Robustness analysis of dynamic trajectory radiotherapy and volumetric modulated arc therapy plans for head and neck cancer.

Background and purpose: Dynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties. Materials and methods: The robustness of DTRT and VMAT plans previously created for 46 H&N cases, prescribed 50-70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties' impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test (α = 5 %). Results: Average NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average differences compared to the nominal scenario were ≤ 3.5 Gy for rotational PS (≤ 3°) and machine-positioning (≤ 2°) uncertainties, <7 Gy for translational PS uncertainties (≤ 5 mm) and < 20 Gy for MLC-positioning uncertainties (≤ 5 mm). Conclusions: DTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.

Organs-at-risk dose and normal tissue complication probability with dynamic trajectory radiotherapy (DTRT) for head and neck cancer.

We compared dynamic trajectory radiotherapy (DTRT) to state-of-the-art volumetric modulated arc therapy (VMAT) for 46 head and neck cancer cases. DTRT had lower dose to salivary glands and swallowing structure, resulting in lower predicted xerostomia and dysphagia compared to VMAT. DTRT is deliverable on C-arm linacs with high dosimetric accuracy.

Towards liquid EPR dosimetry using nitroxides in aqueous solution.

Objective. Water-equivalent dosimeters are desirable for dosimetry in radiotherapy. The present work investigates basic characteristics of novel aqueous detector materials and presents a signal loss approach for electron paramagnetic resonance (EPR) dosimetry.Approach. The proposed principle is based on the radiation dose dependent annihilation of EPR active nitroxides (NO·) in aqueous solutions. Stable nitroxide radicals (3-Maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (MmP), 3-Carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (CmP)) in aqueous solutions containing dimethyl sulfoxide (DMSO) as an additive were filled in glass capillaries for irradiation and EPR readout. Radiation doses ranging from 1 to 64 Gy were applied with a clinical 6 MV flattening filter free photon beam. EPR readout was then performed with a X-band benchtop spectrometer. The dose response, temporal stability and reproducibility of the samples' EPR signal amplitudes as well as the influence of the nitroxide concentration between 10 and 160µM on the absolute signal loss were investigated using MmP. CmP was used to examine the dependence of the dose response on DMSO concentration between 0 and 10 vol%. An indirect effect model was fitted to the experimental data assuming irradiation induced radical reactions as the underlying mechanism.Main results. For an initial MmP concentration of 20µM, absolute EPR signal loss is linear up to a dose of 16 Gy with a yield G(-NO·) of approximately 0.4µmol J-1. Within five weeks upon sample irradiation to doses between 0 and 32 Gy relative EPR signal fluctuations were on average (126 readouts) below 1% (1σ). For c(MmP) ≥ 20µM, absolute signal loss is only weakly dependent on c(MmP), whereas it increases strongly with increasing c(DMSO) in the range 0-5 vol%. An indirect effect model is applicable to describe the reaction mechanism resulting in the observed dose response curve.Significance. Liquids consisting of nitroxides in aqueous solution and small amounts of DMSO (2 vol%) show promising basic characteristics for application as water-equivalent EPR dosimeter materials in radiotherapy. The EPR signal loss is based on an indirect effect mediated by diffusing radicals originating from the radiolysis of the water/DMSO mixture.

Dosimetrically motivated beam-angle optimization for non-coplanar arc radiotherapy with and without dynamic collimator rotation.

BACKGROUND: Non-coplanar techniques have shown to improve the achievable dose distribution compared to standard coplanar techniques for multiple treatment sites but finding optimal beam directions is challenging. Dynamic collimator trajectory radiotherapy (colli-DTRT) is a new intensity modulated radiotherapy technique that uses non-coplanar partial arcs and dynamic collimator rotation. PURPOSE: To solve the beam angle optimization (BAO) problem for colli-DTRT and non-coplanar VMAT (NC-VMAT) by determining the table-angle and the gantry-angle ranges of the partial arcs through iterative 4π fluence map optimization (FMO) and beam direction elimination. METHODS: BAO considers all available beam directions sampled on a gantry-table map with the collimator angle aligned to the superior-inferior axis (colli-DTRT) or static (NC-VMAT). First, FMO is performed, and beam directions are scored based on their contributions to the objective function. The map is thresholded to remove the least contributing beam directions, and arc candidates are formed by adjacent beam directions with the same table angle. Next, FMO and arc candidate trimming, based on objective function penalty score, is performed iteratively until a desired total gantry angle range is reached. Direct aperture optimization on the final set of colli-DTRT or NC-VMAT arcs generates deliverable plans. colli-DTRT and NC-VMAT plans were created for seven clinically-motivated cases with targets in the head and neck (two cases), brain, esophagus, lung, breast, and prostate. colli-DTRT and NC-VMAT were compared to coplanar VMAT plans as well as to class-solution non-coplanar VMAT plans for the brain and head and neck cases. Dosimetric validation was performed for one colli-DTRT (head and neck) and one NC-VMAT (breast) plan using film measurements. RESULTS: Target coverage and conformity was similar for all techniques. colli-DTRT and NC-VMAT plans had improved dosimetric performance compared to coplanar VMAT for all treatment sites except prostate where all techniques were equivalent. For the head and neck and brain cases, mean dose reduction-in percentage of the prescription dose-to parallel organs was on average 0.7% (colli-DTRT), 0.8% (NC-VMAT) and 0.4% (class-solution) compared to VMAT. The reduction in D2% for the serial organs was on average 1.7% (colli-DTRT), 2.0% (NC-VMAT) and 0.9% (class-solution). For the esophagus, lung, and breast cases, mean dose reduction to parallel organs was on average 0.2% (colli-DTRT) and 0.3% (NC-VMAT) compared to VMAT. The reduction in D2% for the serial organs was on average 1.3% (colli-DTRT) and 0.9% (NC-VMAT). Estimated delivery times for colli-DTRT and NC-VMAT were below 4 min for a full gantry angle range of 720°, including transitions between arcs, except for the brain case where multiple arcs covered the whole table angle range. These times are in the same order as the class-solution for the head and neck and brain cases. Total optimization times were 25%-107% longer for colli-DTRT, including BAO, compared to VMAT. CONCLUSIONS: We successfully developed dosimetrically motivated BAO for colli-DTRT and NC-VMAT treatment planning. colli-DTRT and NC-VMAT are applicable to multiple treatment sites, including body sites, with beneficial or equivalent dosimetric performances compared to coplanar VMAT and reasonable delivery times.

Adapting a practical EPR dosimetry protocol to measure output factors in small fields with alanine.

PURPOSE: Modern radiotherapy techniques often deliver small radiation fields. In this work, a practical Electron Paramagnetic Resonance (EPR) dosimetry protocol is adapted and applied to measure output factors (OF) in small fields of a 6 MV radiotherapy system. Correction factors and uncertainties are presented and OFs are compared to the values obtained by following TRS-483 using an ionization chamber (IC). METHODS: Irradiations were performed at 10 cm depth inside a water phantom positioned at 90 cm source to surface distance with a 6 MV flattening filter free photon beam of a Halcyon radiotherapy system. OFs for different nominal field sizes (1 × 1, 2 × 2, 3 × 3, 4 × 4, normalized to 10 × 10 cm2 ) were determined with a PinPoint 3D (PTW 31022) IC following TRS-483 as well as with alanine pellets with a diameter of 4 mm and a height of 2.4 mm. EPR readout was performed with a benchtop X-band spectrometer. Correction factors due to volume averaging and due to positional uncertainties were derived from 2D film measurements. RESULTS: OFs obtained from both dosimeter types agreed within 0.7% after applying corrections for the volume averaging effect. For the used alanine pellets, volume averaging correction factors of 1.030(2) for the 1 × 1 cm2 field and <1.002 for the larger field sizes were determined. The correction factor for positional uncertainties of 1 mm was in the order of 1.018 for the 1 × 1 cm2 field. Combined relative standard uncertainties uc for the OFs resulting from alanine measurements were estimated to be below 1.5% for all field sizes. For IC measurements, uc was estimated to be below 1.0%. CONCLUSIONS: A practical EPR dosimetry protocol is adaptable for precisely measuring OFs in small fields down to 1 × 1 cm2 . It is recommended to consider the effect of positional uncertainties for field sizes <2 × 2 cm2 .

Technical note: A collision prediction tool using Blender.

Non-coplanar radiotherapy treatment techniques on C-arm linear accelerators have the potential to reduce dose to organs-at-risk in comparison with coplanar treatment techniques. Accurately predicting possible collisions between gantry, table and patient during treatment planning is needed to ensure patient safety. We offer a freely available collision prediction tool using Blender, a free and open-source 3D computer graphics software toolset. A geometric model of a C-arm linear accelerator including a library of patient models is created inside Blender. Based on the model, collision predictions can be used both to calculate collision-free zones and to check treatment plans for collisions. The tool is validated for two setups, once with and once without a full body phantom with the same table position. For this, each gantry-table angle combination with a 2° resolution is manually checked for collision interlocks at a TrueBeam system and compared to simulated collision predictions. For the collision check of a treatment plan, the tool outputs the minimal distance between the gantry, table and patient model and a video of the movement of the gantry and table, which is demonstrated for one use case. A graphical user interface allows user-friendly input of the table and patient specification for the collision prediction tool. The validation resulted in a true positive rate of 100%, which is the rate between the number of correctly predicted collision gantry-table combinations and the number of all measured collision gantry-table combinations, and a true negative rate of 89%, which is the ratio between the number of correctly predicted collision-free combinations and the number of all measured collision-free combinations. A collision prediction tool is successfully created and able to produce maps of collision-free zones and to test treatment plans for collisions including visualisation of the gantry and table movement.

Delivery time reduction for mixed photon-electron radiotherapy by using photon MLC collimated electron arcs.

Objective. Electron arcs in mixed-beam radiotherapy (Arc-MBRT) consisting of intensity-modulated electron arcs with dynamic gantry rotation potentially reduce the delivery time compared to mixed-beam radiotherapy containing electron beams with static gantry angle (Static-MBRT). This study aims to develop and investigate a treatment planning process (TPP) for photon multileaf collimator (pMLC) based Arc-MBRT.Approach. An existing TPP for Static-MBRT plans is extended to integrate electron arcs with a dynamic gantry rotation and intensity modulation using a sliding window technique. The TPP consists of a manual setup of electron arcs, and either static photon beams or photon arcs, shortening of the source-to-surface distance for the electron arcs, initial intensity modulation optimization, selection of a user-defined number of electron beam energies based on dose contribution to the target volume and finally, simultaneous photon and electron intensity modulation optimization followed by full Monte Carlo dose calculation. Arc-MBRT plans, Static-MBRT plans, and photon-only plans were created and compared for four breast cases. Dosimetric validation of two Arc-MBRT plans was performed using film measurements.Main results. The generated Arc-MBRT plans are dosimetrically similar to the Static-MBRT plans while outperforming the photon-only plans. The mean heart dose is reduced by 32% on average in the MBRT plans compared to the photon-only plans. The estimated delivery times of the Arc-MBRT plans are similar to the photon-only plans but less than half the time of the Static-MBRT plans. Measured and calculated dose distributions agree with a gamma passing rate of over 98% (3% global, 2 mm) for both delivered Arc-MBRT plans.Significance. A TPP for Arc-MBRT is successfully developed and Arc-MBRT plans showed the potential to improve the dosimetric plan quality similar as Static-MBRT while maintaining short delivery times of photon-only treatments. This further facilitates integration of pMLC-based MBRT into clinical practice.

Impact of the gradient in gantry-table rotation on dynamic trajectory radiotherapy plan quality.

BACKGROUND: To improve organ at risk (OAR) sparing, dynamic trajectory radiotherapy (DTRT) extends VMAT by dynamic table and collimator rotation during beam-on. However, comprehensive investigations regarding the impact of the gantry-table (GT) rotation gradient on the DTRT plan quality have not been conducted. PURPOSE: To investigate the impact of a user-defined GT rotation gradient on plan quality of DTRT plans in terms of dosimetric plan quality, dosimetric robustness, deliverability, and delivery time. METHODS: The dynamic trajectories of DTRT are described by GT and gantry-collimator paths. The GT path is determined by minimizing the overlap of OARs with planning target volume (PTV). This approach is extended to consider a GT rotation gradient by means of a maximum gradient of the path ( G m a x ${G}_{max}$ ) between two adjacent control points ( G = | Δ table angle / Δ gantry angle | $G = | \Delta {{\mathrm{table\ angle}}/\Delta {\mathrm{gantry\ angle}}} |$ ) and maximum absolute change of G ( Δ G m a x ${{\Delta}}{G}_{max}$ ). Four DTRT plans are created with different maximum G&∆G: G m a x ${G}_{max}$ & Δ G m a x ${{\Delta}}{G}_{max}$  = 0.5&0.125 (DTRT-1), 1&0.125 (DTRT-2), 3&0.125 (DTRT-3) and 3&1|(DTRT-4), including 3-4 dynamic trajectories, for three clinically motivated cases in the head and neck and brain region (A, B, and C). A reference VMAT plan for each case is created. For all plans, plan quality is assessed and compared. Dosimetric plan quality is evaluated by target coverage, conformity, and OAR sparing. Dosimetric robustness is evaluated against systematic and random patient-setup uncertainties between ± 3 mm $ \pm 3\ {\mathrm{mm}}$ in the lateral, longitudinal, and vertical directions, and machine uncertainties between ± 4 ∘ $ \pm 4^\circ \ $ in the dynamically rotating machine components (gantry, table, collimator rotation). Delivery time is recorded. Deliverability and delivery accuracy on a TrueBeam are assessed by logfile analysis for all plans and additionally verified by film measurements for one case. All dose calculations are Monte Carlo based. RESULTS: The extension of the DTRT planning process with user-defined G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ to investigate the impact of the GT rotation gradient on plan quality is successfully demonstrated. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , slight (case C, D m e a n , p a r o t i d l . ${D}_{mean,\ parotid\ l.}$ : up to|-1|Gy) and substantial (case A, D 0.03 c m 3 , o p t i c n e r v e r . ${D}_{0.03c{m}^3,\ optic\ nerve\ r.}$ : up to -9.3 Gy, case|B, D m e a n , b r a i n $\ {D}_{mean,\ brain}$ : up to -4.7|Gy) improvements in OAR sparing are observed compared to VMAT, while maintaining similar target coverage. All plans are delivered on the TrueBeam. Expected and actual machine position values recorded in the logfiles deviated by <0.2° for gantry, table and collimator rotation. The film measurements agreed by >96% (2%|global/2 mm Gamma passing rate) with the dose calculation. With increasing G m a x & Δ G m a x ${G}_{max}\& {{\Delta}}{G}_{max}$ , delivery time is prolonged by <2 min/trajectory (DTRT-4) compared to VMAT and DTRT-1. The DTRT plans for case A and B and the VMAT plan for case C plan reveal the best dosimetric robustness for the considered uncertainties. CONCLUSION: The impact of the GT rotation gradient on DTRT plan quality is comprehensively investigated for three cases in the head and neck and brain region. Increasing freedom in this gradient improves dosimetric plan quality at the cost of increased delivery time for the investigated cases. No clear dependency of GT rotation gradient on dosimetric robustness is observed.

Technical note: Feasibility of gating for dynamic trajectory radiotherapy - Mechanical accuracy and dosimetric performance.

BACKGROUND: Dynamic trajectory radiotherapy (DTRT) extends state-of-the-art volumetric modulated arc therapy (VMAT) by dynamic table and collimator rotations during beam-on. The effects of intrafraction motion during DTRT delivery are unknown, especially regarding the possible interplay between patient and machine motion with additional dynamic axes. PURPOSE: To experimentally assess the technical feasibility and quantify the mechanical and dosimetric accuracy of respiratory gating during DTRT delivery. METHODS: A DTRT and VMAT plan are created for a clinically motivated lung cancer case and delivered to a dosimetric motion phantom (MP) placed on the table of a TrueBeam system using Developer Mode. The MP reproduces four different 3D motion traces. Gating is triggered using an external marker block, placed on the MP. Mechanical accuracy and delivery time of the VMAT and DTRT deliveries with and without gating are extracted from the logfiles. Dosimetric performance is assessed by means of gamma evaluation (3% global/2 mm, 10% threshold). RESULTS: The DTRT and VMAT plans are successfully delivered with and without gating for all motion traces. Mechanical accuracy is similar for all experiments with deviations <0.14° (gantry angle), <0.15° (table angle), <0.09° (collimator angle) and <0.08 mm (MLC leaf positions). For DTRT (VMAT), delivery times are 1.6-2.3 (1.6- 2.5) times longer with than without gating for all motion traces except one, where DTRT (VMAT) delivery is 5.0 (3.6) times longer due to a substantial uncorrected baseline drift affecting only DTRT delivery. Gamma passing rates with (without) gating for DTRT/VMAT were ≥96.7%/98.5% (≤88.3%/84.8%). For one VMAT arc without gating it was 99.6%. CONCLUSION: Gating is successfully applied during DTRT delivery on a TrueBeam system for the first time. Mechanical accuracy is similar for VMAT and DTRT deliveries with and without gating. Gating substantially improved dosimetric performance for DTRT and VMAT.

Impact of random outliers in auto-segmented targets on radiotherapy treatment plans for glioblastoma.

AIMS: To save time and have more consistent contours, fully automatic segmentation of targets and organs at risk (OAR) is a valuable asset in radiotherapy. Though current deep learning (DL) based models are on par with manual contouring, they are not perfect and typical errors, as false positives, occur frequently and unpredictably. While it is possible to solve this for OARs, it is far from straightforward for target structures. In order to tackle this problem, in this study, we analyzed the occurrence and the possible dose effects of automated delineation outliers. METHODS: First, a set of controlled experiments on synthetically generated outliers on the CT of a glioblastoma (GBM) patient was performed. We analyzed the dosimetric impact on outliers with different location, shape, absolute size and relative size to the main target, resulting in 61 simulated scenarios. Second, multiple segmentation models where trained on a U-Net network based on 80 training sets consisting of GBM cases with annotated gross tumor volume (GTV) and edema structures. On 20 test cases, 5 different trained models and a majority voting method were used to predict the GTV and edema. The amount of outliers on the predictions were determined, as well as their size and distance from the actual target. RESULTS: We found that plans containing outliers result in an increased dose to healthy brain tissue. The extent of the dose effect is dependent on the relative size, location and the distance to the main targets and involved OARs. Generally, the larger the absolute outlier volume and the distance to the target the higher the potential dose effect. For 120 predicted GTV and edema structures, we found 1887 outliers. After construction of the planning treatment volume (PTV), 137 outliers remained with a mean distance to the target of 38.5 ± 5.0 mm and a mean size of 1010.8 ± 95.6 mm3. We also found that majority voting of DL results is capable to reduce outliers. CONCLUSIONS: This study shows that there is a severe risk of false positive outliers in current DL predictions of target structures. Additionally, these errors will have an evident detrimental impact on the dose and therefore could affect treatment outcome.

Organ-at-risk sparing with dynamic trajectory radiotherapy for head and neck cancer: comparison with volumetric arc therapy on a publicly available library of cases.

BACKGROUND: Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation during beam-on. The aim of the study is to establish DTRT path-finding strategies, demonstrate deliverability and dosimetric accuracy and compare DTRT to state-of-the-art VMAT for common head and neck (HN) cancer cases. METHODS: A publicly available library of seven HN cases was created on an anthropomorphic phantom with all relevant organs-at-risk (OARs) delineated. DTRT plans were generated with beam incidences minimizing fractional target/OAR volume overlap and compared to VMAT. Deliverability and dosimetric validation was carried out on the phantom. RESULTS: DTRT and VMAT had similar target coverage. For three locoregionally advanced oropharyngeal carcinomas and one adenoid cystic carcinoma, mean dose to the contralateral salivary glands, pharynx and oral cavity was reduced by 2.5, 1.7 and 3.1 Gy respectively on average with DTRT compared to VMAT. For a locally recurrent nasopharyngeal carcinoma, D0.03 cc to the ipsilateral optic nerve was above tolerance (54.0 Gy) for VMAT (54.8 Gy) but within tolerance for DTRT (53.3 Gy). For a laryngeal carcinoma, DTRT resulted in higher dose than VMAT to the pharynx and brachial plexus but lower dose to the upper oesophagus, thyroid gland and contralateral carotid artery. For a single vocal cord irradiation case, DTRT spared most OARs better than VMAT. All plans were delivered successfully on the phantom and dosimetric validation resulted in gamma passing rates of 93.9% and 95.8% (2%/2 mm criteria, 10% dose threshold). CONCLUSIONS: This study provides a proof of principle of DTRT for common HN cases with plans that were deliverable on a C-arm linac with high accuracy. The comparison with VMAT indicates substantial OAR sparing could be achieved.

Development of a Monte Carlo based robustness calculation and evaluation tool.

BACKGROUND: Evaluating plan robustness is a key step in radiotherapy. PURPOSE: To develop a flexible Monte Carlo (MC)-based robustness calculation and evaluation tool to assess and quantify dosimetric robustness of intensity-modulated radiotherapy (IMRT) treatment plans by exploring the impact of systematic and random uncertainties resulting from patient setup, patient anatomy changes, and mechanical limitations of machine components. METHODS: The robustness tool consists of two parts: the first part includes automated MC dose calculation of multiple user-defined uncertainty scenarios to populate a robustness space. An uncertainty scenario is defined by a certain combination of uncertainties in patient setup, rigid intrafraction motion and in mechanical steering of the following machine components: angles of gantry, collimator, table-yaw, table-pitch, table-roll, translational positions of jaws, multileaf-collimator (MLC) banks, and single MLC leaves. The Swiss Monte Carlo Plan (SMCP) is integrated in this tool to serve as the backbone for the MC dose calculations incorporating the uncertainties. The calculated dose distributions serve as input for the second part of the tool, handling the quantitative evaluation of the dosimetric impact of the uncertainties. A graphical user interface (GUI) is developed to simultaneously evaluate the uncertainty scenarios according to user-specified conditions based on dose-volume histogram (DVH) parameters, fast and exact gamma analysis, and dose differences. Additionally, a robustness index (RI) is introduced with the aim to simultaneously evaluate and condense dosimetric robustness against multiple uncertainties into one number. The RI is defined as the ratio of scenarios passing the conditions on the dose distributions. Weighting of the scenarios in the robustness space is possible to consider their likelihood of occurrence. The robustness tool is applied on IMRT, a volumetric modulated arc therapy (VMAT), a dynamic trajectory radiotherapy (DTRT), and a dynamic mixed beam radiotherapy (DYMBER) plan for a brain case to evaluate the robustness to uncertainties of gantry-, table-, collimator angle, MLC, and intrafraction motion. Additionally, the robustness of the IMRT, VMAT, and DTRT plan against patient setup uncertainties are compared. The robustness tool is validated by Delta4 measurements for scenarios including all uncertainty types available. RESULTS: The robustness tool performs simultaneous calculation of uncertainty scenarios, and the GUI enables their fast evaluation. For all evaluated plans and uncertainties, the planning target volume (PTV) margin prevented major clinical target volume (CTV) coverage deterioration (maximum observed standard deviation of D 98 % CTV $D98{\% _{{\rm{CTV}}}}$ was 1.3 Gy). OARs close to the PTV experienced larger dosimetric deviations (maximum observed standard deviation of D 2 % chiasma $D2{\% _{{\rm{chiasma}}}}$ was 14.5 Gy). Robustness comparison by RI evaluation against patient setup uncertainties revealed better dosimetric robustness of the VMAT and DTRT plans as compared to the IMRT plan. Delta4 validation measurements agreed with calculations by >96% gamma-passing rate (3% global/2 mm). CONCLUSIONS: The robustness tool was successfully implemented. Calculation and evaluation of uncertainty scenarios with the robustness tool were demonstrated on a brain case. Effects of patient and machine-specific uncertainties and the combination thereof on the dose distribution are evaluated in a user-friendly GUI to quantitatively assess and compare treatment plans and their robustness.

Prospective superficial EPR in-vivo dosimetry study during hypofractionated radiotherapy of breast cancer patients treated with helical tomotherapy.

BACKGROUND: In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). METHODS: In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient's skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. RESULTS: Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. CONCLUSION: Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Implementation and experimental validation of a robust hybrid direct aperture optimization approach for mixed-beam radiotherapy.

PURPOSE: The objectives of the work presented in this paper were to (1) implement a robust-optimization method for deliverable mixed-beam radiotherapy (MBRT) plans within a previously developed MBRT planning framework; (2) perform an experimental validation of the delivery of robust-optimized MBRT plans; and (3) compare PTV-based and robust-optimized MBRT plans in terms of target dose robustness and organs at risk (OAR) sparing for clinical head and neck and brain patient cases. METHODS: A robust-optimization method, which accounts for translational setup errors, was implemented within a previously developed treatment planning framework for MBRT. The framework uses a hybrid direct aperture optimization method combining column generation and simulated annealing. A robust plan was developed and then delivered to an anthropomorphic head phantom using the Developer Mode of a TrueBeam linac. Planar dose distributions were measured and compared to the planned dose. Robust-optimized and PTV-based plans were developed for three clinical patient cases consisting of two head and neck cases and one brain case. The plans were compared in terms of the robustness to 5 mm shifts of the target volume dose as well as in terms of OAR sparing. RESULTS: Using a gamma criterion of 3%/2 mm and a dose threshold of 10%, the agreement between film measurements and dose calculations was better than 97.7% for the total plan and better than 95.5% for the electron component of the plan. For the two head and neck patient cases, the average clinical target volume (CTV) dose homogeneity index (V95%-V107%) over all the considered setup error scenarios was on average 19% lower for the PTV-based plans and it had a larger standard deviation. The robust-optimized plans achieved, on average, a 20% reduction in the OAR doses compared to the PTV-based plans. For the brain patient case, the CTV dose homogeneity index was similar for the two plans, while the OAR doses were 22% lower, on average, for the robust-optimized plan. No clear trend in terms of electron contributions was found across the three patient cases, although robust-optimized plans tended toward higher electron beam energies. CONCLUSIONS: A framework for robust optimization of deliverable MBRT plans has been developed and validated. PTV-based MBRT were found to not be robust to setup errors, while the dose delivered by the robust-optimized plans were clinically acceptable for all considered error scenarios and had better OAR sparing. This study shows that the robust optimization is a promising alternative to conventional PTV margins for MBRT.

Suitability of superficial electron paramagnetic resonance dosimetry for in vivo measurement and verification of cumulative total doses during IMRT: A proof of principle.

PURPOSE: The present study investigates superficial in vivo dosimetry (IVD) by means of a previously proposed electron paramagnetic resonance (EPR) dosimetry system aiming at measuring and verifying total doses delivered by complex radiotherapy treatments. In view of novel regulatory requirements in Germany, differences between measured and planned total doses to the EPR dosimeters are analyzed and compared to reporting thresholds for significant occurrences. METHODS: EPR dosimeters, each consisting of one lithium formate monohydrate (LFM) and one polycrystalline l-alanine (ALA) pellet, were attached to the surface of an anthropomorphic head phantom. Three head and neck treatments with total target doses ranging from 30 to 64Gy were fully delivered to the phantom by helical tomotherapy. During each treatment, eight EPR dosimeters were placed at distinct spots: (i) within or next to the planning target volume (PTV), (ii) near to organs at risk including the parotids and the lenses, (iii) at the thyroid lying out-of-field. EPR read out was always performed after all fractions were delivered. EPR results were compared to thermoluminescence dosimeter (TLD) measurements and to the planned total doses derived from the treatment planning system (TPS). Planned total doses to the EPR dosimeters ranged from about 2 to 64Gy. RESULTS: By taking uncertainties into account, the measured and planned doses were in good agreement. Exceptions occurred mainly at the thyroid (out-of-field) and lenses (extreme sparing). The maximum total dose difference between EPR results and corresponding planned doses was 1.3Gy occurring at the lenses. Remarkably, each LFM and ALA pellet placed within or next to the PTV provided dose values that were within ±4% of the planned dose. Dose deviations from planned dose values were comparable for EPR and TLD measurements. CONCLUSION: The results of this proof of principle study suggests that superficial EPR-IVD is applicable in a wide dose range and in various irradiation conditions - being a valuable tool for monitoring cumulative total doses delivered by complex IMRT treatments. EPR-IVD in combination with helical tomotherapy is suitable to reliably detect local dose deviations at superficial dosimeter spots in the order of current national reporting thresholds for significant occurrences (i.e. 10%/4Gy).

A practical EPR dosimetry system for routine use in radiotherapy: uncertainty analysis of lithium formate dosimeters at the therapeutic dose level.

In electron paramagnetic resonance (EPR) dosimetry, solid dosimeter materials such as alanine (AL) or, more recently, lithium formate monohydrate (LFM) are typically used. These materials offer high potential for applications in radiotherapy based on their favorable dosimetric properties. Nevertheless, EPR dosimetry is not widespread in the clinics. This work presents an uncertainty analysis of EPR dosimetry in the dose range from 1 to 70 Gy using a compact spectrometer and applying a practical procedure being suitable for routine use in radiotherapy. The performances of self-pressed LFM pellets and commercial AL pellets are compared side by side. All pellets had a diameter of 4 mm and a height of 2 mm (AL) or 4 mm (LFM). The mean pellet mass was 35.81 mg and 73.81 mg for AL and LFM, respectively. Before irradiation, the pellets were stored for at least 8 weeks at 34 ± 2% relative humidity. For irradiation, the pellets were put inside an airtight capsule. In total, 25 pellets per material were examined. The pellets were irradiated at a temperature of 25 ± 2.5 (2σ) °C to doses of either 1, 5, 20, 50 or 70 Gy (five pellets per dose value and material) by a clinical 6 MV photon beam. Measurement uncertainties were obtained from five independent readouts per pellet within five weeks following irradiation using a benchtop EPR spectrometer. The measurement time of a single readout was restricted to 10 min per pellet. Dose values were derived from EPR signal amplitudes using a specifically developed spectral fitting procedure. Signal fading characteristics were analyzed and taken into account during evaluation. The relative dose uncertainties (1σ) for a single readout at doses ≥ 5 Gy are below 2.8% (AL) and 1.1% (LFM) but increase to 12.3% (AL) and 2.6% (LFM) at 1 Gy. By averaging five independent readouts, the uncertainties at 1 Gy decrease to 2.6% (AL) and 0.8% (LFM). In terms of dose uncertainty, the LFM pellets are superior to the commercial AL pellets owing to their narrower EPR spectrum and approximately doubled mass resulting in higher EPR signal intensities. In case of the LFM pellets, the EPR dosimetry system shows a high level of precision (< 3%) down to 1 Gy being preferable for applications in radiotherapy. The uncertainties can be further decreased by averaging multiple dose values from independent readouts.

Fully automated brain resection cavity delineation for radiation target volume definition in glioblastoma patients using deep learning.

BACKGROUND: Automated brain tumor segmentation methods are computational algorithms that yield tumor delineation from, in this case, multimodal magnetic resonance imaging (MRI). We present an automated segmentation method and its results for resection cavity (RC) in glioblastoma multiforme (GBM) patients using deep learning (DL) technologies. METHODS: Post-operative, T1w with and without contrast, T2w and fluid attenuated inversion recovery MRI studies of 30 GBM patients were included. Three radiation oncologists manually delineated the RC to obtain a reference segmentation. We developed a DL cavity segmentation method, which utilizes all four MRI sequences and the reference segmentation to learn to perform RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) and estimated volume measurements. RESULTS: Median DC of the three radiation oncologist were 0.85 (interquartile range [IQR]: 0.08), 0.84 (IQR: 0.07), and 0.86 (IQR: 0.07). The results of the automatic segmentation compared to the three different raters were 0.83 (IQR: 0.14), 0.81 (IQR: 0.12), and 0.81 (IQR: 0.13) which was significantly lower compared to the DC among raters (chi-square = 11.63, p = 0.04). We did not detect a statistically significant difference of the measured RC volumes for the different raters and the automated method (Kruskal-Wallis test: chi-square = 1.46, p = 0.69). The main sources of error were due to signal inhomogeneity and similar intensity patterns between cavity and brain tissues. CONCLUSIONS: The proposed DL approach yields promising results for automated RC segmentation in this proof of concept study. Compared to human experts, the DC are still subpar.

Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy.

This review details and discusses the technological quality requirements to ensure the desired quality for stereotactic radiotherapy using photon external beam radiotherapy as defined by the DEGRO Working Group Radiosurgery and Stereotactic Radiotherapy and the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The covered aspects of this review are 1) imaging for target volume definition, 2) patient positioning and target volume localization, 3) motion management, 4) collimation of the irradiation and beam directions, 5) dose calculation, 6) treatment unit accuracy, and 7) dedicated quality assurance measures. For each part, an expert review for current state-of-the-art techniques and their particular technological quality requirement to reach the necessary accuracy for stereotactic radiotherapy divided into intracranial stereotactic radiosurgery in one single fraction (SRS), intracranial fractionated stereotactic radiotherapy (FSRT), and extracranial stereotactic body radiotherapy (SBRT) is presented. All recommendations and suggestions for all mentioned aspects of stereotactic radiotherapy are formulated and related uncertainties and potential sources of error discussed. Additionally, further research and development needs in terms of insufficient data and unsolved problems for stereotactic radiotherapy are identified, which will serve as a basis for the future assignments of the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The review was group peer-reviewed, and consensus was obtained through multiple working group meetings.

Evaluation of a new software prototype for frameless radiosurgery of arteriovenous malformations.

BACKGROUND: In order to locate an arteriovenous malformation, typically, a digital subtraction angiography (DSA) is carried out. To use the DSA for target definition an accurate image registration between CT and DSA is required. Carrying out a non-invasive, frameless procedure, registration of the 2D-DSA images with the CT is critical. A new software prototype is enabling this frameless procedure. The aim of this work was to evaluate the prototype in terms of targeting accuracy and reliability based on phantom measurements as well as with the aid of patient data. In addition, the user's ability to recognize registration mismatches and quality was assessed. METHODS: Targeting accuracy was measured with a simple cubic, as well as with an anthropomorphic head phantom. Clearly defined academic targets within the phantoms were contoured on the CT. These reference structures were compared with the structures generated within the prototype. A similar approach was used with patient data, where the clinically contoured target served as the reference structure. An important error source decreasing the target accuracy comes from registration errors between CT and 2D-DSA. For that reason, the tools in BC provided to the user to check these registrations are very important. In order to check if the user is able to recognize registration errors, a set of different registration errors was introduced to the correctly registered CT and 2D-DSA image data sets of three different patients. Each of six different users rated the whole set of registrations within the prototype. RESULTS: The target accuracy of the prototype was found to be below 0.04 cm for the cubic phantom and below 0.05 cm for the anthropomorphic head phantom. The mean target accuracy for the 15 patient cases was found to be below 0.3 cm. In the registration verification part, almost all introduced registration errors above 1° or 0.1 cm were detected by the six users. Nevertheless, in order to quantify and categorize the possibility to detect mismatches in the registration process more data needs to be evaluated. CONCLUSION: Our study shows, that the prototype is a useful tool that has the potential to fill the gap towards a frameless procedure when treating AVMs with the aid of 2D-DSA images in radiosurgery. The target accuracy of the prototype is similar to other systems already established in clinical routine.

Adaptive step size algorithm to increase efficiency of proton macro Monte Carlo dose calculation.

PURPOSE: To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method. METHODS: The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton's longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT. RESULTS: For material interfaces perpendicular to a proton's direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4. CONCLUSION: An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT.