Inter-observer variability in library plan selection on iterative CBCT and synthetic CT images of cervical cancer patients.

INTRODUCTION: In the Library-of-Plans (LoP) approach, correct plan selection is essential for delivering radiotherapy treatment accurately. However, poor image quality of the cone-beam computed tomography (CBCT) may introduce inter-observer variability and thereby hamper accurate plan selection. In this study, we investigated whether new techniques to improve the CBCT image quality and improve consistency in plan selection, affects the accuracy of LoP selection in cervical cancer patients. MATERIALS AND METHODS: CBCT images of 12 patients were used to investigate the inter-observer variability of plan selection based on different CBCT image types. Six observers were asked to individually select a plan based on clinical X-ray Volumetric Imaging (XVI) CBCT, iterative reconstructed CBCT (iCBCT) and synthetic CTs (sCT). Selections were performed before and after a consensus meeting with the entire group, in which guidelines were created. A scoring by all observers on the image quality and plan selection procedure was also included. For plan selection, Fleiss' kappa (κ) statistical test was used to determine the inter-observer variability within one image type. RESULTS: The agreement between observers was significantly higher on sCT compared to CBCT. The consensus meeting improved the duration and inter-observer variability. In this manuscript, the guidelines attributed the overall results in the plan selection. Before the meeting, the gold standard was selected in 76% of the cases on XVI CBCT, 74% on iCBCT, and 76% on sCT. After the meeting, the gold standard was selected in 83% of the cases on XVI CBCT, 81% on iCBCT, and 90% on sCT. CONCLUSION: The use of sCTs can increase the agreement of plan selection among observers and the gold standard was indicated to be selected more often. It is important that clear guidelines for plan selection are implemented in order to benefit from the increased image quality, accurate selection, and decrease inter-observer variability.

Dosimetric benefit of a library of plans versus single-plan strategy for pre-operative gastric cancer radiotherapy.

BACKGROUND AND PURPOSE: The stomach experiences large volume and shape changes during pre-operative gastric radiotherapy. This study evaluates the dosimetric benefit for organs-at-risk (OARs) of a library of plans (LoP) compared to the traditional single-plan (SP) strategy. MATERIALS AND METHODS: Twelve patients who received SP CBCT-guided pre-operative gastric radiotherapy (45 Gy; 25 fractions) were included. Clinical target volume (CTV) consisted of CTVstomach (i.e., stomach + 10 mm uniform margin minus OARs) and CTVLN (i.e., regional lymph node stations). For LoP, five stomach volumes (approximately equidistant with fixed volumes) were created using a previously developed stomach deformation model (volume = 150-750 mL). Appropriate planning target volume (PTV) margins were calculated for CTVstomach (SP and LoP, separately) and CTVLN. Treatment plans were automatically generated/optimized and the best-fitting library plan was manually selected for each daily CBCT. OARs (i.e., liver, kidneys, heart, spleen, spinal canal) doses were accumulated and dose-volume histogram (DVH) parameters were evaluated. RESULTS: The non-isotropic PTVstomach margins were significantly (p < 0.05) smaller for LoP than SP (median = 13.1 vs 19.8 mm). For each patient, the average PTV was smaller using a LoP (difference range 134-1151 mL). For all OARs except the kidneys, DVH parameters were significantly reduced using a LoP. Differences in mean dose (Dmean) for liver, heart and spleen ranged between -1.8 to 5.7 Gy. For LoP, a benefit of heart Dmean > 4 Gy and spleen Dmean > 2 Gy was found in 4 and 5 patients, respectively. CONCLUSION: A LoP strategy for pre-operative gastric cancer reduced average PTV and reduced OAR dose compared to a SP strategy, thereby potentially reducing risks for radiation-induced toxicities.

Real-time image-guided treatment of mobile tumors in proton therapy by a library of treatment plans: a simulation study.

PURPOSE: To improve target coverage and reduce the dose in the surrounding organs-at-risks (OARs), we developed an image-guided treatment method based on a precomputed library of treatment plans controlled and delivered in real-time. METHODS: A library of treatment plans is constructed by optimizing a plan for each breathing phase of a four dimensional computed tomography (4DCT). Treatments are delivered by simulation on a continuous sequence of synthetic computed tomographies (CTs) generated from real magnetic resonance imaging (MRI) sequences. During treatment, the plans for which the tumor are at a close distance to the current tumor position are selected to deliver their spots. The study is conducted on five liver cases. RESULTS: We tested our approach under imperfect knowledge of the tumor positions with a 2 mm distance error. On average, compared to a 4D robustly optimized treatment plan, our approach led to a dose homogeneity increase of 5% (defined as 1 - D 5 - D 95 prescription $1-\frac{D_5-D_{95}}{\text{prescription}}$ ) in the target and a mean liver dose decrease of 23%. The treatment time was roughly increased by a factor of 2 but remained below 4 min on average. CONCLUSIONS: Our image-guided treatment framework outperforms state-of-the-art 4D-robust plans for all patients in this study on both target coverage and OARs sparing, with an acceptable increase in treatment time under the current accuracy of the tumor tracking technology.

Gastric deformation models for adaptive radiotherapy: Personalized vs population-based strategy.

BACKGROUND AND PURPOSE: To create a library of plans (LoP) for gastric cancer adaptive radiotherapy, accurate predictions of shape changes due to filling variations are essential. The ability of two strategies (personalized and population-based) to predict stomach shape based on filling was evaluated for volunteer and patient data to explore the potential for use in a LoP. MATERIALS AND METHODS: For 19 healthy volunteers, stomachs were delineated on MRIs with empty (ES), half-full (HFS) and full stomach (FS). For the personalized strategy, a deformation vector field from HFS to corresponding ES was acquired and extrapolated to predict FS. For the population-based strategy, the average deformation vectors from HFS to FS of 18 volunteers were applied to the HFS of the remaining volunteer to predict FS (leave-one-out principle); thus, predictions were made for each volunteer. Reversed processes were performed to predict ES. To validate, for seven gastric cancer patients, the volunteer population-based model was applied to their pre-treatment CT to predict stomach shape on 2-3 repeat CTs. For all predictions, volume was made equal to true stomach volume. RESULTS: FS predictions were satisfactory, with median Dice similarity coefficient (mDSC) of 0.91 (population-based) and 0.89 (personalized). ES predictions were poorer: mDSC = 0.82 for population-based; personalized strategy yielded unachievable volumes. Population-based shape predictions (both ES and FS) were comparable between patients (mDSC = 0.87) and volunteers (0.88). CONCLUSION: The population-based model outperformed the personalized model and demonstrated its ability in predicting filling-dependent stomach shape changes and, therefore, its potential for use in a gastric cancer LoP.

Comparison of Library of Plans with two daily adaptive strategies for whole bladder radiotherapy.

BACKGROUND AND PURPOSE: Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments. METHODS AND MATERIALS: Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images. RESULTS: MRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0-23%) compared to 0% (0-20%) and 0% (0-10%), respectively. CONCLUSIONS: Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.

Deformation trajectory prediction using a neural network trained on finite element data-application to library of CTVs creation for cervical cancer.

Purpose. We propose a neural network for fast prediction of realistic, time-parametrized deformations between pairs of input segmentations. The proposed method was used to generate a library of planning CTVs for cervical cancer radiotherapy.Methods.A 3D convolutional neural network (CNN) was introduced to predict a stationary velocity field given the distance maps of the cervix CTV in empty and full bladder anatomy. Diffeomorphic deformation trajectories between the two states were obtained by time integration. Intermediate deformation states were used to populate a library of cervix CTVs. The network was trained on cervix CTV deformations of 20 patients generated by finite element modeling (FEM). Validation was performed on FEM data of 9 healthy volunteers. Additionally, for these subjects, CTV deformations were observed in a series of repeat MR scans as the bladder filled from empty to full. Predicted and FEM libraries were compared, and benchmarked against the observed deformations. Finally, for an independent test set of 20 patients the predicted libraries were evaluated clinically, and compared to the current method.Results.The median Dice score over the validation subjects between the predicted and FEM libraries was >0.95 throughout the deformation, with a median 90 percentile surface distance of <3 mm. The ability to cover observed CTVs was similar for both the FEM-based and the proposed method, with residual offsets being about twice as large as the difference between the two methods. Clinical evaluation showed improved library properties over the method currently used in clinic.Conclusions.We proposed a CNN trained on FEM deformations, which predicts the deformation trajectory between two input states of the cervix CTV in one forward pass. We applied this to CTV library prediction for cervical cancer. The network is able to mimic FEM deformations well, while being much faster and simpler in use.

Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit.

BACKGROUND: To compare online adaptive radiation therapy (ART) to a clinically implemented plan selection strategy (PS) with respect to dose to the organs at risk (OAR) for rectal cancer. METHODS: The first 20 patients treated with PS between May-September 2016 were included. This resulted in 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules with a total of 300 Conebeam CT scans (CBCT). New dual arc VMAT plans were generated using auto-planning for both the online ART and PS strategy. For each fraction bowel bag, bladder and mesorectum were delineated on daily Conebeam CTs. The dose distribution planned was used to calculate daily DVHs. Coverage of the CTV was calculated, as defined by the dose received by 99% of the CTV volume (D99%). The volume of normal tissue irradiated with 95% of the prescribed fraction dose was calculated by calculating the volume receiving 95% of the prescribed fraction or more dose minus the volume of the CTV. For each fraction the difference between the plan selection and online adaptive strategy of each DVH parameter was calculated, as well as the average difference per patient. RESULTS: Target coverage remained the same for online ART. The median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm3 (PS) to 237 cm3 (online-ART)(p < 0.001). Online ART reduced dose to the OARs for all tested dose levels for SCRT and LCRT (p < 0.001). For V15Gy of the bowel bag the median difference over all fractions of all patients was - 126 cm3 in LCRT, while the average difference per patient ranged from - 206 cm3 to - 40 cm3. For SCRT the median difference was - 62 cm3, while the range of the average difference per patient was - 105 cm3 to - 51 cm3. For V15Gy of the bladder the median difference over all fractions of all patients was 26% in LCRT, while the average difference per patient ranged from - 34 to 12%. For SCRT the median difference of V95% was - 8%, while the range of the average difference per patient was - 29 to 0%. CONCLUSIONS: Online ART for rectal cancer reduces dose the OARs significantly compared to a clinically implemented plan selection strategy, without compromising target coverage. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W19_357 # 19.420; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

A biomechanical finite element model to generate a library of cervix CTVs.

PURPOSE: To generate a series of physiologically plausible cervix CTVs by biomechanically modeling organ deformation as a consequence of bladder filling. This series can serve as planning CTVs for radiotherapy treatment of cervical cancer patients using a library of plans (LoP) strategy. METHODS: The model was constructed based on the full and empty bladder scans of 20 cervical cancer patients, for which the bladder, rectum and the clinical target volume (CTV) of the cervix were delineated. Finite element modeling (FEM) was used to deform empty to full bladder anatomy. This deformation comprised two steps. In the first step, the surfaces of the bladder and rectum of the empty bladder anatomy were explicitly deformed to the full bladder anatomy and imported as enforced displacements into the biomechanical model. These surface displacements cause volumetric deformations of the bladder, rectum and cervix CTV meshes, dictated by their respective elastic properties and the type of contact among them. In the second step, the residual offset between the simulated and target CTV was corrected by an additional thin plate spline warp. Intermediate structural outputs of a linear superposition of the biomechanical and residual warp then constituted the library of CTVs for each patient. The residual warp was minimized by optimizing the FEM parameters over the 20 patients. Finally, the model was tested for nine healthy volunteers for which repeat MR scans were available as the bladder filled from empty to full. Small and large movers were identified depending on the extent of CTV motion, and analyzed separately. The proposed method was compared against the method currently used in our institute, in which intermediate structures are linearly interpolated between full and empty bladder anatomy, using a thin plate spline warp. The comparison metrics used were the ability to preserve CTV volume throughout the deformation, and residual offsets between repeat and library CTV. RESULTS: Optimal model parameters were found to be compatible with published values. While for the current method, the median CTV volume shrunk by 4% for large movers halfway the deformation (and by up to 10% for individual cases), the proposed FEM-based method preserved CTV volumes throughout the deformation. Regional residual errors between repeat and library CTV reduced by up to 3 mm when averaged over the group of large movers. For individual cases this regional error reduction could be as large as 8 mm. CONCLUSIONS: We developed a robust and automatic method to create a patient-specific FEM-based LoP. The FEM-based method resulted in more accurate library of planning CTVs as compared to the current method, with the greatest improvements observed for patients with large CTV motion. The biomechanical model simulates volumetric deformations from empty to full bladder anatomy, paving the way for dose accumulation in an LoP setting.

Feasibility of cone beam CT-guided library of plans strategy in pre-operative gastric cancer radiotherapy.

BACKGROUND AND PURPOSE: The stomach displays large anatomical changes in size, shape and position, which implies the need for plan adaptation for gastric cancer patients who receive pre-operative radiotherapy. We evaluated the feasibility and necessity of a CBCT-guided library of plans (LoP) strategy in gastric cancer radiotherapy. METHODS: Eight gastric cancer patients treated with 24-25 fractions of single-plan radiotherapy with daily CBCT imaging were included. The target was delineated on the pre-treatment CT and first 5 CBCTs to create a patient-specific LoP. Plan selections were performed by 12 observers in a training stage (2-3 CBCTs per patient) and an assessment stage (17 CBCTs per patient). The observers were asked to select the smallest plan that encompassed the target on the CBCT. A total of 136 plan selections were evaluated in the assessment stage. RESULTS: Delineations on CBCTs showed that in 90% of the 40 delineated fractions part of the CTV was outside the PTV based on the pre-treatment CT. At least two-thirds of the observers agreed on the selected plan in 65.2% and 70% of the fractions in the training stage and the assessment stage, respectively. For each patient, at least two different plans from the LoP were the most selected plan. CONCLUSION: A CBCT-guided patient-specific LoP strategy is feasible for gastric cancer patients, yielding good agreement in plan selections. Unless generous margins are used to avoid frequent geometric misses, it is likely that part of the target will be missed with single-plan radiotherapy.

Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy.

BACKGROUND: To compare target coverage and dose to the organs at risk in two approaches to rectal cancer: a clinically implemented adaptive radiotherapy (ART) strategy using plan selection, and a non-adaptive (non-ART) strategy. METHODS: The inclusion of the first 20 patients receiving adaptive radiotherapy produced 10 patients with a long treatment schedule (25x2Gy) and 10 patients with a short schedule (5X5Gy). We prepared a library of three plans with different anterior PTV margins to the upper mesorectum, and selected the most appropriate plan on daily Conebeam CT scans (CBCT). We also created a non-adaptive treatment plan with a 20 mm margin. Bowel bag, bladder and target volume were delineated on CBCT. Daily DHVs were calculated based on the dose distribution of the selected and non-adaptive plans. Coverage of the target volume was compared per fraction between the ART and non-ART plans, as was the dose to the bladder and small bowel, assessing the following dose levels: V15Gy, V30Gy, V40Gy, V15Gy and V95% for long treatment schedules, and V15Gy and V95% for short ones. RESULTS: Target volume coverage was maintained from 98.3% (non-ART) to 99.0% (ART)(p = 0.878). In the small bowel, ART appeared to have produced significant reductions in the long treatment schedule at V15Gy, V40Gy, V45Gy and V95% (p <  0.05), but with small absolute differences. The DVH parameters tested for the short treatment schedule did not differ significantly. In the bladder, all DVH parameters in both schedules showed significant reductions (p <  0.05), also with small absolute differences. CONCLUSIONS: The adaptive treatment maintained target coverage and reduced dose to the organs at risk. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center, W19_194 # 19.233.

Margin and PTV volume reduction using a population based library of plans strategy for rectal cancer radiotherapy.

PURPOSE: Day-to-day shape variation in the rectum CTV results in considerable geometric uncertainties during rectal cancer radiotherapy. To ensure coverage a large CTV-to-PTV margin is required. The purpose of this study was to increase the accuracy of treatment delivery by building a population based library of planning CTVs for rectal cancer patients and to evaluate its potential for rectum PTV margin and PTV volume reduction. METHODS: Analysis was done retrospectively on 33 early-stage rectal cancer patients with daily repeat CTs who received short-course pre-operative radiotherapy in 5 fractions of 5 Gy. We created signed distance maps from the planning rectum CTV to each of the repeat CTVs, from which we calculated the group mean, systematic and random error. The correlation between different regions of the rectum CTV was analyzed and used in combination with the distance maps to create the library of nine planning CTVs. For each of the repeat CTVs the best fitting CTV structure in the library was automatically selected defined by the plan that minimized the mean absolute distance between the repeat and library CTV. Residual distance maps were calculated from which a new PTV margin was constructed. Bootstrapping was performed on the margin difference to assess its significance. RESULTS: Residual errors were found to decrease with the number of plans in the library, but adding more than five plans yields negligible further error reduction. Margin reduction of up to 50% was achieved at the upper-anterior site of the mesorectum. The average PTV volume decreased by 15.5% when a library is introduced. CONCLUSIONS: A library of plans strategy for rectal cancer based on population statistics is feasible and results in a considerably reduced average rectum PTV volume compared to conventional radiotherapy.