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.

National Institute of Health (NIH)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Deye, James
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Covington, E L; Ritter, T A; Moran, J M et al. (2016) Technical Report: Evaluation of peripheral dose for flattening filter free photon beams. Med Phys 43:4789
Wahl, Daniel R; Tao, Yebin; Schipper, Matthew et al. (2016) Reply to Yang et al and De Bari et al. J Clin Oncol 34:2799
Kim, Jihun; Saitou, Kazuhiro; Matuszak, Martha M et al. (2016) A finite element head and neck model as a supportive tool for deformable image registration. Int J Comput Assist Radiol Surg 11:1311-7
Wang, Hesheng; Feng, Mary; Jackson, Andrew et al. (2016) Local and Global Function Model of the Liver. Int J Radiat Oncol Biol Phys 94:181-8
Wu, Victor W; Epelman, Marina A; Wang, Hesheng et al. (2016) Optimizing global liver function in radiation therapy treatment planning. Phys Med Biol 61:6465-84
Shilkrut, Mark; Sapir, Eli; Hanasoge, Sheela et al. (2016) Phase I Trial of Dose-escalated Whole Liver Irradiation With Hepatic Arterial Fluorodeoxyuridine/Leucovorin and Streptozotocin Followed by Fluorodeoxyuridine/Leucovorin and Chemoembolization for Patients With Neuroendocrine Hepatic Metastases. Am J Clin Oncol :
Cazoulat, Guillaume; Owen, Dawn; Matuszak, Martha M et al. (2016) Biomechanical deformable image registration of longitudinal lung CT images using vessel information. Phys Med Biol 61:4826-39
Wahl, Daniel R; Stenmark, Matthew H; Tao, Yebin et al. (2016) Outcomes After Stereotactic Body Radiotherapy or Radiofrequency Ablation for Hepatocellular Carcinoma. J Clin Oncol 34:452-9
Hadley, Scott W; Kessler, Marc L; Litzenberg, Dale W et al. (2016) SafetyNet: Streamlining and Automating QA in radiotherapy. J Appl Clin Med Phys 17:5920
Samuels, Stuart E; Tao, Yebin; Lyden, Teresa et al. (2016) Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation. Oral Oncol 54:68-74

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