Evaluation of Deep Learning Clinical Target Volumes Auto-Contouring for Magnetic Resonance Imaging-Guided Online Adaptive Treatment of Rectal Cancer.

Purpose: Segmentation of clinical target volumes (CTV) on medical images can be time-consuming and is prone to interobserver variation (IOV). This is a problem for online adaptive radiation therapy, where CTV segmentation must be performed every treatment fraction, leading to longer treatment times and logistic challenges. Deep learning (DL)-based auto-contouring has the potential to speed up CTV contouring, but its current clinical use is limited. One reason for this is that it can be time-consuming to verify the accuracy of CTV contours produced using auto-contouring, and there is a risk of bias being introduced. To be accepted by clinicians, auto-contouring must be trustworthy. Therefore, there is a need for a comprehensive commissioning framework when introducing DL-based auto-contouring in clinical practice. We present such a framework and apply it to an in-house developed DL model for auto-contouring of the CTV in rectal cancer patients treated with MRI-guided online adaptive radiation therapy. Methods and Materials: The framework for evaluating DL-based auto-contouring consisted of 3 steps: (1) Quantitative evaluation of the model's performance and comparison with IOV; (2) Expert observations and corrections; and (3) Evaluation of the impact on expected volumetric target coverage. These steps were performed on independent data sets. The framework was applied to an in-house trained nnU-Net model, using the data of 44 rectal cancer patients treated at our institution. Results: The framework established that the model's performance after expert corrections was comparable to IOV, and although the model introduced a bias, this had no relevant impact on clinical practice. Additionally, we found a substantial time gain without reducing quality as determined by volumetric target coverage. Conclusions: Our framework provides a comprehensive evaluation of the performance and clinical usability of target auto-contouring models. Based on the results, we conclude that the model is eligible for clinical use.

Online Adaptive MRI-Guided Radiotherapy for Primary Tumor and Lymph Node Boosting in Rectal Cancer.

The purpose of this study was to characterize the motion and define the required treatment margins of the pathological mesorectal lymph nodes (GTVln) for two online adaptive MRI-guided strategies for sequential boosting. Secondly, we determine the margins required for the primary gross tumor volume (GTVprim). Twenty-eight patients treated on a 1.5T MR-Linac were included in the study. On T2-weighted images for adaptation (MRIadapt) before and verification after irradiation (MRIpost) of five treatment fractions per patient, the GTVln and GTVprim were delineated. With online adaptive MRI-guided radiotherapy, daily plan adaptation can be performed through the use of two different strategies. In an adapt-to-shape (ATS) workflow the interfraction motion is effectively corrected by redelineation and the only relevant motion is intrafraction motion, while in an adapt-to-position (ATP) workflow the margin (for GTVln) is dominated by interfraction motion. The margin required for GTVprim will be identical to the ATS workflow, assuming each fraction would be perfectly matched on GTVprim. The intrafraction motion was calculated between MRIadapt and MRIpost for the GTVln and GTVprim separately. The interfraction motion of the GTVln was calculated with respect to the position of GTVprim, assuming each fraction would be perfectly matched on GTVprim. PTV margins were calculated for each strategy using the Van Herk recipe. For GTVln we randomly sampled the original dataset 20 times, with each subset containing a single randomly selected lymph node for each patient. The resulting margins for ATS ranged between 3 and 4 mm (LR), 3 and 5 mm (CC) and 5 and 6 mm (AP) based on the 20 randomly sampled datasets for GTVln. For ATP, the margins for GTVln were 10-12 mm in LR and AP and 16-19 mm in CC. The margins for ATS for GTVprim were 1.7 mm (LR), 4.7 mm (CC) and 3.2 mm anterior and 5.6 mm posterior. Daily delineation using ATS of both target volumes results in the smallest margins and is therefore recommended for safe dose escalation to the primary tumor and lymph nodes.

Effect of intrafraction adaptation on PTV margins for MRI guided online adaptive radiotherapy for rectal cancer.

PURPOSE: To determine PTV margins for intrafraction motion in MRI-guided online adaptive radiotherapy for rectal cancer and the potential benefit of performing a 2nd adaptation prior to irradiation. METHODS: Thirty patients with rectal cancer received radiotherapy on a 1.5 T MR-Linac. On T2-weighted images for adaptation (MRIadapt), verification prior to (MRIver) and after irradiation (MRIpost) of 5 treatment fractions per patient, the primary tumor GTV (GTVprim) and mesorectum CTV (CTVmeso) were delineated. The structures on MRIadapt were expanded to corresponding PTVs. We determined the required expansion margins such that on average over 5 fractions, 98% of CTVmeso and 95% of GTVprim on MRIpost was covered in 90% of the patients. Furthermore, we studied the benefit of an additional adaptation, just prior to irradiation, by evaluating the coverage between the structures on MRIver and MRIpost. A threshold to assess the need for a secondary adaptation was determined by considering the overlap between MRIadapt and MRIver. RESULTS: PTV margins for intrafraction motion without 2nd adaptation were 6.4 mm in the anterior direction and 4.0 mm in all other directions for CTVmeso and 5.0 mm isotropically for GTVprim. A 2nd adaptation, applied for all fractions where the motion between MRIadapt and MRIver exceeded 1 mm (36% of the fractions) would result in a reduction of the PTVmeso margin to 3.2 mm/2.0 mm. For PTVprim a margin reduction to 3.5 mm is feasible when a 2nd adaptation is performed in fractions where the motion exceeded 4 mm (17% of the fractions). CONCLUSION: We studied the potential benefit of intrafraction motion monitoring and a 2nd adaptation to reduce PTV margins in online adaptive MRIgRT in rectal cancer. Performing 2nd adaptations immediately after online replanning when motion exceeded 1 mm and 4 mm for CTVmeso and GTVprim respectively, could result in a 30-50% margin reduction with limited reduction of dose to the bowel.

Benchmarking daily adaptation using fully automated radiotherapy treatment plan optimization for rectal cancer.

Background/purpose: In daily plan adaptation the radiotherapy treatment plan is adjusted just prior to delivery. A simple approach is taking the planning objectives of the reference plan and directly applying these in re-optimization. Here we present a tested method to verify whether daily adaptation without tweaking of the objectives can maintain the plan quality throughout treatment. Materials/methods: For fifteen rectal cancer patients, automated treatment planning was used to generate plans mimicking manual reference plans on the planning scans. For 74 fraction scans (4-5 per patient) an automated plan and a daily adapted plan were generated, where the latter re-optimizes the reference plan objectives without any tweaking. To evaluate the robustness of the daily adaptation, the adapted plans were compared to the autoplanning plans. Results: Median differences between the autoplanning plans on the planning scans and the reference plans were between -1 and 0.2 Gy. The largest interquartile range (1 Gy) was seen for the Lumbar Skin D2%. For the daily scans the PTV D2% and D98% differences between autoplanning and adapted plans were within ± 0.7 Gy, with mean differences within ± 0.3 Gy. Positive differences indicate higher values were obtained using autoplanning. For the Bowelarea + Bladder and the Lumbar Skin the D2% and Dmean differences were all within ± 2.6 Gy, with mean differences between -0.9 and 0.1 Gy. Conclusion: Automated treatment planning can be used to benchmark daily adaptation techniques. The investigated adaptation workflow can robustly perform high quality adaptations without daily adjusting of the patient-specific planning objectives for rectal cancer radiotherapy.

Validation of a 4D-MRI guided liver stereotactic body radiation therapy strategy for implementation on the MR-linac.

Purpose. Accurate tumor localization for image-guided liver stereotactic body radiation therapy (SBRT) is challenging due to respiratory motion and poor tumor visibility on conventional x-ray based images. Novel integrated MRI and radiotherapy systems enable direct in-room tumor visualization, potentially increasing treatment accuracy. As these systems currently do not provide a 4D image-guided radiotherapy strategy, we developed a 4D-MRI guided liver SBRT workflow and validated all steps for implementation on the Unity MR-linac.Materials and Methods. The proposed workflow consists of five steps: (1) acquisition of a daily 4D-MRI scan, (2) 4D-MRI to mid-position planning-CT rigid tumor registration, (3) calculation of daily tumor midP misalignment, (4) plan adaptation using adapt-to-position (ATP) with segment-weights optimization and (5) adapted plan delivery. The workflow was first validated in a motion phantom, performing regular motion at different baselines (±5 to ±10 mm) and patient-derived respiratory signals with varying degrees of irregularity. 4D-MRI derived respiratory signals and 4D-MRI to planning CT registrations were compared to the phantom input, and gamma and dose-area-histogram analyses were performed on the delivered dose distributions on film. Additionally, 4D-MRI to CT registration performance was evaluated in patient images using the full-circle method (transitivity analysis). Plan adaption was further analyzedin-silicoby creating adapted treatment plans for 15 patients with oligometastatic liver disease.Results. Phantom trajectories could be reliably extracted from 4D-MRI scans and 4D-MRI to CT registration showed submillimeter accuracy. The DAH-analysis demonstrated excellent coverage of the dose evaluation structures GTV and GTVTD. The median daily rigid 4D-MRI to midP-CT registration precision in patient images was <2 mm. The ATP strategy restored the target dose without increased exposure to the OARs and plan quality was independent from 3D shift distance in the range of 1-26 mm.Conclusions. The proposed 4D-MRI guided strategy showed excellent performance in all workflow tests in preparation of the clinical introduction on the Unity MR-linac.

Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients.

PURPOSE: Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. METHODS AND MATERIALS: Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. RESULTS: A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. CONCLUSIONS: ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

Breast-shape changes during radiation therapy after breast-conserving surgery.

BACKGROUND & PURPOSE: With the introduction of more conformal techniques for breast cancer radiation therapy (RT), motion management is becoming increasingly important. We studied the breast-shape variability during RT after breast-conserving surgery (BCS). MATERIALS & METHODS: Planning computed tomography (CT) and follow-up cone-beam CT (CBCT) scans were available for 71 fractions of 17 patients undergoing RT after BCS. First, the CT and the CBCT scans were registered on bones. Subsequently, breast-contour data were generated. The CBCT contours were analyzed in 3D in terms of deviations (mean and standard deviation) relative to the contour of the CT scan for the upper medial, lower medial, upper lateral, and lower lateral breast quadrants, and the axilla. RESULTS: Regional systematic and random standard deviations of the breast quadrants varied between 1.5 and 2.1 mm and 1.0-1.6 mm, respectively, and were larger for the axilla (3.0 mm). An absolute average shape change of  ≥4.0 mm in at least one region was present in 21/71 fractions (30%), predominantly in breast volumes > 800 cc (p = <0.01). Furthermore, seroma was associated with larger shape changes (p = 0.04). CONCLUSIONS: Breast-shape variability varies between anatomic locations. Changes in the order of 4 mm are frequently observed during RT, especially for large breasts. This should be taken into account in the development of protocols for partial breast irradiation and boost treatment.

Pre-clinical experience of an adaptive plan library strategy in radiotherapy of rectal cancer: An inter-observer study.

BACKGROUND AND PURPOSE: The clinical target volume (CTV) in radiotherapy of rectal cancer is subject to large deformations. With a plan library strategy, the treatment may be adapted to these deformations. The purpose of this study was to determine feasibility and consistency in plan selection for a plan library strategy in radiotherapy of rectal cancer. MATERIAL AND METHODS: Thirty rectal cancer patients were included in this retrospective study with in total 150 CBCT scans. A library of CTVs was constructed with in-house built software using population statistics on daily rectal deformations. The library consisted of five plans based on: the original CTV, two larger, and two smaller CTVs. An inter-observer study (study-I) was performed to test the consistency in plan choices between four observers (all RTTs). After five months the observers were asked to re-evaluate (study-II) the same set of scans based on refined guidelines. RESULTS: In study-I the observers reached accordance with the majority choice in 69% of cases. This improved to 87% in study-II. The consensus meeting revealed that inconsistency in choices mainly arose from inadequate instructions, which were later clarified and formulated more accurately. CONCLUSION: Plan selection based on daily CBCT scans for rectal cancer patients is feasible, and can be performed consistently by well-trained RTTs.

Monitoring early changes in rectal tumor morphology and volume during 5 weeks of preoperative chemoradiotherapy - An evaluation with sequential MRIs.

PURPOSE: To assess early changes in rectal tumor volume and morphology on sequential MRIs performed during 5 weeks of chemoradiotherapy. MATERIALS AND METHODS: Thirteen patients underwent weekly T2W-MRI during 5 weeks of preoperative radiotherapy (total 50 Gy), starting after the first week of radiation. Two radiologists visually evaluated tumor volume and morphology and one reader manually segmented tumors for each time point to quantitatively calculate tumor volumes. Evolution in tumor volume/morphology was assessed over time and compared between good responders (tumor regression grade (TRG) 1-2) and poor responders (TRG 3-5). RESULTS: Tumor volumes decreased significantly during radiation. Early signs of response were also visually apparent: in the majority of good responders an early fibrotic transformation (week 2-3) as well as a visually estimated early volume reduction of >1/3 (week 1-2), was observed while these early changes only occurred in a minority of poor responders. CONCLUSION: Results of this exploratory pilot study suggest that changes in rectal tumor morphology (fibrosis) and volume can already be observed early during radiation, both when measured quantitatively and when assessed visually. These changes appear to be indicative of the final treatment outcome.

Kilo-voltage cone-beam computed tomography setup measurements for lung cancer patients; first clinical results and comparison with electronic portal-imaging device.

PURPOSE: Kilovoltage cone-beam computed tomography (CBCT) has been developed to provide accurate soft-tissue and bony setup information. We evaluated clinical CBCT setup data and compared CBCT measurements with electronic portal imaging device (EPID) images for lung cancer patients. METHODS AND MATERIALS: The setup error for CBCT scans at the treatment unit relative to the planning CT was measured for 62 patients (524 scans). For 19 of these patients (172 scans) portal images were also made. The mean, systematic setup error (Sigma), and random setup error (sigma) were calculated for the CBCT and the EPID. The differences between CBCT and EPID and the rotational setup error derived from the CBCT were also evaluated. An offline shrinking action level correction protocol, based on the CBCT measurements, was used to reduce systematic setup errors and the impact of this protocol was evaluated. RESULTS: The CBCT setup errors were significantly larger than the EPID setup errors for the cranial-caudal and anterior-posterior directions (p < 0.05). The mean overall setup errors after correction measured with the CBCT were 0.2 mm (Sigma = 1.6 mm, sigma = 2.9 mm) in the left-right, -0.8 mm (Sigma = 1.7 mm, sigma = 4.0 mm) in cranial-caudal and 0.0 mm (Sigma = 1.5 mm, sigma = 2.0 mm) in the anterior-posterior direction. Using our correction protocol only 2 patients had mean setup errors larger than 5 mm, without this correction protocol 51% of the patients would have had a setup error larger than 5 mm. CONCLUSION: Use of CBCT scans provided more accurate information concerning the setup of lung cancer patients than did portal imaging.

Automatic prostate localization on cone-beam CT scans for high precision image-guided radiotherapy.

PURPOSE: Previously, we developed an automatic three-dimensional gray-value registration (GR) method for fast prostate localization that could be used during online or offline image-guided radiotherapy. The method was tested on conventional computed tomography (CT) scans. In this study, the performance of the algorithm to localize the prostate on cone-beam CT (CBCT) scans acquired on the treatment machine was evaluated. METHODS AND MATERIALS: Five to 17 CBCT scans of 32 prostate cancer patients (332 scans in total) were used. For 18 patients (190 CBCT scans), the CBCT scans were acquired with a collimated field of view (FOV) (craniocaudal). This procedure improved the image quality considerably. The prostate (i.e., prostate plus seminal vesicles) in each CBCT scan was registered to the prostate in the planning CT scan by automatic 3D gray-value registration (normal GR) starting from a registration on the bony anatomy. When these failed, registrations were repeated with a fixed rotation point locked at the prostate apex (fixed apex GR). Registrations were visually assessed in 3D by one observer with the help of an expansion (by 3.6 mm) of the delineated prostate contours of the planning CT scan. The percentage of successfully registered cases was determined from the combined normal and fixed apex GR assessment results. The error in gray-value registration for both registration methods was determined from the position of one clearly defined calcification in the prostate gland (9 patients, 71 successful registrations). RESULTS: The percentage of successfully registered CBCT scans that were acquired with a collimated FOV was about 10% higher than for CBCT scans that were acquired with an uncollimated FOV. For CBCT scans that were acquired with a collimated FOV, the percentage of successfully registered cases improved from 65%, when only normal GR was applied, to 83% when the results of normal and fixed apex GR were combined. Gray-value registration mainly failed (or registrations were difficult to assess) because of streaks in the CBCT scans caused by moving gas pockets in the rectum during CBCT image acquisition (i.e., intrafraction motion). The error in gray-value registration along the left-right, craniocaudal, and anteroposterior axes was 1.0, 2.4, and 2.3 mm (1 SD) for normal GR, and 1.0, 2.0, and 1.7 mm (1 SD) for fixed apex GR. The systematic and random components of these SDs contributed approximately equally to these SDs, for both registration methods. CONCLUSIONS: The feasibility of automatic prostate localization on CBCT scans acquired on the treatment machine using an adaptation of the previously developed three-dimensional gray-value registration algorithm, has been validated in this study. Collimating the FOV during CBCT image acquisition improved the CBCT image quality considerably. Artifacts in the CBCT images caused by large moving gas pockets during CBCT image acquisition were the main cause for unsuccessful registration. From this study, we can conclude that CBCT scans are suitable for online and offline position verification of the prostate, as long as the amount of nonstationary gas is limited.

Reproducibility of the bladder shape and bladder shape changes during filling.

The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi-automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to 15 cc/min (mean value: 9 +/- 3 cc/min). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of 0.4 cc/min. The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible (variations<0.3 cm in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to approximately 1.2 cm for bladders with a volume of 200 cc. These large long-term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to predict short-term shape changes. We intend to use this tool for further improvement of image-guided radiotherapy for bladder cancer patients.

Impact of knee support and shape of tabletop on rectum and prostate position.

PURPOSE: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. METHODS AND MATERIALS: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differences of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. RESULTS: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 degrees (SEM 0.8 degrees ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. CONCLUSIONS: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.

Feasibility of geometrical verification of patient set-up using body contours and computed tomography data.

BACKGROUND AND PURPOSE: Body contours can potentially be used for patient set-up verification in external-beam radiotherapy and might enable more accurate set-up of patients prior to irradiation. The aim of this study is to test the feasibility of patient set-up verification using a body contour scanner. MATERIAL AND METHODS: Body contour scans of 33 lung cancer and 21 head-and-neck cancer patients were acquired on a simulator. We assume that this dataset is representative for the patient set-up on an accelerator. Shortly before acquisition of the body contour scan, a pair of orthogonal simulator images was taken as a reference. Both the body contour scan and the simulator images were matched in 3D to the planning computed tomography scan. Movement of skin with respect to bone was quantified based on an analysis of variance method. RESULTS: Set-up errors determined with body-contours agreed reasonably well with those determined with simulator images. For the lung cancer patients, the average set-up errors (mm)+/-1 standard deviation (SD) for the left-right, cranio-caudal and anterior-posterior directions were 1.2+/-2.9, -0.8+/-5.0 and -2.3+/-3.1 using body contours, compared to -0.8+/-3.2, -1.0+/-4.1 and -1.2+/-2.4 using simulator images. For the head-and-neck cancer patients, the set-up errors were 0.5+/-1.8, 0.5+/-2.7 and -2.2+/-1.8 using body contours compared to -0.4+/-1.2, 0.1+/-2.1, -0.1+/-1.8 using simulator images. The SD of the set-up errors obtained from analysis of the body contours were not significantly different from those obtained from analysis of the simulator images. Movement of the skin with respect to bone (1 SD) was estimated at 2.3 mm for lung cancer patients and 1.7 mm for head-and-neck cancer patients. CONCLUSION: Measurement of patient set-up using a body-contouring device is possible. The accuracy, however, is limited by the movement of the skin with respect to the bone. In situations where the error in the patient set-up is relatively large, it is possible to reduce these errors using a computer-aided set-up technique based on contour information.

Application of video imaging for improvement of patient set-up.

BACKGROUND AND PURPOSE: For radiotherapy of prostate cancer, the patient is usually positioned in the left-right (LR) direction by aligning a single marker on the skin with the projection of a room laser. The aim of this study is to investigate the feasibility of a room-mounted video camera in combination with previously acquired CT data to improve patient set-up along the LR axis. MATERIAL AND METHODS: The camera was mounted in the treatment room at the caudal side of the patient. For 22 patients with prostate cancer 127 video and portal images were acquired. The set-up error determined by video imaging was found by matching video images with rendered CT images using various techniques. This set-up error was retrospectively compared with the set-up error derived from portal images. It was investigated whether the number of corrections based on portal imaging would decrease if the information obtained from the video images had been used prior to irradiation. Movement of the skin with respect to bone was quantified using an analysis of variance method. RESULTS: The measurement of the set-up error was most accurate for a technique where outlines and groins on the left and right side of the patient were delineated and aligned individually to the corresponding features extracted from the rendered CT image. The standard deviations (SD) of the systematic and random components of the set-up errors derived from the portal images in the LR direction were 1.5 and 2.1 mm, respectively. When the set-up of the patients was retrospectively adjusted based on the video images, the SD of the systematic and random errors decreased to 1.1 and 1.3 mm, respectively. From retrospective analysis, a reduction of the number of set-up corrections (from nine to six corrections) is expected when the set-up would have been adjusted using the video images. The SD of the magnitude of motion of the skin of the patient with respect to the bony anatomy was estimated to be 1.1 mm. CONCLUSION: Video imaging is an accurate technique for measuring the set-up of prostate cancer patients in the LR direction. The outline of the patient is a more accurate estimate of the set-up of the bony anatomy than the marker on the patient's abdomen.

Inter- and intra-fractional bladder motion during radiotherapy for bladder cancer: a comparison of full and empty bladders.

PURPOSE: To compare inter- and intra-fraction bladder volume variations and bladder wall motion during radiotherapy (RT) for bladder cancer with full and empty bladder protocols. MATERIALS AND METHODS: Bladder volumes, filling rates and bladder wall movement were retrospectively analyzed for 24 patients with at least 4 sets of delineable pre and post treatment cone beam CT (CBCT)-scans. Eight patients were treated with an 'empty bladder' (EB) protocol and sixteen patients with a 'full bladder' (FB) protocol. RESULTS: 24 planning CT-scans and 356 CBCT-scans (178 sets) were analyzed. The average time between pre and post irradiation CBCT was 8min (range 6-18min). Median filling rate was 1.94ml/min and did not differ between EB and FB. Random variation in bladder volume and inter-fraction wall movement was slightly but not significantly larger for FB, whereas intra-fraction bladder wall movement was slightly but not significantly smaller for FB. The largest inter- and intra-fraction bladder wall movement was found in the cranial anterior direction. CONCLUSION: Empty and full bladder protocols show similar inter- and intra-fraction wall motion, and therefore treatment choices could be purely based on organ at risk criteria.

Volume changes in soft tissue sarcomas during preoperative radiotherapy of extremities evaluated using cone-beam CT.

OBJECTIVE: The objective of this study is to quantify volume changes in the gross target volume (GTV) during preoperative radiotherapy for extremity soft tissue sarcomas (ESTS). METHODS: Twenty-seven patients with ESTS, treated with preoperative radiotherapy, were included in this study. Weekly cone-beam CT scans acquired for setup correction were used for GTV delineation in order to quantify volume changes over the course of treatment. Age, anatomical location, tumour type and tumour volume were evaluated as predictive factors for volume changes. Finally, the optimal time point for adaptive intervention was quantified. RESULTS: A GTV increase to a maximum of 28 % occurred in five patients. Thirteen patients showed no change and nine patients (all diagnosed with myxoid liposarcoma (MLS)) showed a GTV decrease to a maximum of 57 % of the GTV volume at start of treatment. In the multivariate analysis, only the relative volume change for tumour type was significant (p = 0.001). The optimal time point for adaptive intervention in non-MLS patients was the first week and for MLS patients the third week. CONCLUSIONS: Volume changes were quantified during preoperative RT of ESTS. Volume decrease was observed only in MLS patients. Individualised treatment resulting in plan adaptations could result in a clinically useful volume reduction for MLS patients.

Assessment of set-up variability during deep inspiration breath hold radiotherapy for breast cancer patients by 3D-surface imaging.

PURPOSE: To quantify set-up uncertainties during voluntary deep inspiration breath hold (DIBH) radiotherapy using 3D-surface imaging in patients with left sided breast cancer. MATERIAL AND METHODS: Nineteen patients were included. Cone-beam CT-scan (CBCT) was used for online set-up correction while patients were instructed to perform a voluntary DIBH. The reproducibility of the DIBH during treatment was monitored with 2D-fluoroscopy and portal imaging. Simultaneously, a surface imaging system was used to capture 3D-surfaces throughout CBCT acquisition and delivery of treatment beams. Retrospectively, all captured surfaces were registered to the planning-CT surface. Interfraction, intra-fraction and intra-beam set-up variability were quantified in left-right, cranio-caudal and anterior-posterior direction. RESULTS: Inter-fraction systematic (Σ) and random (σ) translational errors (1SD) before and after set-up correction were between 0.20-0.50 cm and 0.09-0.22 cm, respectively, whereas rotational Σ and σ errors were between 0.08 and 1.56°. The intra-fraction Σ and σ errors were ≤ 0.14 cm and ≤ 0.47°. The intra-beam SD variability was ≤ 0.08 cm and ≤ 0.28° in all directions. CONCLUSION: Quantification of 3D set-up variability in DIBH RT showed that patients are able to perform a very stable and reproducible DIBH within a treatment fraction. However, relatively large inter-fraction variability requires online image guided set-up corrections.

Cone beam CT assisted irradiation of painful vertebral metastases without prior virtual simulation: a quick and patient friendly procedure.

A procedure is described using diagnostic CT and/or MRI scans to simulate treatment fields for painful vertebral metastases. Cone beam CT guidance subsequently corrects patient setup. Our first 100 patients are analyzed and compared to another 100 patients after conventional simulation. This procedure proved to be quick and patient friendly.

Accuracy evaluation of a 3-dimensional surface imaging system for guidance in deep-inspiration breath-hold radiation therapy.

PURPOSE: To investigate the applicability of 3-dimensional (3D) surface imaging for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT) for patients with left-sided breast cancer. For this purpose, setup data based on captured 3D surfaces was compared with setup data based on cone beam computed tomography (CBCT). METHODS AND MATERIALS: Twenty patients treated with DIBH-RT after breast-conserving surgery (BCS) were included. Before the start of treatment, each patient underwent a breath-hold CT scan for planning purposes. During treatment, dose delivery was preceded by setup verification using CBCT of the left breast. 3D surfaces were captured by a surface imaging system concurrently with the CBCT scan. Retrospectively, surface registrations were performed for CBCT to CT and for a captured 3D surface to CT. The resulting setup errors were compared with linear regression analysis. For the differences between setup errors, group mean, systematic error, random error, and 95% limits of agreement were calculated. Furthermore, receiver operating characteristic (ROC) analysis was performed. RESULTS: Good correlation between setup errors was found: R(2)=0.70, 0.90, 0.82 in left-right, craniocaudal, and anterior-posterior directions, respectively. Systematic errors were ≤0.17 cm in all directions. Random errors were ≤0.15 cm. The limits of agreement were -0.34-0.48, -0.42-0.39, and -0.52-0.23 cm in left-right, craniocaudal, and anterior-posterior directions, respectively. ROC analysis showed that a threshold between 0.4 and 0.8 cm corresponds to promising true positive rates (0.78-0.95) and false positive rates (0.12-0.28). CONCLUSIONS: The results support the application of 3D surface imaging for image guidance in DIBH-RT after BCS.