Prospective evaluation of patient-reported anxiety and experiences with adaptive radiation therapy on an MR-linac.

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.

Paediatric radiation therapy without anaesthesia - Are the children moving?

PURPOSE: Children who require radiation therapy (RT) should ideally be treated awake, without anaesthesia, if possible. Audiovisual distraction is a known method to facilitate awake treatment, but its effectiveness at keeping children from moving during treatment is not known. The aim of this study was to evaluate intrafraction movement of children receiving RT while awake. METHODS: In this prospective study, we measured the intrafraction movement of children undergoing treatment with fractionated RT, using pre- and post-RT cone beam CT (CBCT) with image matching on bony anatomy. Study CBCTs were acquired at first fraction, weekly during RT, and at last fraction. The primary endpoint was the magnitude of vector change between the pre- and post-RT scans. Our hypothesis was that 90 % of CBCT acquisitions would have minimal movement, defined as <3 mm for head-and-neck (HN) treatments and <5 mm for non-HN treatments. RESULTS: A total of 65 children were enrolled and had evaluable data across 302 treatments with CBCT acquisitions. Median age was 11 years (range, 2-18; 1st and 3rd quartiles 7 and 14 years, respectively). Minimal movement was observed in 99.4 % of HN treatments and 97.2 % of non-HN treatments. The study hypothesis of >90 % of evaluations having minimal movement was met. Children who were age >11 years moved less at initial evaluation but tended to move more as a course of radiation progressed, as compared to children who were younger. CONCLUSION: Children receiving RT with audiovisual distraction while awake had small magnitudes of observed intrafraction movement, with minimal movement in >97 % of observed RT fractions. This study validates methods of anaesthesia avoidance using audiovisual distraction for selected children.

Deformable image registration for composite planned doses during adaptive radiation therapy.

INTRODUCTION: Some patients have significant anatomic changes during radiotherapy, necessitating an adaptive repeat CT-simulation and re-planning. This yields two unique planning datasets that introduce uncertainty into total dose records. This study explored the impact of using deformable image registration (DIR) to spatially align repeat CT-simulation images and calculate total planned dose distributions. MATERIALS & METHODS: Data from 5 head-and-neck, 5 lung, and 5 sarcoma patients who had unanticipated re-planning during radiotherapy were analyzed in a treatment planning system (RayStation v6.1 RaySearch Laboratories). Total planned doses to normal tissues were calculated using two methods and the previously generated manual contours defined on each CT. The first method, termed 'parameter addition', simply sums the relevant DVH metrics from the initial and re-planned distributions without spatially registering the CTs. The second, termed 'dose accumulation', uses a validated hybrid contour/intensity-based DIR algorithm to deform initial CT and dose distribution onto the repeat CT and re-planning dose distribution. DVH metrics from the summed distribution on the repeat CT are then calculated. Dose differences for organs-at-risk between parameter addition and dose accumulation ≥100 cGy were assumed to be clinically relevant. To elucidate whether relevant differences were due to registration accuracy or contouring variability between CTs, the analysis was repeated using contours on the first CT and the same contours deformed to the repeat CT with DIR. RESULTS: For all patients, high overall DIR accuracy was verified visually (qualitatively) and numerically (quantitatively) using image similarity and contour-based metrics. All head-and-neck and lung patients, and one sarcoma patient (11 of 15 total) had dose differences between parameter addition and dose accumulation ≥100 cGy, with absolute mean differences of 160 cGy (range 101-436 cGy) seen in 41 of 205 total DVH criteria. In 22 of these 41 criteria, these differences were attributed to contouring variability between CTs. After correcting for contouring variations using DIR, the mean absolute differences in 7 of these 22 criteria with a relevant result (across 6 patients) was 146 cGy (range 100-502 cGy). In only 4 DVH criteria, the DIR mapped contours had higher variations than the original contours. One lung patient had a DVH criteria exceeding the clinical dose constraint by 125 cGy with parameter addition, and with accurate DIR and dose accumulation, the criteria was actually 97 cGy lower than the constraint. CONCLUSIONS: The use of DIR to generate total planned dose records revealed substantial dose differences in most cases compared to commonly used clinical methods (i.e. parameter addition), and altered the planned acceptance criteria in a minority. DIR is recommended to be used for future adaptive re-plans to generate total planned dose records and facilitate accurate re-contouring. More accurate dose records may also improve our understanding of clinical outcomes.

Liver SBRT dose accumulation to assess the impact of anatomic variations on normal tissue doses and toxicity in patients treated with concurrent sorafenib.

BACKGROUND AND PURPOSE: Unexpected liver volume reductions occurred during trials of liver SBRT and concurrent sorafenib. The aims were to accumulate liver SBRT doses to assess the impact of these anatomic variations on normal tissue dose parameters and toxicity. MATERIALS AND METHODS: Thirty-two patients with hepatocellular carcinoma (HCC) or metastases treated on trials of liver SBRT (30-57 Gy, 6 fractions) and concurrent sorafenib were analyzed. SBRT doses were accumulated using biomechanical deformable registration of daily cone-beam CT. Dose deviations (accumulated-planned) for normal tissues were compared for patients with liver volume reductions > 100 cc versus stable volumes, and accumulated doses were reported for three patients with grade 3-5 luminal gastrointestinal toxicities. RESULTS: Patients with reduced (N = 12) liver volumes had larger mean deviations of 0.4-1.3 Gy in normal tissues, versus -0.2-0.4 Gy for stable cases (N = 20), P > 0.05. Deviations > 5% of the prescribed dose occurred in both groups. Two HCC patients with toxicities to small and large bowel had liver volume reductions and deviations to the maximum dose of 4% (accumulated 36.9 Gy) and 3% (accumulated 33.4 Gy) to these organs respectively. Another HCC patient with a toxicity of unknown location plus tumor rupture, had stable liver volumes and deviations to luminal organs of -6% to 4.5% (accumulated < 30.5 Gy). CONCLUSION: Liver volume reductions during SBRT and concurrent sorafenib were associated with larger increases in accumulated dose to normal tissues versus stable liver volumes. These dosimetric changes may have further contributed to toxicities in HCC patients who have higher baseline risks.

Virtual integration of patient education in radiotherapy (VIPER).

Purpose: Pre-radiotherapy patient education led by Radiation Therapists (RTT) has been shown to improve patients' distress and overall experiences. In an effort to offer a remote delivery method while allowing for visual learning and face-to-face communication, this pilot project evaluated the feasibility and acceptability of using virtual videoconferencing for patient education. Methods: This prospective pilot study integrated virtual patient education into standard care. This workflow consisted of a one-on-one, 45-minute tele-education session with an RTT on the day prior to CT-simulation. For this study, patients were offered the option to complete the session using web-based videoconferencing if they had the capability for it. Feasibility was evaluated as the proportion of patients who agreed to and completed virtual education. To evaluate acceptability, patients and RTTs were then emailed post-intervention surveys evaluating their satisfaction with virtual patient education. Results: Over three months 106 of 139 patients (76%) approached consented to virtual education. The median (range) age was 65 (27-93), 69% were male and most had genitourinary (38%) or head-and-neck (29%) cancers. Ninety patients (85%) completed virtual education as planned, with incompletions due to scheduling (8) or patient technical issues (7), or treatment cancellation (1). Sixty-eight patients completed surveys, with the vast majority agreeing virtual education was clear (94%) and helped them prepare (100%), they were comfortable with the technology (96%) and they were satisfied overall (99%). Twelve RTTs responded, suggesting overall that virtual education was higher quality though less feasible than tele-education, and comparable to in-person education. Conclusion: Offering individual, RTT-led virtual education using videoconferencing to patients pre-radiotherapy was feasible and acceptable in this pilot study, and is therefore being recommended as an option for all our patients. Future work will directly compare the effectiveness of in-person versus virtual education, and incorporate individual patient needs and preferences.

MRI evaluation of normal tissue deformation and breathing motion under an abdominal compression device.

PURPOSE: Abdominal compression can minimize breathing motion in stereotactic radiotherapy, though it may impact the positioning of dose-limiting normal tissues. This study quantified the reproducibility of abdominal normal tissues and respiratory motion with the use of an abdominal compression device using MR imaging. METHODS: Twenty healthy volunteers had repeat MR over 3 days under an abdominal compression plate device. Normal tissues were delineated on daily axial T2-weighted MR and compared on days 2 and 3 relative to day 1, after adjusting for baseline shifts relative to bony anatomy. Inter-fraction organ deformation was computed using deformable registration of axial T2 images. Deformation > 5 mm was assumed to be clinically relevant. Inter-fraction respiratory amplitude changes and intra-fraction baseline drifts during imaging were quantified on daily orthogonal cine-MR (70 s each), and changes > 3 mm were assumed to be relevant. RESULTS: On axial MR, the mean inter-fraction normal tissue deformation was > 5 mm for all organs (range 5.1-13.4 mm). Inter-fraction compression device misplacements > 5 mm and changes in stomach volume > 50% occurred at a rate of 93% and 38%, respectively, in one or more directions and were associated with larger adjacent organ deformation, in particular for the duodenum. On cine-MR, inter-fraction amplitude changes > 3 mm on day 2 and 3 relative to day 1 occurred at a rate of < 12.5% (mean superior-inferior change was 1.6 mm). Intra-fraction baseline drifts > 3 mm during any cine-MR acquisition occurred at a rate of 23% (mean superior-inferior changes was 2.4 mm). CONCLUSIONS: Respiratory motion under abdominal compression is reproducible in most subjects within 3 mm. However, inter-fraction deformations greater than 5 mm in normal tissues were common and larger than inter- and intra-fraction respiratory changes. Deformations were driven mostly by variable stomach contents and device positioning. The magnitude of this motion may impact normal tissue dosimetry during stereotactic radiotherapy.

Simulated daily plan adaptation for magnetic resonance-guided liver stereotactic body radiotherapy.

INTRODUCTION: Liver cancers are challenging to treat using image-guided radiotherapy (IGRT) due to motion and deformation of target volumes and organs at risk (OARs), as well as difficulties in visualising liver tumours using cone-beam computed tomography (CBCT) based IGRT. Liver cancer patients may thus benefit from magnetic resonance (MR)-guided daily adaptive re-planning. We evaluated the dosimetric impact of a daily plan adaptation strategy based on daily MR imaging versus CBCT-based IGRT. METHODS: Ten patients were studied who were treated with CBCT-guided five-fraction stereotactic body radiotherapy (SBRT) and underwent MR imaging before each fraction. Simulated reference plans were created on computer tomography (CT) images and adapted plans were created on the daily MR images. Two plan adaptation strategies were retrospectively simulated: (1) translational couch shifts to match liver, mimicking standard CBCT guidance and (2) daily plan adaptation based on reference plan clinical goals and daily target and OAR contours. Dose statistics were calculated for both strategies and compared. RESULTS: Couch shifts resulted in an average reduction in GTV D99% relative to reference plan values of 5.2 Gy (-12.5% of reference values). Daily plan adaptation reduced this to 0.8 Gy (-2.0%). For six patients who were OAR dose-limited on reference plans, couch shifts resulted in OAR dose violations in 28 out of 28 simulated fractions, respectively; no violations occurred using daily plan adaptation. No OAR dose violations occurred using either strategy for the four cases not OAR dose-limited at reference planning. CONCLUSIONS: MR-guided daily plan adaptation ensured OAR dose constraints were met at all simulated treatment fractions while CBCT-based IGRT resulted in a systematic over-dosing of OARs in patients whose doses were limited by OAR dose at the time of reference planning.

Challenges in Reirradiation of Intrahepatic Tumors.

Definitive reirradiation using a stereotactic technique is an effective local treatment option for both recurrent liver metastases and recurrent primary liver cancers. The tolerance of the liver, bile ducts, and surrounding gastrointestinal luminal organs must be respected to ensure safe retreatment. The risks associated with retreatment to these organs must be carefully balanced with the probability of clinical benefit. We present 2 cases for consideration of repeat irradiation along with the opinions of 4 experts, along with conclusions about recommendations.

Extensive Unpredictable Pancreas Cancer Inter-fraction Motion: A Case Report.

We present a case of locally advanced pancreatic cancer with duodenal invasion treated with consolidative chemoradiation, where extensive unpredictable interfraction motion was observed. Initially, two attempts were made to treat with volumetric modulated arc therapy technique. However, due to substantial interfractional motion of the pancreatic head mass relative to the regional nodal areas, the patient was eventually replanned and treated with a four-field box technique. This case highlights the difficulty in delivering conformal radiation to the pancreas and quantifies the movement of the target, the adjacent biliary stent, and regional nodes.

Redefining Ventricular Target Volume in Germinoma: Is Inclusion of Temporal Horns Necessary?

PURPOSE: We reviewed the outcomes of a retrospective germinoma cohort and analyzed radiation therapy plans to determine dosimetric differences for critical structures. METHODS AND MATERIALS: Data from pediatric patients treated with photon radiation for intracranial germinoma were analyzed for clinical outcomes and dosimetry to critical structures, with particular interest in the temporal ventricular horns (TVHs). A consensus contour was generated for TVH-sparing ventricular clinical target volumes (CTVs) via deformable image registration. RESULTS: Twelve and 10 patients had their TVHs included or excluded in their ventricular CTVs, respectively. All patients were living at the time of analysis. One patient relapsed in the fourth ventricle, which had been omitted from the radiation therapy field. Mean dose was significantly lower to the hippocampi (Δ = -578 cGy, P = .0016) and temporal lobes (Δ = -599 cGy, P = .0007) in the TVH-excluded cohort compared with those with TVHs included in the treatment field. CONCLUSIONS: Exclusion of the TVHs from the CTV results in significant dose sparing to the hippocampi and temporal lobes. Clinical outcomes remain excellent with no deaths and no TVH failures. Exclusion of TVHs from the ventricular CTV in germinoma requires prospective study.

Patterns of practice of adaptive re-planning for anatomic variances during cone-beam CT guided radiotherapy.

PURPOSE: Substantial, unanticipated anatomic variances during cone-beam CT (CBCT)-guided radiotherapy can potentially impact treatment accuracy and clinical outcomes. This study assessed patterns of practice of CBCT variances reported by RTTs and subsequent interventions for multiple-disease sites. METHODS: A chart review was conducted at a large cancer centre for patients treated with daily online CBCT-guided radiotherapy. Patients selected for review were identified via RTT-reported variances that then triggered offline multi-disciplinary assessment. Cases were categorized by the type of anatomic variance observed on CBCT and any further interventions recorded such as un-scheduled adaptive re-planning. RESULTS: Over a 1-year period, 287 variances from 261 patients were identified (6.2% of the 4207 patients treated with daily CBCT-guided radiotherapy), most often occurring within the first 5 fractions of the treatment course. Of these variances, 21% (59/287) were re-planned and 3.5% (10/287) discontinued treatment altogether. Lung was the most frequent disease-site (27% of 287 variances) reported with IGRT-related variances although head and neck and sarcoma were most frequently re-planned (19% of 59 re-plans for each site). Technical or clinical rationales for re-planning were not routinely documented in patient medical records. All disease-sites had numerous categories of variances. Three of the four most frequent categories were for tumor-related changes on CBCT, and the re-planning rate was highest for tumor progression at 25%. Normal tissue variances were the second most frequency category, and re-planned in 14% of those cases. CONCLUSION: RTTs identified a wide range of anatomic variances during CBCT-guided radiotherapy. In a minority of cases, these substantially altered the care plan including ad hoc adaptive re-planning or treatment discontinuation. Improved understanding of the clinical decisions in these cases would aid in developing more routine, systematic adaptive strategies.

A simulation study to assess the potential impact of developing normal tissue complication probability models with accumulated dose.

PURPOSE: This study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: Thirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2 Gy per fraction and generalized equivalent uniform dose were calculated for planned and accumulated doses. Stomach and duodenal Lyman-Kutcher-Burman NTCP models (α/ß = 2.5; n = .09) were developed on the basis of planned and accumulated generalized equivalent uniform doses and the differences between the models assessed. In addition, the error in determining the probability of toxicity on the basis of the planned dose was evaluated by comparing planned doses in the NTCP model that were created from accumulated doses. RESULTS: The standard, planned-dose NTCP model overestimates toxicity risk for both the duodenal and stomach models at doses that are below approximately 20 Gy (6 fractions) and underestimates toxicity risk for doses above approximately 20 Gy (6 fractions). Building NTCP models with accumulated rather than planned doses changes the predicted risk by up to 16% (mean: 6%; standard deviation: 7%) for duodenal toxicity and 6% (mean: 2%; standard deviation: 2%) for stomach toxicity. For a protocol that plans a 10% iso-toxicity risk to the duodenum, a 15.7 Gy (6 fractions) maximum dose constraint would be necessary when using standard NTCP models on the basis of a planned dose and a 17.6 Gy (6 fractions) maximum dose would be allowed when using NTCP models on the basis of accumulated doses. CONCLUSIONS: Assuming that accumulated dose is a more accurate representation of the true delivered dose than the planned dose, this simulation study indicates the need for prospective clinical trials to evaluate the impact of building NTCP models on the basis of accumulated doses.

Baseline Albumin-Bilirubin (ALBI) Score in Western Patients With Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy (SBRT).

PURPOSE: To assess the baseline albumin-bilirubin (ALBI) score as a predictor of toxicity and survival in a prospective cohort of Western patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) in 2 prospective trials. METHODS AND MATERIALS: The study included 102 patients with Child-Pugh class A liver disease who received 6-fraction SBRT for HCC. Univariate and multivariable logistic regression investigated factors associated with toxicity, defined as an increase in Child-Pugh score ≥ 2 within 3 months of SBRT. Univariate and multivariable Cox regression analyses investigated factors predictive of overall survival (OS). The ALBI score was analyzed as a continuous and binary variable in separate analyses. RESULTS: On multivariable analysis of toxicity, including the ALBI score as a continuous variable, the ALBI score (odds ratio [OR] per 0.1-unit increase, 1.51; 95% confidence interval [CI] 1.23-1.85; P = .00074), mean liver dose (OR, 1.31; 95% CI 1.02-1.68; P = .036), and dose received by 800 cm3 of normal liver (OR, 1.10; 95% CI 1.01-1.20; P = .028) were significant. When the ALBI score was included as a dichotomous variable, the ALBI grade remained a significant predictor of toxicity (OR, 7.44; 95% CI 2.34-23.70; P = .00069). On multivariable analysis of OS, including the ALBI score as a continuous variable, the ALBI score (hazard ratio [HR] per 0.1-unit increase, 1.09; 95% CI 1.03-1.17; P = .004), tumor thrombus (HR, 1.94; 95% CI 1.23-3.07; P = .004), and treatment in trial 1 versus trial 2 (HR, 1.92; 95% CI 1.23-3.03; P = .004) were significant. Similarly, when the ALBI score was included as a binary variable, the ALBI grade, tumor thrombus, and trial were significant predictors of OS. When the ALBI score was considered, the Child-Pugh score (A6 vs A5) was not significant in multivariable models analyzing toxicity or survival. Concordance statistics indicated models containing the ALBI score were superior to those containing the Child-Pugh score. CONCLUSIONS: The baseline ALBI score was more discriminating than the Child-Pugh score in predicting OS and toxicity in patients with Child-Pugh class A liver disease. The ALBI score should be used as a factor for stratification in future HCC SBRT trials.

Validation of biomechanical deformable image registration in the abdomen, thorax, and pelvis in a commercial radiotherapy treatment planning system.

PURPOSE: The accuracy of deformable image registration tools can vary widely between imaging modalities and specific implementations of the same algorithms. A biomechanical model-based algorithm initially developed in-house at an academic institution was translated into a commercial radiotherapy treatment planning system and validated for multiple imaging modalities and anatomic sites. METHODS: Biomechanical deformable registration (Morfeus) is a geometry-driven algorithm based on the finite element method. Boundary conditions are derived from the model-based segmentation of controlling structures in each image which establishes a point-to-point surface correspondence. For each controlling structure, material properties and fixed or sliding interfaces are assigned. The displacements of internal volumes for controlling structures and other structures implicitly deformed are solved with finite element analysis. Registration was performed for 74 patients with images (mean vector resolution) of thoracic and abdominal 4DCT (2.8 mm) and MR (5.3 mm), liver CT-MR (4.5 mm), and prostate MR (2.6 mm). Accuracy was quantified between deformed and actual target images using distance-to-agreement (DTA) for structure surfaces and the target registration error (TRE) for internal point landmarks. RESULTS: The results of the commercial implementation were as follows. The mean DTA was ≤ 1.0 mm for controlling structures and 1.0-3.5 mm for implicitly deformed structures on average. TRE ranged from 2.0 mm on prostate MR to 5.1 mm on lung MR on average, within 0.1 mm or lower than the image voxel sizes. Accuracy was not overly sensitive to changes in the material properties or variability in structure segmentations, as changing these inputs affected DTA and TRE by ≤ 0.8 mm. Maximum DTA > 5 mm occurred for 88% of the structures evaluated although these were within the inherent segmentation uncertainty for 82% of structures. Differences in accuracy between the commercial and in-house research implementations were ≤ 0.5 mm for mean DTA and ≤ 0.7 mm for mean TRE. CONCLUSIONS: Accuracy of biomechanical deformable registration evaluated on a large cohort of images in the thorax, abdomen and prostate was similar to the image voxel resolution on average across multiple modalities. Validation of this treatment planning system implementation supports biomechanical deformable registration as a versatile clinical tool to enable accurate target delineation at planning and treatment adaptation.

Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. RESULTS: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 109/L vs 150 × 109/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. CONCLUSIONS: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk.

Effect of deformable registration uncertainty on lung SBRT dose accumulation.

PURPOSE: Deformable image registration (DIR) plays an important role in dose accumulation, such as incorporating breathing motion into the accumulation of the delivered dose based on daily 4DCBCT images. However, it is not yet well understood how the uncertainties associated with DIR methods affect the dose calculations and resulting clinical metrics. The purpose of this study is to evaluate the impact of DIR uncertainty on the clinical metrics derived from its use in dose accumulation. METHODS: A biomechanical model based DIR method and a biomechanical-intensity-based hybrid method, which reduced the average registration error by 1.6 mm, were applied to ten lung cancer patients. A clinically relevant dose parameter [minimum dose to 0.5 cm(3) (Dmin)] was calculated for three dose scenarios using both algorithms. Dose scenarios included static (no breathing motion), predicted (breathing motion at the time of planning), and total accumulated (interfraction breathing motion). The relationship between the dose parameter and a combination of DIR uncertainty metrics, tumor volume, and dose heterogeneity of the plan was investigated. RESULTS: Depending on the dose heterogeneity, tumor volume, and DIR uncertainty, in over 50% of the patients, differences greater than 1.0 Gy were observed in the Dmin of the tumor in the static dose calculation on exhale phase of the 4DCT. Such differences were due to the errors in propagating the tumor contours from the reference planning 4DCT phase onto a subsequent 4DCT phase using each DIR algorithm and calculating the dose on that phase. The differences in predicted dose were more subtle when breathing motion was modeled explicitly at the time of planning with only one patient exhibiting a greater than 1.0 Gy difference in Dmin. Dmin differences of up to 2.5 Gy were found in the total accumulated delivered dose due to difference in quantifying the interfraction variations. Such dose uncertainties could potentially be clinically significant. CONCLUSIONS: Reductions in average uncertainty in DIR algorithms by 1.6 mm may have a clinically significant impact on the decision-making metrics used in dose planning and dose accumulation assessment.