Wouter Crijns

Calibrating page sized Gafchromic EBT3 films

PURPOSE The purpose is the development of a novel calibration method for dosimetry with Gafchromic EBT3 films. The method should be applicable for pretreatment verification of volumetric modulated arc, and intensity modulated radiotherapy. Because the exposed area on film can be large for such treatments, lateral scan errors must be taken into account. The correction for the lateral scan effect is obtained from the calibration data itself. METHODS In this work, the film measurements were modeled using their relative scan values (Transmittance, T). Inside the transmittance domain a linear combination and a parabolic lateral scan correction described the observed transmittance values. The linear combination model, combined a monomer transmittance state (T(0)) and a polymer transmittance state (T(∞)) of the film. The dose domain was associated with the observed effects in the transmittance domain through a rational calibration function. On the calibration film only simple static fields were applied and page sized films were used for calibration and measurements (treatment verification). Four different calibration setups were considered and compared with respect to dose estimation accuracy. The first (I) used a calibration table from 32 regions of interest (ROIs) spread on 4 calibration films, the second (II) used 16 ROIs spread on 2 calibration films, the third (III), and fourth (IV) used 8 ROIs spread on a single calibration film. The calibration tables of the setups I, II, and IV contained eight dose levels delivered to different positions on the films, while for setup III only four dose levels were applied. Validation was performed by irradiating film strips with known doses at two different time points over the course of a week. Accuracy of the dose response and the lateral effect correction was estimated using the dose difference and the root mean squared error (RMSE), respectively. RESULTS A calibration based on two films was the optimal balance between cost effectiveness and dosimetric accuracy. The validation resulted in dose errors of 1%-2% for the two different time points, with a maximal absolute dose error around 0.05 Gy. The lateral correction reduced the RMSE values on the sides of the film to the RMSE values at the center of the film. CONCLUSIONS EBT3 Gafchromic films were calibrated for large field dosimetry with a limited number of page sized films and simple static calibration fields. The transmittance was modeled as a linear combination of two transmittance states, and associated with dose using a rational calibration function. Additionally, the lateral scan effect was resolved in the calibration function itself. This allows the use of page sized films. Only two calibration films were required to estimate both the dose and the lateral response. The calibration films were used over the course of a week, with residual dose errors ≤2% or ≤0.05 Gy.

CT characteristics allow identification of patient-specific susceptibility for radiation-induced lung damage

BACKGROUND AND PURPOSE There is a huge difference in radiosensitivity of lungs between patients. The present study aims to identify and quantify patient-specific radiosensitivity based on a single pre-treatment CT scan. MATERIALS AND METHODS 130 lung cancer patients were studied: 60 stereotactic ablative radiotherapy (SABR) treatments and 70 conventional treatments (20 and 30 patients from external datasets, respectively). A 3month-follow-up scan (CT3M) was non-rigidly registered to the planning CT scan (CT0). Changes in Hounsfield Units (ΔHU=HU3M-HU0) inside lung subvolumes were analyzed per dose bin of 5Gy. ΔHU was modeled as a function of local dose using linear and sigmoidal fits. Sigmoidal fit parameters ΔHUmax (saturation level) and D50 (dose corresponding to 50% of ΔHUmax) were collected for all patients. RESULTS Sigmoidal fits outperformed linear fits in the SABR groups for the majority of patients. Sigmoidal dose-responses were also observed in both conventional groups but to a lesser extent. Distributions of D50 and ΔHUmax showed a large variation between patients in all datasets. Higher baseline lung density (p<0.001) was prognostic for higher ΔHUmax in one SABR group. No prognostic factors were found for D50. CONCLUSIONS Baseline CT characteristics are prognostic for radiation-induced lung damage susceptibility.

IMRT-based optimization approaches for volumetric modulated single arc radiotherapy planning

This paper reports on an evaluation of 5 RapidArc optimization approaches vs IMRT. This study includes 11 patients with adenocarcinoma of the prostate. Rectal Normal Tissue Complication Probability is used as a constraint in a dose escalation. RapidArc rectal NTCPs are lower than those of IMRT (p = 0.007). This allows a mean dose escalation of 2.1 Gy([0.7 Gy,3.5 Gy]).

Out-of-field contributions for IMRT and volumetric modulated arc therapy measured using gafchromic films and compared to calculations using a superposition/convolution based treatment planning system.

PURPOSE To quantify the whole-body-dose delivered during the application of new techniques and compare them to the results obtained by treatment planning systems. The ultimate goal being the use of planning data in combination with complication data to assess the impact of low doses of ionizing radiation. METHODS A film technique using gafchromic films to assess low doses was used on simplified phantoms and compared to data from treatment planning systems as well as a simplified whole body dose calculation system (Peridose). The types of treatment include open fields, intensity modulated radiation therapy (IMRT) and volumetric arc treatments. The film measurements were confirmed using TLDs in Alderson phantoms. In addition neutron contributions were measured as these are not taken into account in the current modern treatment planning systems, but can add significantly to the patients whole body dose. RESULTS Dose outside of the treatment plane diminished to 1% of the prescribed dose, this for open fields, IMRT and rotational treatments alike. Noteworthy was an increase at about 20cm from the central plane in IMRT, and in a more limited fashion for volumetric modulated arc treatment. In open fields this was not observed. Treatment planning systems were good at determining the out-of-field doses of single field treatments. In complex plans the TPS underestimated the dose to the patient. At distances greater than 20cm from the field edge, these systems did not predict any dose. The Peridose program performed well in the case of classical treatments. In the case of IMRT treatments, the overall evolution of the dose as a function of the distance to the field was well-modeled. However, an over estimation of the order of 60-80% was observed, leaving the possibility for a corrective factor based on a point measurement. Dose levels over the whole body were of the order 100mGy or higher over a complete treatment for the more complex treatments. Neutron dose levels were of the order single digit mSv for 10MV treatments. For 18MV the level of neutron contribution was in agreement with recent publications, corroborating reports that the dose from neutrons is lower than previously reported.

Dosimetric adaptive IMRT driven by fiducial points

PURPOSE Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy have become standard treatments but are more sensitive to anatomical variations than 3D conformal techniques. To correct for inter- and intrafraction anatomical variations, fast and easy to implement methods are needed. Here, the authors propose a full dosimetric IMRT correction that finds a compromise in-between basic repositioning (the current clinical practice) and full replanning. It simplifies replanning by avoiding a recontouring step and a full dose calculation. It surpasses repositioning by updating the preoptimized fluence and monitor units (MU) using a limited number of fiducial points and a pretreatment (CB)CT. To adapt the fluence the fiducial points were projected in the beams eye view (BEV). To adapt the MUs, point dose calculation towards the same fiducial points were performed. The proposed method is intrinsically fast and robust, and simple to understand for operators, because of the use of only four fiducial points and the beam data based point dose calculations. METHODS To perform our dosimetric adaptation, two fluence corrections in the BEV are combined with two MU correction steps along the beams path. (1) A transformation of the fluence map such that it is realigned with the current target geometry. (2) A correction for an unintended scaling of the penumbra margin when the treatment beams scale to the current target size. (3) A correction for the target depth relative to the body contour and (4) a correction for the target distance to the source. The impact of the correction strategy and its individual components was evaluated by simulations on a virtual prostate phantom. This heterogeneous reference phantom was systematically subjected to population based prostate transformations to simulate interfraction variations. Additionally, a patient example illustrated the clinical practice. The correction strategy was evaluated using both dosimetric (CTV mean dose, conformity index) and clinical (tumor control probability, and normal tissue complication probability) measures. RESULTS Based on the current experiments, the intended target dose and tumor control probability could be assured by the proposed method (TCP ≥ TCP(intended)). Additionally, the conformity index error was more than halved compared to the current clinical practice (ΔCI(95%) from 40% to 16%) resulting in improved organ at risk protection. All the individual correction steps had an added value to the full correction. CONCLUSIONS A limited number of fiducial points (no organ contours required) and an in-room (CB)CT are sufficient to perform a full dosimetric correction for IMRT plans. In the presence of interfraction variation, the corrected plans show superior dose distributions compared to our current clinical practice.

Online adaptation and verification of VMAT

PURPOSE This work presents a method for fast volumetric modulated arc therapy (VMAT) adaptation in response to interfraction anatomical variations. Additionally, plan parameters extracted from the adapted plans are used to verify the quality of these plans. The methods were tested as a prostate class solution and compared to replanning and to their current clinical practice. METHODS The proposed VMAT adaptation is an extension of their previous intensity modulated radiotherapy (IMRT) adaptation. It follows a direct (forward) planning approach: the multileaf collimator (MLC) apertures are corrected in the beams eye view (BEV) and the monitor units (MUs) are corrected using point dose calculations. All MLC and MU corrections are driven by the positions of four fiducial points only, without need for a full contour set. Quality assurance (QA) of the adapted plans is performed using plan parameters that can be calculated online and that have a relation to the delivered dose or the plan quality. Five potential parameters are studied for this purpose: the number of MU, the equivalent field size (EqFS), the modulation complexity score (MCS), and the components of the MCS the aperture area variability (AAV) and the leaf sequence variability (LSV). The full adaptation and its separate steps were evaluated in simulation experiments involving a prostate phantom subjected to various interfraction transformations. The efficacy of the current VMAT adaptation was scored by target mean dose (CTVmean), conformity (CI95%), tumor control probability (TCP), and normal tissue complication probability (NTCP). The impact of the adaptation on the plan parameters (QA) was assessed by comparison with prediction intervals (PI) derived from a statistical model of the typical variation of these parameters in a population of VMAT prostate plans (n = 63). These prediction intervals are the adaptation equivalent of the tolerance tables for couch shifts in the current clinical practice. RESULTS The proposed adaptation of a two-arc VMAT plan resulted in the intended CTVmean (Δ ≤ 3%) and TCP (ΔTCP ≤ 0.001). Moreover, the method assures the intended CI95% (Δ ≤ 11%) resulting in lowered rectal NTCP for all cases. Compared to replanning, their adaptation is faster (13 s vs 10 min) and more intuitive. Compared to the current clinical practice, it has a better protection of the healthy tissue. Compared to IMRT, VMAT is more robust to anatomical variations, but it is also less sensitive to the different correction steps. The observed variations of the plan parameters in their database included a linear dependence on the date of treatment planning and on the target radius. The MCS is not retained as QA metric due to a contrasting behavior of its components (LSV and AAV). If three out of four plan parameters (MU, EqFS, AAV, and LSV) need to lie inside a 50% prediction interval (3/4-50%PI), all adapted plans will be accepted. In contrast, all replanned plans do not meet this loose criterion, mainly because they have no connection to the initially optimized and verified plan. CONCLUSIONS A direct (forward) VMAT adaptation performs equally well as (inverse) replanning but is faster and can be extended to real-time adaptation. The prediction intervals for the machine parameters are equivalent to the tolerance tables for couch shifts in the current clinical practice. A 3/4-50%PI QA criterion accepts all the adapted plans but rejects all the replanned plans.

Regional variability in radiation-induced lung damage can be predicted by baseline CT numbers

BACKGROUND AND PURPOSE Lung volumes are functionally heterogeneous but typically considered uniformly during radiotherapy planning. The present study aims to predict regional differences in radiation-induced lung damage based on pre-treatment CT information. MATERIALS AND METHODS For 42 lung cancer patients (including 15 from an external validation set), two 200cc lung subvolumes (low-density (LD) and high-density (HD)) were auto-segmented in the ipsilateral lung of the planning CT0. After non-rigid registration of 3month follow-up CT scans, sigmoidal dose-density change (ΔHU=HU3M-HU0) response curves were determined for all subvolumes. Predictive factors for the sigmoidal response parameters D50 and saturation level ΔHUmax were analyzed. RESULTS The baseline density difference between LD (mostly in the upper lobe) and HD (mostly in the lower lobe) was on average 102HU. The saturation level ΔHUmax,LD was significantly smaller than ΔHUmax,HD (p=0.03). Expressed as mass density increase relative to the baseline density, saturation levels were 20.7% on average irrespective of baseline density, and they could be predicted in LD and HD subvolumes (AUC=0.70-0.78). Intra-lung differences in D50 were significantly smaller than inter-patient differences. CONCLUSIONS Limited amount of damage was observed in LD subvolumes, while the relative density increase of all subvolumes was well predictable. This could allow dose redistribution preferentially targeting low-density lung regions.

A spectroscopic study of the chromatic properties of GafChromic™EBT3 films

PURPOSE This work provides an interpretation of the chromatic properties of GafChromicEBT3 films based on the chemical nature of the polydiacetylene (PDA) molecules formed upon interaction with ionizing radiation. The EBT3 films become optically less transparent with increasing radiation dose as a result of the radiation-induced polymerization of diacetylene monomers. In contrast to empirical quantification of the chromatic properties, less attention has been given to the underlying molecular mechanism that induces the strong decrease in transparency. METHODS Unlaminated GafChromicEBT3 films were irradiated with a 6 MV photon beam to dose levels up to 20 Gy. The optical absorption properties of the films were investigated using visible (vis) spectroscopy. The presence of PDA molecules in the active layer of the EBT3 films was investigated using Raman spectroscopy, which probes the vibrational modes of the molecules in the layer. The vibrational modes assigned to PDAs were used in a theoretical vis-absorption model to fit our experimental vis-absorption spectra. From the fit parameters, one can assess the relative contribution of different PDA conformations and the length distribution of PDAs in the film. RESULTS Vis-spectroscopy shows that the optical density increases with dose in the full region of the visible spectrum. The Raman spectrum is dominated by two vibrational modes, most notably by the ν(C≡C) and the ν(C=C) stretching modes of the PDA backbone. By fitting the vis-absorption model to experimental spectra, it is found that the active layer contains two distinct PDA conformations with different absorption properties and reaction kinetics. Furthermore, the mean PDA conjugation length is found to be 2-3 orders of magnitude smaller than the crystals PDAs are embedded in. CONCLUSIONS Vis- and Raman spectroscopy provided more insight into the molecular nature of the radiochromic properties of EBT3 films through the identification of the excited states of PDA and the presence of two PDA conformations. The improved knowledge on the molecular composition of EBT3s active layer provides a framework for future fundamental modeling of the dose-response.

Comparison of measured and estimated maximum skin doses during CT fluoroscopy lung biopsies

PURPOSE To measure patient-specific maximum skin dose (MSD) associated with CT fluoroscopy (CTF) lung biopsies and to compare measured MSD with the MSD estimated from phantom measurements, as well as with the CTDIvol of patient examinations. METHODS Data from 50 patients with lung lesions who underwent a CT fluoroscopy-guided biopsy were collected. The CT protocol consisted of a low-kilovoltage (80 kV) protocol used in combination with an algorithm for dose reduction to the radiology staff during the interventional procedure, HandCare (HC). MSD was assessed during each intervention using EBT2 gafchromic films positioned on patient skin. Lesion size, position, total fluoroscopy time, and patient-effective diameter were registered for each patient. Dose rates were also estimated at the surface of a normal-size anthropomorphic thorax phantom using a 10 cm pencil ionization chamber placed at every 30°, for a full rotation, with and without HC. Measured MSD was compared with MSD values estimated from the phantom measurements and with the cumulative CTDIvol of the procedure. RESULTS The median measured MSD was 141 mGy (range 38-410 mGy) while the median cumulative CTDIvol was 72 mGy (range 24-262 mGy). The ratio between the MSD estimated from phantom measurements and the measured MSD was 0.87 (range 0.12-4.1) on average. In 72% of cases the estimated MSD underestimated the measured MSD, while in 28% of the cases it overestimated it. The same trend was observed for the ratio of cumulative CTDIvol and measured MSD. No trend was observed as a function of patient size. CONCLUSIONS On average, estimated MSD from dose rate measurements on phantom as well as from CTDIvol of patient examinations underestimates the measured value of MSD. This can be attributed to deviations of the patients body habitus from the standard phantom size and to patient positioning in the gantry during the procedure.

TH‐E‐BRB‐03: Incorporating a Lateral Scan Effect Correction in a EBT3 Calibration Protocol

Purpose: To use the new EBT3 Gafchromic films for large modulated field dosimetry, a lateral scan correction needs to be performed. We propose a lateral correction built in in the calibration curve. The feasibility of this calibration methodology is evaluated. Methods: The relative scan value (Transmittance, T) is associated with the dose using a rational function with three parameters: T0 the unirradiated transmittance, Tmax the maximal transmittance, and b3 a parameter scaling the impact of the dose. Because, the lateral scan effect is inherent to the scanner transmission system, a parabolic correction is implemented in the calibration function itself, instead of a post calibration correction. To assess a sufficient sampling of both the dose and the lateral dependency in the calibration procedure, eight dose levels are irradiated to two lateral locations on two uncut calibration films (one location per film). The resulting calibration function is validated by delivering known uniform doses on eight strips a single film. The central pixel line of each validation strip is converted to dose for the three (RGB) color channels. To show lateral independence of the measured dose, the central pixel line is divided in five 2 inch ROIs, subsequently, the root mean square error (RMSE) of these ROIs is calculated. Results: The dose errors (1SD) are 2%, 2.2%, and 2% for the red, green, and blue color channel respectively. The red channel dose, without lateral correction, has a maximal RMSE >2.5%, for the outer ROI. The proposed methodology results in a maximal RMSE < 0.5% for all ROIs and all three color channels in a [0.57,4.16]Gy dose range. Conclusions: The scanner‐transmission system with the new EBT3 gafchromic films is calibrated with a calibration protocol incorporating the lateral scan effect. This method reduces the RMSE from 2.5% to 0.5%. Research was supported Ashland Specialty Ingredients Wayne, New Jersey 07470, and PEO Radiation Technology bvba, 2320 Hoogstraten, Belgium. The authors acknowledge David Lewis and Andre Micke for their fruitful discussions.