Radiotherapy (RT) is an integral component in the management of early stage breast cancer following breast conservation and following mastectomy in high-risk patients. Previous reports have clearly documented, however, the potential for cardiac and pulmonary toxicity secondary to radiation injury, particularly in patients treated comprehensively to the regional nodes. Intensity modulated radiotherapy (IMRT) is a new treatment delivery technique that uses a variable intensity pattern determined with the aid of a computerized optimization algorithm. Preliminary results with IMRT in treatment of the breast only are promising with respect to improved target coverage and sparing of normal tissue. No studies to date, however, have prospectively compared the use of IMRT with the best standard three-dimensional (3-D) planning technique, with respect to cardiac and pulmonary exposure, in patients comprehensively treated to the breast/chest wall and regional nodes. Therefore, the long-term objective of the proposed research plan is to study comprehensive RT delivered using IMRT versus the best 3-D standard treatment technique (Partially Wide Tangential Fields (PWTF)). Quantitative indicators of potential cardiac and lung toxicity will be compared to determine the improvements that may be achieved with the new approach.
Specific Aims : (1) Determine a static IMRT plan that significantly spares the heart and lung compared to the best static standard 3-D plan PWTF; (2) Evaluate the effect of delivery-related issues, such as respiratory motion and setup uncertainty, on static PWTF and IMRT plans from Aim 1, and produce plans that compensate for motion. Determine the optimal motion corrected plan between delivery-optimized PWTF and delivery-optimized IMRT. (3) Compare the best delivery-optimized technique from Aim 2 with the best standard 3-D technique, PWTF, in a prospective trial. With the pilot data generated through this proposal, a randomized trial will ultimately be performed comparing these two treatment delivery techniques. Study Design: (1) Establish cost functions that drive the optimization to develop the IMRT plan using heart, lung, opposite breast, and spinal cord constraints while maximizing target coverage to the breast/chest wall and nodes. Optimize the best IMRT plan for 20 static cases and compare the static IMRT plan with PWTF using heart and lung metrics. (2) Measure the distribution of setup errors and motion of target volumes in a cohort of 20 patients. Determine the effect of motion on static IMRT and PWTF dose distributions, and then correct/adjust for motion to determine the best delivery-optimized plan. (3) Study 60 patients treated with either the best delivery-optimized motion corrected plan from Aim 2 or PWTF and compare plans using heart and lung metrics.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA102435-01
Application #
6677069
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Stone, Helen B
Project Start
2004-09-01
Project End
2007-06-30
Budget Start
2004-09-01
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$304,990
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Liss, Adam L; Marsh, Robin B; Kapadia, Nirav S et al. (2017) Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial. Int J Radiat Oncol Biol Phys 97:296-302
Chung, Eugene; Corbett, James R; Moran, Jean M et al. (2013) Is there a dose-response relationship for heart disease with low-dose radiation therapy? Int J Radiat Oncol Biol Phys 85:959-64
Feng, Mary; Moran, Jean M; Koelling, Todd et al. (2011) Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer. Int J Radiat Oncol Biol Phys 79:10-8
Jagsi, Reshma; Moran, Jean; Marsh, Robin et al. (2010) Evaluation of four techniques using intensity-modulated radiation therapy for comprehensive locoregional irradiation of breast cancer. Int J Radiat Oncol Biol Phys 78:1594-603
Lin, Alexander; Moran, Jean M; Marsh, Robin B et al. (2008) Evaluation of multiple breathing states using a multiple instance geometry approximation (MIGA) in inverse-planned optimization for locoregional breast treatment. Int J Radiat Oncol Biol Phys 72:610-6
Jagsi, Reshma; Moran, Jean M; Kessler, Marc L et al. (2007) Respiratory motion of the heart and positional reproducibility under active breathing control. Int J Radiat Oncol Biol Phys 68:253-8