F. DeBlois

Dosimetric and microdosimetric study of contrast-enhanced radiotherapy with kilovolt x-rays.

Kilovolt x-rays are clearly suboptimal compared to MV photon beams for radiotherapy of deep-seated tumours because of the increased attenuation in tissue, causing a rapid dose fall-off. This picture could change drastically when tumours can be labelled with contrast medium, containing high atomic number elements. This causes a significant dose enhancement to the tumour by exploiting the high cross sections for the photo-electric effect for kV x-rays. In this work, we have investigated the dosimetric and microdosimetric characteristics of kV contrast-enhanced radiation therapy (CERT) for different photon energies, contrast-medium concentrations and types (I and Gd). Two idealized patient treatment plans (head and lung) for irradiation with CT-arc beams were calculated. It is shown that the dose enhancement in tumours can be highly significant (up to about sixfold for realistic 80-120 kVp x-ray spectra and an iodine concentration of 50 mg ml-1) but that dose homogeneity in the tumour depends on photon energy, contrast-medium concentration and type, and irradiation scheme. An attempt to optimize the irradiation scheme is discussed. The microdosimetric study of the dose mean lineal energy shows that radiation quality changes in the contrast-medium-labelled region compared to homogeneous tissue are fairly small and limited to 10%. It is concluded that kV-CERT is a promising radiotherapy technique, provided contrast medium can be delivered reliably to tumours.

Validation of Monte Carlo calculated surface doses for megavoltage photon beams.

Recent work has shown that there is significant uncertainty in measuring build-up doses in mega-voltage photon beams especially at high energies. In this present investigation we used a phantom-embedded extrapolation chamber (PEEC) made of Solid Water to validate Monte Carlo (MC)-calculated doses in the dose build-up region for 6 and 18 MV x-ray beams. The study showed that the percentage depth ionizations (PDIs) obtained from measurements are higher than the percentage depth doses (PDDs) obtained with Monte Carlo techniques. To validate the MC-calculated PDDs, the design of the PEEC was incorporated into the simulations. While the MC-calculated and measured PDIs in the dose build-up region agree with one another for the 6 MV beam, a non-negligible difference is observed for the 18 MV x-ray beam. A number of experiments and theoretical studies of various possible effects that could be the source of this discrepancy were performed. The contribution of contaminating neutrons and protons to the build-up dose region in the 18 MV x-ray beam is negligible. Moreover, the MC calculations using the XCOM photon cross-section database and the NIST bremsstrahlung differential cross section do not explain the discrepancy between the MC calculations and measurement in the dose build-up region for the 18 MV. A simple incorporation of triplet production events into the MC dose calculation increases the calculated doses in the build-up region but does not fully account for the discrepancy between measurement and calculations for the 18 MV x-ray beam.

Saturation current and collection efficiency for ionization chambers in pulsed beams

Saturation currents and collection efficiencies in ionization chambers exposed to pulsed megavoltage photon and electron beams are determined assuming a linear relationship between 1/I and 1/V in the extreme near-saturation region, with I and V the chamber current and polarizing voltage, respectively. Careful measurements of chamber current against polarizing voltage in the extreme near-saturation region reveal a current rising faster than that predicted by the linear relationship. This excess current combined with conventional two-voltage technique for determination of collection efficiency may result in an up to 0.7% overestimate of the saturation current for standard radiation field sizes of 10X10 cm2. The measured excess current is attributed to charge multiplication in the chamber air volume and to radiation-induced conductivity in the stem of the chamber (stem effect). These effects may be accounted for by an exponential term used in conjunction with Boags equation for collection efficiency in pulsed beams. The semiempirical model follows the experimental data well and accounts for both the charge recombination as well as for the charge multiplication effects and the chamber stem effect.

Sorafenib in combination with ionizing radiation has a greater anti-tumour activity in a breast cancer model.

High expression of vascular endothelial growth factor (VEGF) in patients with breast cancer has been associated with a poor prognosis, indicating that VEGF could be linked to the efficacy of chemotherapy and radiotherapy. It has also been suggested that radiation resistance is partly due to tumour cell production of angiogenic cytokines, particularly VEGF receptor (VEGFR). This evidence indicates that inhibition of VEGFR might enhance the radiation response. Sorafenib tosylate (Bay 54-9085) is an oral, small-molecule multikinase inhibitor of several targets including RAF/MEK/ERK MAP kinase signalling, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor-beta. Sorafenib has shown clinical efficacy in treating solid tumours such as renal cell and hepatocellular carcinomas. However, strategies are yet to be identified to prolong and maximize the anticancer effect of this multikinase inhibitor. The objective of this study was to determine whether a combination of Sorafenib and radiation will enhance the treatment response in vitro and in vivo. Radio-modulating effect of Sorafenib was assessed by performing clonogenic assays. In addition, cell cycle analyses as well as annexin-V apoptosis assays were performed 24 and 48 h after treatment, respectively. To confirm our in-vitro results, tumour growth delay assays were performed. Our results showed a strong and supra-additive antitumour effect of radiation combined with Sorafenib in vitro (dose enhancement factor of 1.76). The combined therapy demonstrated a strong and significant G2/M cell cycle arrest (combined treatment vs. irradiated alone: P<0.0008). Moreover, annexin-V staining showed a significant increase in the level of apoptosis (combined treatment vs. irradiated alone: P<0.0004). Study of the syngeneic model demonstrated the superior potency of the Sorafenib combined with radiotherapy. Our results demonstrate that higher antitumour activity can be achieved when radiation and Sorafenib are combined.

Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer

Objective Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction. Methods The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated. Results The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV. Conclusions High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.

Measurement of absorbed dose with a bone-equivalent extrapolation chamber.

A hybrid phantom-embedded extrapolation chamber (PEEC) made of Solid Water and bone-equivalent material was used for determining absorbed dose in a bone-equivalent phantom irradiated with clinical radiation beams (cobalt-60 gamma rays; 6 and 18 MV x rays; and 9 and 15 MeV electrons). The dose was determined with the Spencer-Attix cavity theory, using ionization gradient measurements and an indirect determination of the chamber air-mass through measurements of chamber capacitance. The collected charge was corrected for ionic recombination and diffusion in the chamber air volume following the standard two-voltage technique. Due to the hybrid chamber design, correction factors accounting for scatter deficit and electrode composition were determined and applied in the dose equation to obtain absorbed dose in bone for the equivalent homogeneous bone phantom. Correction factors for graphite electrodes were calculated with Monte Carlo techniques and the calculated results were verified through relative air cavity dose measurements for three different polarizing electrode materials: graphite, steel, and brass in conjunction with a graphite collecting electrode. Scatter deficit, due mainly to loss of lateral scatter in the hybrid chamber, reduces the dose to the air cavity in the hybrid PEEC in comparison with full bone PEEC by 0.7% to approximately 2% depending on beam quality and energy. In megavoltage photon and electron beams, graphite electrodes do not affect the dose measurement in the Solid Water PEEC but decrease the cavity dose by up to 5% in the bone-equivalent PEEC even for very thin graphite electrodes (<0.0025 cm). In conjunction with appropriate correction factors determined with Monte Carlo techniques, the uncalibrated hybrid PEEC can be used for measuring absorbed dose in bone material to within 2% for high-energy photon and electron beams.

Electron fluence correction factors for various materials in clinical electron beams.

Relative to solid water, electron fluence correction factors at the depth of dose maximum in bone, lung, aluminum, and copper for nominal electron beam energies of 9 MeV and 15 MeV of the Clinac 18 accelerator have been determined experimentally and by Monte Carlo calculation. Thermoluminescent dosimeters were used to measure depth doses in these materials. The measured relative dose at dmax in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The beams of the Clinac 18 were fully characterized using the EGS4/BEAM system. EGSnrc with the relativistic spin option turned on was used to optimize the primary electron energy at the exit window, and to calculate depth doses in the five phantom materials using the optimized phase-space data. Normalizing all depth doses to the dose maximum in solid water stopping power ratio corrected, measured depth doses and calculated depth doses differ by less than +/- 1% at the depth of dose maximum and by less than 4% elsewhere. Monte Carlo calculated ratios of doses in each material to dose in LiF were used to convert the TLD measurements at the dose maximum into dose at the center of the TLD in the phantom material. Fluence perturbation correction factors for a LiF TLD at the depth of dose maximum deduced from these calculations amount to less than 1% for 0.15 mm thick TLDs in low Z materials and are between 1% and 3% for TLDs in Al and Cu phantoms. Electron fluence ratios of the studied materials relative to solid water vary between 0.83+/-0.01 and 1.55+/-0.02 for materials varying in density from 0.27 g/cm3 (lung) to 8.96 g/cm3 (Cu). The difference in electron fluence ratios derived from measurements and calculations ranges from -1.6% to +0.2% at 9 MeV and from -1.9% to +0.2% at 15 MeV and is not significant at the 1sigma level. Excluding the data for Cu, electron fluence correction factors for open electron beams are approximately proportional to the electron density of the phantom material and only weakly dependent on electron beam energy.

Determination of electron fluence ratios for various materials in an electron beam

To determine the electron beam dose at depth of dose maximum (d/sub max/) in a specific phantom material from the dose at d/sub max/ in water we need the collision stopping power ratio of the material to water and /spl Phi//sub water//sup mat/, the ratio of electron fluence at d/sub max/ in the material to that of water. We have measured depth doses in solid water, bone, lung, aluminum and copper, irradiated in electron beams with nominal energies 9 and 15 MeV with thermoluminescent dosimetry techniques, The measured relative dose at d/sub max/ in the various materials versus that of solid water, when irradiated with the same number of monitor units, has been used to calculate the ratio of electron fluence for the various materials to that of solid water. The results were also verified using Monte Carlo calculations.

Poster — Thur Eve — 55: An automated XML technique for isocentre verification on the Varian TrueBeam

Isocentre verification tests, such as the Winston-Lutz (WL) test, have gained popularity in the recent years as techniques such as stereotactic radiosurgery/radiotherapy (SRS/SRT) treatments are more commonly performed on radiotherapy linacs. These highly conformal treatments require frequent monitoring of the geometrical accuracy of the isocentre to ensure proper radiation delivery. At our clinic, the WL test is performed by acquiring with the EPID a collection of 8 images of a WL phantom fixed on the couch for various couch/gantry angles. This set of images is later analyzed to determine the isocentre size. The current work addresses the acquisition process. A manual WL test acquisition performed by and experienced physicist takes in average 25 minutes and is prone to user manipulation errors. We have automated this acquisition on a Varian TrueBeam STx linac (Varian, Palo Alto, USA). The Varian developer mode allows the execution of custom-made XML script files to control all aspects of the linac operation. We have created an XML-WL script that cycles through each couch/gantry combinations taking an EPID image at each position. This automated acquisition is done in less than 4 minutes. The reproducibility of the method was verified by repeating the execution of the XML file 5 times. The analysis of the images showed variation of the isocenter size less than 0.1 mm along the X, Y and Z axes and compares favorably to a manual acquisition for which we typically observe variations up to 0.5 mm.

33 LINEARIZATION OF THE RADIOCHROMIC FILM DOSIMETRY SYSTEM DOSE RESPONSE

TLDs drops with increasing LET due the track structure of interacting densely ionising radiations. This phenomenon is known as quench effect (QE). Evidently the QF averts the application of tiny TLD chips in “in field” dosimetry relevant to hadron therapy. The light conversion efficiency (LCE) of Lithium Fluoride thermoluminescent dosimeters TLD-700 (LiF:Mg,Ti) decreases with the increasing linear energy transfer (LET) of the interacting radiation particles. On the contrary, the LCE of Beryllium-Oxide increases with increasing LET of the particles impinging on it. By utilizing these two phenomena we have developed a simple technique to estimate the “quench corrected” LET of interacting particles using a pair of thin TLD-700 and BeO chips. Furthermore, the self-attenuation characteristics of both types of TLD were estimated using a spectrophotometer. The TLDs were calibrated using alpha particles from a Am source attenuated using Mylar foils of different thicknesses for the LETTissue: 165, 178 and 195keV/m. The predicted LET estimation range was found to be 1-200 keV/m, encompassing a wide area of interest from Plateau-toBragg Peak region of a therapeutic proton beam to hadron-therapy, based on Carbon ions as well as fast neutrons of different energies.