Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

Background: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR).

Statistical breathing curve sampling to quantify interplay effects of moving lung tumors in a 4D Monte Carlo dose calculation framework.

Purpose: The interplay between respiratory tumor motion and dose application by intensity modulated radiotherapy (IMRT) techniques can potentially lead to undesirable and non-intuitive deviations from the planned dose distribution. We developed a 4D Monte Carlo (MC) dose recalculation framework featuring statistical breathing curve sampling, to precisely simulate the dose distribution for moving target volumes aiming at a comprehensive assessment of interplay effects.

Methods: We implemented a dose accumulation tool that enables dose recalculations of arbitrary breathing curves including the actual breathing curve of the patient.

A deep image-to-image network organ segmentation algorithm for radiation treatment planning: principles and evaluation.

Background: We describe and evaluate a deep network algorithm which automatically contours organs at risk in the thorax and pelvis on computed tomography (CT) images for radiation treatment planning.

Methods: The algorithm identifies the region of interest (ROI) automatically by detecting anatomical landmarks around the specific organs using a deep reinforcement learning technique. The segmentation is restricted to this ROI and performed by a deep image-to-image network (DI2IN) based on a convolutional encoder-decoder architecture combined with multi-level feature concatenation.

Dosimetric Impact of the Positional Imaging Frequency for Hypofractionated Prostate Radiotherapy - A Voxel-by-Voxel Analysis.

Background: To investigate deviations between planned and applied treatment doses for hypofractionated prostate radiotherapy and to quantify dosimetric accuracy in dependence of the image guidance frequency.

Methods: Daily diagnostic in-room CTs were carried out in 10 patients in treatment position as image guidance for hypofractionated prostate radiotherapy. Fraction doses were mapped to the planning CTs and recalculated, and applied doses were accumulated voxel-wise using deformable registration.

Real-time 4DMRI-based internal target volume definition for moving lung tumors.

Purpose: In photon radiotherapy, respiratory-induced target motion can be accounted for by internal target volumes (ITV) or mid-ventilation target volumes (midV) defined on the basis of four-dimensional computed tomography (4D-CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient-specific ITV definition method based on real-time 4D magnetic resonance imaging (rt-4DMRI).

Towards optimal stopping in radiation therapy.

A typical fractionated radiotherapy (RT) course is a long and arduous process, demanding significant financial, physical, and mental commitments from patients. Each additional session of RT significantly increases the physical and psychological burden on patients and leads to higher radiation exposure in organs-at-risk (OAR), while, in some cases, the therapeutic benefits might not be high enough to justify the risks. Today, through technological advancements in molecular biology, imaging, and genetics more information is gathered about individual patient response before, during, and after the treatment.

Feasibility of 4DCBCT-based proton dose calculation: An ex vivo porcine lung phantom study.

Inter-fractional variations of breathing pattern and patient anatomy introduce dose uncertainties in proton therapy. One approach to monitor these variations is to utilize the cone-beam computed tomography (CT, CBCT) scans routinely taken for patient positioning, reconstruct them as 4DCBCTs, and generate 'virtual CTs' (vCTs), combining the accurate CT numbers of the diagnostic 4DCT and the geometry of the daily 4DCBCT by using deformable image registration (DIR). In this study different algorithms for 4DCBCT reconstruction and DIR were evaluated.

Dose-guided patient positioning in proton radiotherapy using multicriteria-optimization.

Proton radiotherapy (PT) requires accurate target alignment before each treatment fraction, ideally utilizing 3D in-room X-ray computed tomography (CT) imaging. Typically, the optimal patient position is determined based on anatomical landmarks or implanted markers. In the presence of non-rigid anatomical changes, however, the planning scenario cannot be exactly reproduced and positioning should rather aim at finding the optimal position in terms of the actually applied dose.

Multi-criterial patient positioning based on dose recalculation on scatter-corrected CBCT images.

Background And Purpose: Our aim was to evaluate the feasibility and potential advantages of dose guided patient positioning based on dose recalculation on scatter corrected cone beam computed tomography (CBCT) image data.

Material And Methods: A scatter correction approach has been employed to enable dose calculations on CBCT images. A recently proposed tool for interactive multicriterial dose-guided patient positioning which uses interpolation between pre-calculated sample doses has been utilized.

Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy.

The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF).

A novel method for interactive multi-objective dose-guided patient positioning.

In intensity-modulated radiation therapy (IMRT), 3D in-room imaging data is typically utilized for accurate patient alignment on the basis of anatomical landmarks. In the presence of non-rigid anatomical changes, it is often not obvious which patient position is most suitable. Thus, dose-guided patient alignment is an interesting approach to use available in-room imaging data for up-to-date dose calculation, aimed at finding the position that yields the optimal dose distribution.

Investigating deformable image registration and scatter correction for CBCT-based dose calculation in adaptive IMPT.

Purpose: This work aims at investigating intensity corrected cone-beam x-ray computed tomography (CBCT) images for accurate dose calculation in adaptive intensity modulated proton therapy (IMPT) for prostate and head and neck (H&N) cancer. A deformable image registration (DIR)-based method and a scatter correction approach using the image data obtained from DIR as prior are characterized and compared on the basis of the same clinical patient cohort for the first time.

Methods: Planning CT (pCT) and daily CBCT data (reconstructed images and measured projections) of four H&N and four prostate cancer patients have been considered in this study.

Feasibility of automated proton therapy plan adaptation for head and neck tumors using cone beam CT images.

Background: Intensity modulated proton therapy (IMPT) of head and neck (H&N) tumors may benefit from plan adaptation to correct for the dose perturbations caused by weight loss and tumor volume changes observed in these patients. As cone beam CT (CBCT) is increasingly considered in proton therapy, it may be possible to use available CBCT images following intensity correction for plan adaptation. This is the first study exploring IMPT plan adaptation on CBCT images corrected and delineated by deformable image registration of the planning CT (pCT) to the CBCT, yielding a virtual CT (vCT).

Comparison of proton therapy treatment planning for head tumors with a pencil beam algorithm on dual and single energy CT images.

Purpose: Dual energy CT (DECT) has recently been proposed as an improvement over single energy CT (SECT) for stopping power ratio (SPR) estimation for proton therapy treatment planning (TP), thereby potentially reducing range uncertainties. Published literature investigated phantoms. This study aims at performing proton therapy TP on SECT and DECT head images of the same patients and at evaluating whether the reported improved DECT SPR accuracy translates into clinically relevant range shifts in clinical head treatment scenarios.

Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy.

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).

Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy.

Comparing cone-beam CT intensity correction methods for dose recalculation in adaptive intensity-modulated photon and proton therapy for head and neck cancer.

Background: Adaptive intensity-modulated photon and proton radiotherapy (IMRT and IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose calculation. We compared two approaches for dose recalculation on the basis of intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images.

Material And Methods: For nine H&N tumor patients, virtual CTs (vCT) were generated by deformable image registration of the planning CT (pCT) to the CBCT.

Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach.

Investigating CT to CBCT image registration for head and neck proton therapy as a tool for daily dose recalculation.

Purpose: Intensity modulated proton therapy (IMPT) of head and neck (H&N) cancer patients may be improved by plan adaptation. The decision to adapt the treatment plan based on a dose recalculation on the current anatomy requires a diagnostic quality computed tomography (CT) scan of the patient. As gantry-mounted cone beam CT (CBCT) scanners are currently being offered by vendors, they may offer daily or weekly updates of patient anatomy.

In vivo measurement of dose distribution in patients' lymphocytes: helical tomotherapy versus step-and-shoot IMRT in prostate cancer.

In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate.

Software for quantitative analysis of radiotherapy: overview, requirement analysis and design solutions.

Radiotherapy is a fast-developing discipline which plays a major role in cancer care. Quantitative analysis of radiotherapy data can improve the success of the treatment and support the prediction of outcome. In this paper, we first identify functional, conceptional and general requirements on a software system for quantitative analysis of radiotherapy.

The critical spot eraser-a method to interactively control the correction of local hot and cold spots in IMRT planning.

Common problems in inverse radiotherapy planning are localized dose insufficiencies like hot spots in organs at risk or cold spots inside targets. These are hard to correct since the optimization is based on global evaluations like maximum/minimum doses, equivalent uniform doses or dose-volume constraints for whole structures. In this work, we present a new approach to locally correct the dose of any given treatment plan.

A method to visualize the uncertainty of the prediction of radiobiological models.

A method for quantitative visualization of the uncertainty in the predicted tumor control probability (TCP) and normal tissue complication probability (NTCP) in radiotherapy has been developed. Uncertainties of TCP and NTCP due to inter-individual variation of the underlying radiosensitivity parameters was simulated by sampling the prescribed dose from a uniform distribution and the radiosensitivity-parameters from a Gaussian distribution. The result is visualized as a scatter-plot superimposed to the population-based dose response curves using the prescribed dose as the common dosimetric variable.

Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial.

Background: Radiotherapy, preferably combined with chemotherapy, is the treatment standard for locally advanced, unresectable non-small cell lung cancer (NSCLC). The tumor response to different therapy protocols is variable, with hypoxia known to be a major factor that negatively influences treatment effectiveness. Visualisation of tumor hypoxia prior to the use of modern radiation therapy strategies, such as intensity modulated radiation therapy (IMRT), might allow optimized dose applications to the target volume, leading to improvement of therapy outcome.