Soft Tissue Alignment Research Articles

Current Management of Acute and Posttraumatic Critical Bone Defects.

Limb reconstruction in patients with critical-sized bone defects remains a challenge due to the availability of various technically demanding treatment options and a lack of standardized decision algorithms. Although no consensus exists, it is apparent from the literature that the combination of patient, surgeon, and institutional collaborations is effective in providing the most efficient care pathway for these patients. Success relies on choosing a particular surgical approach that manages infection, soft tissue defects, stability, and alignment. Recent systematic reviews demonstrate high success rates with the following management options: Ilizarov bone transport, Masquelet (induced membrane) technique, cancellous bone grafting, and vascularized bone grafts.

First-in-human real-time AI-assisted instrument deocclusion during augmented reality robotic surgery.

The integration of Augmented Reality (AR) into daily surgical practice is withheld by the correct registration of pre-operative data. This includes intelligent 3D model superposition whilst simultaneously handling real and virtual occlusions caused by the AR overlay. Occlusions can negatively impact surgical safety and as such deteriorate rather than improve surgical care. Robotic surgery is particularly suited to tackle these integration challenges in a stepwise approach as the robotic console allows for different inputs to be displayed in parallel to the surgeon. Nevertheless, real-time de-occlusion requires extensive computational resources which further complicates clinical integration. This work tackles the problem of instrument occlusion and presents, to the authors' best knowledge, the first-in-human on edge deployment of a real-time binary segmentation pipeline during three robot-assisted surgeries: partial nephrectomy, migrated endovascular stent removal, and liver metastasectomy. To this end, a state-of-the-art real-time segmentation and 3D model pipeline was implemented and presented to the surgeon during live surgery. The pipeline allows real-time binary segmentation of 37 non-organic surgical items, which are never occluded during AR. The application features real-time manual 3D model manipulation for correct soft tissue alignment. The proposed pipeline can contribute towards surgical safety, ergonomics, and acceptance of AR in minimally invasive surgery.

Using sequential bone cutting to titrate soft tissue balance in total knee arthroplasty effectively minimizes soft tissue release

BackgroundAchieving soft tissue balance while maintaining limb alignment within acceptable boundaries is crucial for successful total knee arthroplasty (TKA). We proposed a sequential bone cutting (SBC) technique to titrate the soft tissue balance in robot-assisted TKA to achieve the desired balance with minimum soft tissue release.MethodsIn total, 106 robot-assisted TKAs using the SBC technique were included. The preoperative hip-knee-ankle angle (HKA) was < 10° in 76 and ≥ 10° in 30 knees. The gaps were initially balanced with the help of the pre-resection balancing provided by the robotic system. Soft tissue balance and alignment were quantitatively measured after the initial bone cutting and final bone cutting. Additional adjustments (bone recuts and soft tissue releases) required to address soft tissue imbalance after initial bone cutting were recorded. The frequencies of soft tissue releases, soft tissue balance, and resultant alignment ≤ 3° were compared between non-severe (HKA < 10°) and severe deformity (HKA ≥ 10°) groups.ResultsSoft tissue balance was achieved in 45 knees (42.5%) after initial bone cutting and in 93 knees (87.7%) after final balancing. The postoperative alignment was within 3° from neutral in 87 knees (82.1%) and 3–5° in 17 knees (16.0%). For unbalanced knees (n = 61) after initial bone cutting, soft tissue release was avoided by SBC in 37 knees (60.7%) and was deemed necessary in 24 knees (39.3%). Soft tissue release was more likely to be avoided in the non-severe deformity cohort (86.8% [33 of 38]) than in the severe deformity cohort (17.4% [4 of 23]; p < 0.001). The non-severe deformity cohort showed a significantly higher rate of resultant alignment ≤ 3° from neutral than the severe deformity cohort (90.8% vs. 60.0%; p < 0.001).ConclusionPre-resection balancing is inappropriate to ensure soft tissue balance. The SBC technique is effective in minimizing soft tissue release while maintaining overall alignment within acceptable boundaries.

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

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

Comparison of MR-soft tissue based versus biliary stent based alignment for image guidance in pancreatic SBRT.

The role of biliary stents in image-guided localization for pancreatic cancer has been inconclusive. To date, stent accuracy has been largely evaluated against implanted fiducials on cone beam computed tomography. We aim to use magnetic resonance (MR) soft tissue as a direct reference to examine the geometric and dosimetric impacts of stent-based localization on the newly available MR linear accelerator. Thirty pancreatic cancer patients (132 fractions) treated on our MR linear accelerator were identified to have a biliary stent. In our standard adaptive workflow, patients were set up to the target using soft tissue for image registration and structures were re-contoured on daily MR images. The original plan was then projected on treatment anatomy and dose predicted, followed by plan re-optimization and treatment delivery. These online predicted plans were soft tissue-based and served as reference plans. Retrospective image registration to the stent was performed offline to simulate stent-based localization and the magnitude of shifts was taken as the geometric accuracy of stent localization. New predicted plans were generated based on stent-alignment for dosimetric comparison. Shifts were within 3mm for 90% of the cases (mean=1.5mm); however, larger shifts up to 7.2mm were observed. Average PTV coverage dropped by 1.1% with a maximum drop of 26.8%. The mean increase in V35Gy was 0.15, 0.05, 0.02, and 0.02 cc for duodenum, stomach, small bowel and large bowel, respectively. Stent alignment was significantly worse for all metrics except for small bowel (p=0.07). Overall discrepancy between stent- and soft tissue-alignment was modest; however, large discrepancies were observed for select cases. While PTV coverage loss may be compensated for by using a larger margin, the increase in dose to gastrointestinal organs at risk may limit the role of biliary stents in image-guided localization.

The first patients treated with MR-CBCT soft-tissue matching in a MR-only prostate radiotherapy pathway

IntroductionMagnetic Resonance (MR)-only radiotherapy for prostate cancer has previously been reported using fiducial markers for on-treatment verification. MR-Cone Beam Computed Tomography (CBCT) soft-tissue matching does not require invasive fiducial markers and enables MR-only treatments to other pelvic cancers. This study evaluated the first clinical implementation of MR-only prostate radiotherapy using MR-CBCT soft-tissue matching. MethodsTwenty prostate patients were treated with MR-only radiotherapy using a synthetic (s)CT-optimised plan with MR-CBCT soft-tissue matching. Two MR sequences were acquired: small Field Of View (FOV) for target delineation and large FOV for organs at risk delineation, sCT generation and on-treatment verification. Patients also received a CT for validation. The prostate was independently contoured on the small FOV MR, copied to the registered CT and modified if there were MR-CT soft-tissue alignment differences (MR-CT volume). This was compared to the MR-only volume with a paired t-test. The treatment plan was recalculated on CT and the doses compared. Independent offline CT-CBCT matches for 5/20 fractions were performed by three therapeutic radiographers using the MR-only contours and compared to the online MR-CBCT matches using two one-sided paired t-tests for equivalence within ±1 mm. ResultsThe MR-only volumes were significantly smaller than MR-CT (p = 0.003), with a volume ratio 0.92 ± 0.02 (mean ± standard error). The sCT isocentre dose difference to CT was 0.2 ± 0.1%. MR-CBCT soft-tissue matching was equivalent to CT-CBCT (p < 0.001), with differences of 0.1 ± 0.2 mm (vertical), −0.1 ± 0.2 mm (longitudinal) and 0.0 ± 0.1 mm (lateral). ConclusionsMR-only radiotherapy with soft-tissue matching has been successfully clinically implemented. It produced significantly smaller target volumes with high dosimetric and on-treatment matching accuracy. Implications for practiceMR-only prostate radiotherapy can be safely delivered without using invasive fiducial markers. This enables MR-only radiotherapy to be extended to other pelvic cancers where fiducial markers cannot be used.

An unsupervised image registration method employing chest computed tomography images and deep neural networks

BackgroundDeformable image registration is crucial for multiple radiation therapy applications. Fast registration of computed tomography (CT) lung images is challenging because of the large and nonlinear deformation between inspiration and expiration. With advancements in deep learning techniques, learning-based registration methods are considered efficient alternatives to traditional methods in terms of accuracy and computational cost. MethodIn this study, an unsupervised lung registration network (LRN) with cycle-consistent training is proposed to align two acquired CT-derived lung datasets during breath-holds at inspiratory and expiratory levels without utilizing any ground-truth registration results. Generally, the LRN model uses three loss functions: image similarity, regularization, and Jacobian determinant. Here, LRN was trained on the CT datasets of 705 subjects and tested using 10 pairs of public CT DIR-Lab datasets. Furthermore, to evaluate the effectiveness of the registration technique, target registration errors (TREs) of the LRN model were compared with those of the conventional algorithm (sum of squared tissue volume difference; SSTVD) and a state-of-the-art unsupervised registration method (VoxelMorph). ResultsThe results showed that the LRN with an average TRE of 1.78 ± 1.56 mm outperformed VoxelMorph with an average TRE of 2.43 ± 2.43 mm, which is comparable to that of SSTVD with an average TRE of 1.66 ± 1.49 mm. In addition, estimating the displacement vector field without any folding voxel consumed less than 2 s, demonstrating the superiority of the learning-based method with respect to fiducial marker tracking and the overall soft tissue alignment with a nearly real-time speed. ConclusionsTherefore, this proposed method shows significant potential for use in time-sensitive pulmonary studies, such as lung motion tracking and image-guided surgery.

Total Knee Arthroplasty in Valgus Deformity Made Easy Using Robotic-assisted Predictive Balancing Technique

Total knee arthroplasty (TKA) performed for valgus osteoarthritis (OA) presents a challenge to the arthroplasty surgeon in regards to achieving appropriate soft tissue balance and alignment. Robotic assisted surgery (RAS) with navigation (NAV) has been proposed as a potential solution to assist surgeons when performing these difficult cases. Here, we present the case of a complex primary TKA in a patient with posttraumatic valgus arthritis performed using a novel RAS system with NAV. Appropriate balance was unable to be achieved with bony cuts alone, as the knee was found to be tight laterally in extension following bone preparation. Soft tissue releases were ultimately required. Use of the novel RAS system with NAV allowed for a titrated soft tissue release resulting in a balanced knee without overcorrection of the patient’s deformity. We also present a similar case of a patient with valgus knee OA in which there was residual tightness laterally in flexion. The different management strategies for each of these cases is discussed. Finally, we provide a review of the available literature regarding TKA in valgus knee OA and propose a new classification system and treatment algorithm that can be employed using a novel RAS system with predictive balancing technology to achieve optimal alignment and soft tissue balancing in valgus knees that remain unbalanced following bony cuts.

ECOG-ACRIN Guideline for Contouring and Treatment of Early Stage Anal Cancer Using IMRT/IGRT

PurposePrevious anal cancer guidelines delineate target volumes similarly for all patients with squamous cell carcinoma of the anal canal and/or perianal skin (SCCA), regardless of disease stage. The purpose of this guideline is to provide customized radiation treatment recommendations for early stage (T1-2 N0 M0) anal cancer treated with intensity modulated and image guided radiation therapy (RT). Methods and MaterialsA contouring atlas and radiation treatment recommendations for the ongoing, randomized phase II trial of deintensified chemoradiation for early stage SCCA (EA2182) was created by an expert panel of radiation oncologists. A literature search was conducted to update and expand these recommendations into a guideline for routine clinical use. ResultsFor the majority of cases, we recommend treatment in the supine, frog leg position with the use of a customized immobilization device and daily image guided RT to ensure optimal bone and soft tissue alignment. Vaginal dilators can be used daily during RT to maximize genitalia sparing. We recommend use of a 10-mm margin on the gross tumor plus including the anal complex to create the primary clinical target volume. To define the elective lymph node clinical target volume, we recommend starting with a 7-mm expansion on blood vessels, but then further refining these volumes based on the anatomic location. A 5- to 10-mm planning target volume (PTV) margin is suggested based on institutional setup and patient-specific factors. When using a simultaneous integrated boost technique, a dose of 50.4 Gy to primary PTV and 42 Gy to lymph node PTV, both delivered over 28 fractions, with chemotherapy is appropriate for early stage anal cancer. ConclusionsThis guideline provides anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of intensity modulated and image guided RT for early stage SCCA.

Soft Tissue Release for Varus Knees during Posterior Stabilized Total Knee Arthroplasty: A New Algorithm

Introduction: Total Knee Replacement (TKA) surgeries are frequently performed surgeries used to treat knee osteoarthritis. Several methods of medial soft tissue balancing in the varus knee during total knee replacement surgeries have been reported. Traditionally, they included releasing the superficial Medial Collateral Ligament (sMCL) in severe varus cases by several methods. However, this release can create instability in the knee. The aim of this study was to create an algorithm for soft tissue release in varus osteoarthritic knees and to evaluate its efficacy in achieving intraoperative gap balancing without releasing the superficial MCL. Materials and Methods: One hundred and five varus osteoarthritic knees who received primary posterior stabilized total knee arthroplasties between October 2015 and January 2016 were included in this study. Varus deformities ranged between 10 to 40 degrees. Sequential balancing was done into 5 steps: step 1 – releasing of deep MCL, step 2 – excision of osteophytes, step 3 – excision of scarred tissue in the posteromedial corner, step 4 – excision of the posteromedial capsule and step 5 – release of semimembranosus. The V-STAT® Variable Soft Tissue Alignment Tensor was used to ensure a balanced medial and lateral gap following each step. Once the gaps were balanced, no further soft tissue release were carried out. Results: All knees were balanced without releasing the superficial MCL ligament. The maximum release step necessary was: step 1 (0 cases), step 2 (31 cases), step 3 (35 cases), step 4 (25 cases) and step 5 (14 cases). Conclusion: Superficial medial collateral ligament should not be released during intraoperative varus knees soft tissue balancing in posterior stabilized total knee arthroplasties. Preserving the superficial MCL is beneficial in maintaining implant stability without any increase in the constraint level of the implant even in cases with severe deformity.

Clinical Experience in Prostate Ultrahypofractionated Radiation Therapy With an Online Adaptive Method

PurposeThis study aimed to describe the feasibility of the online adaptive radiation therapy (oART) method developed at the Hospital Quirónsalud Barcelona for prostate cancer, using a standard C-arm linear accelerator (linac) and without the support of artificial intelligence. Methods and MaterialsThe first 18 patients treated at the Hospital Quirónsalud Barcelona with the developed oART method were included. An ultrahypofractionated radiation therapy scheme consisting of 7 × 6.1 Gy was used. Patients were treated on 2 conventional Varian C-arm linacs. For each patient, a reference plan based on a planning computed tomography (pCT) scan was generated using the Eclipse system. On each treatment session, the pCT scan was rigidly registered with the daily cone beam computed tomography (CT) scan. The pCT-based target (prostate) and organs at risk were mapped onto the cone beam CT images and manually adapted to take into account the anatomy of the day. The reference plan was then copied to the cone beam CT scan, and a full reoptimization was done for the current anatomy (adapted plan). For each treatment session, the unaltered reference plan was recomputed on the daily cone beam CT scan by mimicking the soft-tissue alignment performed per our standard procedure (nonadapted plan). Over the 126 adapted sessions from the 18 patients, a dosimetric comparison of adapted against nonadapted plans was done. ResultsA significant difference in the target coverage was found between the adapted and nonadapted plans (97.1 vs 90.4; P < .001) in favor of adapting. Without online adaptation, the optimal coverage of the prostate was not attained in 35% of fractions. Adapting allows for the improvement of the target coverage with compliance of all organ-at-risk dose constraints in all treatment fractions. ConclusionsThe oART technique described in this study is technically feasible with a C-arm linac. To our knowledge, this is the first clinical experience with oART for prostate cancer including full replanning and delivered with a C-arm linac without artificial intelligence capability.

Label-free quantification of soft tissue alignment by polarized Raman spectroscopy

The organization of proteins is an important determinant of functionality in soft tissues. However, such organization is difficult to monitor over time in soft tissue with complex compositions. Here, we establish a method to determine the alignment of proteins in soft tissues of varying composition by polarized Raman spectroscopy (PRS). Unlike most conventional microscopy methods, PRS leverages non-destructive, label-free sample preparation. PRS data from highly aligned muscle layers were utilized to derive a weighting function for aligned proteins via principal component analysis (PCA). This trained weighting function was used as a master loading function to calculate a principal component score (PC1 Score) as a function of polarized angle for tendon, dermis, hypodermis, and fabricated collagen gels. Since the PC1 Score calculated at arbitrary angles was insufficient to determine level of alignment, we developed an Amplitude Alignment Metric by fitting a sine function to PC1 Score with respect to polarized angle. We found that our PRS-based Amplitude Alignment Metric can be used as an indicator of level of protein alignment in soft tissues in a non-destructive manner with label-free preparation and has similar discriminatory capacity among isotropic and anisotropic samples compared to microscopy-based image processing method. This PRS method does not require a priori knowledge of sample orientation nor composition and appears insensitive to changes in protein composition among different tissues. The Amplitude Alignment Metric introduced here could enable convenient and adaptable evaluation of protein alignment in soft tissues of varying protein and cell composition. Statement of significancePolarized Raman spectroscopy (PRS) has been used to characterize the of organization of soft tissues. However, most of the reported applications of PRS have been on collagen-rich tissues and reliant on intensities of collagen-related vibrations. This work describes a PRS method via a multivariate analysis to characterize alignment in soft tissues composed of varying proteins. Of note, the highly aligned muscle layer of mouse skin was used to train a master function then applied to other soft tissue samples, and the degree of anisotropy in the PRS response was evaluated to obtain the level of alignment in tissues. We have demonstrated that this method supports convenient and adaptable evaluation of protein alignment in soft tissues of varying protein and cell composition.

Robotic-assisted vs conventional surgery in medial unicompartmental knee arthroplasty: a clinical and radiological study

BackgroundThe use of unicompartmental knee arthroplasty (UKA) has increased and new technologies have been developed to improve patient survival and satisfaction, soft tissue balance, alignment, and component size. Robot-assisted systems offer an increase in surgical precision and accuracy. The purpose of this study is to evaluate the precision of component position using five radiological parameters in conventional and robotic-assisted medial UKA using the NAVIO system.MethodsA cohort study was designed for patients who underwent medial UKA between April 2017 and March 2019 in a single center. Patients were allocated in the conventional (UKA-C) or robotic-assisted (UKA-R) group. The variables analyzed were age, gender, affected knee side, length of hospital stay, surgical time, and radiological measurements such as anatomical medial distal femoral angle (aMDFA), anatomical medial proximal tibial angle (aMPTA), tibial slope, the sagittal femoral angle, and the component size. A target was defined for each measurement, and a successful UKA was defined if at least four radiological measures were on target after surgery. Also, patients’ reported outcomes were evaluated using the Oxford Knee Score (OKS) and a numeric rating scale (NRS) for pain.ResultsThirty-four patients were included, 18 of them underwent UKA-R. The success rate for UKA in the UKA-R group was 87%; meanwhile, in the UKA-C group this was 28%, this difference was significant and powered (Fisher’s exact test, p = 0.001; 1 − β = 0.95). Also, a 5-point difference in favor of the UKA-R group in the median OKS (p = 0.01), and a significantly lower median NRS for pain (p < 0.000) were found after surgery.ConclusionsUKA-R achieved more precision in the radiological parameters’ measure in this study. Also, UKA-R has a trend towards a better OKS and a lower NRS for pain at short-term follow-up.

4D-CT deformable image registration using multiscale unsupervised deep learning

Deformable image registration (DIR) of 4D-CT images is important in multiple radiation therapy applications including motion tracking of soft tissue or fiducial markers, target definition, image fusion, dose accumulation and treatment response evaluations. It is very challenging to accurately and quickly register 4D-CT abdominal images due to its large appearance variances and bulky sizes. In this study, we proposed an accurate and fast multi-scale DIR network (MS-DIRNet) for abdominal 4D-CT registration. MS-DIRNet consists of a global network (GlobalNet) and local network (LocalNet). GlobalNet was trained using down-sampled whole image volumes while LocalNet was trained using sampled image patches. MS-DIRNet consists of a generator and a discriminator. The generator was trained to directly predict a deformation vector field (DVF) based on the moving and target images. The generator was implemented using convolutional neural networks with multiple attention gates. The discriminator was trained to differentiate the deformed images from the target images to provide additional DVF regularization. The loss function of MS-DIRNet includes three parts which are image similarity loss, adversarial loss and DVF regularization loss. The MS-DIRNet was trained in a completely unsupervised manner meaning that ground truth DVFs are not needed. Different from traditional DIRs that calculate DVF iteratively, MS-DIRNet is able to calculate the final DVF in a single forward prediction which could significantly expedite the DIR process. The MS-DIRNet was trained and tested on 25 patients’ 4D-CT datasets using five-fold cross validation. For registration accuracy evaluation, target registration errors (TREs) of MS-DIRNet were compared to clinically used software. Our results showed that the MS-DIRNet with an average TRE of 1.2 ± 0.8 mm outperformed the commercial software with an average TRE of 2.5 ± 0.8 mm in 4D-CT abdominal DIR, demonstrating the superior performance of our method in fiducial marker tracking and overall soft tissue alignment.

Assessment of setup uncertainty in hypofractionated liver radiation therapy with a breath-hold technique using automatic image registration\u2013based image guidance

BackgroundTarget localization in radiation therapy is affected by numerous sources of uncertainty. Despite measures to minimize the breathing motion, the treatment of hypofractionated liver radiation therapy is further challenged by residual uncertainty coming from involuntary organ motion and daily changes in the shape and location of abdominal organs. To address the residual uncertainty, clinics implement image-guided radiation therapy at varying levels of soft-tissue contrast. This study utilized the treatment records from the patients that have received hypofractionated liver radiation therapy using in-room computed tomography (CT) imaging to assess the setup uncertainty and to estimate the appropriate planning treatment volume (PTV) margins in the absence of in-room CT imaging.MethodsWe collected 917 pre-treatment daily in-room CT images from 69 patients who received hypofractionated radiation therapy to the liver with the inspiration breath-hold technique. For each treatment, the daily CT was initially aligned to the planning CT based on the shape of the liver automatically using a CT-CT alignment software. After the initial alignment, manual shift corrections were determined by visual inspection of the two images, and the corrections were applied to shift the patient to the physician-approved treatment position. Considering the final alignment as the gold-standard setup, systematic and random uncertainties in the automatic alignment were quantified, and the uncertainties were used to calculate the PTV margins.ResultsThe median discrepancy between the final and automatic alignment was 1.1 mm (0–24.3 mm), and 38% of treated fractions required manual corrections of ≥3 mm. The systematic uncertainty was 1.5 mm in the anterior-posterior (AP) direction, 1.1 mm in the left-right (LR) direction, and 2.4 mm in the superior-inferior (SI) direction. The random uncertainty was 2.2 mm in the AP, 1.9 mm in the LR, and 2.2 mm in the SI direction. The PTV margins recommended to be used in the absence of in-room CT imaging were 5.3 mm in the AP, 3.5 mm in the LR, and 5.1 mm in the SI direction.ConclusionsManual shift correction based on soft-tissue alignment is substantial in the treatment of the abdominal region. In-room CT can reduce PTV margin by up to 5 mm, which may be especially beneficial for dose escalation and normal tissue sparing in hypofractionated liver radiation therapy.

Precision of 2 Low-dose Abdomen/Pelvis Cone Beam Computed Tomography Protocols for Alignment to Bone and Soft Tissue in Pediatric Patients Receiving Image Guided Radiation Therapy

PurposeTo evaluate the precision of 2 low-dose cone (LD) beam computed tomography (CBCT) protocols to align to bone and soft tissue for pediatric patients receiving image guided radiation therapy (IGRT) to the abdomen and pelvis. Methods and MaterialsImage-quality evaluation was done for 858 CBCT scans from 46 pediatric patients treated with IGRT from January 2015 to December 2017. The evaluations guided the development of 2 significantly dose-reduced protocols, LD-CBCT1 and a further dose-reduced LD-CBCT2. Representative scans from LD-CBCT1 and LD-CBCT2 from 8 patients with at least 1 CBCT scan from both protocols were registered separately to a bone and soft-tissue landmark on the simulation computed tomography scan. Eighteen identical blinded random offsets were applied to each patient's LD-CBCT1 and LD-CBCT2 from a starting registration that was then realigned using rigid registration. The residual offset between the baseline registration and the final registration attempt was calculated and analyzed using a 1-sided, 1 sample t test to evaluate whether LD-CBCT1, delivering a higher dose, was superior to the lower-dose LD-CBCT2 for bone and soft-tissue alignment. ResultsIn comparing 288 registrations with a bone landmark across 8 patients, no difference was found in the vector magnitude offsets using LD-CBCT 1 (mean [x¯], 0.73 mm; standard deviation [σ], 0.39 mm) and LD-CBCT2 (x¯, 0.74 mm; σ, 0.40 mm; P = .425). Comparing 216 registrations with a soft-tissue landmark across 6 patients, alignment using LD-CBCT2 (x¯, 1.55 mm; σ, 1.08 mm) resulted in larger differences in the vector magnitude of the offsets compared with LD-CBCT1 (x¯, 1.37 mm; σ, 0.74 mm; P = .049). ConclusionsClinics treating pediatric patients should consider implementing a protocol mirroring LD-CBCT2 for abdomen and pelvis IGRT bone alignment. Further evaluation of the precision of LD-CBCTs for soft-tissue alignment is necessary.

Precision of Two Low-Dose Abdomen/Pelvis CBCT Protocols for Alignment to Bone and Soft Tissue in Pediatric Patients Receiving Image-Guided Radiation Therapy

Recommendations for low-dose cone-beam computed tomography (LD-CBCT) protocols for pediatric image-guided radiation therapy (IGRT) are lacking. We aim to evaluate the precision of two LD-CBCT protocols to align to bone and soft tissue landmarks for pediatric patients receiving IGRT to the abdomen and pelvis (A/P). 858 CBCTs from 46 pediatric patients who received IGRT to the A/P starting January 2015 –December 2017 were reviewed. Image quality of CBCTs over this time guided the development of two significantly dose-reduced protocols, LD-CBCT1 (180º rotation, 120 kV, 63 mAs total, 315 frames, S20 collimator) and LD-CBCT2 (180º rotation, 100 kV, 31.5 mAs total, 315 frames, S20 collimator). Eight patients with at least 1 CBCT from both protocols during the course of IGRT were selected for a simulation study, and a representative LD-CBCT1 and LD-CBCT2 scan was registered to the simulation CT (sim-CT) separately aligning to bone and soft tissue. To simulate the process of correcting a setup error to a bone and soft tissue landmark using each protocol, 18 blinded random offsets (max translation 10 mm any x/y/z direction) were applied to each LD-CBCT1 and LD-CBCT2 from a starting registration to bone and a soft tissue structure. Each of the resultant 504 simulated set-up errors was then blindly corrected using rigid registration by a radiation oncologist. The vector magnitude difference (VM= √(x2 + y2 + z2)) between the random offset and final registration attempt was calculated, adjusting for any systematic error in the initial sim-CT↔LD-CBCT1/2 registration. A one-sided paired T-test was used to evaluate if LD-CBCT1, delivering higher dose, was superior to the lower dose LD-CBCT2 for bone and soft tissue alignment.. Age and patient size (using abdominal area) ranges of the eight sample patients with representative LD-CBCT1 and LD-CBCT2 scans were 1-5-9.2 years and 516-954 cm2, respectively. Comparing 288 registrations to a bone landmark across 8 patients, there was no difference in the vector magnitude of the offsets using LD-CBCT 1 (mean [̄x̄], 0.73 mm; standard deviation [σ], 0.39 mm) and LD-CBCT2 (̄x̄, 0.74 mm; σ, 0.40 mm) (p=0.425). Comparing 216 registrations to a soft tissue landmark across 6 patients, alignment using LD-CBCT2 (̄x̄, 1.55 mm; σ, 1.08 mm) resulted in larger differences in the vector magnitude of the offsets compared to LD-CBCT1 (̄x̄, 1.37 mm; σ, 0.74 mm) (p=0.049). Given the particular importance of reducing dose to normal tissue in pediatric patients and the increasing use of IGRT, clinics treating pediatric patients should consider a protocol mirroring LD-CBCT2 validated in this study for A/P IGRT aligned to bone. Delivering higher dose, LD-CBCT1 was slightly superior to LD-CBCT2 for soft tissue alignment, but further investigation is needed given that this study design evaluated the utility in alignment to a kidney structure as the representative soft tissue structure.

Stepwise Development and Justification of Evidence-Based Practice for Bladder Radiotherapy

The introduction of new technology has revolutionized the way radiotherapy is delivered for bladder cancer: developing from the use of basic conventional techniques to a high precision, personalized approach. In order to demonstrate that the new technology is beneficial to the patient and to ensure its safe implementation, there is a need to integrate clinical expertise, patient values and research evidence for the development of evidence-based practice (EBP). The purpose of this presentation is to share our experiences while developing and justifying various EBPs for bladder radiotherapy at our institution. Prior to 2002, bladder patients were treated with a standard 4-field box technique with no image guidance. Since then, a series of prospective and retrospectively studies were conducted to investigate different aspects of bladder radiotherapy, such as accurate definition of treatment volume, inter- and intrafractional bladder volumes changes and surface displacements, conformity and normal organ avoidance for dose distributions, mode and frequency of image-guidance interventions and reliability of image guidance surrogates. At each stage, the impact on geometric and dosimetric precision was quantified as evidence to substantiate the use of EBPs. Based on the finding of the research studies, the following EBPs were implemented: 1) IMRT was adopted as the standard treatment technique to replace 4-field box as it demonstrated superiority in dose conformity, 2) Image guidance was initially performed with Day 1 EPI and bony anatomy. With the introduction of CBCT in 2006, online image guidance was performed daily to improve precision, 3) Radio-opaque marker and bladder wall surface were adopted to be used as image guidance surrogate for partial bladder irradiation after assessing their reliability, 4) A novel method for deriving individualized treatment volume was developed and validated against other methods to demonstrate efficacy on treatment quality. In addition to establishing a very high level of EBP in our institution, we have shared our experiences and knowledge via 9 abstracts and 2 manuscripts at various national, international conferences and peer-reviewed journals. EBPs have been successfully developed, justified and implemented using a combination of clinical expertise and research evidence, to improve the quality of bladder radiotherapy. Currently all bladder patients at our institution are treated with daily image guidance using CBCT with soft tissue alignment, with dose delivered to an individualized clinical target volume and planning target volume using IMRT.

Intra- and inter-fractional liver and lung tumor motions treated with SBRT under active breathing control.

PurposeTo assess intra‐ and inter‐fractional motions of liver and lung tumors using active breathing control (ABC).Methods and MaterialsNineteen patients with liver cancer and 15 patients with lung cancer treated with stereotactic body radiotherapy (SBRT) were included in this retrospective study. All patients received a series of three CTs at simulation to test breath‐hold reproducibility. The centroids of the whole livers and of the lung tumors from the three CTs were compared to assess intra‐fraction variability. For 15 patients (8 liver, 7 lung), ABC‐gated kilovoltage cone‐beam CTs (kV‐CBCTs) were acquired prior to each treatment, and the centroids of the whole livers and of the lung tumors were also compared to those in the planning CTs to assess inter‐fraction variability.ResultsLiver intra‐fractional systematic/random errors were 0.75/0.39 mm, 1.36/0.97 mm, and 1.55/1.41 mm at medial‐lateral (ML), anterior‐posterior (AP), and superior‐inferior (SI) directions, respectively. Lung intra‐fractional systematic/random errors were 0.71/0.54 mm (ML), 1.45/1.10 mm (AP), and 3.95/1.93 mm (SI), respectively. Substantial intra‐fraction motions (>3 mm) were observed in 26.3% of liver cancer patients and in 46.7% of lung cancer patients. For both liver and lung tumors, most inter‐fractional systematic and random errors were larger than the corresponding intra‐fractional errors. However, these inter‐fractional errors were mostly corrected by the treatment team prior to each treatment based on kV CBCT‐guided soft tissue alignment, thereby eliminating their effects on the treatment planning margins.ConclusionsIntra‐fractional motion is the key to determine the planning margins since inter‐fractional motion can be compensated based on daily gated soft tissue imaging guidance of CBCT. Patient‐specific treatment planning margins instead of recipe‐based margins were suggested, which can benefit mostly for the patients with small intra‐fractional motions.

Iterative volume of interest based 4D cone-beam CT.

4D cone-beam CT (CBCT) has potential applications in soft tissue alignment and tumor motion verification at the time of radiation treatment. However, prominent streak artifacts with conventional image reconstructions have limited its clinical use and alternative reconstructions are generally too computationally expensive for the time available. We propose an iterative volume of interest based (I4D VOI) reconstruction technique, where 4D reconstruction is only performed within a VOI, to limit streak artifacts with limited added computation time. The I4D VOI technique is compared to standard cone-beam filtered back projection (FDK), an FDK VOI technique, and unconstrained total variation (TV) minimization by comparing tumor motion quantification errors and image quality. 14 long CBCT scans (6.5 to 12 min) of patients receiving radiation treatment for lung cancer were used for the comparison. Rigid registration between phase images of FDK reconstructions using all projections were used to quantify the gold standard motion. Projections were removed to simulate 2 minute scans and these new projection sets were used for each of the test reconstructions. Excluding two patients where registration failed, the average root mean square (RMS) error for each method was as follows: 1.5 ± 0.2 mm for FDK, 1.4 ± 0.2 mm for FDK VOI, 1.3 ± 0.2 mm for I4D VOI, 1.7 ± 0.4 mm for low regularization TV minimization, and 1.1 ± 0.2 mm for high regularization TV minimization. No significant difference was observed between RMS error for I4D VOI and the other methods, except for unsmoothed FDK VOI (P = 0.02). An increase in RMS error difference between I4D VOI and smoothed FDK VOI was observed going from 2 min to 1 min scans (0.1 mm to 0.3 mm, P = 0.20 to P = 0.09). I4D VOI and FDK VOI reconstruction measured tumor trajectories with equivalent accuracy as TV minimization with improved bony anatomy image quality and computation time (I4D VOI was approximately 15 and 95 times faster than low and high regularization TV minimization, respectively). Within the VOI, streak artifact reduction compared to FDK VOI may be beneficial for tumor visualization and motion measurement, but requires further study.