J Ha

Feasibility of delivering grid therapy using a multileaf collimator

The feasibility of using a multileaf collimator (MLC) for grid therapy is demonstrated in this study. Grids with the projected field openings of 10 mm x 10 mm and 5 mm x 5 mm were created using multiple MLC-shaped fields. The deposited doses were measured with films at different depths in a solid water phantom and compared to those of Cerrobend grid collimators of similar hole sizes and hole separations. At the depth of maximum dose (dmax), the valley-to-peak dose ratios of the MLC grids were found to be about 11% and 19% for the respective 10 mm x 10 mm and 5 mm X 5 mm grid openings, and those of the corresponding grid blocks were about 15% and 20%. To quantify the dose contributed by transmission in the blocked areas due to the limited leaf thickness, Monte Carlo simulations (based on convolution/superposition method) were performed to calculate the doses in the solid water phantom using an ideal MLC with no leakage and perfect divergence in both the leaf end and side. About 7% reduction in the valley-to-peak dose ratio was found for both grid sizes at dmax. The results clearly showed that MLCs can be used to provide grid treatments with at least as good dosimetric properties as those of the Cerrobend grid blocks, though the former would in general require a longer delivery time.

On the sources of drift in a turbine-based spirometer

A systematic study on the sources of drift in a turbine-based spirometer (VMM-400) is presented. The study utilized an air-tight cylinder to pump air through the spirometer in a precise and programmable manner. Factors contributing to the drift were isolated and quantified. The drift due to imbalance in the electronics and the mechanical blade increased from 1% per breathing cycle to as much as 10% when the flow rate decreased from 0.24 to 0.08 l s(-1). A temperature difference of 16 degrees between the ambient and the air in the cylinder contributed about 3.5%. Most significantly, a difference in the breathing between inhalation and exhalation could produce a drift of 40% per breathing cycle, or even higher, depending on the extent of the breathing asymmetry. The origin of this drift was found to be rooted in the differential response of the spirometer to the different flow rate. Some ideas and suggestions for a correction strategy are provided for future work. The present work provides an important first step for eventual utilization of a spirometer as a stand-alone breathing surrogate for gating or tracking radiation therapy.

Effects of tumor motion in GRID therapy

Clinical and biological evidence suggest that the success of GRID therapy in debulking large tumors depends on the high peak-to-valley contrast in the dose distribution. In this study, we show that the peaks and valleys can be significantly blurred out by respiration-induced tumor motion, possibly affecting the clinical outcome. Using a kernel-based Monte Carlo dose engine that incorporates phantom motion, we calculate the dose distributions for a GRID with hexagonally arranged holes. The holes have a diameter of 1.3 cm and a minimum center-to-center separation of 2.1 cm (projected at the isocenter). The phantom moves either in the u parallel direction, which is parallel to a line joining any two nearest neighbors, or in the perpendicular u perpendicular direction. The displacement-time waveform is modeled with a cosn function, with n assigned 1 for symmetric motion, or 6 to simulate a large inhale-exhale asymmetry. Dose calculations are performed on a water phantom for a 6 MV x-ray beam. Near dmax, the static valley dose is 0.12D0, where D0 is the peak static dose. For motion in the u parallel direction, the peak and valley doses vary periodically with the amplitude of motion a and the transverse dose profiles are maximally flat near a=0.8 cm and a=1.9 cm. For the cos waveform, the minimum peak dose (Dpmin) is 0.67D0 and the maximum valley dose (Dvmax) is 0.60D0. Less dose blurring is seen with the cos6 waveform, with Dpmin=0.77D0 and Dvmax=0.45D0. For motion in the u perpendicular direction, the maximum flattening of dose profiles occurs at a=1.5 cm. GRIDs with smaller hole separations produce similar blurring at proportionally smaller amplitudes. The reported clinical response data from GRID therapy seem to indicate that mobile tumors, such as those in the thorax and abdomen, respond worse to GRID treatments than stationary tumors, such as those in the head and neck. To establish a stronger correlation between clinical response and tumor motion, and possibly improve the clinical response rates, it is recommended that prospective GRID therapy trials be conducted with motion compensation strategies, such as respiratory gating.

Scintillation Yield Estimates of Colloidal Cerium-Doped LaF3 Nanoparticles and Potential for “Deep PDT”

A hybrid of radiotherapy and photodynamic therapy (PDT) has been proposed in previously reported studies. This approach utilizes scintillating nanoparticles to transfer energy to attached photosensitizers, thus generating singlet oxygen for local killing of malignant cells. Its effectiveness strongly depends upon the scintillation yield of the nanoparticles. Using a liquid scintillator as a reference standard, we estimated the scintillation yield of Ce0.1La0.9F3/LaF3 core/shell nanoparticles at 28.9 mg/ml in water to be 350 photons/MeV under orthovoltage X-ray irradiation. The subsequent singlet oxygen production for a 60 Gy cumulative dose to cells was estimated to be four orders of magnitude lower than the “Niedre killing dose,” used as a target value for effective cell killing. Without significant improvements in the radioluminescence properties of the nanoparticles, this approach to “deep PDT” is likely to be ineffective. Additional considerations and alternatives to singlet oxygen are discussed.

Evidence of energy transfer in nanoparticle-porphyrins conjugates for radiation therapy enhancement

We report progress towards combining radiation therapy (RT) and photodynamic therapy (PDT) using scintillating nanoparticle (NP)-photosensitizer conjugates. In this approach, scintillating NPs are excited by clinically relevant ionizing radiation sources and subsequently transfer energy to conjugated photosensitizers via FRET, acting as an energy mediator between ionizing radiation and photosensitizer molecules. The excited photosensitizers generate reactive oxygen species that can induce local damage and immune response. Advantages of the scheme include: 1) Compared with traditional radiation therapy, a possible decrease of the total radiation dose needed to eliminate the lesion; 2) Compared with traditional PDT, the ability to target deeper and more highly pigmented lesions; 3) The possibility of additional photosensitizing effects due to the scintillation of the nanoparticles. In this work, the photosensitizer molecule chlorin e6 was covalently bound to the surface of LaF3:Ce NPs. After conjugation, the photoluminescence intensity of NPs decreased, and fluorescence lifetime of conjugated chlorin e6 became sensitive to excitation wavelength, suggesting rapid FRET. In addition, scintillation spectra of nanoparticles were measured. Preliminary calculations suggest that the observed scintillation efficiencies are sufficient to enhance RT. In vitro cancer cell studies suggest conjugates are taken up by cells. Survival curves with radiation exposure suggest that the particles alone cause radiosensitization comparable to that seen with gold nanoparticles.

SU-F-T-76: Total Skin Electron Therapy: An-End-To-End Examination of the Absolute Dosimetry with a Rando Phantom

PURPOSE To examine and validate the absolute dose for total skin electron therapy (TSET) through an end-to-end test with a Rando phantom using optically stimulated luminescent dosimeters (OSLDs) and EBT3 radiochromic films. METHODS A Varian Trilogy linear accelerator equipped with the special procedure 6 MeV HDTSe- was used to perform TSET irradiations using a modified Stanford 6-dual-field technique. The absolute dose was calibrated using a Markus ion chamber at a reference depth of 1.3cm at 100 cm SSD with a field size of 36 × 36 cm at the isocenter in solid water slabs. The absolute dose was cross validated by a farmer ion chamber. Then the dose rate in the unit of cGy/Mu was calibrated using the Markus chamber at the treatment position. OSLDs were used to independently verify the dose using the calibrated dose rate. Finally, a patient treatment plan (200 cGy/cycle) was delivered in the QA mode to a Rando phantom, which had 16 pairs of OSLDs and EBT3 films taped onto its surface at different anatomical positions. The doses recorded were read out to validate the absolute dosimetry for TSET. RESULTS The OSLD measurements were within 7% agreement with the planned dose except the shoulder areas, where the doses recorded were 23% lower on average than those of the planned. The EBT3 film measurements were within 10% agreement with the planned dose except the shoulder and the scalp vertex areas, where the respective doses recorded were 18% and 14% lower on average than those of the planned. The OSLDs gave more consistent dose measurements than those of the EBT3 films. CONCLUSION The absolute dosimetry for TSET was validated by an end-to-end test with a Rando phantom using the OSLDs and EBT3 films. The beam calibration and monitor unit calculations were confirmed.

SU‐F‐T‐88: Field's Metal for Electron Beam Inserts and Blocks

PURPOSE The aim of this work is to show that Fields metal can be used as a viable alternative material to lead-based low-melting temperature alloys (e.g., Cerrobend) for electron beam inserts and blocks. The goal is to eliminate exposure risks associated with lead and cadmium. METHODS Fields metal (51% Indium, 32.5% Bismuth, 16.5% Tin) is a low-melting point eutectic alloy, and is proposed as a lead-free replacement for Cadmium-free alloy (52.5% Bismuth, 32% Lead, 15.5% Tin). The experiments were done using a Varian 21EX linac equipped with 6, 9, 12, and 16 MeV beams. The 10×10 cone was used with 1.8cm thick insert made of Fields metal, Cd-Free alloy or open field. The transmitted radiation was measured using a diode at various depths in water. Block transmission factor (BTF) is determined as the ratio of maximum transmission radiation dose over the dose at dmax of the open field. RESULTS The data shows BTFs for both alloys are very similar, well below 5% for 6, 9, and 12 MeV beams. For 16 MeV, the BTF of the Fields metal is about 5.3%; the Cd-free metal 4.2%. The peak dose of the transmitted radiation occurs less than 1 cm below the water surface, at a much shallower depth than the dmax of the electron beam in the open field. The beam profile shows the maximum block transmission is along the central axis of the beam. CONCLUSION The present study shows that Fields metal can be used to make electron cutouts and blocks for 6, 9, 12, and 16 MeV beams. Because it has a similar density as other lead-based alloys, the same thickness of Fields metal would be adequate for shielding the electron beams. This means that it can be used as a replacement without modification to the existing block holder.

WE‐C‐AUD B‐07: Comparison of Time‐Fractionated and Space‐Fractionated Radiotherapy

Purpose: To study the potential advantage of space‐fractionation (SF) over time‐fractionation (TF) in radiotherapy.Method and Materials: The back skin of mouse was stretched and fixed with two thin titanium plates, exposing a circular window of 1.5cm in diameter. Tumor cells were implanted at the center of the window. When the tumor grew to 6mm, the window was irradiated with either TF or SF schemes: open field irradiation of 13Gy per fraction each day for four days for 52Gy total dose; or 52Gy per fraction through 2mm×2mm grid covering 25% of the open field, but then shifting the grid each day to a previously untreated area so that the entire window received an acute dose of 52Gy over four days. The animals were observed for 51 days and the number of hair within the irradiation window was counted after the mice were euthanized. Results: 17 animals in the TF arm and 12 in the SF arm completed the study. After four days of irradiation, the tumors shrank to completely disappear within 2–3 days for both cohorts. Similar skin reaction and complete fur loss on both sides of the window were observed for both arms. The fur started to grow back at 4 weeks and was white rather than the original gray color. On the beam entry side, the average number of fur was 452 for the TF arm and 860 for the SF arm (p=0.0003). On the beam exit side, the number of fur strands was 223 for the TF arm and 730 for the SF arm (p=0.0001). These results strongly indicate less skin damage with SF. Conclusion: SF allowed us to deliver a higher acute dose but showed much less late‐term normal tissue toxicities. The results show strong evidence that SF has protective effects to normal structures.

SU‐GG‐T‐510: Dose Smearing in GRID Therapy Due to Tumor Motion

Purpose: Clinical and biological evidence suggests that GRID therapy is successful in debulking large tumors because of the high heterogeneity in the dose distribution. In this paper we show that the characteristic peaks and valleys are significantly smeared out by motion, possibly affecting clinical outcomes. Method and Materials: Using a Monte Carlo engine that emulates phantom motion, we calculate dose for a hexagonal GRID, with 1.3 cm wide holes separated by 2.1 cm at isocenter. We study motion in the z‐direction, parallel to rows of holes, or in the perpendicular x‐direction. The displacement‐time waveform follows a cos n pattern, with n assigned 1 or 6 to account for a range of inhale‐exhale asymmetry. Dose calculations are performed for 6 MV x‐rays. Results: Near d max, the static valley dose is 0.12 D 0, where D 0 is the peak static dose. For a sinusoidal z‐motion with amplitude a, the minimum peak (D p‐min) and maximum valley (D v‐max) occur at a ≈ 0.8 cm with values 0.67 D 0 and 0.60 D 0 respectively. As a is increased, contributions from neighboring holes make the peaks and valleys vary periodically with a. Less degradation is seen with asymmetric cos6 type motion, with D p‐min = 0.77 D 0 and D v‐max = 0.45 D 0 . For both waveforms, 0.7 cm amplitude lowers the peaks by 20% of D 0, whereas 0.4 cm amplitude raises the valleys by this amount. The corresponding amplitudes for x‐motion are 0.7 and 1.3 cm. Thus, motion effects may be alleviated by properly choosing the grid orientation. GRIDs with smaller hole separations yield motion effects at smaller amplitudes. Conclusion: The results correlate with the clinical finding that tumors in abdominal and thoracic areas respond poorly compared to those in static areas such as skin and head & neck. Thus motion compensation may be necessary to maintain the efficacy of GRID therapy.

TU‐C‐M100J‐07: A Systematic Study On the Sources of Drift in a Turbine‐Based Spirometer Using a Breathing Simulator

Purpose: To systemically isolate and quantify the contributions of different sources of signal drift in turbine‐based spirometry. Method and Materials: To get a repeatable response from the VMM‐400 spirometer, we used a breathing simulator made of an airtight cylinder. The cylinders piston was driven by a motor to force the air in/out of the cylinder to the spirometer. A heating blanket was used to heat the cylinder, so that the in/out air would have different temperature. The piston position, thereby the cylinder air volume, was determined using a position sensor.Results: Our data show that even when the piston was driven sinusoidally and the heating blanket was off, the spirometer exhibits a drift per cycle of 3.4% of the maximum tidal air volume due to the differential response of its turbine blade. Reversing the direction of in/out flow simply changes the drift direction. With the heating on, the drift accumulates an additional 4% per cycle. The added drift is due to the expanded air volume from the heating. The most significant drift was observed when the piston was driven in a saw‐tooth pattern, either with a fast inhale followed by a slow exhale or visa versa. The difference in the measured volume between the two breathing phases can be as large as 60% or more due to the failure of the spirometer to register the volume in the low flow‐rate phase and the air needed to be spent on reversing the blade at the end of the fast‐changing phase. Conclusions: The drift due to the blade asymmetry and temperature stays the same per breathing cycle (3.4% and 4%), and can be corrected in real‐time. The drift due to breathing asymmetry can vary between cycles because of patient irregular breathing; the correction would most likely be complex (i.e., nonlinear).