value of this variation was added to the machine specific systematic error of the CT HU number and quantified as the uncertainty of the CT HU to protonstopping power conversion curve. It was added to the total uncertainties (proton range and lateral profile), when PTV margins were implemented in the TPS. Conclusions: The relative linear stopping powers of 9 different tissue equivalent materials were measured using a range of uniformly scanned proton beam energies. These values were compared with predicted stopping powers calculated using current prescriptions and quantified as uncertainties of the CT HU to protonstopping power calibration curve. This work supports the accuracy of the protonstopping power implementation in the TPS and implicit the accuracy of patient treatment at HUPTI.

SU-E-T-227: Patient Treatment Quality Assurance for a Uniformly Scanned Proton Therapy Beam

Purpose: To describe the main quality assurance (QA) procedures undertaken at the Hampton University Proton Therapy Institute (HUPTI) in preparation for patient treatment via the uniform scanning (US)proton beam delivery technique using two source to axis distances (SADs). Methods and Materials: HUPTI currently uses a uniformly scanned proton beam for patient treatments. Patient specific apertures and compensators (properly scaled to account for the dual SADs) are used to shape the field laterally and to conform to the target volume longitudinally. Machined part QA is performed by using in‐house software to convert the DICOM output from Eclipse into images which represent the aperture and compensator shapes after correcting for the dual SADs. These images are matched to the physical shapes of the apertures and compensators to ensure correct machining. The beam QA measurements include the absorbed dose (output factor) at the center of the Spread‐Out Bragg Peak (Mid‐SOBP) in accordance with the International Atomic Energy Agencys Report TRS‐398; a verification of the lateral planar dose profile at isocenter measured with a 2D ion chamber array (IBA‐MATRIXX); and the depth dose profile measured along isocenter with a multi‐layer ion chamber (MLIC‐IBA‐ZEBRA). Results: The QA measurements for approximately 30 patients who have been treated at HUPTI utilizing the US technique will be presented. Analysis of the lateral and depth dose profiles exhibits agreement with the Varian Eclipse Proton Treatment Planning System within acceptable limits (less than 2%). Dose measurements are within the 5% accuracy recommended by International Commission on Radiation Units and Measurements (ICRU) and are well described by empirical modeling. Conclusions: The Quality Assurance Program at HUPTI has demonstrated that the prescription of protonradiationdose designed by the radiationoncology team is being delivered to each cancer patient under our care with the highest precision and accuracy possible.

SU‐FF‐T‐19: Accelerated Partial Breast Irradiation With Shielded MammoSite‐Type Applicator

Purpose: We propose a method to improve delivery of APBI and therefore improve patient access to BCT. Method and Materials: BCT in conjunction with accelerated partial breast irradiation (APBI), using for instance the Hologic MammoSite applicator, is becoming popular due to the good dose distribution, and relatively short five day treatment procedure. Brachytherapy‐based APBI procedures typically work by implanting a double lumen balloon catheter in the lumpectomy cavity of breast following surgery. The balloon is inflated with an iodine‐based material mixed with saline. If the skin to balloon distance is less than 7mm, the procedure may not be recommended due to adverse skin reactions leading to poor cosmesis. This problem could be avoided by partially shielding the radiation dose to the skin by introducing a thin layer of high density material (high Z powder) inside the balloon catheter. In this case, the metalpowders may be controlled by a relatively weak external magnetic field applied externally to the patient to form an internal shielding layer inside the balloon in the region of concern, thus avoiding radiation damage to the skin.Results: Our preliminary results indicate that if, for example, the skin‐to‐balloon spacing is only 4 mm, when about 2 mm thin layer of ironpowders arranged internally under that segment of surface of the MammoSite balloon will decrease the skindose to an acceptable level. Our laboratory tests show that only a slight magnetic filed is required to bring such a small amount of ferrous powders to controllable configuration. Conclusion: The suggested approach will improve cosmetic outcome for all APBI patients treated, in addition to increasing survival expectancy and minimizing negative side effects.

SU‐FF‐T‐277: Measuring High Energy Neutrons at a 230 MeV Proton Therapy Facility

Purpose: Examine neutron field spectrum and angular distributioncharacteristic to medium‐energy (230 MeV) proton accelerator facilities. Measure effectively the high energyneutron component of the radiation field. Method and Materials: Primary shielding walls in modern proton therapy facilities are typically made of an over 7′ thick of ordinary (2.3 g/cm3) concrete. Our analysis demonstrate that behind such a thick wall in forward direction with respect to the proton beam neutrons with energies greater than 8 MeV still contribute considerably to the total dose. High energyneutron contribution in lateral direction is potentially even larger. Traditionally neutron rem‐meters are designed to have their response function match well an appropriate (ICRP 1990, or NCRP‐38) fluence‐to‐dose conversion function over an energy range extending from thermal (0.025 ev) to 10 MeV. We have performed over thirty measurements of the neutrondose equivalent at various locations in and around a state‐of‐the‐art 230 MeV proton therapy facility using the Wide EnergyNeutron Detection Instrument (WENDI) that has a useful energy response in the energy range from thermal to 5 GeV. Results: We have obtained neutron attenuation lengths in forward and lateral directions from our measurements most appropriate for use at 230 MeV proton therapy facilities (PTFs) and compared our results with some previously published values. We have also obtained a new parameterization for neutron attenuation in the maze suitable for modern PTFs. Conclusion: In surveying and area monitoring modern PTFs the neutron detector of choice must be capable of detecting with sufficient efficiency the high energy component of the neutron field to avoid large dose underestimation in an environment where greater than 8 MeV neutrons may have a significant contribution. New maze attenuation parameterization will provide for adequate maze design in these facilities, where previously used attenuation models provided at best for a marginal maze design.

SU-FF-T-162: Significance of RBE Optimization in Proton Radiotherapy and Its Impact in the Low Energy Treatment Case

Purpose: Current treatment planning systems use a constant Relative Biological Effectiveness (RBE) value of 1.1 for protonradiotherapy treatments ‐ irrespective of the tumor volume, location, tissue type, initial energy of the proton beam or dose/fraction. However, research shows that the RBE value is not constant and it increases significantly in particular, over the distal falloff region of the Bragg peak. Uncertainty associated with both the calculation and effect of dose delivered to the tumor region compels physicians to consider a relatively larger Clinical Treatment Volume (CTV). This error margin may be reduced by incorporating appropriate variable RBE corrections and thereby facilitating optimization of the CTV. Method and Materials: In order to most effectively make use of this treatment modality, we suggest it is important to adopt biological cellular dose response models for tumors for implementation into treatment planning systems. An RBE model based on the existing Microdosimetric‐Kinetic (MKM) based model with a modification in one of its parameters namely beta(p), in the high LET range (20–33 keV per micrometer) can be used for the calculation of biological dose.Results: The described model is able to calculate the biological dose distribution of the clinical proton energies, taking into consideration both the physical and biological parameters of the incoming beam line and tissue type. The models accuracy in RBE calculations and computational speed makes it convenient for implementation purposes. Conclusions: The existing MKM based RBE model, making use of both the linear quadratic and track structure models, is a viable candidate for high energy (>70 MeV) treatments. Similarly, a modified version of this MKM based model has to be used for low energy (∼up to 70 MeV) applications, such as the treatment of ocular tumors.