Liver Stereotactic Body Radiation Therapy Research Articles

Stereotactic body radiotherapy for hepatocellular carcinoma in the setting of poor liver function: A case series.

493 Background: Role of stereotactic body radiotherapy (SBRT) to the liver for patients with poor hepatic function after transcatheter arterial chemoembolization (TACE) has not been established. We reviewed results of SBRT for men with hepatocellular carcinoma (HCC) and Child-Pugh (CP) score ≥ 8 cirrhosis after TACE. Methods: Following a median of 3 TACE treatments, five males with severe cirrhosis received SBRT for persistent or progressive HCC in 2011-14. Clinico-pathologic characteristics and treatment details were retrospectively retrieved. Results: Median age at diagnosis was 55 years (range, 48 – 55). Median interval between cancer diagnosis and SBRT was 38 months (range, 3 – 60). All 5 patients experienced decline in CP score after TACE, for a median of drop of 1 point (range, 1 – 3) between the initiation of TACE and referral for radiotherapy. At time of SBRT, 4 had CP class B and 1 class C cirrhosis with median CP score of 9 (range, 8 – 11). There were no distant metastases and one patient had extrahepatic tumor extension. Three of 5 exhibited clinical symptoms of decompensated cirrhosis within 30 days before radiotherapy and one had portal vein thrombosis. Median MELD score at SBRT was 15 (range, 12 – 18). SBRT to a median total dose of 27.5 Gray (range, 27.5 – 30) was delivered in 5 once daily fractions. Median radiotherapy course duration was 9 days (range, 5 – 18). All patients had single radiation therapy targets with median largest tumor dimension of 3.6 cm (range, 2.4 – 6.2). Median planned target volume was 24 cm3(range, 17 – 197). Sorafenib was given prior to SBRT to one patient, concurrently to one, and sequentially after radiotherapy to another. There were no acute complications. Two patients died within 20 days from completion of SBRT. Median follow up for surviving > 20 days was 10 months (range, 5 – 13). None experienced radiographic tumor progression after radiotherapy. Estimated overall survival was 40% at 6 months (95% confidence intervals, 0 – 83.8%). Conclusions: For HCC patients with CP score ≥ 8 following TACE, prognosis after liver SBRT was poor.

Adjuvant stereotactic body radiotherapy (SBRT) for resected primary and metastatic liver cancers.

487 Background: Stereotactic body radiotherapy (SBRT) has been shown to be a safe and effective treatment for hepatobiliary cancers. However, little is known about the efficacy of adjuvant SBRT for resected liver tumors with positive margins. We examined the characteristics and outcomes of patients who received adjuvant SBRT for both primary and metastatic cancers of the liver. Methods: We retrospectively reviewed the charts of patients who had received liver SBRT from 2009-2015 at our institution. During that time frame, 11 patients were identified as having received adjuvant SBRT post resection. Patient data such as age, gender, portal vein thrombosis, cirrhosis, ECOG performance status, prior liver directed therapies, and SBRT dose were collected. Descriptive statistics were used for analysis given the small number of patients in this series. Results: Median age at the time of treatment was 63 years (range 51-79), and the majority of patients (72.7%) were male. Seven tumors (63.6%) were hepatocellular carcinomas, and 4 (36.4%) were adenocarcinomas. Of the tumors with adenocarcinoma histology, 3 were cholangiocarcinomas and one was metastatic colorectal cancer. Ten patients (90.9%) were treated for positive margins, and one was treated for inferior vena cava (IVC) invasion. Seven patients (63.6%) had no other liver-directed treatment prior to adjuvant SBRT. Two patients received systemic therapy prior to SBRT. Median EQD2 was 83.3 Gy (range 60-126), and 81.8% of patients received 5 fractions. There were no grade 3 or above late toxicities from treatment. Median follow-up was 14.1 months (range 5.4-38.1). None of the treated tumors progressed locally. Six patients (54.5%) progressed elsewhere in the liver, and one patient experienced distant metastatic progression. One patient experienced both intrahepatic progression and distant metastatic progression. Conclusions: Adjuvant SBRT appears to be a safe and feasible adjuvant treatment in patients with primary liver resection for either primary liver cancer or metastatic disease who are at high risk of recurrence.

Dosimetric impact of Lipiodol in stereotactic body radiation therapy on liver after trans-arterial chemoembolization.

Stereotactic body radiation therapy (SBRT) combining trans-arterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study is aimed to estimate the dose enhancement in Lipiodol's proximity and to evaluate the dose calculation accuracy of the Acuros XB (AXB) algorithm and anisotropic analytical algorithm (AAA) in the Eclipse treatment planning system (TPS) (ver. 11, Varian Medical Systems, Palo Alto, USA), compared with that of the Monte Carlo (MC) calculation (using BEAMnrc/DOSXYZnrc code) for a virtual phantom and a treatment plan for liver SBRT after TACE. The MC calculation accuracy was validated by comparing its results with the percent depth dose (PDD) and the off-axis ratio (OAR) measured using a water-equivalent phantom containing Lipiodol. The dose difference in Lipiodol's proximity and the inhomogeneity correction accuracies of the AAA, AXB algorithm, and MC calculation were evaluated by calculating the PDDs and OARs for the virtual phantom with Lipiodol and the lateral profile for the clinical plan data. The measured data and the MC results agreed within 3%. The average dose in the Lipiodol uptake region was higher by 8.1% for the virtual phantom and 6.0% for the clinical case compared to that in regions without Lipiodol uptake. For the virtual phantom, compared with the MC calculation, the AAA and the AXB algorithm underestimated the doses immediately upstream of the Lipiodol region by 5.0% and 4.2%, in the Lipiodol region by 7.4% and 9.8%, and downstream of the Lipiodol region by 5.5% and 3.9% respectively. These discrepancy between the AXB and MC calculations were due to the incorrect assignment of Lipiodol material properties. Namely, the bone material was assigned automatically by the AXB algorithm as the materials for the AXB algorithm do not contain iodine, which is the main constituent of Lipiodol. The MC calculation indicated a larger and more accurate dose increase in Lipiodol compared with the TPS algorithms. The observed dose enhancement in the tumor area could be clinically significant.

Identification of the suitable leaf margin for liver stereotactic body radiotherapy with flattening filter-free beams

The purpose of this study is to identify the suitable leaf margin for liver stereotactic body radiotherapy (SBRT) with flattening filter-free (FFF) beams, as compared with that with flattening filter (FF) beams. SBRT treatment planning for 10 patients with liver cancer was performed using 10-MV FFF and FF beams obtained from a Varian TrueBeam (Varian Medical Systems, Palo Alto, CA) linear accelerator. Each plan was generated with the leaf margin to the planning target volume (PTV) ranging from −3 to 5 mm. The prescription dose at D95 (dose covering 95% of the volume) was 48 Gy in 4 fractions to the PTV. The following dosimetric parameters were evaluated quantitatively: homogeneity index (HI), conformity index (CI), gradient index (GI), the normal liver receiving a dose greater than or equal to 20 Gy (V20), and the mean normal liver dose. The HI for FFF and FF beams increased as the leaf margin decreased. The leaf margins that achieved the best CI and GI were 0.1 and −0.3 mm for FFF beams, and 0.1 and −0.9 mm for FF beams. The liver V20 and the mean liver dose reached their minimum values at leaf margins of −0.8 and 0.0 mm for FFF beams, and −0.8 and 0.0 mm for FF beams. The suitable leaf margin for SBRT planning did not differ significantly for FFF and FF beams. Our data showed that, for both FFF and FF beams, a leaf margin of 0 or −1 mm was optimal for liver SBRT planning in terms of both target coverage and normal tissue sparing.

P21. Treatment planning for liver stereotactic body radiation therapy using FFF photon beams

Introduction Since April 2015, patients are treated in our department with liver stereotactic body radiation therapy on a linear accelerator equipped with flattening filter free (FFF) photon beams. The energy and the use of respiratory gating are adapted for each patient. This study presents the results for the first 14 patients. Material and methods. Three gold fiducials are implanted inside or in the vicinity of the lesion 7–10 days prior planning imaging. The minimum 4 h fasting patient undergoes first a 4D CT scan with systematic audio coaching and a thoracic thermoplastic mask (Orfit Industries, Wijnegem, Belgium). An MRI scan in treatment position is acquired and registered to the CT images based on the fiducials. The radiation oncologist outlines the GTV on each of the six respiratory phases. A 6 phases ITV (entire breathing cycle) and a 3 phases ITV (expiratory phases) are then created. The corresponding PTVs are created by adding a 5 mm margin. When the ratio PTV 6/ PTV 3 is higher than 1.5, the treatment is achieved with respiratory gating. The beam used is a conformal dynamic arc of 180 to 200° amplitude, conformed to the PTV. 10 MV FFF beams were preferably used as the dose rate is higher than for 6 MV FFF beams (2400 and 1200 MU/min respectively). For organs at risk, constraints from Timmerman et al. [1] were used. Results For the past year, 14 patients have been treated (8 with 3 fractions of 18 Gy, 3 with 5 fractions of 11 Gy and 3 with 5 fractions of 10 Gy), without any restriction on PTV size (from 11 to 273 cm 3 ). The prescription isodose is 80%. 5 patients were treated in free breathing (PTV 6) and 9 with respiratory gating (PTV 3). Sometimes it has been necessary to treat with respiratory gating in order to fulfill the constraints to the organs at risk. The systematic comparison for the first 10 patients between the two FFF energies showed that the dosimetric objectives were fulfilled similarly for both energy except when the PTV was close to an organ at risk. In this case, better results were obtained with 6MV FFF beam. Conclusion Despite the fact that the liver is a very mobile organ, it has been possible to treat some patients in free breathing, without compromising the dosimetric objectives, thus allowing a better patient comfort (treatment time 3 times faster). The 10 MV FFF with its 2400 MU/min dose rate was most often used, allowing treatment times lower than 10 min even with respiratory gating and the highest prescribed dose.

50. Magnetic Resonance Imaging optimization for liver SBRT: Breath-triggered acquisition in treatment position to improve lesion contouring

Introduction Magnetic Resonance Imaging (MRI) acquisition in treatment position was implemented in our institution for the need of stereotactic body radiotherapy (SBRT) program. During imaging acquisition, significant liver motion is usually observed due to breathing motion. The aim of this study is to report the benefits of setting out a breath-triggered MRI protocol optimized for radiotherapy (RT) planning in order to account for liver motion. Material and methods Prior to imaging, three internal gold fiducials were implanted under echo or CT guidance in the vicinity of the lesion site in order to improve images registration, patient’s positioning and target volume tracking during SBRT treatment. A 4D CT scan was acquired in treatment position. Images were reconstructed in six phases across the respiratory cycle with CT50 being the exhale image set used for MR image registration. MRI was acquired with a 18-channel design body ex coil on a 1.5T MR scan. The patients were set up with the same immobilization and positioning devices as for CT imaging thanks to a MR compatible table. The three sequences were systematically used:- For lesion visualization, axial single shot fast spin echo T2-weighted (T2) with fat saturation was first acquired with breath triggering on exhale. – Fiducials are visible on ultra-fast gradient echo T1-weighted DIXON (T1 DIXON) water reconstructed images acquired in exhale breath hold. – Lesion are also well defined after injected T1-weighted Fast Low Angle Shot (T1 TFL) imaging sequence acquired with breath triggering on expiration phase. Gold fiducials are also visible on this sequence. Slice thickness was set to 2 mm and all sequences were acquired in the same plane with the same slice position in order to ease image registration in the treatment planning software. The entire MRI protocol acquisition lasts around 20 min depending on the regularity of the patient’s breathing pattern. Results The lesion was not always visible on 4D CT scan, even on images with contrast enhancement hence the need of MRI to better define the lesion. Target motion range was assessed based on fiducials’ displacement. Most frequently, treatment planning is performed on expiration phases but when lesion movement is small with breathing, target contouring is done over all phases and treatment planning is achieved in free breathing. The use of the same table and immobilization device for MRI minimized uncertainties due to patient position for image registration. An example of MR/CT50 registration and target volume definition is illustrated on Fig. 1. Download : Download high-res image (447KB) Download : Download full-size image Conclusion The use of MR imaging sequences optimized to account for fiducial visualization and tumor delineation allow high precision target delineation for treatment planning. Increasing cases of patients eligible for SBRT and its proof of benefit have stimulated the effort to setup and improve new imaging protocols at our institute for a personalized and optimal SBRT treatment. Recent developments in 4D MRI demonstrated the possibility to sort and reconstruct the images according to the respiratory phases [1] , [2] , [3] . Future implementation of 4D MRI in our institution would allow better registration with 4D CT planning over the entire breathing cycle and delineation accuracy will benefit from significant improvements.

Evaluation of reproducibility of tumor repositioning during multiple breathing cycles for liver stereotactic body radiotherapy treatment

AimTo evaluate the tumor repositioning during gated volumetric modulated arc therapy (VMAT) for liver stereotactic body radiotherapy(SBRT) treatment using implanted fiducial markers and intrafraction kilovoltage (kV) images acquired during dose delivery. Materials and methodsSince 2012, 47 liver cancer patients with implanted fiducial markers were treated using the gated VMAT technique with a Varian Truebeam STx linear accelerator. The fiducial markers were implanted inside or close to the tumor target before treatment simulation. They were defined at the maximum inhalation and exhalation phases on a 4-dimensionnal computed tomography (4DCT) acquisition. During the treatment, kV images were acquired just before the beam-on at each breathing cycle at maximum exhalation and inhalation phases to verify the fiducial markers positions. For the five first fractions of treatment in the first ten consecutive patients, a total of 2705 intrafraction kV images were retrospectively analyzed to assess the differences between expected and actual positions of the fiducial markers along the cranio-caudal (CC) direction during the exhalation phase. ResultsThe mean absolute intrafractional fiducial marker deviation along the CC direction was 1.0mm at the maximum exhalation phase. In 99%, 95% and 90% cases, the fiducial marker deviations were ≤4.5mm, 2.8mm and 2.2mm, respectively. ConclusionIntrafraction kV images allowed us to ensure the consistency of tumor repositioning during treatment. In 99% cases, the fiducial marker deviations were ≤4.5mm corresponding to our 5mm treatment margin. This margin seems to be well-adapted to the gated VMAT SBRT treatment in liver disease.

Robotic intrafractional US guidance for liver SABR: System design, beam avoidance, and clinical imaging.

To present a system for robotic 4D ultrasound (US) imaging concurrent with radiotherapy beam delivery and estimate the proportion of liver stereotactic ablative body radiotherapy (SABR) cases in which robotic US image guidance can be deployed without interfering with clinically used VMAT beam configurations. The image guidance hardware comprises a 4D US machine, an optical tracking system for measuring US probe pose, and a custom-designed robot for acquiring hands-free US volumes. In software, a simulation environment incorporating the LINAC, couch, planning CT, and robotic US guidance hardware was developed. Placement of the robotic US hardware was guided by a target visibility map rendered on the CT surface by using the planning CT to simulate US propagation. The visibility map was validated in a prostate phantom and evaluated in patients by capturing live US from imaging positions suggested by the visibility map. In 20 liver SABR patients treated with VMAT, the simulation environment was used to virtually place the robotic hardware and US probe. Imaging targets were either planning target volumes (PTVs, range 5.9-679.5 ml) or gross tumor volumes (GTVs, range 0.9-343.4 ml). Presence or absence of mechanical interference with LINAC, couch, and patient body as well as interferences with treated beams was recorded. For PTV targets, robotic US guidance without mechanical interference was possible in 80% of the cases and guidance without beam interference was possible in 60% of the cases. For the smaller GTV targets, these proportions were 95% and 85%, respectively. GTV size (1/20), elongated shape (1/20), and depth (1/20) were the main factors limiting the availability of noninterfering imaging positions. The robotic US imaging system was deployed in two liver SABR patients during CT simulation with successful acquisition of 4D US sequences in different imaging positions. This study indicates that for VMAT liver SABR, robotic US imaging of a relevant internal target may be possible in 85% of the cases while using treatment plans currently deployed in the clinic. With beam replanning to account for the presence of robotic US guidance, intrafractional US may be an option for 95% of the liver SABR cases.

Using a Knowledge-Based Planning Model for Quality Assurance of Liver Stereotactic Body Radiation Therapy Plans

Using a Knowledge-Based Planning Model for Quality Assurance of Liver Stereotactic Body Radiation Therapy Plans

A Monoscopic X-ray Image-Based Position Monitoring System for Liver Stereotactic Body Radiation Therapy

A Monoscopic X-ray Image-Based Position Monitoring System for Liver Stereotactic Body Radiation Therapy

Efficacy of Liver Stereotactic Body Radiation Therapy as Primary Treatment or Following Transarterial Chemoembolization (TACE) in Patients With HCC

Efficacy of Liver Stereotactic Body Radiation Therapy as Primary Treatment or Following Transarterial Chemoembolization (TACE) in Patients With HCC

Motion Mitigation Appears to Decrease the Risk of Chest Wall Morbidity for Tumors Located

Motion Mitigation Appears to Decrease the Risk of Chest Wall Morbidity for Tumors Located <3 cm From the Chest Wall During Liver Stereotactic Body Radiation Therapy

Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results

BackgroundMotion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment. Materials and methodsBetween May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5mm from the ITV. Dose prescription ranged from 40 to 50Gy in 5–10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients. ResultsWith a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes.In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved “in field”. 12 patients had an intrahepatic progression “out of field”.Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91mm (0–6mm). ConclusionThe clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating.

Optimizing global liver function in radiation therapy treatment planning

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose () (conventional ‘ model’), the so-called perfusion-weighted () (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting , fEUD, and GLF plans delivering the same target are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to more liver function than the fEUD () plan does in 2D cases, and up to in 3D cases. The GLF and fEUD plans worsen in of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

WE‐H‐BRC‐02: Failure Mode and Effect Analysis of Liver Stereotactic Body Radiotherapy

Purpose:To identify areas of improvement in our liver stereotactic body radiation therapy (SBRT) program, using failure mode and effect analysis (FMEA).Methods:A multidisciplinary group consisting of one physician, three physicists, one dosimetrist and two therapists was formed. A process map covering 10 major stages of the liver SBRT program from the initial diagnosis to post treatment follow‐up was generated. A total of 102 failure modes, together with their causes and effects, were identified. The occurrence (O), severity (S) and lack of detectability (D) were independently scored. The ranking was done using the risk probability number (RPN) defined as the product of average O, S and D numbers for each mode. The scores were normalized to remove inter‐observer variability, while preserving individual ranking order. Further, a correlation analysis on the overall agreement on rank order of all failure modes resulted in positive values for successive pairs of evaluators. The failure modes with the highest RPN value were considered for further investigation.Results:The average normalized RPN values for all modes were 39 with a range of 9 to 103. The FMEA analysis resulted in the identification of the top 10 critical failures modes as: Incorrect CT‐MR registration, MR scan not performed in treatment position, patient movement between CBCT acquisition and treatment, daily IGRT QA not verified, incorrect or incomplete ITV delineation, OAR contours not verified, inaccurate normal liver effective dose (Veff) calculation, failure of bolus tracking for 4D CT scan, setup instructions not followed for treatment and plan evaluation metrics missed.Conclusion:The application of FMEA to our liver SBRT program led to the identification and possible improvement of areas affecting patient safety.

SU‐G‐JeP4‐06: Evaluation of Interfractional and Intrafractional Tumor Motion in Stereotactic Liver Radiotherapy, Based On Four‐Dimensional Cone‐Beam Computed Tomography Using Fiducial Markers

Purpose:The purpose of this study was to evaluate the interfractional and intrafractional motion of liver tumors in stereotactic body radiation therapy (SBRT), based on four‐dimensional cone‐beam computed tomography using fiducial markers. (4D‐CBCT).Methods:Seven patients with liver tumors were treated by SBRT with abdominal compression (AC) in five fractions with image guidance based on 4D‐CBCT. The 4D‐CBCT studies were performed to determine the individualized internal margin for the planning simulation. The interfractional and intrafractional changes of liver tumor motion for all patients was measured, based on the planning simulation 4D‐CBCT, pre‐SBRT 4D‐CBCT, and post‐SBRT 4D‐CBCT. The interfractional motion change was calculated from the difference in liver tumor amplitude on pre‐SBRT 4D‐CBCT relative to that of the planning simulation 4D‐CBCT for each fraction. The intrafractional motion change was calculated from the difference between the liver tumor amplitudes of the pre‐ and post‐SBRT 4D‐CBCT for each fraction. Significant interfractional and intrafractional changes in liver tumor motion were defined as a change ≥3 mm. Statistical analysis was performed using the Pearson correlation.Results:The values of the mean amplitude of liver tumor, as indicated by planning simulation 4D‐CBCT, were 1.6 ± 0.8 mm, 1.6 ± 0.9 mm, and 4.9 ± 2.2 mm in the left‐right (LR), anterior‐posterior (AP), and superior‐inferior (SI) directions, respectively. Pearson correlation coefficients between the liver tumor amplitudes, based on planning simulation 4D‐CBCT, and pre‐SBRT 4D‐CBCT during fraction treatment in the LR, AP, and SI directions were 0.6, 0.7, and 0.8, respectively. Interfractional and intrafractional motion changes of ≥3 mm occurred in 23% and 3% of treatment fractions, respectively.Conclusion:The interfractional and intrafractional changes of liver tumor motion were small in most patients who received liver SBRT with AC. In addition, planning simulation 4D‐CBCT was useful for representing liver tumor movement in patients undergoing SBRT.This work was supported by JSPS KAKENHI Grant Number 26861004.

A graphical user interface (GUI) toolkit for the calculation of three-dimensional (3D) multi-phase biological effective dose (BED) distributions including statistical analyses

A toolkit has been developed for calculating the 3-dimensional biological effective dose (BED) distributions in multi-phase, external beam radiotherapy treatments such as those applied in liver stereotactic body radiation therapy (SBRT) and in multi-prescription treatments. This toolkit also provides a wide range of statistical results related to dose and BED distributions. MATLAB 2010a, version 7.10 was used to create this GUI toolkit. The input data consist of the dose distribution matrices, organ contour coordinates, and treatment planning parameters from the treatment planning system (TPS). The toolkit has the capability of calculating the multi-phase BED distributions using different formulas (denoted as true and approximate). Following the calculations of the BED distributions, the dose and BED distributions can be viewed in different projections (e.g. coronal, sagittal and transverse). The different elements of this toolkit are presented and the important steps for the execution of its calculations are illustrated. The toolkit is applied on brain, head & neck and prostate cancer patients, who received primary and boost phases in order to demonstrate its capability in calculating BED distributions, as well as measuring the inaccuracy and imprecision of the approximate BED distributions. Finally, the clinical situations in which the use of the present toolkit would have a significant clinical impact are indicated.

Availability of applying diaphragm matching with the breath-holding technique in stereotactic body radiation therapy for liver tumors

PurposeImage-guided radiotherapy (IGRT) based on bone matching can produce large target-positioning errors because of expiration breath-hold reproducibility during stereotactic body radiation therapy (SBRT) for liver tumors. Therefore, the feasibility of diaphragm-based 3D image matching between planning computed tomography (CT) and pretreatment cone-beam CT was investigated. MethodsIn 59 liver SBRT cases, Lipiodol uptake after transarterial chemoembolization was defined as a tumor marker. Further, the relative isocenter coordinate that was obtained by Lipiodol matching was defined as the reference coordinate. The distance between the relative isocenter coordinate and reference coordinate, which was obtained from diaphragm matching and bone matching techniques, was defined as the target positioning error. Furthermore, the target positioning error between liver matching and Lipiodol matching was evaluated. ResultsThe positioning errors in all directions by the diaphragm matching were significantly smaller than those obtained by using by the bone matching technique (p < 0.05). Further, the positioning errors in the A-P and C-C directions that were obtained by using liver matching were significantly smaller than those obtained by using bone matching (p < 0.05). The estimated PTV margins calculated by the formula proposed by van Herk for diaphragm matching, liver matching, and bone matching were 5.0 mm, 5.0 mm, and 11.6 mm in the C-C direction; 3.6 mm, 2.4 mm, and 6.9 mm in the A-P direction; and 2.6 mm, 4.1 mm, and 4.6 mm in the L-R direction, respectively. ConclusionsDiaphragm matching-based IGRT may be an alternative image matching technique for determining liver tumor positions in patients.

Evaluation of 3D vs 4D Cone-beam CT (CBCT) Target Localization Methods for Free Breathing Liver Stereotactic Body Radiotherapy (SBRT)

Purpose/Aim: Liver cancer patients with minimal amplitude of breathing or unable to tolerate breath-hold for radiotherapy are treated free-breathing with image guided SBRT. The purpose of this study is to assess the accuracy and reproducibility of automated registration of 3D versus 4D CBCT in target localization for free-breathing liver stereotactic body radiotherapy (SBRT). Method/Process: Daily localization CBCT images are acquired and any positional discrepancies corrected prior to treatment delivery for free-breathing liver SBRT. For image-guided radiotherapy (IGRT) at our institution, amplitudes of breathing 5 mm undergo 3D-CBCT acquisition while larger breathers (> 5 mm) utilize a 4D-CBCT workflow for target localization. Retrospective analysis of translational (T) and rotational (R) displacements of treated fractions was performed through 3 methods: 3D-CBCT dual registration using bony anatomy (T+R) and average liver position (T+R); 3D-CBCT registration using average liver position (T+R) followed by 4D-CBCT registration to the liver exhale position (T); and 4D-CBCT registration to the liver exhale position (T). Each retrospective image registration was performed automatically by the imaging software, and evaluated by three independent observers who performed manual adjustments to ensure clinical target coverage. Krippendorff’s alpha was used to assess agreement between the methods. Results/Benefits/Challenges: Ten liver cancer patients treated for 30-50 Gy over 5 or 6 fractions, with amplitudes of breathing motion ranging from 3.6 13 mm, were included. A total of 54 CBCT images were analyzed by each observer. Mean (+/SD) observer disagreement for 3D-CBCT dual registration was 1.1 0.8 mm, 2.1 1.3 mm, and 1.4 1.3 mm in the right-left, cranio-caudal and anterior posterior direction respectively. Agreement between observers was very high with Krippendorff’s alpha greater than 0.81 in all directions. Dual registration on 3D-CBCT and 4D-CBCT of the liver produced similar shifts; the root-mean-square (RMS) difference between mean manual and automatic techniques was 0.75mm in a 3D vector. Registration using 4D-CBCT to the liver exhale position alone produced an RMS observer error of 0.72 mm. Automatic matches of 3D and 4D liver registrations converged at small amplitudes, indicating a single 4DCBCT workflow is sufficient for any amplitude of breathing motion. Inter-observer variability between the 3 observers and automatic imaging software matches was smallest with 4D-CBCT liver exhale registration alone. Conclusion/Impact/Outcomes: Automatic registration using 4D-CBCT provides accurate target localization and is unaffected by larger breathing amplitudes as seen with 3D-CBCT image registration. Fourdimensional CBCT reduces the inter-observer variability and potential for systematic error, making it a desirable approach for free breathing liver IG-SBRT.

Knowledge-based planning for stereotactic body radiation therapy (SBRT) of the liver.

375 Background: SBRT is emerging as a treatment option for patients with unresectable liver tumors. However, generating high quality liver SBRT plans is technically challenging and user-dependent. Aiming for high tumor doses and low normal tissue doses can demand lengthy planning times and result in plans of inconsistent quality. This study investigates knowledge-based planning (KBP) as a standardized method to ensure efficacy, safety, and efficiency for SBRT plans and allow for broader use of this therapy. Methods: SBRT treatment plans were manually optimized for 55 liver cancer cases by an expert liver dosimetrist in a commercial treatment planning system (Varian Eclipse v13.6). Each volumetric modulated arc therapy plan was approved by a physician using strict criteria for target coverage and normal tissue sparing. The plans were used to create a custom model in a KBP system (RapidPlan, Varian Eclipse v13.6) designed to improve both efficiency and standardization of quality. To validate the model, 15 new cases were optimized manually by an expert liver dosimetrist and then semi-automatically using the KBP model. The validation plans were compared based on target coverage, normal tissue sparing, and planning time. Results: Compared to manual plans created by an expert liver dosimetrist, KBP-generated plans showed similar target coverage and improved normal tissue sparing with similar planning times. Mean and minimum target doses were similar, as was D98, p &gt; 0.2 for all. Normal tissue complication probability for liver damage was marginally lower with KBP, mean 3 vs. 1%, p = 0.07. Doses to adjacent organs including stomach, heart, and bowel were similar. Manual planning required a median and mean time of 15 and 20 minutes, respectively, range 8-55 min. KBP required similar times of 12 and 19 min, range 8-50 min. 9 of 15 KBP cases were automated, while 6 plans required dosimetrist improvement. Conclusions: Using KBP, high quality plans for liver SBRT can be created automatically or semi-automatically. These plans are comparable to those generated by an expert liver dosimetrist. KBP could be used to standardize treatments between institutions, particularly when experience with liver SBRT is limited.