BackgroundAlthough radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and theoretical advantages of avoiding functional lung during radiotherapy, to our knowledge this premise has never been tested via a prospective randomized clinical trial.Methods/DesignEligible patients will have Stage III NSCLC with intent to receive concurrent chemoradiotherapy (CRT). Every patient will undergo a pre-treatment functional lung imaging study using hyperpolarized 3He MRI in order to identify the spatial distribution of normally-ventilated lung. Before randomization, two clinically-approved radiotherapy plans will be devised for all patients on trial, termed standard and avoidance. The standard plan will be designed without reference to the functional state of the lung, while the avoidance plan will be optimized such that dose to functional lung is as low as reasonably achievable. Patients will then be randomized in a 1:1 ratio to receive either the standard or the avoidance plan, with both the physician and the patient blinded to the randomization results. This study aims to accrue a total of 64 patients within two years. The primary endpoint will be a pulmonary quality of life (QOL) assessment at 3 months post-treatment, measured using the functional assessment of cancer therapy–lung cancer subscale. Secondary endpoints include: pulmonary QOL at other time-points, provider-reported toxicity, overall survival, progression-free survival, and quality-adjusted survival.DiscussionThis randomized, double-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity and quality of life in patients receiving concurrent CRT for locally advanced NSCLC.Trial registrationClinicaltrials.gov identifier: NCT02002052.

SPECT-based DFH parameters appear to be useful as predictors of RP.

PurposeIn this work, we propose a new method of calibrating cone beam computed tomography (CBCT) data sets for radiotherapy dose calculation and plan assessment. The motivation for this patient‐specific calibration (PSC) method is to develop an efficient, robust, and accurate CBCT calibration process that is less susceptible to deformable image registration (DIR) errors.MethodsInstead of mapping the CT numbers voxel‐by‐voxel with traditional DIR calibration methods, the PSC methods generates correlation plots between deformably registered planning CT and CBCT voxel values, for each image slice. A linear calibration curve specific to each slice is then obtained by least‐squares fitting, and applied to the CBCT slice's voxel values. This allows each CBCT slice to be corrected using DIR without altering the patient geometry through regional DIR errors.A retrospective study was performed on 15 head‐and‐neck cancer patients, each having routine CBCTs and a middle‐of‐treatment re‐planning CT (reCT). The original treatment plan was re‐calculated on the patient's reCT image set (serving as the gold standard) as well as the image sets produced by voxel‐to‐voxel DIR, density‐overriding, and the new PSC calibration methods. Dose accuracy of each calibration method was compared to the reference reCT data set using common dose‐volume metrics and 3D gamma analysis. A phantom study was also performed to assess the accuracy of the DIR and PSC CBCT calibration methods compared with planning CT.ResultsCompared with the gold standard using reCT, the average dose metric differences were ≤ 1.1% for all three methods (PSC: −0.3%; DIR: −0.7%; density‐override: −1.1%). The average gamma pass rates with thresholds 3%, 3 mm were also similar among the three techniques (PSC: 95.0%; DIR: 96.1%; density‐override: 94.4%).ConclusionsAn automated patient‐specific calibration method was developed which yielded strong dosimetric agreement with the results obtained using a re‐planning CT for head‐and‐neck patients.

Purpose Application of low intensity electric fields to interfere with tumor growth is being increasingly recognized as a promising new cancer treatment modality. Intratumoral modulation therapy (IMT) is a developing technology that uses multiple electrodes implanted within or adjacent tumor regions to deliver electric fields to treat cancer. In this study, the determination of optimal IMT parameters was cast as a mathematical optimization problem, and electrode configurations, programming, optimization, and maximum treatable tumor size were evaluated in the simplest and easiest to understand spherical tumor model. The establishment of electrode placement and programming rules to maximize electric field tumor coverage designed specifically for IMT is the first step in developing an effective IMT treatment planning system. Methods Finite element method electric field computer simulations for tumor models with 2 to 7 implanted electrodes were performed to quantify the electric field over time with various parameters, including number of electrodes (2 to 7), number of contacts per electrode (1 to 3), location within tumor volume, and input waveform with relative phase shift between 0 and 2π radians. Homogeneous tissue specific conductivity and dielectric values were assigned to the spherical tumor and surrounding tissue volume. In order to achieve the goal of covering the tumor volume with a uniform threshold of 1 V/cm electric field, a custom least square objective function was used to maximize the tumor volume covered by 1 V/cm time averaged field, while maximizing the electric field in voxels receiving less than this threshold. An additional term in the objective function was investigated with a weighted tissue sparing term, to minimize the field to surrounding tissues. The positions of the electrodes were also optimized to maximize target coverage with the fewest number of electrodes. The complexity of this optimization problem including its non‐convexity, the presence of many local minima, and the computational load associated with these stochastic based optimizations led to the use of a custom pattern search algorithm. Optimization parameters were bounded between 0 and 2π radians for phase shift, and anywhere within the tumor volume for location. The robustness of the pattern search method was then evaluated with 50 random initial parameter values. Results The optimization algorithm was successfully implemented, and for 2 to 4 electrodes, equally spaced relative phase shifts and electrodes placed equidistant from each other was optimal. For 5 electrodes, up to 2.5 cm diameter tumors with 2.0 V, and 4.1 cm with 4.0 V could be treated with the optimal configuration of a centrally placed electrode and 4 surrounding electrodes. The use of 7 electrodes allow for 3.4 cm diameter coverage at 2.0 V and 5.5 cm at 4.0 V. The evaluation of the optimization method using 50 random initial parameter values found the method to be robust in finding the optimal solution. Conclusions This study has established a robust optimiza...

Previous work has indicated HDR-BT needles may be manually segmented using SR3D images with insertion depth errors ≤3 mm and ≤5 mm for 83% and 92% of needles, respectively. The algorithm shows promise for reducing the time required for the segmentation of straight HDR-BT needles, and future work involves improving needle tip localization performance through improved image quality and modeling curvilinear trajectories.

Purpose The goal of this work was to develop and evaluate a fast inverse direct aperture optimization (FIDAO) algorithm for IMRT treatment planning and plan adaptation. Methods A previously proposed fluence map optimization algorithm called fast inverse dose optimization (FIDO) was extended to optimize the aperture shapes and weights of IMRT beams. FIDO is a very fast fluence map optimization algorithm for IMRT that finds the global minimum using direct matrix inversion without unphysical negative beam weights. In this study, an equivalent second‐order Taylor series expansion of the FIDO objective function was used, which allowed for the objective function value and gradient vector to be computed very efficiently during direct aperture optimization, resulting in faster optimization. To evaluate the speed gained with FIDAO, a proof‐of‐concept algorithm was developed in MATLAB using an interior‐point optimization method to solve the reformulated aperture‐based FIDO problem. The FIDAO algorithm was used to optimize four step‐and‐shoot IMRT cases: on the AAPM TG‐119 phantom as well as a liver, prostate, and head‐and‐neck clinical cases. Results were compared with a conventional DAO algorithm that uses the same interior‐point method but using the standard formulation of the objective function and its gradient vector. Results A substantial gain in optimization speed was obtained with the prototype FIDAO algorithm compared to the conventional DAO algorithm while producing plans of similar quality. The optimization time (number of iterations) for the prototype FIDAO algorithm vs the conventional DAO algorithm was 0.3 s (17) vs 56.7 s (50); 2.0 s (28) vs 134.1 s (57); 2.5 s (26) vs 180.6 s (107); and 6.7 s (20) vs 469.4 s (482) in the TG‐119 phantom, liver, prostate, and head‐and‐neck examples, respectively. Conclusions A new direct aperture optimization algorithm based on FIDO was developed. For the four IMRT test cases examined, this algorithm executed approximately 70–200 times faster without compromising the IMRT plan quality.

IMPORTANCE Palliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear. OBJECTIVE To examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT. DESIGN, SETTING, AND PARTICIPANTS Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between

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