Assessment of lung doses in patients undergoing total body irradiation for haematological malignancies with and without lung shielding.

INTRODUCTION: Total body irradiation (TBI) practices vary considerably amongst centres, and the risk of treatment related toxicities remains unclear. We report lung doses for 142 TBI patients who underwent either standing TBI with lung shield blocks or lying TBI without blocks. METHODS: Lung doses were calculated for 142 TBI patients treated between June 2016 and June 2021. Patients were planned using Eclipse (Varian Medical Systems) using AAA_15.6.06 for photon dose calculations and EMC_15.6.06 for electron chest wall boost fields. Mean and maximum lung doses were calculated. RESULTS: Thirty-seven patients (26.2%) were treated standing using lung shielding blocks with 104 (73.8%) treated lying down. Lowest relative mean lung doses were achieved using lung shielding blocks in standing TBI, reducing the mean lung doses to 75.2% of prescription (9.9 Gy), ±4.1% (range 68.6-84.1%) for a prescribed dose of 13.2 Gy in 11 fractions, including contributions from electron chest wall boost fields, compared to 12 Gy in 6 fraction lying TBI receiving 101.6% mean lung dose (12.2 Gy) ±2.4% (range 95.2-109.5%) (P ≪ 0.05). Patients treated lying down with 2 Gy single fraction received the highest relative mean lung dose on average, with 108.4% (2.2 Gy) ±2.6% of prescription (range 103.2-114.4%). CONCLUSION: Lung doses have been reported for 142 TBI patients using the lying and standing techniques described herein. Lung shielding blocks significantly reduced mean lung doses despite the addition of electron boost fields to the chest wall.

Dose assessment for daily cone-beam CT in lung radiotherapy patients and its combination with treatment planning.

With the increased use of X-ray imaging for patient alignment in external beam radiation therapy, particularly with cone-beam computed tomography (CBCT), the additional dose received by patients has become of greater consideration. In this study, we analysed the radiation dose from CBCT for clinical lung radiotherapy and assessed its relative contribution when combined with radiation treatment planning for a variety of lung radiotherapy techniques. The Monte Carlo simulation program ImpactMC was used to calculate the 3D dose delivered by a Varian TrueBeam linear accelerator to patients undergoing thorax CBCT imaging. The concomitant dose was calculated by simulating the daily CBCT irradiation of ten lung cancer patients. Each case was planned with a total dose of 50-60 Gy to the target lesion in 25-30 fractions using the 3DCRT or IMRT plan and retrospectively planned using VMAT. For each clinical case, the calculated CBCT dose was summed with the planned dose, and the dose to lungs, heart, and spinal cord were analysed according to conventional dose conformity metrics. Our results indicate greater variations in dose to the heart, lungs, and spinal cord based on planning technique, (3DCRT, IMRT, VMAT) than from the inclusion of daily cone-beam imaging doses over 25-30 fractions. The average doses from CBCT imaging per fraction to the lungs, heart and spinal cord were 0.52 ± 0.10, 0.49 ± 0.15 and 0.39 ± 0.08 cGy, respectively. Lung dose variations were related to the patient's size and body composition. Over a treatment course, this may result in an additional mean absorbed dose of 0.15-0.2 Gy. For lung V5, the imaging dose resulted in an average increase of ~ 0.6% of the total volume receiving 5 Gy. The increase in V20 was more dependent on the planning technique, with 3DCRT increasing by 0.11 ± 0.09% with imaging and IMRT and VMAT increasing by 0.17 ± 0.05% and 0.2 ± 0.06%, respectively. In this study, we assessed the concomitant dose for daily CBCT lung cancer patients undergoing radiotherapy. The additional radiation dose to the normal lungs from daily CBCT was found to range from 0.15 to 0.2 Gy when the patient was treated with 25-30 fractions. Consideration of potential variation in relative biological effectiveness between kilovoltage imaging and megavoltage treatment dose was outside the scope of this study. Regardless of this, our results show that the assessment of imaging dose can be incorporated into the treatment planning process and the relative effect on overall dose distribution was small compared to the difference among planning techniques.

A system for real-time monitoring of breath-hold via assessment of internal anatomy in tangential breast radiotherapy.

The deep inspiration breath-hold (DIBH) technique assists in sparing the heart, lungs, and liver during breast radiotherapy (RT). The quality of DIBH is currently assessed via surrogates which correlate to varying degrees with the patient's internal anatomy. Since modern linacs are equipped with an electronic portal imaging device (EPID), images of the irradiated anatomy streamed from EPIDs and analyzed in real time could significantly improve assessment of the quality of DIBH. A system has been developed to quantify the quality of DIBH during tangential breast RT by analyzing the "beam's eye view" images of the treatment fields. The system measures the lung depth (LD) and the distance from the breast surface to the posterior tangential radiation field edge (skin distance, SD) at three user-defined locations. LD and SD measured in real time in EPID images of two RT phantoms showing different geometrical characteristics of their chest wall regions (computed tomography dose index [CTDI] and "END-TO-END" stereotactic body radiation therapy [E2E SBRT]) were compared with ground truth displacements provided by a precision motion platform. Performance of the new system was evaluated via static and dynamic (sine wave motion) measurements of LD and SD, covering clinical situations with stable and unstable breath-hold. The accuracy and precision of the system were calculated as the mean and standard deviation of the differences between the ground truth and measured values. The accuracy of the static measurements of LD and SD for the CTDI phantom was 0.31 (1.09) mm [mean (standard deviation)] and -0.10 (0.14) mm, respectively. The accuracy of the static measurements for E2E SBRT phantom was 0.01 (0.18) mm and 0.05 (0.08) mm. The accuracy of the dynamic LD and SD measurements for the CTDI phantom was -0.50 (1.18) mm and 0.01 (0.12) mm, respectively. The accuracy of the dynamic measurements for E2E SBRT phantom was -0.03 (0.19) mm and 0.01 (0.11) mm.

Calculation algorithms and penumbra: Underestimation of dose in organs at risk in dosimetry audits.

PURPOSE: The aim of this study is to investigate overdose to organs at risk (OARs) observed in dosimetry audits in Monte Carlo (MC) algorithms and Linear Boltzmann Transport Equation (LBTE) algorithms. The impact of penumbra modeling on OAR dose was assessed with the adjustment of MC modeling parameters and the clinical relevance of the audit cases was explored with a planning study of spine and head and neck (H&N) patient cases. METHODS: Dosimetric audits performed by the Australian Clinical Dosimetry Service (ACDS) of 43 anthropomorphic spine plans and 1318 C-shaped target plans compared the planned dose to doses measured with ion chamber, microdiamond, film, and ion chamber array. An MC EGSnrc model was created to simulate the C-shape target case. The electron cut-off energy Ecut(kinetic) was set at 500, 200, and 10 keV, and differences between 1 and 3 mm voxel were calculated. A planning study with 10 patient stereotactic body radiotherapy (SBRT) spine plans and 10 patient H&N plans was calculated in both Acuros XB (AXB) v15.6.06 and Anisotropic Analytical Algorithm (AAA) v15.6.06. The patient contour was overridden to water as only the penumbral differences between the two different algorithms were under investigation. RESULTS: The dosimetry audit results show that for the SBRT spine case, plans calculated in AXB are colder than what is measured in the spinal cord by 5%-10%. This was also observed for other audit cases where a C-shape target is wrapped around an OAR where the plans were colder by 3%-10%. Plans calculated with Monaco MC were colder than measurements by approximately 7% with the OAR surround by a C-shape target, but these differences were not noted in the SBRT spine case. Results from the clinical patient plans showed that the AXB was on average 7.4% colder than AAA when comparing the minimum dose in the spinal cord OAR. This average difference between AXB and AAA reduced to 4.5% when using the more clinically relevant metric of maximum dose in the spinal cord. For the H&N plans, AXB was cooler on average than AAA in the spinal cord OAR (1.1%), left parotid (1.7%), and right parotid (2.3%). The EGSnrc investigation also noted similar, but smaller differences. The beam penumbra modeled by Ecut(kinetic)  = 500 keV was steeper than the beam penumbra modeled by Ecut(kinetic)  = 10 keV as the full scatter is not accounted for, which resulted in less dose being calculated in a central OAR region where the penumbra contributes much of the dose. The dose difference when using 2.5 mm voxels of the center of the OAR between 500 and 10 keV was 3%, reducing to 1% between 200 and 10 keV. CONCLUSIONS: Lack of full penumbral modeling due to approximations in the algorithms in MC based or LBTE algorithms are a contributing factor as to why these algorithms under-predict the dose to OAR when the treatment volume is wrapped around the OAR. The penumbra modeling approximations also contribute to AXB plans predicting colder doses than AAA in areas that are in the vicinity of beam penumbra. This effect is magnified in regions where there are many beam penumbras, for example in the spinal cord for spine SBRT cases.

Automated assessment of functional lung imaging with 68Ga-ventilation/perfusion PET/CT using iterative histogram analysis.

PURPOSE: Functional lung mapping from Ga68-ventilation/perfusion (V/Q) PET/CT, which has been shown to correlate with pulmonary function tests (PFTs), may be beneficial in a number of clinical applications where sparing regions of high lung function is of interest. Regions of clumping in the proximal airways in patients with airways disease can result in areas of focal intense activity and artefact in ventilation imaging. These artefacts may even shine through to subsequent perfusion images and create a challenge for quantitative analysis of PET imaging. We aimed to develop an automated algorithm that interprets the uptake histogram of PET images to calculate a peak uptake value more representative of the global lung volume. METHODS: Sixty-six patients recruited from a prospective clinical trial underwent both V/Q PET/CT imaging and PFT analysis before treatment. PET images were normalised using an iterative histogram analysis technique to account for tracer hotspots prior to the threshold-based delineation of varying values. Pearson's correlation between fractional lung function and PFT score was calculated for ventilation, perfusion, and matched imaging volumes at varying threshold values. RESULTS: For all functional imaging thresholds, only FEV1/FVC PFT yielded reasonable correlations to image-based functional volume. For ventilation, a range of 10-30% of adapted peak uptake value provided a reasonable threshold to define a volume that correlated with FEV1/FVC (r = 0.54-0.61). For perfusion imaging, a similar correlation was observed (r = 0.51-0.56) in the range of 20-60% adapted peak threshold. Matched volumes were closely linked to ventilation with a threshold range of 15-35% yielding a similar correlation (r = 0.55-0.58). CONCLUSIONS: Histogram normalisation may be implemented to determine the presence of tracer clumping hotspots in Ga-68 V/Q PET imaging allowing for automated delineation of functional lung and standardisation of functional volume reporting.

Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency.

PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). CONCLUSIONS: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable.

NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy.

INTRODUCTION: In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients. METHODS: Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose. RESULTS: Reduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy. CONCLUSION: 18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases. TRIAL REGISTRATION: POPSTAR, 'Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy', Universal Trial Number U1111-1140-7563 , Registered 17th April 2013.

CyberKnife® fixed cone and Iris™ defined small radiation fields: Assessment with a high-resolution solid-state detector array.

PURPOSE: The challenges of accurate dosimetry for stereotactic radiotherapy (SRT) with small unflattened radiation fields have been widely reported in the literature. In this case, suitable dosimeters would have to offer a submillimeter spatial resolution. The CyberKnife® (Accuray Inc., Sunnyvale, CA, USA) is an SRT-dedicated linear accelerator (linac), which can deliver treatments with submillimeter positional accuracy using circular fields. Beams are delivered with the desired field size using fixed cones, the InCise™ multileaf collimator or a dynamic variable-aperture Iris™ collimator. The latter, allowing for field sizes to be varied during treatment delivery, has the potential to decrease treatment time, but its reproducibility in terms of output factors (OFs) and dose profiles (DPs) needs to be verified. METHODS: A 2D monolithic silicon array detector, the "Octa", was evaluated for dosimetric quality assurance (QA) for a CyberKnife system. OFs, DPs, percentage depth-dose (PDD) and tissue maximum ratio (TMR) were investigated, and results were benchmarked against the PTW SRS diode. Cross-plane, in-plane and 2 diagonal dose profiles were measured simultaneously with high spatial resolution (0.3 mm). Monte Carlo (MC) simulations with a GEANT4 (GEometry ANd Tracking 4) tool-kit were added to the study to support the experimental characterization of the detector response. RESULTS: For fixed cones and the Iris, for all field sizes investigated in the range between 5 and 60 mm diameter, OFs, PDDs, TMRs, and DPs in terms of FWHM measured by the Octa were accurate within 3% when benchmarked against the SRS diode and MC calculations. CONCLUSIONS: The Octa was shown to be an accurate dosimeter for measurements with a 6 MV FFF beam delivered with a CyberKnife system. The detector enabled real-time dosimetric verification for the variable aperture Iris collimator, yielding OFs and DPs consistent with those obtained with alternative methods.

Assessment of leakage dose in vivo in patients undergoing radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Accurate quantification of the relatively small radiation doses delivered to untargeted regions during breast irradiation in patients with breast cancer is of increasing clinical interest for the purpose of estimating long-term radiation-related risks. Out-of-field dose calculations from commercial planning systems however may be inaccurate which can impact estimates for long-term risks associated with treatment. This work compares calculated and measured dose out-of-field and explores the application of a correction for leakage radiation. MATERIALS AND METHODS: Dose calculations of a Boltzmann transport equation solver, pencil beam-type, and superposition-type algorithms from a commercial treatment planning system (TPS) were compared with in vivo thermoluminescent dosimetry (TLD) measurements conducted out-of-field on the contralateral chest at points corresponding to the thyroid, axilla and contralateral breast of eleven patients undergoing tangential beam radiotherapy for breast cancer. RESULTS: Overall, the TPS was found to under-estimate doses at points distal to the radiation field edge with a modern linear Boltzmann transport equation solver providing the best estimates. Application of an additive correction for leakage (0.04% of central axis dose) improved correlation between the measured and calculated doses at points greater than 15 cm from the field edge. CONCLUSIONS: Application of a correction for leakage doses within peripheral regions is feasible and could improve accuracy of TPS in estimating out-of-field doses in breast radiotherapy.

Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high-density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross-sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in- and out-of field at various distances from the beam isocenter to assess activation caused in-field by photo-activation, and neutron activation which occurs both in and out-of-field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma-ray emissions and their half-lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD-100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in-field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. 53 Fe, 56 Mn, and 52 V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

Practical Assessment of Bronchoscopically Inserted Fiducial Markers for Image Guidance in Stereotactic Lung Radiotherapy.

INTRODUCTION: Stereotactic radiotherapy is a high-dose precision technique necessitating accurate target visualization through either cone beam computed tomography (CBCT) or planar imaging with implanted fiducial markers. We have investigated the properties for image guidance using fiducial markers implanted through minimally invasive bronchoscopy. METHODS: Two fiducial marker types were implanted endobronchially in 10 patients undergoing radical radiation treatment for non-small cell lung cancer (eight using Visicoil linear fiducial markers [IBA Dosimetry GmbH, Schwarzenbruck Germany] and two using superDimension and superLock two-band markers [Covidien Inc., Minneapolis, MN]). Patients underwent four-dimensional computed tomography imaging for treatment planning and after completion of treatment to investigate marker movement. As part of the image guidance assessment, megavolt electronic portal images (EPIs) were acquired in addition to kilovolt planar and CBCT (Varian Medical Systems, Palo Alto, CA) images. RESULTS: In two of 10 patients (both receiving Visicoil markers), marker migration was observed before treatment. In patients with stable markers, both types were clearly visible in planar kilovolt imaging; however, in EPIs the markers could be detected only in selected beam directions in which bony interference was minimal. Diagnostic computed tomography scanning was able to demonstrate the markers with clarity, but significant starring artifacts were observed in CBCT. This was particularly problematic in patients with some lateral component of tumor motion during breathing. CONCLUSIONS: The potential for fiducial migration must be considered and investigated if bronchoscopic implantation of fiducial markers is performed. The choice of marker is a compromise between trying to minimize CBCT artifacts while enabling visualization in EPI imaging, which is an ideal tool to verify gated radiotherapy delivery.

A randomised phase II trial of Stereotactic Ablative Fractionated radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the lung (TROG 13.01 SAFRON II).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases. METHODS/DESIGN: The TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study. DISCUSSION: Fractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR. TRIALS REGISTRATION: ACTRN12613001157763 , registered 17th October 2013.

Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.

PURPOSE: To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). METHODS AND MATERIALS: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). RESULTS: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. CONCLUSIONS: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.

Accuracy and Utility of Deformable Image Registration in (68)Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy.

PURPOSE: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. METHODS: (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. RESULTS: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. CONCLUSIONS: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment.

On the use of Gafchromic EBT3 films for validating a commercial electron Monte Carlo dose calculation algorithm.

This study aims to investigate the effects of oblique incidence, small field size and inhomogeneous media on the electron dose distribution, and to compare calculated (Elekta/CMS XiO) and measured results. All comparisons were done in terms of absolute dose. A new measuring method was developed for high resolution, absolute dose measurement of non-standard beams using Gafchromic® EBT3 film. A portable U-shaped holder was designed and constructed to hold EBT3 films vertically in a reproducible setup submerged in a water phantom. The experimental film method was verified with ionisation chamber measurements and agreed to within 2% or 1 mm. Agreement between XiO electron Monte Carlo (eMC) and EBT3 was within 2% or 2 mm for most standard fields and 3% or 3 mm for the non-standard fields. Larger differences were seen in the build-up region where XiO eMC overestimates dose by up to 10% for obliquely incident fields and underestimates the dose for small circular fields by up to 5% when compared to measurement. Calculations with inhomogeneous media mimicking ribs, lung and skull tissue placed at the side of the film in water agreed with measurement to within 3% or 3 mm. Gafchromic film in water proved to be a convenient high spatial resolution method to verify dose distributions from electrons in non-standard conditions including irradiation in inhomogeneous media.

CT perfusion imaging in response assessment of pulmonary metastases undergoing stereotactic ablative radiotherapy.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment technique for pulmonary metastases in which conventional Response Evaluation Criteria in Solid Tumours (RECIST) may be inadequate. This study aims to assess the utility of CT perfusion imaging in response assessment of pulmonary metastases after SABR. METHODS: In this ethics board-approved prospective study, 11 patients underwent a 26-Gy single fraction of SABR to pulmonary metastases. CT perfusion imaging occurred prior to and at 14 and 70 days post-SABR. Blood flow (mL/100 mL/min), blood volume (mL/100 mL), time to peak (seconds) and surface permeability (mL/100 mL/min), perfusion parameters of pulmonary metastases undergoing SABR, were independently assessed by two radiologists. Inter-observer variability was analysed. CT perfusion results were analysed for early response assessment comparing day 14 with baseline scans and for late response by comparing day 70 with baseline scans. The largest diameter of the pulmonary metastases undergoing SABR was recorded. RESULTS: Ten patients completed all three scans and one patient had baseline and early response assessment CT perfusion scans only. There was strong level of inter-observer agreement of CT perfusion interpretation with a median intraclass coefficient of 0.87 (range 0.20-0.98). Changes in all four perfusion parameters and tumour sizes were not statistically significant. CONCLUSION: CT perfusion imaging of pulmonary metastases is a highly reproducible imaging technique that may provide additional response assessment information above that of conventional RECIST, and it warrants further study in a larger cohort of patients undergoing SABR.

Trans Tasman Radiation Oncology Group: Development of the Assessment of New Radiation Oncology Technology and Treatments (ANROTAT) Framework.

INTRODUCTION: The study aim was to develop a generic framework to derive the parameters to populate health-economic models for the rapid evaluation of new techniques and technologies in radiation oncology. METHODS: A draft framework was developed through horizon scanning for relevant technologies, literature review to identify framework models, and a workshop program with radiation oncology professionals, biostatisticians, health economists and consumers to establish the Framework's structure. It was tested using four clinical protocols, comparing intensity modulated with 3D conformal therapy (post-prostatectomy, anal canal and nasopharynx) and image-guided radiation therapy techniques with off-line review of portal imaging (in the intact prostate). RESULTS: The draft generic research framework consisted of five sequential stages, each with a number of components, and was assessed as to its suitability for deriving the evidence needed to populate the decision-analytic models required for the health-economic evaluations. A final Framework was established from this experience for use by future researchers to provide evidence of clinical efficacy and cost-utility for other novel techniques. The four clinical treatment sites tested during the project were considered suitable to use in future evaluations. CONCLUSIONS: Development of a generic research framework to predict early and long-term clinical outcomes, combined with health-economic data, produced a generally applicable method for the rapid evaluation of new techniques and technologies in radiation oncology. Its application to further health technology assessments in the radiation oncology sector will allow further refinement and support its generalisability.

Risk factors for radiotherapy incidents and impact of an online electronic reporting system.

BACKGROUND AND PURPOSE: To ascertain the rate, type, significance, trends and the potential risk factors associated with radiotherapy incidents in a large academic department. MATERIALS AND METHODS: Data for all radiotherapy activities from July 2001 to January 2011 were reviewed from radiotherapy incident reporting forms. Patient and treatment data were obtained from the radiotherapy record and verification database (MOSAIQ) and the patient database (HOSPRO). Logistic regression analyses were performed to determine variables associated with radiotherapy incidents. RESULTS: In that time, 65,376 courses of radiotherapy were delivered with a reported incident rate of 2.64 per 100 courses. The rate of incidents per course increased (1.96 per 100 courses to 3.52 per 100 courses, p<0.001) whereas the proportion of reported incidents resulting in >5% deviation in dose (10.50 to 2.75%, p<0.001) had decreased after the introduction of an online electronic reporting system. The following variables were associated with an increased rate of incidents: afternoon treatment time, paediatric patients, males, inpatients, palliative plans, head-and-neck, skin, sarcoma and haematological malignancies. In general, complex plans were associated with higher incidence rates. CONCLUSION: Radiotherapy incidents were infrequent and most did not result in significant dose deviation. A number of risk factors were identified and these could be used to highlight high-risk cases in the future. Introduction of an online electronic reporting system resulted in a significant increase in the number of incidents being reported.

Angular dependence of the response of the nanoDot OSLD system for measurements at depth in clinical megavoltage beams.

PURPOSE: The purpose of this investigation was to assess the angular dependence of a commercial optically stimulated luminescence dosimeter (OSLD) dosimetry system in MV x-ray beams at depths beyond d(max) and to find ways to mitigate this dependence for measurements in phantoms. METHODS: Two special holders were designed which allow a dosimeter to be rotated around the center of its sensitive volume. The dosimeter's sensitive volume is a disk, 5 mm in diameter and 0.2 mm thick. The first holder rotates the disk in the traditional way. It positions the disk perpendicular to the beam (gantry pointing to the floor) in the initial position (0°). When the holder is rotated the angle of the disk towards the beam increases until the disk is parallel with the beam ("edge on," 90°). This is referred to as Setup 1. The second holder offers a new, alternative measurement position. It positions the disk parallel to the beam for all angles while rotating around its center (Setup 2). Measurements with five to ten dosimeters per point were carried out for 6 MV at 3 and 10 cm depth. Monte Carlo simulations using GEANT4 were performed to simulate the response of the active detector material for several angles. Detector and housing were simulated in detail based on microCT data and communications with the manufacturer. Various material compositions and an all-water geometry were considered. RESULTS: For the traditional Setup 1 the response of the OSLD dropped on average by 1.4% ± 0.7% (measurement) and 2.1% ± 0.3% (Monte Carlo simulation) for the 90° orientation compared to 0°. Monte Carlo simulations also showed a strong dependence of the effect on the composition of the sensitive layer. Assuming the layer to completely consist of the active material (Al2O3) results in a 7% drop in response for 90° compared to 0°. Assuming the layer to be completely water, results in a flat response within the simulation uncertainty of about 1%. For the new Setup 2, measurements and Monte Carlo simulations found the angular dependence of the dosimeter to be below 1% and within the measurement uncertainty. CONCLUSIONS: The dosimeter system exhibits a small angular dependence of approximately 2% which needs to be considered for measurements involving other than normal incident beams angles. This applies in particular to clinical in vivo measurements where the orientation of the dosimeter is dictated by clinical circumstances and cannot be optimized as otherwise suggested here. When measuring in a phantom, the proposed new setup should be considered. It changes the orientation of the dosimeter so that a coplanar beam arrangement always hits the disk shaped detector material from the thin side and thereby reduces the angular dependence of the response to within the measurement uncertainty of about 1%. This improvement makes the dosimeter more attractive for clinical measurements with multiple coplanar beams in phantoms, as the overall measurement uncertainty is reduced. Similarly, phantom based postal audits can transition from the traditional TLD to the more accurate and convenient OSLD.

An automated voxelized dosimetry tool for radionuclide therapy based on serial quantitative SPECT/CT imaging.

PURPOSE: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy. METHODS: Serial quantitative SPECT∕CT images were acquired at 4, 24, and 72 h for 28 (177)Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose based on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1). RESULTS: Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes. CONCLUSIONS: The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in individual patients.