G. Coutrakon

Microdosimetry spectra of the Loma Linda proton beam and relative biological effectiveness comparisons

Protons have long been recognized as low LET radiation in radiotherapy. However, a detailed account of LET (linear energy transfer) and RBE (relative biological effectiveness) changes with incident beam energy and depth in tissue is still unresolved. This issue is particularly important for treatment planning, where the physical dose prescription is calculated from a RBE using cobalt as the reference radiation. Any significant RBE changes with energy or depth will be important to incorporate in treatment planning. In this paper we present microdosimetry spectra for the proton beam at various energies and depths and compare the results to cell survival studies performed at Loma Linda. An empirically determined biological weighting function that depends on lineal energy is used to correlate the microdosimetry spectra with cell survival data. We conclude that the variations in measured RBE with beam energy and depth are small until the distal edge of the beam is reached. On the distal edge, protons achieve stopping powers as high as 100 keV/micron, which is reflected in the lineal energy spectra taken there. Lineal energy spectra 5 cm beyond the distal edge of the Bragg peak also show a high LET component but at a dose rate 600 times smaller than observed inside the proton field.

Leakage and scatter radiation from a double scattering based proton beamline

Proton beams offer several advantages over conventional radiation techniques for treating cancer and other diseases. These advantages might be negated if the leakage and scatter radiation from the beamline and patient are too large. Although the leakage and scatter radiation for the double scattering proton beamlines at the Loma Linda University Proton Treatment Facility were measured during the acceptance testing that occurred in the early 1990s, recent discussions in the radiotherapy community have prompted a reinvestigation of this contribution to the dose equivalent a patient receives. The dose and dose equivalent delivered to a large phantom patient outside a primary proton field were determined using five methods: simulations using Monte Carlo calculations, measurements with silver halide film, measurements with ionization chambers, measurements with rem meters, and measurements with CR-39 plastic nuclear track detectors. The Monte Carlo dose distribution was calculated in a coronal plane through the simulated patient that coincided with the central axis of the beam. Measurements with the ionization chambers, rem meters, and plastic nuclear track detectors were made at multiple locations within the same coronal plane. Measurements with the film were done in a plane perpendicular to the central axis of the beam and coincident with the surface of the phantom patient. In general, agreement between the five methods was good, but there were some differences. Measurements and simulations also tended to be in agreement with the original acceptance testing measurements and results from similar facilities published in the literature. Simulations illustrated that most of the neutrons entering the patient are produced in the final patient-specific aperture and precollimator just upstream of the aperture, not in the scattering system. These new results confirm that the dose equivalents received by patients outside the primary proton field from primary particles that leak through the nozzle are below the accepted standards for x-ray and electron beams. The total dose equivalent outside of the field is similar to that received by patients undergoing treatments with intensity modulated x-ray therapy. At the center of a patient for a whole course of treatment, the dose equivalent is comparable to that delivered by a single whole-body XCT scan.

Water-equivalent path length calibration of a prototype proton CT scanner

PURPOSE The authors present a calibration method for a prototype proton computed tomography (pCT) scanner. The accuracy of these measurements depends upon careful calibration of the energy detector used to measure the residual energy of the protons that passed through the object. METHODS A prototype pCT scanner with a cesium iodide (CsI(Tl)) crystal calorimeter was calibrated by measuring the calorimeter response for protons of 200 and 100 MeV initial energies undergoing degradation in polystyrene plates of known thickness and relative stopping power (RSP) with respect to water. Calibration curves for the two proton energies were obtained by fitting a second-degree polynomial to the water-equivalent path length versus calorimeter response data. Using the 100 MeV calibration curve, the RSP values for a variety of tissue-equivalent materials were measured and compared to values obtained from a standard depth-dose range shift measurement using a water-tank. A cylindrical water phantom was scanned with 200 MeV protons and its RSP distribution was reconstructed using the 200 MeV calibration. RESULTS It is shown that this calibration method produces measured RSP values of various tissue-equivalent materials that agree to within 0.5% of values obtained using an established water-tank method. The mean RSP value of the water phantom reconstruction was found to be 0.995 ± 0.006. CONCLUSIONS The method presented provides a simple and reliable procedure for calibration of a pCT scanner.

A performance study of the Loma Linda proton medical accelerator

More than three years have passed since Loma Linda treated the first cancer patient with the worlds first proton accelerator dedicated to radiation therapy. Since that time, over 1000 patients have completed treatments and the facility currently treats more than 45 patients per day. With a typical intensity of 3 x 10(10) protons per pulse and 27 pulses per minute, dose rates of 90-100 cGy/min are easily achieved on a 20-cm diameter field. In most cases, patient treatment times are 2 min, much less than the patient alignment time required before each treatment. Nevertheless, there is considerable medical interest in increasing field sizes up to 40-cm diameter while keeping dose rates high and treatment times low. In this article, beam measurements relevant to intensity studies are presented and possible accelerator modifications for upgrades are proposed. It is shown that nearly all intensity losses can be ascribed to the large momentum spread of the injected beam and occur at or near the injection energy of 2 MeV. The agreement between calculations and measurements appears quite good. In addition, optimum beam characteristics for a new injector are discussed based upon the momentum acceptance and space charge limits of the Loma Linda synchrotron.

A prototype beam delivery system for the proton medical accelerator at Loma Linda.

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerators commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Two-dimensional and quasi-three-dimensional dosimetry of hadron and photon beams with the Magic Cube and the Pixel Ionization Chamber.

Two detectors for fast two-dimensional (2D) and quasi-three-dimensional (quasi-3D) verification of the dose delivered by radiotherapy beams have been developed at University and Istituto Nazionale di Fisica Nucleare (INFN) of Torino. The Magic Cube is a stack of strip-segmented ionization chambers interleaved with water-equivalent slabs. The parallel plate ionization chambers have a sensitive area of 24 x 24 cm2, and consist of 0.375 cm wide and 24 cm long strips. There are a total of 64 strips per chamber. The Magic Cube has been tested with the clinical proton beam at Loma Linda University Medical Centre (LLUMC), and was shown to be capable of fast and precise quasi-3D dose verification. The Pixel Ionization Chamber (PXC) is a detector with pixel anode segmentation. It is a 32 x 32 matrix of 1024 cylindrical ionization cells arranged in a square 24 x 24 cm2 area. Each cell has 0.4 cm diameter and 0.55 cm height, at a pitch of 0.75 cm separates the centre of adjacent cells. The sensitive volume of each single ionization cell is 0.07 cm3. The detectors are read out using custom designed front-end microelectronics and a personal computer-based data acquisition system. The PXC has been used to verify dynamic intensity-modulated radiotherapy for head-and-neck and breast cancers.

Low-Dose Photons Modify Liver Response to Simulated Solar Particle Event Protons

Abstract Gridley, D. S., Coutrakon, G. B., Rizvi, A., Bayeta, E. J. M., Luo-Owen, X., Makinde, A. Y., Baqai, F., Koss, P., Slater, J. M. and Pecaut, M. J. Low-Dose Photons Modify Liver Response to Simulated Solar Particle Event Protons. Radiat. Res. 169, 280–287 (2008). The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons (57Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event.

Calibration of a proton beam energy monitor.

Delivery of therapeutic proton beams requires an absolute energy accuracy of +/-0.64 to 0.27 MeV for patch fields and a relative energy accuracy of +/-0.10 to 0.25 MeV for tailoring the depth dose distribution using the energy stacking technique. Achromatic switchyard tunes, which lead to better stability of the beam incident onto the patient, unfortunately limit the ability of switchyard magnet tesla meters to verify the correct beam energy within the tolerances listed above. A new monitor to measure the proton energy before each pulse is transported through the switchyard has been installed into a proton synchrotron. The purpose of this monitor is to correct and/or inhibit beam delivery when the measured beam energy is outside of the tolerances for treatment. The monitor calculates the beam energy using data from two frequency and eight beam position monitors that measure the revolution frequency of the proton bunches and the effective offset of the orbit from the nominal radius of the synchrotron. The new energy monitor has been calibrated by measuring the range of the beam through water and comparing with published range-energy tables for various energies. A relationship between depth dose curves and range-energy tables was first determined using Monte Carlo simulations of particle transport and energy deposition. To reduce the uncertainties associated with typical scanning water phantoms, a new technique was devised in which the beam energy was scanned while fixed thickness water tanks were sandwiched between two fixed parallel plate ionization chambers. Using a multitude of tank sizes, several energies were tested to determine the nominal accelerator orbit radius. After calibration, the energy reported by the control system matched the energy derived by range measurements to better than 0.72 MeV for all nine energies tested between 40 and 255 MeV with an average difference of -0.33 MeV. A study of different combinations of revolution frequency and radial offsets to test the envelope of algorithm accuracy demonstrated a relative accuracy of +/-0.11 MeV for small energy changes between 126 and 250 MeV. These new measurements may serve as a data set for benchmarking range-energy relationships.

Response of Extracellular Matrix Regulators in Mouse Lung after Exposure to Photons, Protons and Simulated Solar Particle Event Protons

Abstract Tian, J., Pecaut, M. J., Coutrakon, G. B., Slater, J. M. and Gridley, D. S. Response of Extracellular Matrix Regulators in Mouse Lung after Exposure to Photons, Protons and Simulated Solar Particle Event Protons. Radiat. Res. 172, 30-41 (2009). This study compared the effects of photons (γ rays), protons and simulated solar particle event protons (sSPE) on the expression of profibrotic factors/extracellular matrix (ECM) regulators in lung tissue after whole-body irradiation. TGF-β1, matrix metalloproteinase 2 and 9 (MMP-2, -9), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, -2) were assessed on days 4 and 21 in lungs from C57BL/6 mice exposed to 0 Gy or 2 Gy photons (0.7 Gy/min), protons (0.9 Gy/min) and sSPE (0.056 Gy/h). RT-PCR, histological and immunohistochemical techniques were used. The most striking changes included (1) up-regulation of TGF-β1 by photons and sSPE, but not protons, at both times, (2) MMP-2 enhancement by photons and sSPEs, (3) TIMP-1 up-regulation by photons at both times, and (4) more collagen accumulation after exposure to either photons or sSPE than after exposure to protons. The findings demonstrate that expression of important ECM regulators was highly dependent upon the radiation regimen as well as the time after exposure. The data further suggest that irradiation during an SPE may increase an astronauts risk for pulmonary complications. The greater perturbations after photon exposure compared to proton exposure have clinical implications and warrant further investigation.

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.