OC-0549: Improving the clinical applicability of markerless lung tumour tracking with contrast-enhanced kV imaging

In-room kV imaging is widely applied for intrafraction motion compensation in image-guided radiation therapy (IGRT). The low contrast of lung tumours in kV images and the overlap of high-intensity surrounding structures, such as the mediastinum, may limit the applicability of IGRT techniques in lung cancer treatments. The aim of this study is to apply a CT-based contrast enhancement method to improve markerless lung tumour tracking in kV images, thus enhancing the potential of X-raybased image guidance in lung cancer patients

Salvage stereotactic body radiotherapy for isolated lymph node recurrent prostate cancer : single institution series of 94 consecutive patients and 124 lymph nodes

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Adaptive mathematical model of tumor response to radiotherapy based on CBCT data

Mathematical modeling of tumor response to radiotherapy has the potential of enhancing the quality of the treatment plan, which can be even tailored on an individual basis. Lack of extensive in vivo validation has prevented, however, reliable clinical translation of modeling outcomes. Image guided radiotherapy (IGRT) is a consolidated treatment modality based on computed tomographic (CT) imaging for tumor delineation and volumetric cone beam CT data for periodic checks during treatment. In this work, a macroscopic model of tumor growth and radiation response is proposed, being able to adapt along the treatment course as volumetric tumor data become available. Model parameter learning was based on cone beam CT images in 13 uterine cervical cancer patients, subdivided into three groups (G1, G2, G3) according to tumor type and treatment. Three groupspecific parameter sets (PS1, PS2 and PS3) on one general parameter set (PSa) were applied. The corresponding average model fitting errors were 14, 18, 13 and 21%, respectively. The model adaptation testing was performed using volume data of three patients, other than the ones involved in the parameter learning. The extrapolation performance of the general model was improved, while comparable prediction errors were found for the groupspecific approach. This suggests that an on-line parameter tuning can overcome the limitations of a suboptimal patient stratification, which appeared otherwise a critical issue

The Role of Regularization in Deformable Image Registration for Head and Neck Adaptive Radiotherapy

Deformable image registration provides a robust mathematical framework to quantify morphological changes that occur along the course of external beam radiotherapy treatments. As clinical reliability of deformable image registration is not always guaranteed, algorithm regularization is commonly introduced to prevent sharp discontinuities in the quantified deformation and achieve anatomically consistent results. In this work we analyzed the influence of regularization on two different registration methods, i.e. B-Splines and Log Domain Diffeomorphic Demons, implemented in an open-source platform. We retrospectively analyzed the simulation computed tomography (CTsim) and the corresponding re-planning computed tomography (CTrepl) scans in 30 head and neck cancer patients. First, we investigated the influence of regularization levels on hounsfield units (HU) information in 10 test patients for each considered method. Then, we compared the registration results of the open-source implementation at selected best performing regularization levels with a clinical commercial software on the remaining 20 patients in terms of mean volume overlap, surface and center of mass distances between manual outlines and propagated structures. The regularized B-Splines method was not statistically different from the commercial software. The tuning of the regularization parameters allowed open-source algorithms to achieve better results in deformable image registration for head and neck patients, with the additional benefit of a framework where regularization can be tuned on a patient specific basis

Scale invariant feature transform in adaptive radiation therapy: a tool for deformable image registration assessment and re-planning indication

Adaptive radiation therapy (ART) aims at compensating for anatomic and pathological changes to improve delivery along a treatment fraction sequence. Current ART protocols require time-consuming manual updating of all volumes of interest on the images acquired during treatment. Deformable image registration (DIR) and contour propagation stand as a state of the ART method to automate the process, but the lack of DIR quality control methods hinder an introduction into clinical practice. We investigated the scale invariant feature transform (SIFT) method as a quantitative automated tool (1) for DIR evaluation and (2) for re-planning decision-making in the framework of ART treatments. As a preliminary test, SIFT invariance properties at shape-preserving and deformable transformations were studied on a computational phantom, granting residual matching errors below the voxel dimension. Then a clinical dataset composed of 19 head and neck ART patients was used to quantify the performance in ART treatments. For the goal (1) results demonstrated SIFT potential as an operator-independent DIR quality assessment metric. We measured DIR group systematic residual errors up to 0.66 mm against 1.35 mm provided by rigid registration. The group systematic errors of both bony and all other structures were also analyzed, attesting the presence of anatomical deformations. The correct automated identification of 18 patients who might benefit from ART out of the total 22 cases using SIFT demonstrated its capabilities toward goal (2) achievement

Modeling the interplay between tumor volume regression and oxygenation in uterine cervical cancer during radiotherapy treatment

This paper describes a patient-specific mathematical model to predict the evolution of uterine cervical tumors at a macroscopic scale, during fractionated external radiotherapy. The model provides estimates of tumor re-growth and dead-cell reabsorption, incorporating the interplay between tumor regression rate and radiosensitivity, as a function of the tumor oxygenation level. Model parameters were estimated by minimizing the difference between predicted and measured tumor volumes, these latter being obtained from a set of 154 serial cone-beam computed tomography (CBCT) scans acquired on 16 patients along the course of the therapy. The model stratified patients according to two different estimated dynamics of dead-cell removal and to the predicted initial value of the tumor oxygenation. The comparison with a simpler model demonstrated an improvement in fitting properties of this approach (fitting error average value <5%, p<0.01), especially in case of tumor late responses, which can hardly be handled by models entailing a constant radiosensitivity, failing to model changes from initial severe hypoxia to aerobic conditions during the treatment course. The model predictive capabilities suggest the need of clustering patients accounting for cancer cell-line, tumor staging, as well as microenvironment conditions (e.g. oxygenation level)

Kinetic Models for Predicting Cervical Cancer Response to Radiation Therapy on Individual Basis Using Tumor Regression Measured In Vivo With Volumetric Imaging

This article describes a macroscopic mathematical modeling approach to capture the interplay between solid tumor evolution and cell damage during radiotherapy. Volume regression profiles of 15 patients with uterine cervical cancer were reconstructed from serial cone-beam computed tomography data sets, acquired for image-guided radiotherapy, and used for model parameter learning by means of a genetic-based optimization. Patients, diagnosed with either squamous cell carcinoma or adenocarcinoma, underwent different treatment modalities (image-guided radiotherapy and image-guided chemo-radiotherapy). The mean volume at the beginning of radiotherapy and the end of radiotherapy was on average 23.7 cm(3) (range: 12.7-44.4 cm(3)) and 8.6 cm(3) (range: 3.6-17.1 cm(3)), respectively. Two different tumor dynamics were taken into account in the model: the viable (active) and the necrotic cancer cells. However, according to the results of a preliminary volume regression analysis, we assumed a short dead cell resolving time and the model was simplified to the active tumor volume. Model learning was performed both on the complete patient cohort (cohort-based model learning) and on each single patient (patient-specific model learning). The fitting results (mean error: ∼16% and ∼6% for the cohort-based model and patient-specific model, respectively) highlighted the model ability to quantitatively reproduce tumor regression. Volume prediction errors of about 18% on average were obtained using cohort-based model computed on all but 1 patient at a time (leave-one-out technique). Finally, a sensitivity analysis was performed and the data uncertainty effects evaluated by simulating an average volume perturbation of about 1.5 cm(3) obtaining an error increase within 0.2%. In conclusion, we showed that simple time-continuous models can represent tumor regression curves both on a patient cohort and patient-specific basis; this discloses the opportunity in future to exploit such models to predict how changes in the treatment schedule (number of fractions, doses, intervals among fractions) might affect the tumor regression on an individual basis

Multi atlas based segmentation: Should we prefer the best atlas group over the group of best atlases?

Multi atlas based segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases. Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split into two groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle selection, where atlases are chosen by the highest dice similarity coefficient (DSC) with the target, was performed. This was compared to oracle group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, convolutional neural networks were designed to predict the best group of atlases. The results were also compared with the selection strategy based on normalized mutual information (NMI). Oracle group was proven to be significantly better than classic oracle selection (p < 10−5). Atlas group selection led to a median ± interquartile DSC of 0.740 ± 0.084, 0.718 ± 0.086 and 0.670 ± 0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676 ± 0.113, 0.632 ± 0.104 and 0.606 ± 0.118 (p < 0.001) as well as classic oracle selection. The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS