Sensitivity and specificity of Monte Carlo based independent secondary dose computation for detecting modulation-related dose errors in intensity modulated radiotherapy.

BACKGROUND: The recent availability of Monte Carlo based independent secondary dose calculation (ISDC) for patient-specific quality assurance (QA) of modulated radiotherapy requires the definition of appropriate, more sensitive action levels, since contemporary recommendations were defined for less accurate ISDC dose algorithms. PURPOSE: The objective is to establish an optimum action level and measure the efficacy of a Monte Carlo ISDC software for pre-treatment QA of intensity modulated radiotherapy treatments. METHODS: The treatment planning system and the ISDC were commissioned by their vendors from independent base data sets, replicating a typical real-world scenario. In order to apply Receiver-Operator-Characteristics (ROC), a set of treatment plans for various case classes was created that consisted of 190 clinical treatment plans and 190 manipulated treatment plans with dose errors in the range of 1.5-2.5%. All 380 treatment plans were evaluated with ISDC in the patient geometry. ROC analysis was performed for a number of Gamma (dose-difference/distance-to-agreement) criteria. QA methods were ranked according to Area under the ROC curve (AUC) and optimum action levels were derived via Youden's J statistics. RESULTS: Overall, for original treatment plans, the mean Gamma pass rate (GPR) for Gamma(1%, 1 mm) was close to 90%, although with some variation across case classes. The best QA criterion was Gamma(2%, 1 mm) with GPR > 90% and an AUC of 0.928. Gamma criteria with small distance-to-agreement had consistently higher AUC. GPR of original treatment plans depended on their modulation degree. An action level in terms of Gamma(1%, 1 mm) GPR that decreases with modulation degree was the most efficient criterion with sensitivity = 0.91 and specificity = 0.95, compared with Gamma(3%, 3 mm) GPR > 99%, sensitivity = 0.73 and specificity = 0.91 as a commonly used action level. CONCLUSIONS: ISDC with Monte Carlo proves highly efficient to catch errors in the treatment planning process. For a Monte Carlo based TPS, dose-difference criteria of 2% or less, and distance-to-agreement criteria of 1 mm, achieve the largest AUC in ROC analysis.

Locally advanced NSCLC: a plea for sparing the ipsilateral normal lung-prospective, clinical trial with DART-bid (dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily) by VMAT.

BACKGROUND: In radiation treatment of locally advanced non-small cell lung cancer (LA-NSCLC), 'margins' from internal target volumes to planning target volumes in the range of 12 to 23 mm are reported, and avoiding exposure of the contralateral lung is common practice. We investigated prospectively an approach with tight margins (7 mm) and maximal sparing of the ipsilateral normal lung. Mature results for the first endpoint (pneumonitis) and further toxicities are reported. METHODS: Primary tumors were treated by VMAT with 73.8-90.0 Gy in positive correlation to tumor volumes, nodes with 61.2 Gy, a restricted volume of nodes electively with 45 Gy. Fractional doses of 1.8 Gy bid, interval 8 h. Before radiotherapy, two cycles platin-based chemotherapy were given. 12 patients finished maintenance therapy with Durvalumab. Median follow up time for all patients is 19.4 months, for patients alive 27.0 months (3.4-66.5 months). RESULTS: 100 consecutive, unselected patients with LA-NSCLC in stages II through IVA were enrolled (UICC/AJCC, 8th edition). No acute grade 4/5 toxicity occurred. Pneumonitis grade 2 and 3 was observed in 12% and 2% of patients, respectively; lowering the risk of pneumonitis grade ≥ 2 in comparison to the largest study in the literature investigating pneumonitis in LA-NSCLC, is significant (p < 0.0006). Acute esophageal toxicity grade 1, 2 and 3 occurred in 12%, 57% and 3% of patients, respectively. Two patients showed late bronchial stricture/atelectasis grade 2. In two patients with lethal pulmonary haemorrhages a treatment correlation cannot be excluded. Median overall survival for all stage III patients, and for those with 'RTOG 0617 inclusion criteria' is 46.6 and 50.0 months, respectively. CONCLUSIONS: Overall toxicity is low. In comparison to results in the literature, maximal sparing the ipsilateral normal lung lowers the risk for pneumonitis significantly. TRIAL REGISTRATION: Ethics committee of Vorarlberg, Austria; EK-0.04-105, Registered 04/09/2017-Retrospectively registered. http://www.ethikkommission-vorarlberg.at.

Evaluation of 4-Hz log files and secondary Monte Carlo dose calculation as patient-specific quality assurance for VMAT prostate plans.

PURPOSE: In this study, 4-Hz log files were evaluated with an independent secondary Monte Carlo dose calculation algorithm to reduce the workload for patient-specific quality assurance (QA) in clinical routine. MATERIALS AND METHODS: A total of 30 randomly selected clinical prostate VMAT plans were included. The used treatment planning system (TPS) was Monaco (Elekta, Crawley), and the secondary dose calculation software was SciMoCa (Scientific-RT, Munich). Monaco and SciMoCa work with a Monte Carlo algorithm. A plausibility check of Monaco and SciMoCa was performed using an ionization chamber in the BodyPhantom (BP). First, the original Monaco RT plans were verified with SciMoCa (pretreatment QA). Second, the corresponding 4-Hz log files were converted into RT log file plans and sent to SciMoCa as on-treatment QA. MLC shift errors were introduced for one prostate plan to determine the sensitivity of on-treatment QA. For pretreatment and on-treatment QA, a gamma analysis (2%/1mm/20%) was performed and dosimetric values of PTV and OARs were ascertained in SciMoCa. RESULTS: Plausibility check of TPS Monaco vs. BP measurement and SciMoCa vs. BP measurement showed valid accuracy for clinical VMAT QA. Using SciMoCa, there was no significant difference in PTV Dmean between RT plan and RT log file plan. Between pretreatment and on-treatment QA, PTV metrics, femur right and left showed no significant dosimetric differences as opposed to OARs rectum and bladder. The overall gamma passing rate (GPR) ranged from 96.10% to 100% in pretreatment QA and from 93.50% to 99.80% in on-treatment QA. MLC shift errors were identified for deviations larger than -0.50 mm and +0.75 mm using overall gamma criterion and PTV Dmean. CONCLUSION: SciMoCa calculations of Monaco RT plans and RT log file plans are in excellent agreement to each other. Therefore, 4-Hz log files and SciMoCa can replace labor-intensive phantom-based measurements as patient-specific QA.

Error sensitivity of a log file analysis tool compared with a helical diode array dosimeter for VMAT delivery quality assurance.

PURPOSE: Integrating log file analysis with LINACWatch® (LW) into clinical routine as part of the quality assurance (QA) process could be a time-saving strategy that does not compromise on quality. The purpose is to determine the error sensitivity of log file analysis using LINACWatch® compared with a measurement device (ArcCHECK®, AC) for VMAT delivery QA. MATERIALS AND METHODS: Multi-leaf collimator (MLC) errors, collimator angle errors, MLC shift errors and dose errors were inserted to analyze error detection sensitivity. A total of 36 plans were manipulated with different magnitudes of errors. The gamma index protocols for AC were 3%/3 mm/Global and 2%/2 mm/Global, as well as 2%/2 mm/Global, and 1.5%/1.5 mm/Global for LW. Additionally, deviations of the collimator and monitor units between TPS and log file were calculated as RMS values. A 0.125 cm3 ionization chamber was used to independently examine the effect on dose. RESULTS: The sensitivity for AC was 20.4% and 49.6% vs 63.0% and 86.5% for LW, depending on the analysis protocol. For MLC opening and closing errors, the detection rate was 19.0% and 47.7% for AC vs 50.5% and 75.5% for LW. For MLC shift errors, it was 29.6% and 66.7% for AC vs 66.7% and 83.3% for LW. AC could detect 25.0% and 44.4% of all collimator errors. Log file analysis detected all collimator errors using 1° detection level. 13.2% and 42.4% of all dose errors were detected by AC vs 59.0% and 92.4% for LW using gamma analysis. Using RMS value, all dose errors were detected by LW (1% detection level). CONCLUSION: The results of this study clearly show that log file analysis is an excellent complement to phantom-based delivery QA of VMAT plans. We recommend a 1.5%/1.5 mm/Global criteria for log file-based gamma calculations. Log file analysis was implemented successfully in our clinical routine for VMAT delivery QA.

Linking log files with dosimetric accuracy--A multi-institutional study on quality assurance of volumetric modulated arc therapy.

PURPOSE: To systematically evaluate machine specific quality assurance (QA) for volumetric modulated arc therapy (VMAT) based on log files by applying a dynamic benchmark plan. METHODS AND MATERIALS: A VMAT benchmark plan was created and tested on 18 Elekta linacs (13 MLCi or MLCi2, 5 Agility) at 4 different institutions. Linac log files were analyzed and a delivery robustness index was introduced. For dosimetric measurements an ionization chamber array was used. Relative dose deviations were assessed by mean gamma for each control point and compared to the log file evaluation. RESULTS: Fourteen linacs delivered the VMAT benchmark plan, while 4 linacs failed by consistently terminating the delivery. The mean leaf error (±1SD) was 0.3±0.2 mm for all linacs. Large MLC maximum errors up to 6.5 mm were observed at reversal positions. Delivery robustness index accounting for MLC position correction (0.8-1.0) correlated with delivery time (80-128 s) and depended on dose rate performance. Dosimetric evaluation indicated in general accurate plan reproducibility with γ(mean)(±1 SD)=0.4±0.2 for 1 mm/1%. However single control point analysis revealed larger deviations and attributed well to log file analysis. CONCLUSION: The designed benchmark plan helped identify linac related malfunctions in dynamic mode for VMAT. Log files serve as an important additional QA measure to understand and visualize dynamic linac parameters.

Experimental verification of a commercial Monte Carlo-based dose calculation module for high-energy photon beams.

The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (gamma) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% +/- 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 x 10 cm(2) field at the first density interface from tissue to lung equivalent material. Small fields (2 x 2 cm(2)) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% +/- 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D gamma-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for gamma(>1) was 4.7% +/- 3.7%, the average gamma(1%) value was 1.19 +/- 0.16 and the mean 2D gamma-value was 0.44 +/- 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

Advanced kernel methods vs. Monte Carlo-based dose calculation for high energy photon beams.

PURPOSE: The aim of this study was to compare the dose calculation accuracy of advanced kernel-based methods and Monte Carlo algorithms in commercially available treatment planning systems. MATERIALS AND METHODS: Following dose calculation algorithms and treatment planning (TPS) systems were compared: the collapsed cone (CC) convolution algorithm available in Oncentra Masterplan, the XVMC Monte Carlo algorithm implemented in iPlan and Monaco, and the analytical anisotropic algorithm (AAA) implemented in Eclipse. Measurements were performed with a calibrated ionization chamber and radiochromic EBT type films in a homogenous polystyrene phantom and in heterogeneous lung phantoms. Single beam tests, conformal treatment plans and IMRT plans were validated. Dosimetric evaluations included absolute dose measurements, 1D gamma-evaluation of depth-dose curves and profiles using 2mm and 2% dose difference criteria for single beam tests, and gamma-evaluation of axial planes for composite treatment plans applying 3mm and 3% dose difference criteria. RESULTS: Absolute dosimetry revealed no large differences between MC and advanced kernel dose calculations. 1D gamma-evaluation showed significant discrepancies between depth-dose curves in different phantom geometries. For the CC algorithm gamma(mean) values were 0.90+/-0.74 vs. 0.43+/-0.41 in heterogeneous vs. homogeneous conditions and for the AAA gamma(mean) values were 1.13+/-0.91 vs. 0.41+/-0.28, respectively. In general, 1D gamma results obtained with both MC TPS were similar in both phantoms and on average equal to 0.5 both for profiles and depth-dose curves. The results obtained with the CC algorithm in heterogeneous phantoms were slightly better in comparison to the AAA algorithm. The 2D gamma-evaluation results of IMRT plans and four-field plans showed smaller mean gamma-values for MC dose calculations compared to the advanced kernel algorithms (gamma(mean) for four-field plan and IMRT obtained with Monaco MC were 0.28 and 0.5, respectively, vs. 0.40 and 0.54 for the AAA). CONCLUSION: All TPS investigated in this study demonstrated accurate dose calculation in homogenous and heterogeneous phantoms. Commercially available TPS with Monte Carlo option performed best in heterogeneous phantoms. However, the difference between the CC and the MC algorithms was found to be small.

Registration of DRRs and portal images for verification of stereotactic body radiotherapy: a feasibility study in lung cancer treatment.

Image guidance has become a pre-requisite for hypofractionated radiotherapy where the applied dose per fraction is increased. Particularly in stereotactic body radiotherapy (SBRT) for lung tumours, one has to account for set-up errors and intrafraction tumour motion. In our feasibility study, we compared digitally reconstructed radiographs (DRRs) of lung lesions with MV portal images (PIs) to obtain the displacement of the tumour before irradiation. The verification of the tumour position was performed by rigid intensity based registration and three different merit functions such as the sum of squared pixel intensity differences, normalized cross correlation and normalized mutual information. The registration process then provided a translation vector that defines the displacement of the target in order to align the tumour with the isocentre. To evaluate the registration algorithms, 163 test images were created and subsequently, a lung phantom containing an 8 cm(3) tumour was built. In a further step, the registration process was applied on patient data, containing 38 tumours in 113 fractions. To potentially improve registration outcome, two filter types (histogram equalization and display equalization) were applied and their impact on the registration process was evaluated. Generated test images showed an increase in successful registrations when applying a histogram equalization filter whereas the lung phantom study proved the accuracy of the selected algorithms, i.e. deviations of the calculated translation vector for all test algorithms were below 1 mm. For clinical patient data, successful registrations occurred in about 59% of anterior-posterior (AP) and 46% of lateral projections, respectively. When patients with a clinical target volume smaller than 10 cm(3) were excluded, successful registrations go up to 90% in AP and 50% in lateral projection. In addition, a reliable identification of the tumour position was found to be difficult for clinical target volumes at the periphery of the lung, close to backbone or diaphragm. Moreover, tumour movement during shallow breathing strongly influences image acquisition for patient positioning. Recapitulating, 2D/3D image registration for lung tumours is an attractive alternative compared to conventional CT verification of the tumour position. Nevertheless, size and location of the tumour are limiting parameters for an accurate registration process.

A practical method to calculate head scatter factors in wedged rectangular and irregular MLC shaped beams for external and internal wedges.

Factor based methods for absorbed dose or monitor unit calculations are often based on separate data sets for open and wedged beams. The determination of basic beam parameters can be rather time consuming, unless equivalent square methods are applied. When considering irregular wedged beams shaped with a multileaf collimator, parametrization methods for dosimetric quantities, e.g. output ratios or wedge factors as a function of field size and shape, become even more important. A practical method is presented to derive wedged output ratios in air (S(c,w)) for any rectangular field and for any irregular MLC shaped beam. This method was based on open field output ratios in air (S(c)) for a field with the same collimator setting, and a relation f(w) between S(c,w) and S(c). The relation f(w) can be determined from measured output ratios in air for a few open and wedged fields including the maximum wedged field size. The function f(w) and its parametrization were dependent on wedge angle and treatment head design, i.e. they were different for internal and external wedges. The proposed method was tested for rectangular wedged fields on three accelerators with internal wedges (GE, Elekta, BBC) and two accelerators with external wedges (Varian). For symmetric regular beams the average deviation between calculated and measured S(c,w) / S(c) ratios was 0.3% for external wedges and about 0.6% for internal wedges. Maximum deviations of 1.8% were obtained for elongated rectangular fields on the GE and ELEKTA linacs with an internal wedge. The same accuracy was achieved for irregular MLC shaped wedged beams on the accelerators with MLC and internal wedges (GE and Elekta), with an average deviation < 1% for the fields tested. The proposed method to determine output ratios in air for wedged beams from output ratios of open beams, combined with equivalent square approaches, can be easily integrated in empirical or semi-empirical methods for monitor unit calculations.

On empirical methods to determine scatter factors for irregular MLC shaped beams.

Multileaf collimators (MLCs) are in clinical use for more than a decade and are a well accepted tool in radiotherapy. For almost each MLC design different empirical or semianalytical methods have been presented for calculating output ratios in air for irregularly shaped beams. However, until now no clear recommendations have been given on how to handle irregular fields shaped by multileaf collimators for independent monitor unit (MU) verification. The present article compares different empirical methods, which have been proposed for independent MU verification, to determine (1) output ratios in air (Sc) and (2) phantom scatter factors (Sp) for irregular MLC shaped fields. Ten dedicated field shapes were applied to five different types of MLCs (Elekta, Siemens, Varian, Scanditronix, General Electric). All calculations based on empirical relations were compared with measurements and with calculations performed by a treatment planning system with a fluence based algorithm. For most irregular MLC shaped beams output ratios in air could be adequately modeled with an accuracy of about 1%-1.5% applying a method based on the open field aperture defined by the leaf and jaw setting combined with the equivalent square formula suggested by Vadash and Bjärngard [P. Vadash and B. E. Bjärngard, Med. Phys. 20, 733-734 (1993)]. The accuracy of this approach strongly depends on the inherent head scatter characteristics of the accelerator in use and on the irregular field under consideration. Deviations of up to 3% were obtained for fields where leaves obscure central parts of the flattening filter. Simple equivalent square methods for Sp calculations in irregular fields did not provide acceptable results (deviations mostly >3%). Sp values derived from Clarkson integration, based on published tables of phantom scatter correction factors, showed the same accuracy level as calculations performed using a pencil beam algorithm of a treatment planning system (in a homogeneous media). The separation of head scatter and phantom scatter contributions is strongly recommended for irregular MLC shaped beams as both contributions have different factors of influence. With rather simple methods Sc and Sp can be determined for independent MU calculation with an accuracy better than 1.5% for most clinical situations encountered in conformal radiotherapy.