Cancer treatments are now designed to uniformly treat the "average" patient. The "safe" dose is dictated by the most sensitive 5-15% of the patient population. However, this population-based approach is also accompanied by low expectations of tumor control. Similarly, radiation treatments have been designed to treat the tumor uniformly, although we know from biological and clinical studies that tumors have a heterogeneous response to treatment. We hypothesize that a treatment design that Integrates pretreatment patient factors with an adaptation strategy that uses the first part of treatment to assess tumor and normal tissue sensitivity will permit us to optimize therapy for the individual patient rather than giving a population-averaged treatment that is likely to be less effective. Thi proposal comprises 4 scientific Projects and 4 shared resource Cores within an integrated plan of action: Project 1 and 2 will focus on tumors within the liver and lung. These two sites were chosen for clinical demonstration as their current control rates are low and, as the volume of the harboring normal tissue organ irradiated is the critical factor in toxicity, they offer a great opportunity for adaptation. We will use physiological imaging and other methods to individualize dose redistribution in normal tissues to lower toxicity while also heterogeneously irradiating resistant tumor sub-volumes to improve outcome. Project 3 will establish the spatial and temporal precision of imaging-based methods for both tumor targeting and normal tissue response. Project 4 will develop, investigate, and improve decision support tools to take advantage of predictive models for adaptive therapy patient management. Core A provides administrative and statistical support, Core B will support the clinical therapy planning and delivery, Core C will provide analysis of all Imaging data and Core D will handle software design. We feel that we are developing a new paradigm for radiation therapy and recognize only a few other programs in the world with our ability to develop a system that combines biological assays of toxicity, imaging, planning, delivery, and clinical leadership to safely adapt therapy based on each individual's characteristics and response to therapy.

Public Health Relevance

Radiation therapy can cure patients with localized cancer, but a major limitation is that our treatments are based on the average patient. This program project will establish a framework for optimizing therapy based on the responses of individual patients. The methods developed and tested here will contribute to changing the paradigm within which cancer therapy is practiced, thus improving the efficacy and the safety of radiation therapy for al patients.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
2P01CA059827-16A1
Application #
8609639
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Deye, James
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Hunter, Klaudia U; Lee, Oliver E; Lyden, Teresa H et al. (2014) Aspiration pneumonia after chemo-intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors. Head Neck 36:120-5
Vainshtein, Jeffrey M; Spector, Matthew E; McHugh, Jonathan B et al. (2014) Refining risk stratification for locoregional failure after chemoradiotherapy in human papillomavirus-associated oropharyngeal cancer. Oral Oncol 50:513-9
Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H; Chenevert, Thomas et al. (2014) Response-driven imaging biomarkers for predicting radiation necrosis of the brain. Phys Med Biol 59:2535-47
Stenmark, Matthew H; Cao, Yue; Wang, Hesheng et al. (2014) Estimating functional liver reserve following hepatic irradiation: adaptive normal tissue response models. Radiother Oncol 111:418-23
Hunter, Klaudia U; Schipper, Matthew; Feng, Felix Y et al. (2013) Toxicities affecting quality of life after chemo-IMRT of oropharyngeal cancer: prospective study of patient-reported, observer-rated, and objective outcomes. Int J Radiat Oncol Biol Phys 85:935-40
Wilkie, Joel R; Matuszak, Martha M; Feng, Mary et al. (2013) Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises. Med Phys 40:071708
Vainshtein, Jeffrey; Eisbruch, Avraham (2013) Function, muscles, and sparing by IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 85:577-8
Cao, Yue; Wang, Hesheng; Johnson, Timothy D et al. (2013) Prediction of liver function by using magnetic resonance-based portal venous perfusion imaging. Int J Radiat Oncol Biol Phys 85:258-63
Hunter, Klaudia U; Fernandes, Laura L; Vineberg, Karen A et al. (2013) Parotid glands dose-effect relationships based on their actually delivered doses: implications for adaptive replanning in radiation therapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys 87:676-82
Farjam, Reza; Parmar, Hemant A; Noll, Douglas C et al. (2012) An approach for computer-aided detection of brain metastases in post-Gd T1-W MRI. Magn Reson Imaging 30:824-36

Showing the most recent 10 out of 200 publications