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BACKGROUND AND PURPOSE: Target volume definitions for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) vary substantially. Some groups aim to treat the primary tumor only, whereas others include elective lymph nodes (eLNs). eLNs close to the primary tumor are often included unintentionally within the treatment volume, depending on the respective treatment philosophies. We aimed to measure the percentages of anatomical coverage of eLNs by comparing four different contouring guidelines. PATIENTS AND METHODS: Planning target volumes (PTVs) were contoured using planning computed tomography (CT) scans of 11 patients with PDAC based on the Oxford, RTOG (Radiation Therapy Oncology Group), Michigan, and SCALOP (Selective Chemoradiation in Advanced Localised Pancreatic Cancer trial) guidelines. Clinical target volumes (CTVs) included the peripancreatic, para-aortic, paracaval, celiac trunk, superior mesenteric, and portal vein lymph node areas. Volumetric comparisons of the coverage of all eLN regions were conducted to illustrate the differences between the four contouring strategies. RESULTS: The PTV sizes of the RTOG and Oxford guidelines were comparable. The SCALOP and Michigan PTV sizes were similar to each other and significantly smaller than the RTOG and Oxford PTVs. A large variability of eLN coverage was found for the various subregions according to the respective contouring strategies. CONCLUSION: This is the first study to directly compare the percentage of anatomical coverage of eLNs according to four PTVs in the same patient cohort. Potential practical consequences are discussed in detail.

The lack of soft tissue contrast and artifacts due to variable gas filling make image guidance in precision radiation therapy for GI tract challenging. Anatomical structures in the tumor proximity can be used as surrogates as bony landmarks may be some distance from the target and inappropriate for target localization. We propose that oral contrast may aid in reproducible soft tissue visualization at treatment delivery and it is less invasive than fiducial marker insertion. This may be more useful in patients undergoing radiation therapy for hepatobiliary tract tumors where duodenal identification will aid in safe treatment delivery.

Pancreatic adenocarcinoma patients have a poor prognosis, with the fi ve-year overall survival rate 5% [1]. Treatment options for these patients may include pre-operative or defi nitive chemo-radiotherapy (CRT). Patterns of failure suggest that inclusion of elective lymph nodes in the treatment volume may improve local control [2]. These extended volumes, in conjunction with large margins to account for breathing motion, generate substantial planning treatment volumes (PTV) which may increase the risk of gastro-intestinal (GI) toxicity. Several publications have investigated the use of intensity-modulated radiotherapy (IMRT) [3 – 7] and intensity-modulated arc therapy (IMAT) [8 – 11] for treatment of pancreatic cancer, where the improved dose conformation may reduce dose to surrounding normal tissue, and allow dose escalation for improved local control. Despite studies showing a correlation between dosimetric parameters and GI toxicity for three-dimensional (3D)-RT and IMRT [12] there is some debate over dose constraints for stomach, duodenum and small bowel. Differences in organ delineation and prescribed dose may limit the comparison of dose-volume histogram (DVH) parameters, and a standard dose-volume analysis is often limited to only a few points in the DVH data, which may not always correspond directly to a clinical outcome. However, radiobiological modelling evaluates treatment plans by analysing the entire DVH and reducing this multifactorial comparison into a single clinically relevant parameter. As the parameters used for modelling normal tissue complication probability (NTCP) are derived from observed rates of toxicity in clinical trials, these parameters should be cited as a range of values (e.g. covering a 95% confi dence interval). Each parameter set is specifi c for a selected endpoint and is also dependent on the patient cohort and the treatment technique used. Careful comparison of the predicted complications with observed clinical toxicity is required to validate each set of NTCP parameters which may be found in the literature [13]. Nonetheless, radiobiological modelling may be useful for assessing different planning techniques and dose prescriptions, and has been applied to compare predicted toxicity to stomach and duodenum for a dose escalation study using tomotherapy plans for pancreatic cancer [5]. The current study compares the use of NTCP models and dose-volume metrics to analyse RapidArc (IMAT) and three-dimensional conformal treatment (3D-RT) plans for locally-advanced pancreatic cancer (LAPC). Using commercially available biological evaluation software module (Eclipse, Varian, Palo Alto

Background and purpose Contouring of target volumes varies significantly in radiotherapy of pancreatic ductal adenocarcinoma (PDAC). There is a lack of consensus as to whether elective lymph nodes (eLN's) should be included or not in the planning target volume (PTV). In the present study we analyzed the dosimetric coverage of the eLN's and organs at risk (OAR) by comparing four different contouring guidelines. Methods and materials PTVs were delineated with (Oxford and RTOG guidelines) or without (Michigan and SCALOP guidelines) including the eLNs in eleven patients with PDAC. eLNs included the peripancreatic, paraaortic, paracaval, celiac trunk, superior mesenteric and portal vein clinical target volumes (CTVs). A 3D-CRT plan (50.40 Gy in 28 fractions) was performed to analyze and compare the dosimetric coverage of all eLNs and OAR between the 4 contouring guidelines. Results The size of Oxford and RTOG PTVs was comparable and significantly larger than the SCALOP and Michigan PTVs. Interestingly the eLNs received a significant amount of incidental dose irradiation by PTV-based plans that only aimed to treat the tumor without the eLNs. The dosimetric coverage of eLN presented a large variability according to the respective contouring methods. The difference in the size of the 4 PTVs was reflected to the dose distribution at the OAR. Conclusions Our study provides important information regarding the impact of different contouring guidelines on the dose distribution to the eLNs and the OAR in patients with locally advanced PDAC treated with radiotherapy. © 2013 Elsevier Ireland Ltd. All rights reserved.

PURPOSE: this report aims to provide an overview on radiotherapy and chemotherapy in extrahepatic biliary duct carcinoma (BDC). PATIENTS AND METHODS: a PubMed research identified clinical trials in BDC through April 1, 2010 including randomised controlled trials, SEER analyses and retrospective trials. Additionally, publications on the technical progress of radiotherapy in or close to the liver were analysed. RESULTS: most patients with cholangiocarcinoma present with unresectable disease (80-90%), and more than half of the resected patients relapse within 1 year. Adjuvant and palliative treatment options need to be chosen carefully since 50% of the patients are older than 70 years at diagnosis. Adjuvant radiotherapy or chemotherapy after complete resection (R0) has not convincingly shown a prolongation of survival but radiotherapy did after R1 resection. However, data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy in patients with marginally resectable disease. For patients with unresectable biliary tract carcinoma (BTC), palliative stenting was previously the treatment of choice. But recent SEER analyses show that radiotherapy prolongs survival, relieves symptoms and contributes to biliary decompression and should be regarded as the new standard. Novel technical advances in radiotherapy may allow for dose-escalation and could significantly improve outcome for patients with cholangiocarcinoma. CONCLUSION: both the literature and recent technical progress corroborate the role of radiotherapy in BDC offering chances for novel clinical trials. Progress is less pronounced in chemotherapy.

Purpose Interfraction and intrafraction changes in amplitude of liver motion were assessed in patients with liver cancer treated with kV cone beam computed tomography (CBCT)-guided stereotactic body radiation therapy (SBRT). Methods and Materials A total of 314 CBCTs obtained with the patient in the treatment position immediately before and after each fraction, and 29 planning 4DCTs were evaluated in 29 patients undergoing six-fraction SBRT for unresectable liver cancer, with (n = 15) and without (n = 14) abdominal compression. Offline, the CBCTs were sorted into 10 bins, based on phase of respiration. Liver motion amplitude was measured using liver-to-liver alignment from the end-exhale and end-inhale CBCT and four-dimensional CT reconstructions. Inter- and intrafraction amplitude changes were measured from the difference between the pre-SBRT CBCTs relative to the planning four-dimensional CT, and from the pre-SBRT and post-SBRT CBCTs, respectively. Results Mean liver motion amplitude for all patients (range) was 1.8 (0.1–7.0), 8.0 (0.1–18.8), and 4.3 (0.1–12.1) mm in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) directions, respectively. Mean absolute inter- and intrafraction liver motion amplitude changes were 1.0 (ML), 1.7 (CC), and 1.6 (AP) mm and 1.3 (ML), 1.6 (CC), and 1.9 (AP) mm, respectively. No significant correlations were found between intrafraction amplitude change and intrafraction time (range, 4:56–25:37min:sec), and between inter- and intrafraction amplitude changes and liver motion amplitude. Intraobserver reproducibility (σ, n = 29 fractions) was 1.3 (ML), 1.4 (CC), and 1.4 (AP) mm. Conclusions For the majority of liver SBRT patients, the change in liver motion amplitude was minimal over the treatment course and showed no apparent relationships with the magnitude of liver motion and intrafraction time.

Purpose: To evaluate the residual error in liver position using breath-hold kilovoltage (kV) cone-beam computed tomography (CT) following on-line orthogonal megavoltage (MV) image-guided breath-hold liver cancer conformal radiotherapy. Methods and Materials: Thirteen patients with liver cancer treated with 6-fraction breath-hold conformal radiotherapy were investigated. Before each fraction, orthogonal MV images were obtained during exhale breath-hold, with repositioning for offsets >3 mm, using the diaphragm for cranio-caudal (CC) alignment and vertebral bodies for medial-lateral (ML) and anterior posterior (AP) alignment. After repositioning, repeat orthogonal MV images, orthogonal kV fluoroscopic movies, and kV cone-beam CTs were obtained in exhale breath-hold. The cone-beam CT livers were registered to the planning CT liver to obtain the residual setup error in liver position. Results: After repositioning, 78 orthogonal MV image pairs, 61 orthogonal kV image pairs, and 72 kV cone-beam CT scans were obtained. Population random setup errors (σ) in liver position were 2.7 mm (CC), 2.3 mm (ML), and 3.0 mm (AP), and systematic errors (Σ) were 1.1 mm, 1.9 mm, and 1.3 mm in the superior, medial, and posterior directions. Liver offsets >5 mm were observed in 33% of cases; offsets >10 mm and liver deformation >5 mm were observed in a minority of patients. Conclusions: Liver position after radiation therapy guided with MV orthogonal imaging was within 5 mm of planned position in the majority of patients. kV cone-beam CT image guidance should improve accuracy with reduced dose compared with orthogonal MV image guidance for liver cancer radiation therapy.

Purpose: To measure the intrabreath-hold liver motion and the intrafraction and interfraction reproducibility of liver position relative to vertebral bodies using an active breathing coordinator (ABC) in patients with unresectable liver cancer treated with hypofractionated stereotactic body radiation therapy (SBRT). Methods: Tolerability of ABC and organ motion during ABC was assessed using kV fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT scans in the ABC breath-hold position were acquired at simulation to estimate the volumetric intrafraction reproducibility of the liver relative to the vertebral bodies. In addition, preceding each radiation therapy fraction, with the liver immobilized using ABC, repeat anteroposterior (AP) megavoltage verification images were obtained. Off-line alignments were completed to determine intrafraction reproducibility (from repeat images obtained before one treatment) and interfraction reproducibility (from comparisons of the final image for each fraction with the AP) of diaphragm position relative to vertebral bodies. For each image set, the vertebral bodies were aligned, and the resultant craniocaudal (CC) offset in diaphragm position was measured. Liver position during ABC was also evaluated from kV fluoroscopy acquired at the time of simulation, kV fluoroscopy at the time of treatment, and from MV beam’s-eye view movie loops acquired during treatment. Results: Twenty-one of 34 patients were screened to be suitable for ABC. The average free breathing range of these patients was 13 mm (range, 5–1 mm). Fluoroscopy revealed that the average maximal diaphragm motion during ABC breath-hold was 1.4 mm (range, 0–3.4 mm). The MV treatment movie loops confirmed diaphragm stability during treatment. For a measure of intrafraction reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in 14 patients was conducted. The average mean difference in the liver surface position was −0.9 mm, −0.5 mm, and 0.2 mm in the CC, AP, and medial-lateral (ML) directions, with a standard deviation of 1.5 mm, 1.5 mm, and 1.5 mm, respectively. Ninety-five percent of the liver surface had an absolute differences in position between repeat ABC CT scans of less than 4.1 mm, 3.3 mm, and 3.3 mm in the CC, AP, and ML directions, respectively. Analysis of 257 MV AP images from patients treated using ABC revealed an average intrafraction CC reproducibility (σ) of diaphragm relative to vertebral bodies of 1.5 mm (range, 0.6–3.9 mm). The average interfraction CC reproducibility (σ) was 3.4 mm (range, 1.5–7.9 mm), indicating less day-to-day reproducibility of diaphragm position relative to vertebral bodies. The average absolute intra and interfraction CC offset in diaphragm position relative to vertebral bodies was 1.7 and 3.7 mm, respectively, with 86% of intrafraction and 54% of interfraction absolute offsets 3.0 mm or less. Conclusions: Intrafraction reproducibility of liver position using ABC is good in the majority of screened patients. However, interfraction reproducibility is worse, suggesting a need for image guidance.

Introduction In the absence of volumetric image-guided radiotherapy (IGRT) with or without intravenous contrast, IGRT with two-dimensional (2D) imaging can improve the accuracy and precision of radiation delivery by correcting the largest sources of geometric uncertainty, facilitating the delivery of higher doses to the tumor and/or reduced doses to normal tissues. The purpose of this work was to estimate dosimetric impact of 2D IGRT for patients undergoing breath hold liver stereotactic body radiotherapy (SBRT). Materials/Methods Offline residual offsets were determined using orthogonal image pairs acquired with patients positioned with external setup marks (non-IGRT) and following IGRT and repositioning (IGRT) for 30 patients treated with 6-fraction liver SBRT. The diaphragm was used as a surrogate for the liver for craniocaudal positioning, and the vertebral bodies for anterioposterior and right-left positioning, with a 3-mm threshold. The planned dose distributions were shifted by the measured IGRT and non-IGRT offsets. Total doses to target volumes and organs at risk (OAR) were calculated and compared to the prescribed plans. Results A total of 643 images (416-MV electronic portal images; 227 kV cone beam computed tomography projection images) were evaluated. Residual non-IGRT offsets frequently exceeded 3 mm (72%), resulting in clinically significant variations from the prescribed minimum planning target volume dose (mean change –6.5 Gy; P =.0150). The population mean reductions in minimum gross tumor volume doses (standard deviation (σ) to 0.5 mL with were 7.2 Gy (6.3) and 4.7 Gy (6.1) for non-IGRT and IGRT, respectively. The mean population increase in maximum OAR dose (to 0.5 mL) was largest for bowel (2.7 Gy, σ = 5.5 Gy) for non-IGRT. Conclusions IGRT significantly improves concordance of delivered doses with planned doses for liver target volumes and OARs.

Background Intensity-modulated radiotherapy (IMRT) may allow improvement in plan quality for treatment of liver cancer, however increasing radiation modulation complexity can lead to increased uncertainties and requirements for quality assurance. This study assesses whether target coverage and normal tissue avoidance can be maintained in liver cancer intensity-modulated radiotherapy (IMRT) plans by systematically reducing the complexity of the delivered fluence. Methods An optimal baseline six fraction individualized IMRT plan for 27 patients with 45 liver cancers was developed which provided a median minimum dose to 0.5 cc of the planning target volume (PTV) of 38.3 Gy (range, 25.9-59.5 Gy), in 6 fractions, while maintaining liver toxicity risk Results Reduction in the number of segments was achieved for all 27 plans from a median of 48 segments (range 34-52) to 19 segments (range 6-30), without exceeding normal tissue dose objectives and maintaining equivalent PTVD95 and similar PTV Equivalent Uniform Dose (EUD(-20)) IMRT plans with fewer segments had significantly less monitor units (mean, 1892 reduced to 1695, p = 0.012), but also reduced dose conformity (mean, RTOG Conformity Index 1.42 increased to 1.53 p = 0.001). Conclusions Tumour coverage and normal tissue objectives were maintained with simplified liver IMRT, at the expense of reduced conformity.

Purpose To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration. Methods and Materials Twenty-one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale computed tomography (CT) for 27–60 Gy in six fractions, were included. A biomechanical model–based deformable image registration algorithm retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified. Results Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was −1 (−14 to 8) to minimum tumor, −4 (−15 to 0) to maximum bowel, −4 (−25 to 1) to maximum duodenum, 2 (−1 to 9) to maximum esophagus, −2 (−13 to 4) to maximum stomach, 0 (−3 to 4) to mean liver, and −1 (−5 to 1) and −2 (−7 to 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues. Conclusion Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases as a result of breathing motion. These changes may not be accurately accounted for with rigid motion.

Purpose Abdominal compression (AC) can be used to reduce respiratory liver motion in patients undergoing liver stereotactic body radiotherapy. The purpose of the present study was to measure the changes in three-dimensional liver tumor motion with and without compression using cine-magnetic resonance imaging. Patients and Methods A total of 60 patients treated as a part of an institutional research ethics board-approved liver stereotactic body radiotherapy protocol underwent cine T2-weighted magnetic resonance imaging through the tumor centroid in the coronal and sagittal planes. A total of 240 cine-magnetic resonance imaging sequences acquired at one to three images each second for 30–60 s were evaluated using an in-house–developed template matching tool (based on the coefficient correlation) to measure the magnitude of the tumor motion. The average tumor edge displacements were used to determine the magnitude of changes in the caudal–cranial (CC) and anteroposterior (AP) directions, with and without AC. Results The mean tumor motion without AC of 11.7 mm (range, 4.8–23.3) in the CC direction was reduced to 9.4 mm (range, 1.6–23.4) with AC. The tumor motion was reduced in both directions (CC and AP) in 52% of the patients and in a single direction (CC or AP) in 90% of the patients. The mean decrease in tumor motion with AC was 2.3 and 0.6 mm in the CC and AP direction, respectively. Increased motion occurred in one or more directions in 28% of patients. Clinically significant (>3 mm) decreases were observed in 40% and increases in Conclusion AC can significantly reduce three-dimensional liver tumor motion in most patients, although the magnitude of the reduction was smaller than previously reported.

To evaluate diffusion weighted magnetic resonance imaging (DWI) in liver and liver cancers during and following conformal radiotherapy (RT). To determine the feasibility of using changes in apparent diffusion coefficients (ADC) as a potential surrogate for tumour control or normal tissue injury.Patients on a six-fraction conformal liver RT protocol underwent DW-MRI at the time of treatment planning, during RT (week one and two) and one month following RT. Diffusion weighted MR images were acquired in exhale breath hold, using b-values of 0 and 600. Regions of interest (ROIs) corresponding to maximal tumour dose, high-dose peri-tumour liver, irradiated normal liver, non-irradiated liver, and spleen were analyzed on ADC maps.Eleven patients (four hepatocellular carcinoma, five liver metastases, two cholangiocarcinoma) were evaluated. The baseline median tumour ADC of 1.56 x 10(-3)mm(2)/sec increased to 1.89 x 10(-3)mm(2)/sec at RT week one, to 1.91 x 10(-3)mm(2)/sec during week two and to 2.01 x 10(-3)mm(2)/sec at one month following treatment (p0.0001). Early increases in mean ADC were correlated with higher dose and sustained tumour response, whereas RECIST and volume changes on T2 images were not. Peri-tumour mean ADC also increased, from 1.40 x 10(-3)mm(2)/sec (baseline) to 1.55 x 10(-3)mm(2)/sec (RT week 2) and 1.64 x 10(-3)mm(2)/sec (follow-up). Small ADC changes were seen in the irradiated liver, and no significant changes were seen in the un-irradiated liver.Changes in tumour ADC were seen during RT. Larger increases were correlated with higher doses and increased likelihood of response.

Purpose For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. Methods and Materials Evaluable patients were treated in a Research Ethics Board–approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCT scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house–developed finite-element model–based deformable registration (MORFEUS). Results We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left–right (LR), anterior–posterior (AP), and superior–inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left–right, anterior–posterior, and superior–inferior directions, respectively. Conclusions Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver registrations on respiratory sorted CBCT scans were small in most patients (

Purpose To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal risk of liver toxicity in a treatment planning study. Methods and Materials A total of 26 CRT plans were evaluated. Prescription doses (24–54 Gy within six fractions) were individualized on the basis of the effective liver volume irradiated maintaining ≤5% risk of radiation-induced liver disease. The dose constraints included bowel (0.5 cm 3 ) and stomach (0.5 cm 3 ) to ≤30 Gy, spinal cord to ≤25 Gy, and planning target volume (PTV) to ≤140% of the prescribed dose. Two groups were evaluated: (1) PTV overlapping or directly adjacent to serial functioning normal tissues ( n = 14), and (2) the liver as the dose-limiting normal tissue ( n = 12). IMRT plans using direct machine parameter optimization maintained the CRT plan beam arrangements, an estimated radiation-induced liver disease risk of 5%, and underwent dose escalation, if all normal tissue constraints were maintained. Results IMRT improved PTV coverage in 19 of 26 plans (73%). Dose escalation was feasible in 9 cases by an average of 3.8 Gy (range, 0.6–13.2) in six fractions. Three of seven plans without improved PTV coverage had small gross tumor volumes (≤105 cm 3 ) already receiving 54 Gy, the maximal prescription dose allowed. In the remaining cases, the PTV range was 9.6–689 cm 3 ; two had overlapped organs at risk; and one had four targets. IMRT did not improve these plans owing to poor target coverage ( n = 2) and nonliver ( n = 2) dose limits. Conclusion Direct machine parameter optimization IMRT improved PTV coverage while maintaining normal tissue tolerances in most CRT liver plans. Dose escalation was possible in a minority of patients.

PURPOSE: To quantify the improvements in online target localization using kV cone beam CT (CBCT) with deformable registration. METHODS AND MATERIAL: Twelve patients treated under a 6 fraction liver cancer radiation therapy protocol were imaged in breath hold using kV CBCT at each treatment fraction. The images were imported into the treatment planning software and rigidly registered by fitting the liver, identified on the daily kV CBCT image, into the liver contours, previously drawn on the planning CT. The liver was then manually contoured on each CBCT image. Deformable registration was automatically performed, aligning the CT liver to the liver on each CBCT image using MORFEUS, a biomechanical model based deformable registration algorithm. The tumor, defined on planning CT, was mapped onto the CBCT, through MORFEUS. The center of mass (COM) displacement of the tumor was computed. RESULTS: The mean (SD) displacement magnitude (absolute value) of the COM following deformable registration was 0.08 (0.07), 0.10 (0.11), and 0.10 (0.17) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COM was 0.34, 0.65, and 0.97 cm in the LR, AP, and SI directions, respectively. Fifteen percent of the treatment fractions had a COM displacement of greater than 0.3 cm and 33% of patients had at least 1 fraction with a displacement of greater than 0.3 cm. The deformable registration, excluding the manual contouring of the liver, was performed in less than 1 minute, on average. DISCUSSION: Rigid registration of the liver volume between planning CT and verification kV CBCT localizes the tumor to within 0.3 cm for the majority (66%) of patients; however, larger offsets in tumor position can be observed due to liver deformation.

To measure the three-dimensional motion of liver tumors using cine-magnetic resonance imaging (MRI) and compare it to the liver motion assessed using fluoroscopy.Liver and liver tumor motion were investigated in the first 36 patients with primary (n = 20) and metastatic (n = 16) liver cancer accrued to our Phase I stereotactic radiotherapy study. At simulation, all patients underwent anteroposterior fluoroscopy, and the maximal diaphragm excursion in the craniocaudal (CC) direction was observed. Cine-MRI using T(2)-weighted single shot fast spin echo sequences were acquired in three orthogonal planes during free breathing through the centroid of the most dominant liver tumor. ImageJ software was used to measure the maximal motion of the tumor edges in each plane. The intra- and interobserver reproducibility was also quantified.The average CC motion of the liver at fluoroscopy was 15 mm (range, 5-41). On cine-MRI, the average CC tumor motion was 15.5 mm (range, 6.9-35.4), the anteroposterior motion was 10 mm (range, 3.7-21.6), and the mediolateral motion was 7.5 mm (range, 3.8-14.8). The fluoroscopic CC diaphragm motion did not correlate well with the MRI CC tumor motion (r = 0.25). The mean intraobserver error was2 mm in the CC, anteroposterior, and mediolateral directions, and 90% of measurements between observers were within 3 mm.The results of our study have shown that cine-MRI can be used to directly assess liver tumor motion in three dimensions. Tumor motion did not correlate well with the diaphragm motion measured using kilovoltage fluoroscopy. The tumor motion data from cine-MRI can be used to facilitate individualized planning target volume margins to account for breathing motion.

A highly individualized stereotactic body radiotherapy (SBRT) strategy was developed to allow a wide spectrum of patients with liver cancer to be treated. This phase I/II study encompasses individualization of immobilization, radiation planning, PTV margin determination, image guidance strategy and prescription dose. Active breathing control breath hold is used to immobilize the liver when feasible. Image guidance strategies include orthogonal MV images and orthogonal kV fluoroscopy using the diaphragm for a surrogate for the liver, and kV cone beam CT using the liver or tumour for guidance. The prescription dose is individualized to maintain the same estimated risk of radiation-induced liver disease (RILD), based on a normal tissue complication probability (NTCP) model, with a maximum permitted dose of 60 Gy in 6 fractions. Since August 2003, 79 patients with hepatocellular carcinoma (33), intrahepatic cholangiocarcinoma (12) and liver metastases (34) were treated. The median tumour volume was 293 cm3 (2.9-3 088 cm3). The median prescribed dose was 36.6 Gy (24.0 Gy-57.0 Gy) in 6 fractions. The median effective liver volume irradiated was 45% (9-80%). Sixty percent of patients were treated with breath hold to immobilize their liver. Intra-fraction reproducibility (sigma) of the liver with repeat breath holds was excellent (1.5 mm); however inter-fraction reproducibility (sigma) was worse (3.4 mm). Image guidance reduced the residual systematic and random setup errors significantly.

Purpose: A six-fraction, high-precision radiotherapy protocol for unresectable liver cancer has been developed in which active breathing control (ABC) is used to immobilize the liver and daily megavoltage (MV) imaging and repositioning is used to decrease geometric uncertainties. We report the accuracy of setup in the first 20 patients consecutively treated using this approach. Methods and materials: After setup using conventional skin marks and lasers, orthogonal MV images were acquired with the liver immobilized using ABC. The images were aligned to reference digitally reconstructed radiographs using the diaphragm for craniocaudal (CC) alignment and the vertebral bodies for anterior-posterior (AP) and mediolateral (ML) alignment. Adjustments were made for positioning errors >3 mm. Verification imaging was repeated after repositioning to assess for residual positioning error. Offline image matching was conducted to determine the setup accuracy using this approach compared with the initial setup error before repositioning. Real-time beam’s-eye-view MV movies containing an air-diaphragm interface were also evaluated. Results: A total of 405 images were evaluated from 20 patients. Repositioning occurred in 109 of 120 fractions because of offsets >3 mm. Three to eight beam angles, with up to four segments per field, were used for each isocenter. Breath holds of up to 27 s were used for imaging and treatment. The average time from the initial verification image to the last treatment beam was 21 min. Image guidance and repositioning reduced the population random setup errors (σ) from 6.5 mm (CC), 4.2 mm (ML), and 4.7 mm (AP) to 2.5 mm (CC), 2.8 mm (ML), and 2.9 mm (AP). The average individual random setup errors (σ) were reduced from 4.5 mm (CC), 3.2 mm (AP), and 2.5 mm (ML) to 2.2 mm (CC), 2.0 mm (AP), and 2.0 mm (ML). The standard deviation of the distribution of systematic deviations (Σ) was also reduced from 5.1 mm (CC), 3.4 mm (ML), and 3.1 mm (AP) to 1.4 mm (CC), 2.0 mm (ML), and 1.9 mm (AP) with image guidance and repositioning. The average absolute systematic errors were reduced from 4.1 mm (CC), 2.4 mm (AP), and 3.1 (ML) to 1.1 mm (CC), 1.3 mm (AP), and 1.6 mm (ML). Analysis of 52 real-time beam’s-eye-view MV movies revealed an average absolute CC offset in diaphragm position of 1.9 mm. Conclusion: Image guidance with orthogonal MV imaging and ABC for stereotactic body radiotherapy for liver cancer is feasible, improving setup accuracy compared with ABC without daily imaging and repositioning.

Purpose: To compare image‐guided accuracy for stereotactic radiotherapy of the liver in terms of reproducibility and targeting confidence. Method and Materials: The study involved eight patients treated for inoperable liver metastases or hepatobiliary carcinoma. Each treatment fraction, these patients were imaged and repositioned using orthogonal portal images acquired in AP and lateral views. Repositioning occurred when the measured offset exceed 3mm in any of the cranio‐caudal (CC), anterior‐posterior (AP), and medio‐lateral (ML) directions. A second pair of orthogonal images assessed the residual setup accuracy. Orthogonal fluoroscopy sessions, each lasting 30 s, were acquired; some prior, but most after radiotherapy delivery. All images were acquired with the patient under active breathing control. All treatments were performed using a conventional medicallinear accelerator equipped with a kilovoltage x‐ray source and flat‐panel detector mounted at 90 degrees from the linac beam central axis. The right diaphragm was used as a surrogate for the liver position. The reproducibility and stability of the diaphragm was thus analysed for a total of 48 fractions. Results: After initial setup and repositioning, the residual setup error determined from portal images was 2.6 (CC), 3.0 (AP), and 2.6 mm (ML); conversely, the residual setup error measured from the kilovoltage fluoroscopy sessions was 3.2 (CC), 3.1 (AP), and 2.1 mm (ML). Conclusion: Daily portal imaging and repositioning based on these images improves setup accuracy. Similar accuracy is shown from kilovoltage fluoroscopy analysis. On‐line fluoroscopy can potentially assess patient position prior and after delivery of radiation therapy, and provide a baseline for cone‐beam CT analysis. Conflict of Interest:: This work is supported, in part, by Elekta Radiation Oncology. LD is supported by an ASCO career development award.

Purpose: To compare the spatial and volumetric differences in livertumor definition based on triphasic IV contrastCT and Gadoliniumcontrast MR. Method and Materials: Changes in patient and liver position and differences in CT and MR imaging make an accurate comparison of tumor representation challenging, as deformation of the liver occurs. A deformable registration method has been developed to generate geometrically resolved views of the different image sets using finite element modeling to take advantage of the biomechanical relationship between the anatomical representations on each modality. The liver and livertumors are contoured on the CT and MR, using a treatment planning system. A guided surface projection method is used to identify and account for the geometric discrepancies of the liver, allowing a direct comparison of the MR and CTtumors.Results: Triphasic CT and Gadolinium MR images were obtained at end exhale. Differences in tumor volume and center of mass and in the surface area differing by greater than 3 mm in spatial position (PSA3) were measured for patients with liver metastases, cholangiocarcinoma and hepatoma. The tumor comparisons were done following registration of the liver to resolve geometric discrepancies. The average tumor volume change was 52% (19–121%). The average center of mass change was 0.4 cm (0.1–0.6 cm). The average PSA3 was 49% (28–60%). Initial results show that MR GTV was larger then CT GTV in patients with hepatoma, smaller in cholangiocarcinoma and variable in metastases. Conclusion: Deformable image registration improves the spatial correlation of the MR and CT defined liver GTVs compared to rigid body registration alone. This deformable image registration method preserves the spatial integrity of the tumor, while resolving the geometric differences between the MR and CTliver.Conflict of Interest: Research supported in part by Varian Medical Systems. LD is an ASCO career development award recipient.

Purpose: This study aims to investigate the impact of atlas‐based auto‐contouring upon the accuracy of contouring for operators with varying training and familiarity with a particular contouring convention. Methods: A set of ten head and neck CT datasets were contoured by Contourer 1 and validated by another expert clinician. A single dataset was selected to serve as an atlas to auto‐contour the remaining nine cases using commercial deformable image registration software (Mirada RTx, Mirada Medical, UK). For each of these nine cases, the brainstem, spinal cord, all parotid and submandibular glands were independently contoured by Contourers 1, 2 and 3 (a) manually from scratch and (b) by editing the auto‐contours. Contourer 2 was familiar with the contouring convention of the atlas whilst Contourer 3 was not. Dice similarity coefficient (DSC) was used to compare manual contours and the edited contours against the original contours of Contourer 1 . Results: Mean DSC for all structures for Contourers 1, 2 and 3 were 0.89, 0.85 and 0.66 for the scratch contours and 0.87, 0.84 and 0.74 for the edited auto‐contours. The greatest effect of using the auto‐contours for Contourer 3 DSC occurred for the parotids (0.52 to 0.67) and submandibular glands (0.77 to 0.85) and the least for the brainstem (0.84 to 0.85) and cord (0.55 to 0.55). Conclusion: Atlas‐based auto‐contouring using deformable image registration was found to improve the accuracy of Contourer 3 only and only for the parotids and submandibular glands. DSC for Contourers 1 and 2 are largely unaffected by auto‐contours. This suggests that familiarity with contouring convention, or lack thereof, is an important factor in assessing auto‐contouring efficacy but that auto‐contouring may improve accuracy to a standard. Within a clinical setting, or for clinical trials, atlas‐based contouring may have benefit in training and quality assurance in developing consensus. G.S,M.G and T.K are employees of Mirada Medical and there was no conflict of interest with the research submitted.

The risk of radiation induced liver disease (RILD) can be estimated using a normal tissue complication probability (NTCP) model. Our institution uses an NTCP model in a six fraction dose escalation study in which each patient is treated with individualized prescription doses to maintain iso-toxicity. The starting dose level in this study is the prescription dose leading to 5% NTCP (or a maximum of 9 Gy per fraction).

Background External skin marks or radiological bone structures have traditionally been used as positioning references in conventional radiotherapy (RT). However, these are poor surrogates for liver tumor position which is not fixed to the skeleton but is better correlated with diaphragm position. PTV margins must be large enough to account for uncertainty in tumour position using such localization methods. In addition, the liver moves due to breathing, again requiring PTV margins to be increased, resulting in increased normal tissue irradiation.