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Integ Cancer Therapy

Junfeng Zhu, Hamidreza Badri, Kevin Leder
The design of optimal protocols plays an important role in cancer treatment. However, in clinical applications, the outcomes under the optimal protocols are sensitive to variations of parameter settings such as drug effects and the attributes of age, weight, and health conditions in human subjects. One approach to overcoming this challenge is to formulate the problem of finding an optimal treatment protocol as a robust optimization problem (ROP) that takes parameter uncertainty into account. In this chapter, we describe a method to model toxicity uncertainty...
2018: Methods in Molecular Biology
Zhiwei Ji, Bing Wang, Ke Yan, Ligang Dong, Guanmin Meng, Lei Shi
BACKGROUND: In recent years, the integration of 'omics' technologies, high performance computation, and mathematical modeling of biological processes marks that the systems biology has started to fundamentally impact the way of approaching drug discovery. The LINCS public data warehouse provides detailed information about cell responses with various genetic and environmental stressors. It can be greatly helpful in developing new drugs and therapeutics, as well as improving the situations of lacking effective drugs, drug resistance and relapse in cancer therapies, etc...
December 21, 2017: BMC Systems Biology
Mehdi Mahnam, Michel Gendreau, Nadia Lahrichi, Louis-Martin Rousseau
In this paper, we propose a novel heuristic algorithm for the volumetric modulated arc therapy (VMAT) treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture conguration is modeled in the columns and the dose distribution and time restriction in the rows...
May 19, 2017: Physics in Medicine and Biology
Ching-Chih Lee, Chien-Yu Huang, Yaoh-Shinag Lin, Kuo-Ping Chang, Chao-Chuan Chi, Ming-Yee Lin, Hsing-Hao Su, Ting-Shou Chang, Hung-Chih Chen, Ching-Chieh Yang
Importance: Inflammatory status is associated with outcome in oral squamous cell carcinoma (OSCC). Combining the preoperative neutrophil to lymphocyte ratio (NLR) and histopathologic features may provide clinicians with more exact information regarding the prognosis of OSCC. Objective: To compare the prognostic performance of the routinely used pathologic TNM staging with a new staging category that incorporates the NLR and histopathologic features. Design, Setting, and Participants: This retrospective cohort study included 396 patients with newly diagnosed OSCC who underwent major surgery at a medical center from January 1, 2006, through December 31, 2013...
April 1, 2017: JAMA Otolaryngology—Head & Neck Surgery
T Chiu, T Long, A Modiri, Z Tian, A Sawant, Y Yan, S Jiang, X Gu
PURPOSE: To develop an efficient and effective trajectory optimization methodology for 4π dynamic conformal arc treatment (4π DCAT) with synchronized gantry and couch motion; and to investigate potential clinical benefits for stereotactic body radiation therapy (SBRT) to breast, lung, liver and spine tumors. METHODS: The entire optimization framework for 4π DCAT inverse planning consists of two parts: 1) integer programming algorithm and 2) particle swarm optimization (PSO) algorithm...
June 2016: Medical Physics
E Lee, F Yuan, A Templeton, R Yao, J Chu
PURPOSE: The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation...
June 2016: Medical Physics
Yu An, Jianming Liang, Steven E Schild, Martin Bues, Wei Liu
BACKGROUND AND PURPOSE: Intensity-modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. We applied a probabilistic framework (chance-constrained optimization) in IMPT planning to hedge against the influence of uncertainties. MATERIAL AND METHODS: We retrospectively selected one patient with lung cancer, one patient with head and neck (H&N) cancer, and one with prostate cancer for this analysis...
January 2017: Medical Physics
Y An, J Liang, W Liu
PURPOSE: We propose to apply a probabilistic framework, namely chanceconstrained optimization, in the intensity-modulated proton therapy (IMPT) planning subject to range and patient setup uncertainties. The purpose is to hedge against the influence of uncertainties and improve robustness of treatment plans. METHODS: IMPT plans were generated for a typical prostate patient. Nine dose distributions are computed - the nominal one and one each for ±5mm setup uncertainties along three cardinal axes and for ±3...
June 2015: Medical Physics
Wenhua Cao, Gino Lim, Li Liao, Yupeng Li, Shengpeng Jiang, Xiaoqiang Li, Heng Li, Kazumichi Suzuki, X Ronald Zhu, Daniel Gomez, Xiaodong Zhang
Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To 'scan' the target volume, the proton beam is controlled by varying its energy to penetrate the patient's body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20 m s(-1), changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment...
November 7, 2014: Physics in Medicine and Biology
Pablo Santibáñez, Marc Gaudet, John French, Emma Liu, Scott Tyldesley
PURPOSE: To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. METHODS AND MATERIALS: Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center...
July 15, 2014: International Journal of Radiation Oncology, Biology, Physics
Hamed Yarmand, Brian Winey, David Craft
Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as 'apertures'. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs...
September 7, 2013: Physics in Medicine and Biology
Daniel Stöckel, Oliver Müller, Tim Kehl, Andreas Gerasch, Christina Backes, Alexander Rurainski, Andreas Keller, Michael Kaufmann, Hans-Peter Lenhof
UNLABELLED: The deregulation of biochemical pathways plays a central role in many diseases like cancer or Parkinsons's disease. In silico tools for calculating these deregulated pathways may help to gain new insights into pathogenic mechanisms and may open novel avenues for therapy stratification in the sense of personalized medicine. Here, we present NetworkTrail, a web service for the detection of deregulated pathways and subgraphs in biological networks. NetworkTrail uses a state-of-the-art integer linear programming-based approach for this task and offers interfaces to the Biological Network Analyzer (BiNA) and Cytoscape Web for visualizing the resulting subnetworks...
July 1, 2013: Bioinformatics
Shaowu Tang, Jong-Hyeon Jeong
The median failure time is often utilized to summarize survival data because it has a more straightforward interpretation for investigators in practice than the popular hazard function. However, existing methods for comparing median failure times for censored survival data either require estimation of the probability density function or involve complicated formulas to calculate the variance of the estimates. In this article, we modify a K-sample median test for censored survival data (Brookmeyer and Crowley, 1982, Journal of the American Statistical Association 77, 433-440) through a simple contingency table approach where each cell counts the number of observations in each sample that are greater than the pooled median or vice versa...
September 2012: Biometrics
Sacha D Nandlall, Edward Jackson, Constantin-C Coussios
Thermal ablation by high-intensity focused ultrasound (HIFU) shows great promise as a noninvasive cancer therapy. This work proposes a novel method of real-time HIFU treatment monitoring that uses the passively monitored acoustic signal emanating from the focus during HIFU exposure. We performed 212 exposures in seven freshly excised ox livers using 1.067-MHz HIFU at a 95% duty cycle for a range of insonation durations and acoustic intensities. Acoustic emissions were recorded using a 15-MHz passive detector aligned confocally and coaxially with the HIFU transducer...
June 2011: Ultrasound in Medicine & Biology
Y Zinchenko, T Craig, H Keller, T Terlaky, M Sharpe
Radiation therapy is an important modality in treating various cancers. Various treatment planning and delivery technologies have emerged to support intensity modulated radiation therapy (IMRT), creating significant opportunities to advance this type of treatment. However, one of the fundamental questions in treatment planning and optimization, 'can we produce better treatment plans relying on the existing delivery technology?' still remains unanswered, in large part due to the underlying computational complexity of the problem, which, in turn, often stems from the optimization model being non-convex...
June 21, 2008: Physics in Medicine and Biology
Mala L Radhakrishnan, Bruce Tidor
Drug resistance is a significant obstacle in the effective treatment of diseases with rapidly mutating targets, such as AIDS, malaria, and certain forms of cancer. Such targets are remarkably efficient at exploring the space of functional mutants and at evolving to evade drug binding while still maintaining their biological role. To overcome this challenge, drug regimens must be active against potential target variants. Such a goal may be accomplished by one drug molecule that recognizes multiple variants or by a drug "cocktail"--a small collection of drug molecules that collectively binds all desired variants...
May 2008: Journal of Chemical Information and Modeling
Michael Stiglmayr, Raphael Schwarz, Kathrin Klamroth, Günter Leugering, Jörg Lohscheller
Oncologic therapy of laryngeal cancer may necessitate a total excision of the larynx which results in loss of voice. Voice rehabilitation can be achieved using mucosal tissue vibrations at the upper part of the esophagus which serves as substitute voice generating element (PE segment). The quality of the substitute voice is closely related to vibratory characteristics of the PE segment. By means of a high-speed camera the dynamics of the PE segment can be recorded in real-time. Using image processing the deformations of the PE segment are extracted from the image series as deforming contours...
June 2008: Medical Image Analysis
Greg Bednarz, Darek Michalski, Pramila R Anne, Richard K Valicenti
The results of optimization of inverse treatment plans depend on a choice of the objective function. Even when the optimal solution for a given cost function can be obtained, a better solution may exist for a given clinical scenario and it could be obtained with a revised objective function. In the approach presented in this work mixed integer programming was used to introduce a new volume-based objective function, which allowed for minimization of the number of under- or overdosed voxels in selected structures...
June 21, 2004: Physics in Medicine and Biology
Gunnar Steineck, Karin Bergmark, Lars Henningsohn, Massoud al-Abany, Paul W Dickman, Asgeir Helgason
In order to suggest therapy modifications with the aim of diminishing the risk of therapy-induced long-term distressful symptoms in cancer survivors, data are needed relating details of therapy to the long-term symptom situation. In this article, the concepts and means used to assess the latter while developing the Radiumhemmet scale for symptom assessment are described. The focus is on the subjective long-term situation, and symptoms as a perceived abnormality are defined. For conceptual clarity, one symptom at a time is considered, excluding scales in which items are summarized...
2002: Acta Oncologica
M Langer, R Brown, P Kijewski, C Ha
PURPOSE: An optimization algorithm improves the distribution of dose among discrete points in tissues, but tolerance depends on the distribution of dose across a continuous volume. This report asks whether an exact algorithm can be completed when enough points are taken to accurately model a dose-volume constraint. METHODS AND MATERIALS: Trials were performed using a 3-dimensional model of conformal therapy of lung cancer. Trials were repeated with different limits placed on the fraction of lung which could receive > 20 Gy...
June 15, 1993: International Journal of Radiation Oncology, Biology, Physics
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