Indications of Online Adaptive Replanning Based On Organ Deformation.

PURPOSE: Although vital to account for interfractional variations during radiation therapy, online adaptive replanning (OLAR) is time-consuming and labor-intensive compared with the repositioning method. Repositioning is enough for minimal interfractional deformations. Therefore, determining indications for OLAR is desirable. We introduce a method to rapidly determine the need for OLAR by analyzing the Jacobian determinant histogram (JDH) obtained from deformable image registration between reference (planning) and daily images. METHODS AND MATERIALS: The proposed method was developed and tested based on daily computed tomography (CT) scans acquired during image guided radiation therapy for prostate cancer using an in-room CT scanner. Deformable image registration between daily and reference CT scans was performed. JDHs were extracted from the prostate and a uniform surrounding 10-mm expansion. A classification tree was trained to determine JDH metrics to predict the need for OLAR for a daily CT set. Sixty daily CT scans from 12 randomly selected prostate cases were used as the training data set, with dosimetric plans for both OLAR and repositioning used to determine their class. The resulting classification tree was tested using an independent data set of 45 daily CT scans from 9 other patients with 5 CT scans each. RESULTS: Of a total of 27 JDH metrics tested, 5 were identified predicted whether OLAR was substantially superior to repositioning for a given fraction. A decision tree was constructed using the obtained metrics from the training set. This tree correctly identified all cases in the test set where benefits of OLAR were obvious. CONCLUSIONS: A decision tree based on JDH metrics to quickly determine the necessity of online replanning based on the image of the day without segmentation was determined using a machine learning process. The process can be automated and completed within a minute, allowing users to quickly decide which fractions require OLAR.

A Technique to Rapidly Generate Synthetic Computed Tomography for Magnetic Resonance Imaging-Guided Online Adaptive Replanning: An Exploratory Study.

PURPOSE: To develop an automatic, accurate, atlas-based technique for synthetic computed tomography (sCT) generation to be used for online adaptive replanning during magnetic resonance imaging (MRI)-guided radiation therapy (RT). METHODS AND MATERIALS: The proposed method uses deformable image registration (DIR) of daily MRI and reference computed tomography (CT) with additional corrections to maintain bone rigidity and to transfer random air regions by thresholding. The DIR is performed with constraints on the bony structures using a special algorithm of ADMIRE (Elekta). The air regions are delineated from low-signal regions on the daily MRI and forced to air density. The bone regions in the MRI (already determined from the CT) are separated from the air regions because both bone and air have low signal density in MRI. All these steps are automated. The generated sCT is compared with reference CT and the alternative voxel-based CT (bCT) for 4 extracranial sites (head and neck, thorax, abdomen, pelvis) in terms of mean absolute error (MAE), gamma analysis of 3-dimensional doses, and dose volume histogram parameters. RESULTS: Both MAE and dosimetric analysis results were favorable for the proposed sCT generation method. The average MAE for the sCT/bCT were 25.5/66.7, 25.9/65.3, 24.8/44.2 and 16.6/47.7 for head and neck, thorax, abdomen, and pelvis, respectively, and the gamma analysis (1.5%, 2 mm) yielded 98.7/97.1, 99.1/93.9, 99.5/99.4, 99.7/99.4, respectively, for those sites. CONCLUSIONS: The proposed method generates equal or more accurate sCT than those from the bulk density assignment, without the need for multiple MRI sequences. This method can be fully automated and applicable for online adaptive replanning.

An online replanning method using warm start optimization and aperture morphing for flattening-filter-free beams.

PURPOSE: In a situation where a couch shift for patient positioning is not preferred or prohibited (e.g., MR-linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening-filter-free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here the authors propose a new two-step process to address both the translational effect of FFF beams and the target deformation. METHODS: The replanning method consists of an offline and an online step. The offline step is to create a series of preshifted-plans (PSPs) obtained by a so-called "warm start" optimization (starting optimization from the original plan, rather than from scratch) at a series of isocenter shifts. The PSPs all have the same number of segments with very similar shapes, since the warm start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by picking the closest PSP or linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated and almost instantaneous (no optimization or dose calculation needed). The previously developed SAM algorithm is then applied for daily deformation. The authors tested the method on sample prostate and pancreas cases. RESULTS: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. Plan interpolation method is effective in diminishing the unflat beam effect and may allow reducing the required number of PSPs. The whole process takes the same time as the previously reported SAM process (5-10 min). CONCLUSIONS: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation except the delineation of target contour required by the SAM process.

Technical Note: A fast online adaptive replanning method for VMAT using flattening filter free beams.

PURPOSE: To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams. METHODS: A software tool was developed to interface with a VMAT research planning system, which enables the input and output of beam and machine parameters of VMAT plans. The SAM algorithm was used to modify multileaf collimator positions for each segment aperture based on the changes of the target from the planning (CT/MR) to daily image [CT/CBCT/magnetic resonance imaging (MRI)]. The leaf travel distance was controlled for large shifts to prevent the increase of VMAT delivery time. The SAM algorithm was tested for 11 patient cases including prostate, pancreatic, and lung cancers. For each daily image set, three types of VMAT plans, image-guided radiation therapy (IGRT) repositioning, SAM adaptive, and full-scope reoptimization plans, were generated and compared. RESULTS: The SAM adaptive plans were found to have improved the plan quality in target and/or critical organs when compared to the IGRT repositioning plans and were comparable to the reoptimization plans based on the data of planning target volume (PTV)-V100 (volume covered by 100% of prescription dose). For the cases studied, the average PTV-V100 was 98.85% ± 1.13%, 97.61% ± 1.45%, and 92.84% ± 1.61% with FFF beams for the reoptimization, SAM adaptive, and repositioning plans, respectively. The execution of the SAM algorithm takes less than 10 s using 16-CPU (2.6 GHz dual core) hardware. CONCLUSIONS: The SAM algorithm can generate adaptive VMAT plans using FFF beams with comparable plan qualities as those from the full-scope reoptimization plans based on daily CT/CBCT/MRI and can be used for online replanning to address interfractional variations.

Gradient maintenance: A new algorithm for fast online replanning.

PURPOSE: Clinical use of online adaptive replanning has been hampered by the unpractically long time required to delineate volumes based on the image of the day. The authors propose a new replanning algorithm, named gradient maintenance (GM), which does not require the delineation of organs at risk (OARs), and can enhance automation, drastically reducing planning time and improving consistency and throughput of online replanning. METHODS: The proposed GM algorithm is based on the hypothesis that if the dose gradient toward each OAR in daily anatomy can be maintained the same as that in the original plan, the intended plan quality of the original plan would be preserved in the adaptive plan. The algorithm requires a series of partial concentric rings (PCRs) to be automatically generated around the target toward each OAR on the planning and the daily images. The PCRs are used in the daily optimization objective function. The PCR dose constraints are generated with dose-volume data extracted from the original plan. To demonstrate this idea, GM plans generated using daily images acquired using an in-room CT were compared to regular optimization and image guided radiation therapy repositioning plans for representative prostate and pancreatic cancer cases. RESULTS: The adaptive replanning using the GM algorithm, requiring only the target contour from the CT of the day, can be completed within 5 min without using high-power hardware. The obtained adaptive plans were almost as good as the regular optimization plans and were better than the repositioning plans for the cases studied. CONCLUSIONS: The newly proposed GM replanning algorithm, requiring only target delineation, not full delineation of OARs, substantially increased planning speed for online adaptive replanning. The preliminary results indicate that the GM algorithm may be a solution to improve the ability for automation and may be especially suitable for sites with small-to-medium size targets surrounded by several critical structures.

A phase I/II study piloting accelerated partial breast irradiation using CT-guided intensity modulated radiation therapy in the prone position.

BACKGROUND AND PURPOSE: External beam accelerated partial breast irradiation (EB-aPBI) is noninvasive with broader potential applicability than aPBI using brachytherapy. However, it has inherent challenges in daily reproducibility. Image-guide radiotherapy (IGRT) can improve daily reproducibility, allowing smaller treatment margins. Our institution proposed IG-IMRT in the prone position to evaluate dose homogeneity, conformality, normal tissue avoidance, and reliable targeting for EB-aPBI. We report preliminary results and toxicity from a phase I/II study evaluating the feasibility of EB-aPBI in the prone position using IG-IMRT. MATERIALS AND METHODS: Twenty post-menopausal women with node-negative breast cancer, excised tumors <3.0 cm, negative sentinel lymph node biopsy, and surgical clips demarcating the lumpectomy cavity underwent prone EB-aPBI using IG-IMRT on an IRB-approved phase I/II study. All patients underwent CT planning in the prone position. The lumpectomy cavity PTV represented a 2.0 cm expansion. 38.5 Gy was delivered in 10 fractions over 5 days, such that 95% of the prescribed dose covered >99% of the PTV. Dose constraints for the whole breast, lungs and heart were met. RESULTS: The median patient age was 61.5. Mean tumor size was 1.0 cm. 35% of patients had DCIS. Median PTV was 243 cc (108-530) and median breast reference volume was 1698 cc (647-3627). Average daily shifts for IGRT were (0.6, -4.6, 1.7 mm) with standard deviations of (6.3, 6.5, 6.4mm). Acute toxicity was G1 erythema in 80%, and G2 erythema, G2 fatigue, and G2 breast pain each occurred in 1 patient. With a median follow-up of 18.9 months (12-35), 40% of patients have G1 fibrosis and 30% have G1 hyperpigmentation. 95% of patients have good to excellent cosmesis. There have been no recurrences. CONCLUSIONS: These data demonstrate that EB-aPBI in the prone position using IG-IMRT is well tolerated, yields good dosimetric conformality, and results in promising early toxicity profiles.

Comparison of various online strategies to account for interfractional variations for pancreatic cancer.

PURPOSE: To identify practical techniques to address the large interfractional variations for pancreas irradiation by comparing various used/proposed online strategies. METHODS AND MATERIALS: The daily computed tomography (CT) images acquired using a respiration-gated in-room CT (CTVision; Siemens) for 10 pancreatic cancer patients treated with image guided radiation therapy (IGRT) were analyzed. The contours of the pancreas and organs at risk on each daily CT set were generated by populating from the planning CT using a deformable registration tool (ABAS; Elekta) with manual editing. Nine online strategies were considered: (1) standard IGRT (ie, IGRT with 0-mm additional margin [AM]); (2) IGRT with 2-mm AM; (3) IGRT with 5-mm AM; (4) IGRT with plan renormalized to maintain 95% planning target volume (PTV) coverage; (5) full-scale reoptimization; (6) reoptimization starting from the original plan; (7) segment aperture morphing (SAM) from the original plan, based on PTV shape change; (8) SAM plus segment weight optimization; and (9) reoptimization starting from the SAM plan. One-way analysis of variance was applied to plan qualities for the 9 strategies to assess statistical significance in difference. RESULTS: The 3 IGRT strategies (1-3) lead to either inadequate PTV coverage or higher doses to critical structures, indicating that the additional margins alone are not adequate to account for the changes. The full-scale reoptimization results in the best plan but requires the delineation of several structures, which is time consuming. The SAM strategy (7) was the fastest one, because it requires delineating only 1 structure (target), and its plan quality was comparable to that for the full-scale reoptimization. CONCLUSION: Online replanning strategies can lead to either reduced organs-at-risk dose and/or improved target coverage as compared with the current practice of IGRT. The SAM-based online replanning is comparable to full-scale reoptimization and is efficient for practical use.

Interfractional target variations for partial breast irradiation.

PURPOSE: In this work, we quantify the interfractional variations in the shape of the clinical target volume (CTV) by analyzing the daily CT data acquired during CT-guided partial breast irradiation (PBI) and compare the effectiveness of various repositioning alignment strategies considered to account for the variations. METHODS AND MATERIALS: The daily CT data for 13 breast cancer patients treated with PBI in either prone (10 patients) or supine (3 patients) with daily kV CT guidance using CT on Rails (CTVision, Siemens, Malvern, PA) were analyzed. For approximately 25 points on the surface of the CTV, deformation vectors were calculated by means of deformable image registration and verified by visual inspection. These were used to calculate the distances along surface normals (DSN), which directly related to the required margin expansions for each point. The DSN values were determined for seven alignment methods based on volumetric imaging and also two-dimensional projections (portal imaging). RESULTS: The margin expansion necessary to cover 99% of all points for all days was 2.7 mm when utilizing the alignment method based on deformation field data (the best alignment method). The center-of-mass based alignment yielded slightly worse results (a margin of 4.0 mm), and shifts obtained by operator placement (7.9 mm), two-dimensional-based methods (7.0-10.1 mm), and skin marks (13.9 mm) required even larger margin expansions. Target shrinkage was evident for most days by the negative values of DSN. Even with the best alignment, the range of DSN values could be as high as 7 mm, resulting in a large amount of normal tissue irradiation, unless adaptive replanning is employed. CONCLUSION: The appropriate alignment method is important to minimize the margin requirement to cover the significant interfractional target deformations observed during PBI. The amount of normal tissue unnecessarily irradiated is still not insignificant, and can be minimized if adaptive radiotherapy is applied.

Internal margin assessment using cine MRI analysis of deglutition in head and neck cancer radiotherapy.

PURPOSE: Intensity-modulated radiation therapy (IMRT) is a promising treatment modality for patients with head and neck cancer (HNC). The dose distributions from IMRT are static and, thus, are unable to account for variations and/or uncertainties in the relationship between the patient (region being treated) and the beam. Organ motion comprises one such source of this uncertainty, introduced by physiological variation in the position, size, and shape of organs during treatment. In the head and neck, the predominant source of this variation arises from deglutition (swallowing). The purpose of this study was to investigate whether cinematographic MRI (cine MRI) could be used to determine asymmetric (nonuniform) internal margin (IM) components of tumor planning target volumes based on the actual deglutition-induced tumor displacement. METHODS: Five head and neck cancer patients were set up in treatment position on a 3 T MRI scanner. Two time series of single-slice, sagittal, cine images were acquired using a 2D FLASH sequence. The first time series was a 12.8 min scan designed to capture the frequency and duration of deglutition in the treatment position. The second time series was a short, 15 s scan designed to capture the displacement of deglutition in the treatment position. Deglutition frequency and mean swallow duration were estimated from the long time series acquisition. Swallowing and resting (nonswallowing) events were identified on the short time series acquisition and displacement was estimated based on contours of gross tumor volume (GTV) generated at each time point of a particular event. A simple linear relationship was derived to estimate 1D asymmetric IMs in the presence of resting- and deglutition-induced displacement. RESULTS: Deglutition was nonperiodic, with frequency and duration ranging from 2.89-24.18 mHz and from 3.86 to 6.10 s, respectively. The deglutition frequency and mean duration were found to vary among patients. Deglutition-induced maximal GTV displacements ranged from 0.00 to 28.36 mm with mean and standard deviation of 4.72 +/- 3.18, 3.70 +/- 2.81, 2.75 +/- 5.24, and 10.40 +/- 10.76 mm in the A, P, I, and S directions, respectively. Resting-induced maximal GTV displacement ranged from 0.00 to 5.59 mm with mean and standard deviation of 3.01 +/- 1.80, 1.25 +/- 1.10, 3.23 +/- 2.20, and 2.47 +/- 1.11 mm in the A, P, I, and S directions, respectively. For both resting and swallowing states, displacement along the S-I direction dominated displacement along the A-P direction. The calculated IMs were dependent on deglutition frequency, ranging from 3.28-4.37 mm for the lowest deglutition frequency patient to 3.76-6.43 mm for the highest deglutition frequency patient. A statistically significant difference was detected between IMs calculated for P and S directions (p = 0.0018). CONCLUSIONS: Cine MRI is able to capture tumor motion during deglutition. Swallowing events can be demarcated by MR signal intensity changes caused by anatomy containing fully relaxed spins that move medially into the imaging plane during deglutition. Deglutition is nonperiodic and results in dynamic changes in the tumor position. Deglutition-induced displacements are larger and more variable than resting displacements. The nonzero mean maximum resting displacement indicates that some tumor motion occurs even when the patient is not swallowing. Asymmetric IMs, derived from deglutition frequency, duration, and directional displacement, should be employed to account for tumor motion in HNC RT.

Online adaptive replanning method for prostate radiotherapy.

PURPOSE: To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. METHODS AND MATERIALS: The new "SAM+SWO" scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. RESULTS: For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 +/- 2 minutes. CONCLUSION: The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT.

An on-line replanning method for head and neck adaptive radiotherapy.

Daily setup for head and neck (HN) radiotherapy (RT) can vary randomly due to neck rotation and anatomy change. These differences cannot be totally corrected by the current practice of image guided RT with translational repositioning. The authors present a novel rapid correction scheme that can be used on-line to correct both interfractional setup variation and anatomy change for HN RT. The scheme consists of two major steps: (1) Segment aperture morphing (SAM) and (2) segment weight optimization (SWO). SAM is accomplished by applying the spatial relationship between the apertures and the contours of the planning target and organs at risk (OARs) to the new target and OAR contours. The new target contours are transferred from planning target contours to the CT of the day by means of deformable registration (MIMVISTA). The dose distribution for each new aperture was generated using a planning system with a fast dose engine and hardware and was input into a newly developed SWO package using fast sequential quadratic programming. The entire scheme was tested based on the daily CT images acquired for representative HN IMRT cases treated with a linac and CT-on-Rails combo. It was found that the target coverage and/or OAR sparing was degraded based on the CT of the day with the current standard repositioning from rigid registration. This degradation can be corrected by the SAM/SWO scheme. The target coverage and OAR sparing for the SAM/SWO plans were found to be equivalent to the original plan. The SAM/SWO process took 5-8 min for the head and neck cases studied. The proposed aperture morphing with weight optimization is an effective on-line approach for correcting interfractional patient setup and anatomic changes for head and neck cancer radiotherapy.

An on-line replanning scheme for interfractional variations.

Ability of online adaptive replanning is desirable to correct for interfraction anatomic changes. A full-scope replanning/reoptimization with the current planning techniques takes too long to be practical. A novel online replanning strategy to correct for interfraction anatomic changes in real time is presented. The scheme consists of three steps: (1) rapidly delineating targets and organs at risk on the computed tomography of the day by modifying original planning contours using robust tools in a semiautomatic manner, (2) online segment aperture morphing (SAM) (adjusting beam/ segment apertures) by applying the spatial relationship between the planning target contour and the apertures to the new target contour, and (3) performing segment weight optimization (SWO) for the new apertures if necessary. The entire scheme was tested for direct-aperture-based IMRT on representative prostate and abdomen cases. Dose volume histograms obtained with the online scheme are practically equivalent to those obtained with full-scope reoptimization. For the days of small to moderate organ deformations, only the SAM is necessary, while for the large deformation days, both SAM and SWO are required to adequately account for the deformation. Both the SAM and SWO programs can be completed within 1 min, and the overall process can be completed within 10 min. The proposed SAM-SWO scheme is practically comparable to full-scope reoptimization, but is fast enough to be implemented for on-line adaptive replanning, enabling dose-guided RT.

Direct aperture optimization-based intensity-modulated radiotherapy for whole breast irradiation.

PURPOSE: To investigate the technical and dosimetric advantages and the efficacy of direct aperture optimized intensity-modulated radiation therapy (DAO-IMRT) over standard (e.g., beamlet optimized) IMRT and conventional three-dimensional conformal radiotherapy (3D-CRT) for whole breast irradiation in supine and prone positions. METHODS AND MATERIALS: We retrospectively designed DAO-IMRT plans for 15 breast cancer patients in supine (10 patients) and prone (5 patients) positions with a goal of uniform dose coverage of the whole breast. These DAO-IMRT plans were compared with standard IMRT using beamlet optimization and conventional 3D-CRT plans using wedges. All plans used opposed tangential beam arrangements. RESULTS: In all cases, the DAO-IMRT plans were equal to or better than those generated with 3D-CRT and standard beamlet-IMRT. For supine cases, DAO-IMRT provided higher uniformity index (UI, defined as the ratio of the dose to 95% of breast volume to the maximum dose) than either 3D-CRT (0.88 vs. 0.82; p = 0.026) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). Direct aperture optimized IMRT also gave lower lung doses than either 3D-CRT (V20 = 7.9% vs. 8.6%; p = 0.024) or beamlet-IMRT (V20 = 8.4% vs. 9.7%; p = 0.0008) for supine patients. For prone patients, DAO-IMRT provided higher UI than either 3D-CRT (0.89 vs. 0.83; p = 0.027) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). The planning time for DAO-IMRT was approximately 75% less than that of 3D-CRT. The monitor units for DAO-IMRT were approximately 60% less than those of beamlet-IMRT. CONCLUSION: Direct aperture optimized IMRT improved the overall quality of dose distributions as well as the planning and delivery efficiency for treating whole breast in both supine and prone positions.