The survival of patients with locally advanced cervix cancer and intermediate risk prostate cancer is compromised by suboptimal local/regional control. We hypothesize that by integrating brachytherapy primary tumor treatment with highly conformal IMRT that accurately delivers dose-per-fraction escalation to regions of known primary and metastatic nodal disease not adequately treated by brachytherapy will allow overall treatment time to be reduced and biologically effective dose to be increased beyond levels considered safe with current technology. To achieve these goals we will collaborate with Projects 1 and 2 to apply and clinically validate deformable image registration tools for accurately transferring information from biological imaging studies to planning x-ray computed tomography (CT) images (voxel labeling), mapping brachytherapy dose distributions onto IMRT planning images, and constructing 4-dimensional models (4D voxel trajectories) of patient anatomy based upon serial CT imaging. We will investigate a family of image-guided adaptive radiation therapy (IGART) based upon 4D voxel trajectories, probabilistic treatment planning, and off- and on-line plan adaptations to compensate for changes in patient anatomy.
The aim of IGART is to minimize geometric delivery uncertainties arising from setup error and internal tissue motion so that dose-per-fraction escalation can be administered to the target tissue with minimum margins and maximum normal tissue avoidance.
In Specific Aim 1. we will perform clinical studies in the two patient populations and implement and validate tools for quantifying 3D tissue deformation uncertainties and investigate methods for minimizing systematic errors arising from voxel labeling and brachytherapy dose mapping.
Specific Aim 2 will develop approaches for constructing 4D voxel trajectories from serial CT images and assess their uncertainties. Optimal methods for estimating the patient's 4D anatomy configuration prior to each day's treatment will be investigated.
Specific Aim 3 will perform simulated virtual clinical trials to identify and optimize the most appropriate form of IGART for maximizing clinical benefit relative to costs.
In Specific Aim 4. a prototype of the IGART process selected for clinical implementation will be developed. Clinical studies will be performed to confirm IGART feasibility and dose targeting accuracy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA116602-05
Application #
8256663
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2011
Total Cost
$286,022
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Shieh, Chun-Chien; Caillet, Vincent; Dunbar, Michelle et al. (2017) A Bayesian approach for three-dimensional markerless tumor tracking using kV imaging during lung radiotherapy. Phys Med Biol 62:3065-3080
Hugo, Geoffrey D; Weiss, Elisabeth; Sleeman, William C et al. (2017) A longitudinal four-dimensional computed tomography and cone beam computed tomography dataset for image-guided radiation therapy research in lung cancer. Med Phys 44:762-771
Shieh, Chun-Chien; Keall, Paul J; Kuncic, Zdenka et al. (2015) Markerless tumor tracking using short kilovoltage imaging arcs for lung image-guided radiotherapy. Phys Med Biol 60:9437-54
Jan, Nuzhat; Hugo, Geoffrey D; Mukhopadhyay, Nitai et al. (2015) Respiratory motion variability of primary tumors and lymph nodes during radiotherapy of locally advanced non-small-cell lung cancers. Radiat Oncol 10:133
Shieh, Chun-Chien; Kipritidis, John; O'Brien, Ricky T et al. (2015) Improving thoracic four-dimensional cone-beam CT reconstruction with anatomical-adaptive image regularization (AAIR). Phys Med Biol 60:841-68
Kipritidis, John; Hugo, Geoffrey; Weiss, Elisabeth et al. (2015) Measuring interfraction and intrafraction lung function changes during radiation therapy using four-dimensional cone beam CT ventilation imaging. Med Phys 42:1255-67
Xu, Huijun; Gordon, J James; Siebers, Jeffrey V (2015) Coverage-based treatment planning to accommodate delineation uncertainties in prostate cancer treatment. Med Phys 42:5435-43
Watkins, W Tyler; Moore, Joseph A; Gordon, James et al. (2014) Multiple anatomy optimization of accumulated dose. Med Phys 41:111705
Xu, Huijun; Vile, Douglas J; Sharma, Manju et al. (2014) Coverage-based treatment planning to accommodate deformable organ variations in prostate cancer treatment. Med Phys 41:101705
Shieh, Chun-Chien; Kipritidis, John; O'Brien, Ricky T et al. (2014) Image quality in thoracic 4D cone-beam CT: a sensitivity analysis of respiratory signal, binning method, reconstruction algorithm, and projection angular spacing. Med Phys 41:041912

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