Van Herk Margin Formula Research Articles

Planning Target Volume Margin Quantification of Retroperitoneal Tumors Using Robotic Stereotactic Body Radiotherapy with Spine Tracking

Stereotactic body radiotherapy treatment (SBRT) is an effective modality for treating primary and oligometastatic malignant lesions. Appropriate planning target volume (PTV) margins are essential when delivering SBRT to maximize target prescription coverage while minimizing dose to surrounding organs-at-risk. Spine tracking uses boney spinal anatomy as a surrogate for tumor localization during treatment delivery on robotic linear accelerator platforms that employ intrafraction kV x-ray imaging. The aim of this study was to quantify the PTV margin needed when spine tracking was used for tumor localization when treating retroperitoneal metastatic lesions with robotic SBRT. A single institution chart review was performed and identified 16 patients with retroperitoneal tumors treated stereotactically over 19 courses in 103 fractions. Daily cone-beam computed tomography (CBCT) images that were registered based on tumor position at the time of treatment were analyzed. Rigid registrations were re-performed aligning the position of the spine on the CBCT relative to its position on the planning CT. Shifts from the treatment position were recorded and per-patient mean shifts and standard deviations were calculated. Van Herk's margin recipe was used to determine the additional PTV margin required if spine tracking was used instead of soft tissue alignment. Patient tumors were stratified and compared based on proximity to the vertebral column (≤1 cm vs >1 cm) and location within the retroperitoneum (superior vs inferior to the renal artery). Student's t-test was used to compare statistical differences of shifts based on location. The additional margins calculated by van Herk's margin recipe to adequately cover the target volumes within the 95% isodose surface for 90% of the entire patient cohort in the vertical, longitudinal, and lateral directions were 2.7, 2.8, and 2.8 mm, respectively. When tumors were stratified by proximity to the vertebral column, average longitudinal (p<0.001) and total shifts (p<0.001) were statistically significant. Isometric PTV expansions of 3, 4, and 5 mm would have encompassed 55%, 76%, and 86% of the maximum total shifts for lesions >1 cm from the vertebral column versus 94%, 100%, and 100% for lesions ≤1 cm. When stratified by location within the retroperitoneum, isometric PTV expansions of 3, 4, and 5 mm would have encompassed 82%, 94%, and 100% of the maximum total shifts for lesions superior to the renal artery versus 78%, 94%, and 98% for lesions inferior to the renal artery. When treating retroperitoneal tumors with robotic SBRT, a minimum isometric margin expansion between 3 to 5 mm when creating the PTV is recommended if spine tracking is used for intrafraction tumor localization. Target volumes adjacent to the vertebral column may have PTV margins decreased to ≤4 mm without compromising target coverage.

Comparison of cone beam computed tomography (CBCT)-based image guided radiotherapy approaches in the reduction of setup uncertainties during deep inspiration breath-hold radiotherapy (DIBH-RT) for left breast cancer

Advances in radiotherapy has allowed higher cure rates for cancer such as breast and thus, it is important to reduce the possible radiation side effects from exposure to other organs such as the heart. Deep inspiration breath-hold radiotherapy technique (DIBH-RT) significantly reduces cardiac dose during left breast radiotherapy, but the patient setup requires careful adoption of image guidance radiotherapy technique (IGRT) approaches. This study investigates the effectiveness of cone beam computed tomography (CBCT)-based IGRT protocols for patients' inter-fraction set-up correction. Setup error data from two patients’ groups; A and B who had daily CBCT and first 3 fractions + weekly CBCT imaging respectively, were analysed. This constitutes a total of 13 left breast cancer patients treated using DIBH-RT at Advanced Medical Dental Institute (AMDI), Universiti Sains Malaysia (USM), Malaysia. The analysis was performed using MATLAB (MathWorks Inc Natick MA) to calculate the mean setup errors. The population systematic (∑) and random (σ) errors were calculated for non-IGRT, online, and two offline IGRT protocols; no action level (NAL) and extended no action level (eNAL) for each patient group. The corresponding planning target volume (PTV) margin and its percentage reduction for each of the IGRT protocols were established using van Herk margin recipe. The least population systematic setup error and PTV margin were found when using the online protocol (∑X/Y/Z = 0.17/0.22/0.31 mm; PTVX/Y/Z = 0.71/0.92/1.28 mm) followed by eNAL (∑X/Y/Z = 1.32/1.94/1.85 mm; PTVX/Y/Z = 5.75/7.99/8.46 mm), NAL (∑X/Y/Z = 1.45/2.26/1.84 mm; PTVX/Y/Z = 6.27/8.93/8.46 mm) and non-IGRT (∑X/Y/Z = 2.28/3.35/3.10 mm; PTVX/Y/Z = 7.77/10.85/10.93 mm). Up to 90% in PTV margin reduction is achieved with the online protocol. In conclusion, the use of IGRT during DIBH-RT for left breast cancer patients reduces patient set-up error and allows the use of tighter PTV margins. The online IGRT protocol was shown to be more effective in the reduction of errors and the PTV margin followed by eNAL and NAL offline IGRT protocols.

In-vivo quality assurance of dynamic tumor tracking (DTT) for liver SABR using EPID images.

To assess dynamic tumor tracking (DTT) target localization uncertainty for in-vivo marker-based stereotactic ablative radiotherapy (SABR) treatments of the liver using electronic-portal-imaging-device (EPID) images. The Planning Target Volume (PTV) margin contribution for DTT is estimated. Phantom and patient EPID images were acquired during non-coplanar 3DCRT-DTT delivered on a Vero4DRT linac. A chain-code algorithm was applied to detect Multileaf Collimator (MLC)-defined radiation field edges. Gold-seed markers were detected using a connected neighbor algorithm. For each EPID image, the absolute differences between the measured center-of-mass (COM) of the markers relative to the aperture-center (Tracking Error, (ET )) was reported in pan, tilt, and 2D-vector directions at the isocenter-plane. An acrylic cube phantom implanted with gold-seed markers was irradiated with non-coplanar 3DCRT-DTT beams and EPID images collected. Patient Study: Eight liver SABR patients were treated with non-coplanar 3DCRT-DTT beams. All patients had three to four implanted gold-markers. In-vivo EPID images were analyzed. Phantom Study: On the 125 EPID images collected, 100% of the markers were identified. The average±SD of ET were 0.24±0.21, 0.47±0.38, and 0.58±0.37mm in pan, tilt and 2D directions, respectively. Patient Study: Of the 1430 EPID patient images acquired, 78% had detectable markers. Over all patients, the average±SD of ET was 0.33±0.41mm in pan, 0.63±0.75mm in tilt and 0.77±0.80mm in 2D directions The random 2D-error, σ, for all patients was 0.79mm and the systematic 2D-error, Σ, was 0.20mm. Using the Van Herk margin formula 1.1mm planning target margin can represent the marker based DTT uncertainty. Marker-based DTT uncertainty can be evaluated in-vivo on a field-by-field basis using EPID images. This information can contribute to PTV margin calculations for DTT.

Towards mid-position based Stereotactic Body Radiation Therapy using online magnetic resonance imaging guidance for central lung tumours.

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac.Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk’s margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins.Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; ). Automatically derived margins agreed within one millimeter with manually derived margins.Conclusions: This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage.

Assessment of planning target volume margins in 1.5 T magnetic resonance‐guided stereotactic body radiation therapy for localized prostate cancer

AbstractObjectiveWe aimed to determine the planning target volume margins applicable to magnetic resonance‐guided stereotactic body radiation therapy (MRgSBRT) of localized prostate cancer on a 1.5 T MR‐Linac.MethodsA total of 10 patients with low‐ to intermediate‐risk prostate cancer were retrospectively enrolled. All patients received five‐fraction MRgSBRT treatments, and underwent daily endorectal ballooning and bladder control. Five patients were implanted with the hydrogel rectal spacer. Three MR scans at each fraction were acquired to evaluate the intrafractional prostate motion. The required planning target volume margin was determined using the van Herk margin recipe based on direct MR‐MR prostate registration. The set‐up margin for localization using bony anatomy was also estimated.ResultsThe mean and standard deviation of translational displacement in left‐right (LR), superior‐inferior (SI), and anterior‐posterior (AP) directions were –0.3 ± 0.7, 2.0 ± 1.5, and 1.4 ± 1.1 mm, respectively. Planning target volume margins over the MRgSBRT fraction duration were 2.8 (LR), 5.3 (SI), and 3.9 mm (AP). Set‐up margins were estimated to 2.6 (LR), 3.3 (SI), and 3.3 mm (AP). Prostate motion increased considerably with treatment duration. Adapt‐to‐position had smaller intrafractional motions than adapt‐to‐shape. The rectal spacer insignificantly (p &gt; 0.1) reduced the prostate motion in SI and AP.ConclusionOnline workflow efficiency enhancement and intrafractional motion monitoring are vital for planning target volume margin reduction and precision enhancement in MRgSBRT.

Ramifications of Setup Margin Use During Frameless Stereotactic Radiosurgery/Therapy With Gamma Knife Icon Cone-Beam Computed Tomography (CBCT): A Dosimetric Study.

ObjectiveThe objective is to explore the possibility of optimal/rational application of setup margin during treatment planning for frameless stereotactic Gamma Knife radiosurgery/therapy.MethodsUncertainty measurements for frameless Gamma Knife Icon treatment were used to calculate the necessary setup margin via four different published recipes and these margins were subsequently applied to treatment plans of 30 previously treated patients and replans were generated meeting comparable plan quality metrics. All plans were then analyzed based on the ability to maintain normal tissue dose tolerances and the relative increase in target dose coverage probability using a pass/fail scoring system based on published normal tissue dose constraints and an in-house developed optimal scoring method.ResultsGross tumor volume/planning target volume (GTV/PTV) size strongly correlated with both meeting normal tissue tolerances and optimal scores for single fraction plans corroborating published clinical outcomes. The Van Herk Margin Formula (VHMF) and Parker margin formulae were indicated as good candidates for high probabilities of both meeting normal tissue goals and high optimal scores which generally translated to just over 1 mm in GTV to PTV margin.ConclusionFor single fraction treatment, GTV size is highly significant in predicting failure to meet normal tissue goals whereas whether setup margin was used was not a significant predictor. Setup margin can rationally be applied when fraction number is dictated by clinically indicated metrics regarding GTV size of greater or less than 4 cc. 1 mm is a reasonable practical application of margin added to GTV to ensure physical prescription dose target coverage for most cases when clinically desired based on disease type and intended outcome.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy

PurposeWe conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and MaterialsPatients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. ResultsThe trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. ConclusionsTraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

Automated algorithm for calculation of setup corrections and planning target volume margins for offline image-guided radiotherapy protocols.

PurposeEach radiotherapy center should have a site‐specific planning target volume (PTV) margins and image‐guided (IG) radiotherapy (IGRT) correction protocols to compensate for the geometric errors that can occur during treatment. This study developed an automated algorithm for the calculation and evaluation of these parameters from cone beam computed tomography (CBCT)‐based IG‐intensity modulated radiotherapy (IG‐IMRT) treatment.Methods and materialsA MATLAB algorithm was developed to extract the setup errors in three translational directions (x, y, and z) from the data logged by the CBCT system during treatment delivery. The algorithm also calculates the resulted population setup error and PTV margin based on the van Herk margin recipe and subsequently estimates their respective values for no action level (NAL) and extended no action level (eNAL) offline correction protocols. The algorithm was tested on 25 head and neck cancer (HNC) patients treated using IG‐IMRT.ResultsThe algorithms calculated that the HNC patients require a PTV margin of 3.1, 2.7, and 3.2 mm in the x‐, y‐, and z‐direction, respectively, without IGRT. The margin can be reduced to 2.0, 2.2, and 3.0 mm in the x‐, y‐, and z‐direction, respectively, with NAL and 1.6, 1.7, and 2.2 mm in the x‐, y‐, and z‐direction, respectively, with eNAL protocol. The results obtained were verified to be the same with the margins calculated using an Excel spreadsheet. The algorithm calculates the weekly offline setup error correction values automatically and reduces the risk of input data error observed in the spreadsheet.ConclusionsIn conclusion, the algorithm provides an automated method for optimization and reduction of PTV margin using logged setup errors from CBCT‐based IGRT.

New target volume delineation and PTV strategies to further personalise radiotherapy

Target volume delineation uncertainty (DU) is arguably one of the largest geometric uncertainties in radiotherapy that are accounted for using planning target volume (PTV) margins. Geometrical uncertainties are typically derived from a limited sample of patients. Consequently, the resultant margins are not tailored to individual patients. Furthermore, standard PTVs cannot account for arbitrary anisotropic extensions of the target volume originating from DU. We address these limitations by developing a method to measure DU for each patient by a single clinician. This information is then used to produce PTVs that account for each patient’s unique DU, including any required anisotropic component. We do so using a two-step uncertainty evaluation strategy that does not rely on multiple samples of data to capture the DU of a patient’s gross tumour volume (GTV) or clinical target volume. For simplicity, we will just refer to the GTV in the following. First, the clinician delineates two contour sets; one which bounds all voxels believed to have a probability of belonging to the GTV of 1, while the second includes all voxels with a probability greater than 0. Next, one specifies a probability density function for the true GTV boundary position within the boundaries of the two contours. Finally, a patient-specific PTV, designed to account for all systematic errors, is created using this information along with measurements of the other systematic errors. Clinical examples indicate that our margin strategy can produce significantly smaller PTVs than the van Herk margin recipe. Our new radiotherapy target delineation concept allows DUs to be quantified by the clinician for each patient, leading to PTV margins that are tailored to each unique patient, thus paving the way to a greater personalisation of radiotherapy.

Coping with interfraction time trends in tumor setup.

PurposeInterfraction tumor setup variations in radiotherapy are often reduced with image guidance procedures. Clinical target volume (CTV)–planning target volume (PTV) margins are then used to deal with residual errors. We have investigated characterization of setup errors in patient populations with explicit modelling of occurring interfraction time trends.MethodsThe core of a “trendline characterization” of observed setup errors in a population is a distribution of trendlines, each obtained by fitting a straight line through a patient's daily setup errors. Random errors are defined as daily deviations from the trendline. Monte Carlo simulations were performed to predict the impact of offline setup correction protocols on residual setup errors in patient populations with time trends. A novel CTV‐PTV margin recipe was derived that assumes that systematic underdosing of tumor edges in multiple consecutive fractions, as caused by trend motion, should preferentially be avoided. Similar to the well‐known approach by van Herk et al. for conventional error characterization (no explicit modelling of trends), only a predefined percentage of patients (generally 10%) was allowed to have nonrandom (systematic + trend) setup errors outside the margin. Additionally, a method was proposed to avoid erroneous results in Monte Carlo simulations with setup errors, related to decoupling of error sources in characterizations. The investigations were based on a database of daily measured setup errors in 835 prostate cancer patients that were treated with 39 fractions, and on Monte Carlo–generated patient populations with time trends.ResultsWith conventional characterization of setup errors in patient populations with time trends, predicted standard deviations of residual systematic errors (Σres) after application of an offline correction protocol could be underestimated by more than 50%, potentially resulting in application of too small margins. With the new trendline characterization this was avoided. With the novel CTV‐PTV margin recipe with an allowed 10% of patients having nonrandom errors outside the margin, the observed percentage was 10.0% ± 0.2%. When using conventional characterization of errors and the van Herk margin recipe, on average 58.0% ± 24.3% of patients had errors outside the margin, while 10% was prescribed. For populations with no time trends, the novel recipe simplifies to the generally applied M=2.5Σ+0.7σ formula proposed by van Herk et al.ConclusionsIn populations with time trends in setup errors, the use of trendline characterizations in Monte Carlo simulations for establishment of residual errors after a setup correction protocol can avoid application of erroneous margins. The novel margin recipe can be used to accurately control the percentage of patients with nonrandom errors outside the margin. In case of daily image guidance of patients with multiple targets with differential motion, the recipe can be used to establish margins for the targets that are not the primary target for the image guidance (e.g., nodal regions). Probabilistic planning might be improved by using trendline characterization for modelling of setup errors. Population analyses of interfraction setup errors need to take into account potential time trends.

1 Comparison of target coverage for two motion-encompassing methods for lung stereotactic body radiotherapy by using in-treatment 4D cone-beam CT

Introduction Recently, in-treatment 4D cone-beam CT (4D-CBCTin-treat) has been implemented in clinic allowing the acquisition of respiratory correlated CBCT projections concurrently with the beam delivery. With this imaging modality, the actual 4D target locations during treatment can be visualized at the end of each fraction. 4D-CBCTin-treat provides reliable information to evaluate actual target coverage during treatment and to verify planning target volume (PTV) adequacy for lung stereotactic body radiotherapy (SBRT). The purpose of this study was to compare in-treatment target coverage for two motion-encompassing PTV strategies: an internal target volume (ITV) based approach and the mid-ventilation (MidV) based approach. Methods Data from 27 lung cancer patients treated with a frameless SBRT technique using a volumetric modulated arc therapy (VMAT) were selected. For each patient, a 4D-CT was used for treatment planning. For the ITV-based approach, we applied the PTV setting currently used at our institute for lung SBRT: ITV was determined by contouring the target on 10 respiration phases and a generic 4 mm margin was then added to create the PTV. For the MidV-based approach, PTV was defined around the tumor closest to its time-weighted mean position (MidV CT phase) using the Van Herk margin recipe [1] . At each fraction, the target was localized using a 4D-CBCT on-line registration procedure and a 4D-CBCTin-treat was acquired during the VMAT delivery. The clinical target volume (CTV) was delineated in 10 respiration phases on all 4D-CBCTin-treat images reconstructed during the treatment course. We defined target coverage per treatment as the percentage of the CTV included within the PTV averaged over respiration phases and fractions. Results A total of 93 4D-CBCTin-treat were delineated. Mean target coverage per treatment was 98.6% (min: 93.4%) and 98.9% (min: 93.5%) for ITV and MidV approaches respectively. Mean PTV volume was 18.1 cc (min: 2.9 cc, max: 50.7 cc) and 18.6 cc (min: 5.4 cc, max: 49.9 cc) for ITV and MidV approaches respectively. Compared to the MidV, the ITV-based strategy using a 4 mm PTV margin resulted to a non-statistically significant difference neither for target coverage (p = 0.401) nor for PTV volume (p = 0.186). Conclusions With a fast VMAT delivery technique and a 4D image guidance protocol, a 4 mm PTV margin can be safely applied when using the ITV-based strategy for frameless lung SBRT. This ITV-based PTV setting provides equivalent irradiated volumes and tumor coverage than the MidV approach.

Exploring the Margin Recipe for Online Adaptive Radiation Therapy for Intermediate-Risk Prostate Cancer: An Intrafractional Seminal Vesicles Motion Analysis

To provide a benchmark for seminal vesicle (SV) margin selection to account for intrafractional motion and to investigate the effectiveness of 2 motion surrogates in predicting intrafractional SV coverage. Fifteen prostate patients were studied. Each patient had 5 pairs (1 patient had 4 pairs) of pretreatment and posttreatment cone beam CTs (CBCTs). Each pair of CBCTs was registered on the basis of prostate fiducial markers. All pretreatment SVs were expanded with 1-, 2-, 3-, 4-, 5-, and 8-mm isotropic margins to form a series of planning target volumes, and their intrafractional coverage to the posttreatment SV determined the "ground truth" for exact coverage. Two motion surrogates, the center of mass (COM) and the border of contour, were evaluated by the use of Pearson product-moment correlation coefficient and exponential fitting for predicting SV underdosage. Action threshold of each surrogate was calculated. The margin for each surrogate was calculated according to a traditional margin recipe. Ninety-five percent posttreatment SV coverage was achieved in 9%, 53%, 73%, 86%, 95%, and 97% of fractions with 1-, 2-, 3-, 4-, 5-, and 8-mm margins, respectively. The 5-mm margins provided 95% intrafractional SV coverage in over 90% of fractions. The correlation between the COM and border was weak, moderate, and strong in the left-right (L-R), anterior-posterior (A-P), and superior-inferior (S-I) directions, respectively. Exponential fitting gave the underdosage threshold of 4.5 and 7.0mm for the COM and border. The Van Herk margin recipe recommended 0-, 0.5-, and 0.8-mm margins in the L-R, A-P, and S-I directions based on the COM, and 1.2-, 3.9-, and 2.5-mm margins based on the border. Five-millimeter isotropic margins for the SV constitute the minimum required to mitigate the intrafractional motion. Both the COM and the border are acceptable predictors for SV underdosage with 4.5- and 7.0-mm action threshold. Traditional margin based on the COM or border underestimates the margin.

Quantification of vaginal motion associated with daily endorectal balloon placement during whole pelvis radiotherapy for gynecologic cancers

Background and purposeTo quantify intra-treatment vaginal motion in women treated with daily endorectal balloon (ERB) placement and external beam radiotherapy for gynecologic cancers. Materials and methodsEighteen post-hysterectomy women with gynecologic cancers underwent computed tomography (CT) simulation scans and daily treatment with ERB. Fiducial markers were placed at the vaginal apex prior to simulation and patients were counseled on a pre-treatment bladder filling protocol. Weekly to biweekly verification CT scans were used to calculate the intra-treatment change in bladder volumes, rectal volumes, and fiducial coordinates along all axes. The planning target volume (PTV) margins required to encompass 95% of intra-treatment fiducial movement were calculated using the van Herk margin recipe. ResultsThe median bladder volume was 223 (range, 29–879)cc for verification CT scans. Mean intra-treatment fiducial displacements were 1.7 (range, 0–9.1)mm, 2.9 (range, 0–15.5)mm, and 2.5 (range, 0–11.8)mm along the left–right (L/R), superior–inferior (S/I), and anterior–posterior (A/P) axes, respectively. The van Herk PTV margins were 3mm (L/R), 10mm (S/I) and 7mm (A/P). ConclusionWhen compared to existing studies, the use of daily ERB with post-hysterectomy radiotherapy reduces vaginal motion along the A/P axis. The impact of variable bladder filling on vaginal motion is most evident along the S/I axis.

Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer

ABSTRACTBackground. The bladder is a tumour site well suited for adaptive radiotherapy (ART) due to large inter-fractional changes, but it also displays considerable intra-fractional motion. The aim of this study was to assess target coverage with a clinically applied method for plan selection ART and to estimate population-based and patient-specific intra-fractional margins, also relevant for a future re-optimisation strategy.Material and methods. Nine patients treated in a clinical phase II ART trial of daily plan selection for bladder cancer were included. In the library plans, 5 mm isotropic margins were added to account for intra-fractional changes. Pre-treatment and weekly repeat magnetic resonance imaging (MRI) series were acquired in which a full three-dimensional (3D) volume was scanned every second min for 10 min (a total of 366 scans in 61 series). Initially, the bladder clinical target volume (CTV) was delineated in all scans. The t = 0 min scan was then rigidly registered to the planning computed tomography (CT) and plan selections were simulated using the CTV_0 (at t = 0 min). To assess intra-fractional motion, coverage of the CTV_10 (at t = 10 min) was quantified using the applied PTV. Population-based margins were calculated using the van Herk margin recipe while patient-specific margins were calculated using a linear model.Results. For 49% of the cases, the CTV_10 extended more than 5 mm outside the CTV_0. However, in 58 of the 61 cases (97%) CTV_10 was covered by the selected PTV. Population-based margins of 14 mm Sup/Ant, 9 mm Post and 5 mm Inf/Lat were sufficient to cover the bladder. Using patient-specific margins, the overlap between PTV and bowel-cavity was reduced from 137 cm3 with the plan selection strategy to 24 cm3.Conclusion. In this phase II ART trial, 5 mm isotropic margin for intra-fractional motion was sufficient even though considerable intra-fractional motion was observed. In online re-optimised ART, population-based margin can be applied although patient-specific margins are preferable.

An imaging evaluation of the simultaneously integrated boost breast radiotherapy technique.

IntroductionTo evaluate in-field megavoltage (MV) imaging of simultaneously integrated boost (SIB) breast fields to determine its feasibility in treatment verification for the SIB breast radiotherapy technique, and to assess whether the current-imaging protocol and treatment margins are sufficient.MethodsFor nine patients undergoing SIB breast radiotherapy, in-field MV images of the SIB fields were acquired on days that regular treatment verification imaging was performed. The in-field images were matched offline according to the scar wire on digitally reconstructed radiographs. The offline image correction results were then applied to a margin recipe formula to calculate safe margins that account for random and systematic uncertainties in the position of the boost volume when an offline correction protocol has been applied.ResultsAfter offline assessment of the acquired images, 96% were within the tolerance set in the current department-imaging protocol. Retrospectively performing the maximum position deviations on the Eclipse™ treatment planning system demonstrated that the clinical target volume (CTV) boost received a minimum dose difference of 0.4% and a maximum dose difference of 1.4% less than planned. Furthermore, applying our results to the Van Herk margin formula to ensure that 90% of patients receive 95% of the prescribed dose, the calculated CTV margins were comparable to the current departmental procedure used.ConclusionBased on the in-field boost images acquired and the feasible application of these results to the margin formula the current CTV-planning target volume margins used are appropriate for the accurate treatment of the SIB boost volume without additional imaging.

SU‐E‐J‐140: Availability of Using Diaphragm Matching in Stereotactic Body Radiotherapy (SBRT) at the Time in Breath‐Holding SBRT for Liver Cancer

Purpose:IGRT based on the bone matching may produce a larger target positioning error in terms of the reproducibility of the expiration breath hold. Therefore, the feasibility of the 3D image matching between planning CT image and pretreatment CBCT image based on the diaphragm matching was investigated.Methods:In fifteen‐nine liver SBRT cases, Lipiodol, uptake after TACE was outlined as the marker of the tumor. The relative coordinate of the isocenter obtained by the contrast matching was defined as the reference coordinate. The target positioning difference between diaphragm matching and bone matching were evaluated by the relative coordinate of the isocenter from the reference coordinate obtained by each matching technique. In addition, we evaluated PTV margins by van Herk setup margin formula.Results:The target positioning error by the diaphragm matching and the bone matching was 1.31±0.83 and 3.10±2.80 mm in the cranial‐caudal(C‐C) direction, 1.04±0.95 and 1.62±1.02 mm in the anterior‐posterior(A‐P) direction, 0.93±1.19 and 1.12±0.94 mm in the left‐right(L‐R) direction, respectively. The positioning error by the diaphragm matching was significantly smaller than the bone matching in the C‐C direction (p&lt;0.05). The setup margin of diaphragm matching and bone matching that we had calculated based on van Herk margin formula was 4.5mm and 6.2mm(C‐C), and 3.6mm and 6.3mm(A‐P), and 2.6mm and 4.5mm(L‐R), respectively.Conclusion:IGRT based on a diaphragm matching could be one alternative image matching technique for the positioning of the patients with liver tumor.

A novel method to quantify and compare anatomical shape: application in cervix cancer radiotherapy

Adaptive radiation therapy (ART) had been proposed to restore dosimetric deficiencies during treatment delivery. In this paper, we developed a technique of Geometric reLocation for analyzing anatomical OBjects' Evolution (GLOBE) for a numerical model of tumor evolution under radiation therapy and characterized geometric changes of the target using GLOBE. A total of 174 clinical target volumes (CTVs) obtained from 32 cervical cancer patients were analyzed. GLOBE consists of three main steps; step (1) deforming a 3D surface object to a sphere by parametric active contour (PAC), step (2) sampling a deformed PAC on 642 nodes of icosahedron geodesic dome for reference frame, and step (3) unfolding 3D data to 2D plane for convenient visualization and analysis. The performance was evaluated with respect to (1) convergence of deformation (iteration number and computation time) and (2) accuracy of deformation (residual deformation). Based on deformation vectors from planning CTV to weekly CTVs, target specific (TS) margins were calculated on each sampled node of GLOBE and the systematic (Σ) and random (σ) variations of the vectors were calculated. Population based anisotropic (PBA) margins were generated using van Herk's margin recipe. GLOBE successfully modeled 152 CTVs from 28 patients. Fast convergence was observed for most cases (137/152) with the iteration number of 65 ± 74 (average ± STD) and the computation time of 13.7 ± 18.6 min. Residual deformation of PAC was 0.9 ± 0.7 mm and more than 97% was less than 3 mm. Margin analysis showed random nature of TS-margin. As a consequence, PBA-margins perform similarly to ISO-margins. For example, PBA-margins for 90% patients' coverage with 95% dose level is close to 13 mm ISO-margins in the aspect of target coverage and OAR sparing. GLOBE demonstrates a systematic analysis of tumor motion and deformation of patients with cervix cancer during radiation therapy and numerical modeling of PBA-margin on 642 locations of CTV surface.

PlanJury: probabilistic plan evaluation revisited

Purpose: Over a decade ago, the 'Van Herk margin recipe paper' introduced plan evaluation through DVH statistics based on population distributions of systematic and random errors. We extended this work for structures with correlated uncertainties (e.g. lymph nodes or parotid glands), and considered treatment plans containing multiple (overlapping) dose distributions (e.g. conventional lymph node and hypo-fractionated tumor doses) for which different image guidance protocols may lead to correlated errors.Methods: A command-line software tool 'PlanJury' was developed which reads 3D dose and structure data exported from a treatment planning system. Uncertainties are specified by standard deviations and correlation coefficients. Parameters control the DVH statistics to be computed: e.g. the probability of reaching a DVH constraint, or the dose absorbed at given confidence in a (combined) volume. Code was written in C++ and parallelized using OpenMP. Testing geometries were constructed using idealized spherical volumes and dose distributions.Results: Negligible stochastic noise could be attained within two minutes computation time for a single target. The confidence to properly cover both of two targets was 90% for two synchronously moving targets, but decreased by 7% if the targets moved independently. For two partially covered organs at risk the confidence of at least one organ below the mean dose threshold was 40% for synchronous motion, 36% for uncorrelated motion, but only 20% for either of the organs separately. Two abutting dose distributions ensuring 91% confidence of proper target dose for correlated motions led to 28% lower confidence for uncorrelated motions as relative displacements between the doses resulted in cold spots near the target.Conclusions: Probabilistic plan evaluation can efficiently be performed for complicated treatment planning situations, thus providing important plan quality information unavailable in conventional PTV based evaluations.

Experimental validation of the van Herk margin formula for lung radiation therapy

To validate the van Herk margin formula for lung radiation therapy using realistic dose calculation algorithms and respiratory motion modeling. The robustness of the margin formula against variations in lesion size, peak-to-peak motion amplitude, tissue density, treatment technique, and plan conformity was assessed, along with the margin formula assumption of a homogeneous dose distribution with perfect plan conformity. 3DCRT and IMRT lung treatment plans were generated within the ORBIT treatment planning platform (RaySearch Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic respiratory motion induced errors were simulated using deformable registration and dose accumulation tools available within ORBIT for simulated cases of varying lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan conformities. A detailed comparison between the margin formula dose profile model, the planned dose profiles, and penumbra widths was also conducted to test the assumptions of the margin formula. Finally, a correction to account for imperfect plan conformity was tested as well as a novel application of the margin formula that accounts for the patient-specific motion trajectory. The van Herk margin formula ensured full clinical target volume coverage for all 3DCRT and IMRT plans of all conformities with the exception of small lesions in soft tissue. No dosimetric trends with respect to plan technique or lesion size were observed for the systematic and random error simulations. However, accumulated plans showed that plan conformity decreased with increasing tumor motion amplitude. When comparing dose profiles assumed in the margin formula model to the treatment plans, discrepancies in the low dose regions were observed for the random and systematic error simulations. However, the margin formula respected, in all experiments, the 95% dose coverage required for planning target volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV margins were estimated. The penumbra widths calculated in lung tissue for each plan were found to be very similar to the 6.4 mm value assumed by the margin formula model. The plan conformity correction yielded inconsistent results which were largely affected by image and dose grid resolution while the trajectory modified PTV plans yielded a dosimetric benefit over the standard internal target volumes approach with up to a 5% decrease in the V20 value. The margin formula showed to be robust against variations in tumor size and motion, treatment technique, plan conformity, as well as low tissue density. This was validated by maintaining coverage of all of the derived PTVs by 95% dose level, as required by the formal definition of the PTV. However, the assumption of perfect plan conformity in the margin formula derivation yields conservative margin estimation. Future modifications to the margin formula will require a correction for plan conformity. Plan conformity can also be improved by using the proposed trajectory modified PTV planning approach. This proves especially beneficial for tumors with a large anterior-posterior component of respiratory motion.

Planning 4-dimensional Computational Tomography (4DCT) Cannot Adequately Represent Daily Intrafractional Motion of Abdominal Tumors

To evaluate whether the planning 4DCT can adequately represent daily motion of abdominal tumors in regularly fractionated and stereotactic patients. Intrafractional tumor motion of 10 abdominal (4 pancreas-fractionated and 6 liver- stereotactic) patients with implanted fiducials were measured based on daily orthogonal fluoroscopic movies over 38 treatment fractions. Movies were taken immediately before and after treatment at 8 ± 3 and 19 ± 6 minutes apart for fractionated and stereotactic patients, respectively. For evaluating daily breathing pattern variation, the standard deviations (SD) of the breathing amplitude and the baseline were measured for each fraction. The needed internal margin for at least 90% of tumor coverage was calculated based on 95 and 5 percentile of daily 3-D tumor motion. The planning internal margin was generated by fusing 4DCT motion from all phase-bins. The disagreement between needed and planning internal margin was analyzed fraction by fraction in three motion axes (superior-inferior [SI], anterior-posterior [AP], and left-right [LR]). The 4DCT margin was considered as an over-/under-estimation of daily motion when disagreement exceeded at least 3 mm in SI, and/or 1.2 mm in AP and LR, which were equal to the 4DCT image resolution in corresponding axis. Finally the additional internal margin to account for breathing variation was suggested using the Van Herk margin formula. The breathing amplitude varied from breath to breath and day to day, with a mean SD ranging from 2 to 5 mm intrafractionally and 1 to 3 mm interfractionally in the primary motion axis of SI. The breathing baseline also shifted from breath to breath, with a mean SD ranging from 1 to 2 mm in the SI direction. The amplitude variation and baseline shift were also observed in AP and LR, but to a lesser extent. The needed internal margin disagreed with the 4DCT margin in 92% of the fractions. The 4DCT overestimated daily 3-D motion in 39% of the fractions in 7/10 patients, and underestimated in 53% of the fractions in 8/10 patients. The underestimated motion was up to 7, 9, and 3 mm in SI, AP, and LR. To account for change of breathing pattern from 4DCT to daily treatment, the additional margins needed in SI, AP and LR were 1.9, 1.3, and 1.9 mm for fractionated patients, and much larger values of 5.3, 4.5, and 1.9 mm for stereotactic patients. The internal margin derived from 4D-CT cannot encompass intrafractional breathing motion due to inter- and intra-fractional variability of breathing pattern, especially for stereotactic patients who tend to have longer treatment time and hence larger breathing variation. The additional anisotropic margins in all three motion axes were necessary to ensure an adequate treatment delivery.