iCONE-SRS: Development of inverse treatment planning for cone-based stereotactic radiosurgery.

PURPOSE: At present, commercially available treatment planning systems (TPS) only offer manual planning functionality for cone-based stereotactic radiosurgery (SRS) leading to labor intensive treatment planning. Our objective was to reduce treatment planning time through development of a simple inverse TPS for cone-based SRS. METHODS: The iCONE TPS was developed using MATLAB (R2015a, The MathWorks Inc.) and serves as an inverse planning adjunct to a commercially available TPS. Simulated annealing is used to determine optimal table angle, gantry start and stop angles, and cone sizes for a user-defined number of non-coplanar arcs relative to user-defined dose objectives. iCONE and clinically generated plans were compared through a retrospective planning study of 60 patients treated for 1-3 brain metastases (total of 100 lesions). RESULTS: Planning target volume (PTV) coverage was enforced for all plans through normalization. PTV maximum dose was constrained to be within 120%-135% of the prescription dose. The median conformity index for iCONE plans was 1.35, 1.33, and 1.32 for 1, 2, and 3-target cases respectively corresponding to a median increase of 0.05 (range = -0.1 to 0.5, P < 0.05), 0.06 (range = -0.83 to 0.53, P < 0.05), and 0.03 (range = -1.21 to 0.74, P > 0.05) relative to the clinical plans. No clinically significant differences were found with respect to the dose to organs-at-risk. Median iCONE planning times were approximately a factor of five lower than consensus estimates for manual planning provided by local experienced SRS planners. CONCLUSIONS: A simple inverse TPS for cone-based SRS was developed. Plan quality was found to be similar to manually generated plans; however, degradation was observed in some cases highlighting the need for continued oversight and manual adjustment by experienced planners if implemented in the clinic. A factor of five reduction in treatment planning time was estimated.

Automated prediction of dosimetric eligibility for hypofractionated prostate radiotherapy.

Clinical implementation of hypofractionated prostate radiotherapy (PROFIT trial, NCT003046759) represents an opportunity to significantly reduce the burden of treatment on the patient and clinic. However, efficacy was only demonstrated among the patient demographic who could meet the trial dose constraints and so it is necessary to emulate this triage step in clinical practice. The purpose of this study was to build a convenient tool to address the challenge of determining patient eligibility for hypofractionated treatment within the clinic. The tool was implemented within the EclipseTM treatment planning system using the scripting environment. Prior to planning a new case, the script computes and displays in a plot the fractional overlap of rectal and bladder wall with the planning target volume. Radial decision boundaries separate the plot into three zones and the new case is then classified as "feasible", "uncertain", or "not feasible". The radial decision boundaries were derived from a retrospective analysis of the overlap values and dosimetric eligibility of 150 patients with intermediate risk prostate cancer. Two-fold cross validation with repetitions demonstrated an average prediction accuracy of over 90%. The tool has been integrated into our clinical planning workflow to enable early identification of the need for planning consults and rapid a-priori determination of dosimetric eligibility for hypofractionated radiotherapy. The tool can be readily adopted by other centres since the underlying metrics can be evaluated without scripting if desired.

A generalized parametric response mapping method for analysis of multi-parametric imaging: A feasibility study with application to glioblastoma.

PURPOSE: Parametric response map (PRM) analysis of functional imaging has been shown to be an effective tool for early prediction of cancer treatment outcomes and may also be well-suited toward guiding personalized adaptive radiotherapy (RT) strategies such as sub-volume boosting. However, the PRM method was primarily designed for analysis of longitudinally acquired pairs of single-parameter image data. The purpose of this study was to demonstrate the feasibility of a generalized parametric response map analysis framework, which enables analysis of multi-parametric data while maintaining the key advantages of the original PRM method. METHODS: MRI-derived apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) maps acquired at 1 and 3-months post-RT for 19 patients with high-grade glioma were used to demonstrate the algorithm. Images were first co-registered and then standardized using normal tissue image intensity values. Tumor voxels were then plotted in a four-dimensional Cartesian space with coordinate values equal to a voxel's image intensity in each of the image volumes and an origin defined as the multi-parametric mean of normal tissue image intensity values. Voxel positions were orthogonally projected onto a line defined by the origin and a pre-determined response vector. The voxels are subsequently classified as positive, negative or nil, according to whether projected positions along the response vector exceeded a threshold distance from the origin. The response vector was selected by identifying the direction in which the standard deviation of tumor image intensity values was maximally different between responding and non-responding patients within a training dataset. Voxel classifications were visualized via familiar three-class response maps and then the fraction of tumor voxels associated with each of the classes was investigated for predictive utility analogous to the original PRM method. Independent PRM and MPRM analyses of the contrast-enhancing lesion (CEL) and a 1 cm shell of surrounding peri-tumoral tissue were performed. Prediction using tumor volume metrics was also investigated. Leave-one-out cross validation (LOOCV) was used in combination with permutation testing to assess preliminary predictive efficacy and estimate statistically robust P-values. The predictive endpoint was overall survival (OS) greater than or equal to the median OS of 18.2 months. RESULTS: Single-parameter PRM and multi-parametric response maps (MPRMs) were generated for each patient and used to predict OS via the LOOCV. Tumor volume metrics (P ≥ 0.071 ± 0.01) and single-parameter PRM analyses (P ≥ 0.170 ± 0.01) were not found to be predictive of OS within this study. MPRM analysis of the peri-tumoral region but not the CEL was found to be predictive of OS with a classification sensitivity, specificity and accuracy of 80%, 100%, and 89%, respectively (P = 0.001 ± 0.01). CONCLUSIONS: The feasibility of a generalized MPRM analysis framework was demonstrated with improved prediction of overall survival compared to the original single-parameter method when applied to a glioblastoma dataset. The proposed algorithm takes the spatial heterogeneity in multi-parametric response into consideration and enables visualization. MPRM analysis of peri-tumoral regions was shown to have predictive potential supporting further investigation of a larger glioblastoma dataset.

An augmented parametric response map with consideration of image registration error: towards guidance of locally adaptive radiotherapy.

Parametric response map (PRM) analysis is a voxel-wise technique for predicting overall treatment outcome, which shows promise as a tool for guiding personalized locally adaptive radiotherapy (RT). However, image registration error (IRE) introduces uncertainty into this analysis which may limit its use for guiding RT. Here we extend the PRM method to include an IRE-related PRM analysis confidence interval and also incorporate multiple graded classification thresholds to facilitate visualization. A Gaussian IRE model was used to compute an expected value and confidence interval for PRM analysis. The augmented PRM (A-PRM) was evaluated using CT-perfusion functional image data from patients treated with RT for glioma and hepatocellular carcinoma. Known rigid IREs were simulated by applying one thousand different rigid transformations to each image set. PRM and A-PRM analyses of the transformed images were then compared to analyses of the original images (ground truth) in order to investigate the two methods in the presence of controlled IRE. The A-PRM was shown to help visualize and quantify IRE-related analysis uncertainty. The use of multiple graded classification thresholds also provided additional contextual information which could be useful for visually identifying adaptive RT targets (e.g. sub-volume boosts). The A-PRM should facilitate reliable PRM guided adaptive RT by allowing the user to identify if a patient's unique IRE-related PRM analysis uncertainty has the potential to influence target delineation.

A Gauss-Newton approach to joint image registration and intensity correction.

We develop a new efficient numerical methodology for automated simultaneous registration and intensity correction of images. The approach separates the intensity correction term from the images being registered in a regularized expression. Our formulation is consistent with the existing non-parametric image registration techniques, however, an extra additive intensity correction term is carried throughout. An objective functional is formed for which the corresponding Hessian and Jacobian is computed and employed in a multi-level Gauss-Newton minimization approach. In this paper, our experiments are based on elastic regularization on the transformation and total variation on the intensity correction. Validations on dynamic contrast enhanced MR abdominal images for both real and simulated data verified the efficacy of the model. The pursued approach is flexible in which we can exploit various forms of regularization on the transformation and the intensity correction.