N Paudel

Estimation of the risk of secondary malignancy arising from whole-breast irradiation: comparison of five radiotherapy modalities, including TomoHDA

The risk of secondary cancer from radiation treatment remains a concern for long-term breast cancer survivors, especially those treated with radiation at the age younger than 45 years. Treatment modalities optimally maximize the dose delivery to the tumor while minimizing radiation doses to neighboring organs, which can lead to secondary cancers. A new TomoTherapy treatment machine, TomoHDATM, can treat an entire breast with two static but intensity-modulated beams in a slice-by-slice fashion. This feature could reduce scattered and leakage radiation doses. We compared the plan quality and lifetime attributable risk (LAR) of a second malignancy among five treatment modalities: three-dimensional conformal radiation therapy, field-in-field forward-planned intensity-modulated radiation therapy, inverse-planned intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, and TomoDirect mode on the TomoHDA system. Ten breast cancer patients were selected for retrospective analysis. Organ equivalent doses, plan characteristics, and LARs were compared. Out-of-field organ doses were measured with radio-photoluminescence glass dosimeters. Although the IMRT plan provided overall better plan quality, including the lowest probability of pneumonitis, it caused the second highest LAR. The TomoTherapy plan provided plan quality comparable to the IMRT plan and posed the lowest total LAR to neighboring organs. Therefore, it can be a better treatment modality for younger patients who have a longer life expectancy.

A novel property of gold nanoparticles: Free radical generation under microwave irradiation

PURPOSE Gold nanoparticles (GNPs) are known to be effective mediators in microwave hyperthermia. Interaction with an electromagnetic field, large surface to volume ratio, and size quantization of nanoparticles (NPs) can lead to increased cell killing beyond pure heating effects. The purpose of this study is to explore the possibility of free radical generation by GNPs in aqueous media when they are exposed to a microwave field. METHODS A number of samples with 500 mM 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in 20 ppm GNP colloidal suspensions were scanned with an electron paramagnetic resonance (EPR)/electron spin resonance spectrometer to generate and detect free radicals. A fixed (9.68 GHz) frequency microwave from the spectrometer has served for both generation and detection of radicals. EPR spectra obtained as first derivatives of intensity with the spectrometer were double integrated to get the free radical signal intensities. Power dependence of radical intensity was studied by applying various levels of microwave power (12.5, 49.7, and 125 mW) while keeping all other scan parameters the same. Free radical signal intensities from initial and final scans, acquired at the same power levels, were compared. RESULTS Hydroxyl radical (OH⋅) signal was found to be generated due to the exposure of GNP-DMPO colloidal samples to a microwave field. Intensity of OH⋅ signal thus generated at 12.5 mW microwave power for 2.8 min was close to the intensity of OH⋅ signal obtained from a water-DMPO sample exposed to 1.5 Gy ionizing radiation dose. For repeated scans, higher OH⋅ intensities were observed in the final scan for higher power levels applied between the initial and the final scans. Final intensities were higher also for a shorter time interval between the initial and the final scans. CONCLUSIONS Our results observed for the first time demonstrate that GNPs generate OH⋅ radicals in aqueous media when they are exposed to a microwave field. If OH⋅ radicals can be generated close to deoxyribonucleic acid of cells by proper localization of NPs, NP-aided microwave hyperthermia can yield cell killing via both elevated temperature and free radical generation.

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors

Abstract Introduction: Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear–quadratic cell survival model. Material and Methods: HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. Results: The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1–5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2t) value of 0·5. In addition, the mean ± SD of TR values for SF2t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2t value of 0.5. Conclusion: HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

Helical tomotherapy to LINAC plan conversion utilizing RayStation Fallback planning

Abstract RaySearch RayStation Fallback (FB) planning module can generate an equivalent backup radiotherapy treatment plan facilitating treatment on other linear accelerators. FB plans were generated from the RayStation FB module by simulating the original plan target and organ at risk (OAR) dose distribution and delivered in various backup linear accelerators. In this study, helical tomotherapy (HT) backup plans used in Varian TrueBeam linear accelerator were generated with the RayStation FB module. About 30 patients, 10 with lung cancer, 10 with head and neck (HN) cancer, and 10 with prostate cancer, who were treated with HT, were included in this study. Intensity‐modulated radiotherapy Fallback plans (FB‐IMRT) were generated for all patients, and three‐dimensional conformal radiotherapy Fallback plans (FB‐3D) were only generated for lung cancer patients. Dosimetric comparison study evaluated FB plans based on dose coverage to 95% of the PTV volume (R95), PTV mean dose (Dmean), Paddicks conformity index (CI), and dose homogeneity index (HI). The evaluation results showed that all IMRT plans were statistically comparable between HT and FB‐IMRT plans except that PTV HI was worse in prostate, and PTV R95 and HI were worse in HN multitarget plans for FB‐IMRT plans. For 3D lung cancer plans, only the PTV R95 was statistically comparable between HT and FB‐3D plans, PTV Dmean was higher, and CI and HI were worse compared to HT plans. The FB plans using a TrueBeam linear accelerator generally offer better OAR sparing compared to HT plans for all the patients. In this study, all cases of FB‐IMRT plans and 9/10 cases of FB‐3D plans were clinically acceptable without further modification and optimization once the FB plans were generated. However, the statistical differences between HT and FB‐IMRT/3D plans might not be of any clinically significant. One FB‐3D plan failed to simulate the original plan without further optimization.

Thin-film CdTe detector for microdosimetric study of radiation dose enhancement at gold-tissue interface.

Presence of interfaces between high and low atomic number (Z) materials, often encountered in diagnostic imaging and radiation therapy, leads to radiation dose perturbation. It is characterized by a very narrow region of sharp dose enhancement at the interface. A rapid falloff of the dose enhancement over a very short distance from the interface makes the experimental dosimetry nontrivial. We use an in-house-built inexpensive thin-film Cadmium Telluride (CdTe) photodetector to study this effect at the gold-tissue interface and verify our experimental results with Monte Carlo (MC) modeling. Three-micron thick thin-film CdTe photodetectors were fabricated in our lab. One-, ten- or one hundred-micron thick gold foils placed in a tissue-equivalent-phantom were irradiated with a clinical Ir-192 high-dose-rate (HDR) source and current measured with a CdTe detector in each case was compared with the current measured for all uniform tissue-equivalent phantom. Percentage signal enhancement (PSE) due to each gold foil was then compared against MC modeled percentage dose enhancement (PDE), obtained from the geometry mimicking the experimental setup. The experimental PSEs due to 1, 10, and 100 μm thick gold foils at the closest measured distance of 12.5 μm from the interface were 42.6±10.8, 137.0±11.9, and 203.0±15.4, respectively. The corresponding MC modeled PDEs were 38.1±1., 164±1, and 249±1, respectively. The experimental and MC modeled values showed a closer agreement at the larger distances from the interface. The dose enhancement in the vicinity of gold-tissue interface was successfully measured using an in-house-built, high-resolution CdTe-based photodetector and validated with MC simulations. A close agreement between experimental and the MC modeled results shows that CdTe detector can be utilized for mapping interface dose distribution encountered in the application of ionizing radiation. PACS number(s): 29.40.Wk, 73.50.Pz, 87.53.Jw, 87.55.K.Presence of interfaces between high and low atomic number (Z) materials, often encountered in diagnostic imaging and radiation therapy, leads to radiation dose perturbation. It is characterized by a very narrow region of sharp dose enhancement at the interface. A rapid falloff of dose enhancement over a very short distance from the interface makes the experimental dosimetry nontrivial. We use an in‐house‐built inexpensive thin‐film Cadmium Telluride (CdTe) photodetector to study this effect at the gold‐tissue interface and verify our experimental results with Monte Carlo (MC) modeling. Three‐micron thick thin‐film CdTe photodetectors were fabricated in our lab. One‐, ten‐ or one hundred‐micron thick gold foils placed in a tissue‐equivalent‐phantom were irradiated with a clinical Ir‐192 high‐dose‐rate (HDR) source and current measured with a CdTe detector in each case was compared with the current measured for all uniform tissue‐equivalent phantom. Percentage signal enhancement (PSE) due to each gold foil was then compared against MC modeled percentage dose enhancement (PDE), obtained from the geometry mimicking the experimental setup. The experimental PSEs due to 1, 10, and 100 μm thick gold foils at the closest measured distance of 12.5 μm from the interface were 42.6±10.8, 137.0±11.9, and 203.0±15.4, respectively. The corresponding MC modeled PDEs were 38.1±1., 164±1, and 249±1, respectively. The experimental and MC modeled values showed a closer agreement at the larger distances from the interface. The dose enhancement in the vicinity of gold‐tissue interface was successfully measured using an in‐house‐built, high‐resolution CdTe‐based photodetector and validated with MC simulations. A close agreement between experimental and the MC modeled results shows that CdTe detector can be utilized for mapping interface dose distribution encountered in the application of ionizing radiation. PACS number(s): 29.40.Wk, 73.50.Pz, 87.53.Jw, 87.55.K‐

SU‐E‐T‐346: Effect of Jaw Position On Dose to Critical Structures in 3‐D Conformal Radiotherapy Treatment of Pancreatic Cancer

Purpose: Three-dimensional conformal therapy remains a valid and widely used modality for pancreatic radiotherapy treatment. It usually meets dose constraints on critical structures. However, careful positioning of collimation jaws can reduce dose to the critical structures. Here we investigate the dosimetric effect of jaw position in MLC-based 3-D conformal treatment planning on critical structures. Methods: We retrospectively selected seven pancreatic cancer patients treated with 3-D conformal radiotherapy. We started with treatment plans (Varian Truebeam LINAC, Eclipse TPS, AAA, 18MV) having both x and y jaws aligned with the farthest extent of the block outline (8mm around PTV). Then we subsequently moved either both x-jaws or all x and y jaws outwards upto 3 cm in 1 cm increments and investigated their effect on average and maximum dose to neighboring critical structures keeping the same coverage to treatment volume. Results: Lateral displacement of both x-jaws by 1cm each increased kidney and spleen mean dose by as much as 1.7% and 1.3% respectively and superior inferior displacement increased liver, right kidney, stomach and spleen dose by as much as 2.1%, 2%, 5.2% and 1.6% respectively. Displacement of all x and y-jaws away by 1cm increased the mean dose to liver, right kidney, left kidney, bowels, cord, stomach and spleen by as much as 4.9%, 5.9%, 2.1%, 2.8%, 7.4%, 10.4% and 4.2% respectively. Percentage increase in mean dose due to 2 and 3cm jaw displacement increased almost linearly with the displaced distance. Changes in maximum dose were much smaller (mostly negligible) than the changes in mean dose. Conclusion: Collimation jaw position affects dose mostly to critical structures adjacent to it. Though treatment plans with MLCs conforming the block margin usually meet dose constraints to critical structures, keeping jaws all the way in, to the edge of the block reduces dose to the critical structures during radiation treatment.

WE-G-BRE-05: Nanoparticle-Aided Microwave Hyperthermia Is Accompanied By Free Radical Generation and Enhanced Cell Kill

PURPOSE Hyperthermia, an established method of cancer treatment used in adjuvant to radiation and chemotherapy, can utilize metallic nanoparticles (NPs) for tumor heating with a microwave electromagnetic field. The high surface-area-to-volume ratio of nanoparticles makes them effective catalysts for free radical generation, thus amplifying the cell-killing effect of hyperthermia. We explore the effect of gold and platinum NPs in generating free radicals in aqueous media under a microwave field. METHODS Spin trap 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was mixed separately with 3.2 nm Mesogold and Mesoplatinum colloidal nanoparticle suspensions in deionized water to trap radicals. The mixtures were injected into a number of glass capillaries and exposed to the 9.68GHz microwave field of an electron paramagnetic resonance (EPR) spectrometer. The microwave radiation from the spectrometer served to both generate and detect the trapped radicals. Each sample was scanned at 12mW microwave power to obtain the initial signal of hydroxyl radicals (OH.), then at 39.8mW followed by 79.8 or 125mW, and finally re-scanned at 12mW. Radical signal intensities obtained by double integration of EPR spectra from the initial and the final scans were then compared. RESULTS Nanoparticle samples had no intentionally-added free radicals before the initial measurement. While samples with DMPO-water solution showed no OH. signal, all those with AuNPs or PtNPs developed an OH. signal during their first exposure to the microwave field. Depending upon the applied microwave power and time interval between the initial and the final EPR scans, an OH. intensity increase of ∼10-60% was found. This contradicts the typical trend of exponential decay of the OH. signal with time. CONCLUSION The consistent increase in OH. intensity establishes that gold and platinum nanoparticles facilitate free radical generation under microwave irradiation. Our results suggest that NP-aided hyperthermia is accompanied by the generation of free radicals, which enhance the cell-killing effects of hyperthermia.

Study of Image Qualities From 6D Robot–Based CBCT Imaging System of Small Animal Irradiator:

Purpose: To assess the quality of cone beam computed tomography images obtained by a robotic arm-based and image-guided small animal conformal radiation therapy device. Method and Materials: The small animal conformal radiation therapy device is equipped with a 40 to 225 kV X-ray tube mounted on a custom made gantry, a 1024 × 1024 pixels flat panel detector (200 μm resolution), a programmable 6 degrees of freedom robot for cone beam computed tomography imaging and conformal delivery of radiation doses. A series of 2-dimensional radiographic projection images were recorded in cone beam mode by placing and rotating microcomputed tomography phantoms on the “palm’ of the robotic arm. Reconstructed images were studied for image quality (spatial resolution, image uniformity, computed tomography number linearity, voxel noise, and artifacts). Results: Geometric accuracy was measured to be 2% corresponding to 0.7 mm accuracy on a Shelley microcomputed tomography QA phantom. Qualitative resolution of reconstructed axial computed tomography slices using the resolution coils was within 200 μm. Quantitative spatial resolution was found to be 3.16 lp/mm. Uniformity of the system was measured within 34 Hounsfield unit on a QRM microcomputed tomography water phantom. Computed tomography numbers measured using the linearity plate were linear with material density (R 2 > 0.995). Cone beam computed tomography images of the QRM multidisk phantom had minimal artifacts. Conclusion: Results showed that the small animal conformal radiation therapy device is capable of producing high-quality cone beam computed tomography images for precise and conformal small animal dose delivery. With its high-caliber imaging capabilities, the small animal conformal radiation therapy device is a powerful tool for small animal research.

Dosimetric and radiobiological comparison for quality assurance of IMRT and VMAT plans

Abstract Introduction The gamma analysis used for quality assurance of a complex radiotherapy plan examines the dosimetric equivalence between planned and measured dose distributions within some tolerance. This study explores whether the dosimetric difference is correlated with any radiobiological difference between delivered and planned dose. Methods VMAT or IMRT plans optimized for 14 cancer patients were calculated and delivered to a QA device. Measured dose was compared against planned dose using 2‐D gamma analysis. Dose volume histograms (for various patient structures) obtained by interpolating measured data were compared against the planned ones using a 3‐D gamma analysis. Dose volume histograms were used in the Poisson model to calculate tumor control probability for the treatment targets and in the Sigmoid dose–response model to calculate normal tissue complication probability for the organs at risk. Results Differences in measured and planned dosimetric data for the patient plans passing at ≥94.9% rate at 3%/3 mm criteria are not statistically significant. Average ± standard deviation tumor control probabilities based on measured and planned data are 65.8±4.0% and 67.8±4.1% for head and neck, and 71.9±2.7% and 73.3±3.1% for lung plans, respectively. The differences in tumor control probabilities obtained from measured and planned dose are statistically insignificant. However, the differences in normal tissue complication probabilities for larynx, lungs‐GTV, heart, and cord are statistically significant for the patient plans meeting ≥94.9% passing criterion at 3%/3 mm. Conclusion A ≥90% gamma passing criterion at 3%/3 mm cannot assure the radiobiological equivalence between planned and delivered dose. These results agree with the published literature demonstrating the inadequacy of the criterion for dosimetric QA and suggest for a tighter tolerance.

TU-H-BRC-07: Therapeutic Benefit in Spatially Fractionated Radiotherapy (GRID) Using Helical Tomotherapy

PURPOSE The aim of this project is to study the therapeutic ratio (TR) for helical Tomotherapy (HT) based spatially fractionated radiotherapy (GRID). Estimation of TR was based on the linear-quadratic cell survival model by comparing the normal cell survival in a HT GRID to that of a uniform dose delivery in an open-field for the same tumor survival. METHODS HT GRID plan was generated using a patient specific virtual GRID block pattern of non-divergent, cylinder shaped holes using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT GRID irradiation to an open field irradiation with an equivalent dose that result in the same tumor cell SF. The ratio was estimated from DVH data on ten patient plans with deep seated, bulky tumor approved by the treating radiation oncologist. Dependence of the TR values on radio-sensitivity of the tumor cells and prescription dose were also analyzed. RESULTS The mean ± standard deviation (SD) of TR was 4.0±0.7 (range: 3.1 to 5.5) for the 10 patients with single fraction dose of 20 Gy and tumor cell SF of 0.5 at 2 Gy. In addition, mean±SD of TR = 1±0.1 and 18.0±5.1 were found for tumor with SF of 0.3 and 0.7, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the TR to 2.0±0.2 and 1.2±0.04 for a tumor cell SF of 0.5 at 2 Gy. In this study, the SF of normal cells was assumed to be 0.5 at 2 Gy. CONCLUSION HT GRID displayed a significant therapeutic advantage over uniform dose from an open field irradiation. TR increases with the radioresistance of the tumor cells and with prescription dose.