Jerry M. Slater

Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Analysis of a Metalloporphyrin Antioxidant Mimetic (MnTE-2-PyP) as a Radiomitigator: Prostate Tumor and Immune Status

Due to radiation-induced immune depression and development of pathologies such as cancer, there is increasing urgency to identify radiomitigators that are effective when administered after radiation exposure. The main goal of this study was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body exposed to 2 Gy γ-rays (Co-60), i.e., well below a lethal dose, followed by subcutaneous implantation of 5 × 105 RM-9 prostate tumor cells and initiation of MnTE-2-PyP treatment (day 0); interval between each procedure was 1–2 h. The drug was administered daily (12 times). Tumor progression was monitored and immunological analyses were performed on a subset per group on day 12. Animals treated with MnTE-2-PyP alone had significantly slower tumor growth compared to mice that did not receive the drug (P < 0.05), while radiation alone had no effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly increased spleen mass relative to body mass; the numbers of splenic white blood cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes, and platelets, were high compared to one of more of the other groups (P < 0.05). The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated immune parameters, but mitigation of the effects of 2 Gy total-body irradiation were minimal.

Evaluation of normal tissue exposure in patients receiving radiotherapy for pancreatic cancer based on RTOG 0848

BACKGROUNDnPancreatic cancer is a highly aggressive malignancy. Chemoradiotherapy (CRT) is utilized in many cases to improve locoregional control; however, toxicities associated with radiation can be significant given the location of the pancreas. RTOG 0848 seeks to evaluate chemoradiation using either intensity-modulated radiation therapy (IMRT) or 3D conformal photon radiotherapy (3DCRT) modalities as an adjuvant treatment. The purpose of this study is to quantify the dosimetric changes seen when using IMRT or 3D CRT photon modalities, as well as proton radiotherapy, in patients receiving CRT for cancer of the pancreas treated per RTOG 0848 guidelines.nnnMATERIALSnTen patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using IMRT and 3DCRT as well as proton radiotherapy were created for each patient. All planning volumes were created per RTOG 0848 protocol. Dose-volume histograms (DVH) were calculated and analyzed in order to compare plans between the three modalities. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord.nnnRESULTSnThere was no difference between the IMRT and 3DCRT plans in dose delivered to the kidneys, liver, or bowel. The proton radiotherapy plans were found to deliver lower mean total kidney doses, mean liver doses, and liver D1/3 compared to the IMRT plans. The proton plans also gave less mean liver dose, liver D1/3, bowel V15, and bowel V50 in comparison to the 3DCRT.nnnCONCLUSIONSnFor patients receiving radiotherapy per ongoing RTOG 0848 for pancreatic cancer, there was no significant difference in normal tissue sparing between IMRT and 3DCRT treatment planning. Therefore, the choice between the two modalities should not be a confounding factor in this study. The proton plans also demonstrated improved OAR sparing compared to both IMRT and 3DCRT treatment plans.

Correction: Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space

[This corrects the article on p. e75097 in vol. 8.].

Protons Offer Reduced Tissue Exposure for Patients Receiving Radiation Therapy for Pancreatic Cancer

Abstract Purpose: Pancreatic cancer is a highly aggressive malignancy. Chemoradiation therapy (CRT) is used in many cases to improve local-regional control; however, toxicities associated with radiation can be significant given the location of the pancreas. The purpose of this study is to quantify the dosimetric changes seen when using photons or protons in patients receiving CRT for cancer of the pancreas. Patients and Methods: Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients underwent simulation with contrast-enhanced computed tomography imaging. Separate treatment plans using proton radiation therapy, intensity-modulated radiation therapy, and 3-dimensional photon radiation therapy modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the 3 modalities. The organs at risk evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statis...

TU-H-CAMPUS-TeP1-03: Magnetically Focused Proton Irradiation of Small Volume Radiosurgery Targets

PURPOSEnTo investigate the use of magnetic focusing for small volume proton radiosurgery targets using a triplet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies METHODS: Fourteen quadrupole magnets consisting of 24 segments of radiation hard samarium-cobalt adhered into k=3 Halbach cylinders with various field gradients (100 to 250 T/m) were designed and manufactured. Triplet combinations of the magnets were placed on a positioning track on our Gantry 1 treatment table. Unmodulated 127 MeV proton beams with initial diameters of 3 to 20 mm were delivered to a water tank using single-stage scattering. Depth and transverse dose distributions were measured using a PTW PR60020 diode detector and EBT3 film, respectively. This data was compared with unfocused passively collimated beams. Monte Carlo simulations were also performed - both for comparison with experimental data and to further investigate the potential of triplet magnetic focusing.nnnRESULTSnExperimental results using 150 T/m gradient magnets and 15 to 20 mm initial diameter beams show peak to entrance dose ratios that are ∼ 43 to 48 % larger compared with spot size matched 8 mm collimated beams (ie, transverse profile full-widths at 90% maximum dose match within 0.5 mm of focused beams). In addition, the focusing beams were ∼ 3 to 4.4 times more efficient per MU in dose to target delivery. Additional results using different magnet combinations will also be presented.nnnCONCLUSIONnOur results suggest that triplet magnetic focusing could reduce entrance dose and beam number while delivering dose to small (∼≤ 10 mm diameter) radiosurgery targets in less time compared to unfocused beams. Immediate clinical applications include those associated with proton radiosurgery and functional radiosurgery of the brain and spine, however other treatment sites can be also envisioned. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10-1).

SU-F-T-211: Evaluation of a Dual Focusing Magnet System for the Treatment of Small Proton Targets

PURPOSEnTo investigate magnetic focusing for small volume proton targets using a doublet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies METHODS: Monte Carlo computer simulations were performed using the Geant4 toolkit to compare dose depositions of proton beams transported through two focusing magnets or in their absence. Proton beams with energies of 127 MeV and initial diameters of 5, 8 and 10 mm were delivered through two identical focusing magnets similar to those currently in experimental use at Loma Linda University Medical Center. Analogous experiments used optimized configurations based on the simulation results. Dose was measured by a diode detector and Gafchromic EBT3 film and compared to simulation data. Based on results from the experimental data, an additional set of simulations was performed with an initial beam diameter of 18 mm and a two differing length magnets (40mm & 68mm).nnnRESULTSnExperimental data matched well with Monte Carlo simulations. However, under conditions necessary to produce circular beam spots at target depth, magnetically focused beams using two identical 40 mm length magnets did not meet all of our performance criteria of circular beam spots, improved peak to entrance (P/E) dose ratios and dose delivery efficiencies. The simulations using the longer 68 mm 2nd magnet yielded better results with 34% better P/E dose ratio and 20-50% better dose delivery efficiencies when compared to unfocused 10 mm beams.nnnCONCLUSIONnWhile magnetic focusing using two magnets with identical focusing power did not yield desired results, ongoing Monte Carlo simulations suggest that increasing the length of the 2nd magnet to 68 mm could improve P/E dose ratios and dose efficiencies. Future work includes additional experimental validation of the longer 2nd magnet setup as well as experiments with triplet magnet systems. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10-1).

SU‐F‐T‐126: Microdosimetic Evaluation of Proton Energy Distributions in the Vicinity of Metal Implants

PURPOSEnTo evaluate the impact of titanium and surgical stainless steel implants on the microscopic dose distribution in proton treatment plans METHODS: Geant4 Monte Carlo simulations were used to analyze the microdosimetric distribution of proton radiation in the vicinity of 3.1 mm thick CP Grade 4 titanium (Ti) or 316 stainless steel (SS316) plates in a water phantom. Additional simulations were performed using either water, or water with a density equivalent to the respective metals (Tiwater, SS316water) (to reflect common practice in treatment planning). Implants were placed at the COM of SOBPs of 157 MeV (range of ∼15 cm in water) protons with 30 or 60 mm modulation. Primary and secondary particle dose and fluence, frequency-weighted and dose-weighted average lineal energy, average radiation quality factor, dose equivalent and energy deposition histograms in the plate vicinity were compared.nnnRESULTSnPreliminary results show frequency-weighted (yf) and dose-weighted lineal energy (yd) was increased downstream of the Ti plate (yf = 3.1 keV/µm; yd = 5.5 keV/µm) and Tiwater (yf = 4.1 keV/µm; yd = 6.8 keV/µm) compared to that of water (ie, the absence of a plate) (yf = 2.5 keV/µm; yd = 4.5 keV/µm). In addition, downstream proton dose deposition was also elevated due to the presence of the Ti plate or Tiwater. The additional dose deposited at higher lineal energy implies that tissues downstream of the plate will receive a higher dose equivalent. Detailed analyses of the Ti, Tiwater, SS316, and SS316 water simulations will be presented.nnnCONCLUSIONnThe presence of high-density materials introduces changes in the spatial distribution of radiation in the vicinity of an implant. Further work quantifying these effects could be incorporated into future treatment planning systems resulting in more accurate treatment plans. This project was sponsored with funding from the Department of Defense (DOD # W81XWH-10-2-0192).

SU-E-T-239: Design and Evaluation of a Nozzle Shielding System in Passively Scattered Proton Therapy

Purpose: To design, implement and evaluate a shielding system that will reduce out-of-field dose experienced by the patient and associated electronic systems in passively scattered proton therapy treatment. Methods: A multi-stage neutron shielding system was retrofitted to the Gantry 1 treatment nozzle at Loma Linda University Medical Center. The system uses multiple borated polyethylene plates staged after the primary beam modifying devices to attenuate and absorb neutrons produced by such devices. This arrangement locates increasing levels of shielding between the sources of secondary particles in the nozzle and the patient. Additionally, the design of this shielding structure allows it to be easily retrofitted to an existing proton nozzle system without impacting design or treatment beam characteristics. The effectiveness of the shielding was evaluated both through experimental measurements and Geant4 Monte Carlo simulations. Results: Measurements were completed with Landauer Luxel+ dosimeters that use optically stimulated luminescence and CR-39 to detect fast neutrons, thermal neutrons, protons, photons and beta particles. Measurements of a 250 MeV proton beam indicated that the shielding system reduced out-of-field dose to the patient by almost half with dose equivalent values at 50 and 40 cm from the field edge decreasing from 0.965 and 1.262 mSv/Gy to 0.596 and 0.777 mSv/Gy respectively. The installation of the multi-stage shielding system also reduced dose equivalent experienced by electronic systems installed in the treatment room by up to 80%. Geant4 simulations were also used to evaluate the neutron fluence at various positions in the treatment room as well as provide information on microdosimetry spectra within the patient and treatment room. Conclusion: The shielding system described above proved to be an effective an inexpensive method of reducing out-of-field doses to the patient and electronic systems and can be easily retrofitted to existing passive scattering nozzles.

SU-E-T-446: Evaluation of the Dosimetric Properties of a Diode Detector to Proton Radiosurgery

PURPOSEnTo test the PTW PR60020 proton dosimetry diode in radiation fields relevant to proton radiosurgery applications and evaluate its suitability as a high resolution, real time dosimetry device.nnnMETHODSnData was collected using our standard nominal radiosurgery energies of 126 MeV and 155 MeV through a single stage scattering system, corresponding to a range of 9.7 and 15 cm in water respectively. Various beam modulations were tested as part of this study. Depth dose and beam profile measurements were completed with the PTW PR60020 dosimetry diode with comparative measurements using a PTW Markus ionization chamber and EBT2 Gafchromic film. Monte Carlo simulations were also completed for comparison.nnnRESULTSnThe single 1 mm2 by 20 μm thick sensitive volume allowed for high spatial resolution measurements while maintaining sufficient sensitive volume to ensure that measurements could be completed without excessive beam delivery. Depth dose profiles exhibited negligible LET dependence which typically impacts film and other solid state dosimetry devices, while beam ranges measured with the PTW diode were within 1 mm of ion chamber data. In an edge on arrangement beam profiles were also measured within 0.5 mm full-width at half-maximum at various depths as compared to film and simulation data.nnnCONCLUSIONnThe PTW PR60020 proved to be a very useful radiation metrology apparatus for proton radiosurgery applications. Its waterproof and rugged construction allowed for easy deployment in phantoms or water tanks that are commonly used in proton radiosurgery QA. Dosimetrically, the diode exhibited negligible LET dependence as a function of depth, while in edge on arrangement to the incident proton beam it facilitated the measurement of beam profiles with a spatial resolution comparable to both Monte Carlo and film measurements. This project was sponsored in part by funding from the Department of Defense (DOD# W81XWH-BAA-10-1).