The long-term goal of this project is to increase non-small cell lung cancer (NSCLC) tumor control without increasing treatment toxicity by adapting therapy to the individual patient's response. This goal will be carried out through two specific aims.
Aim 1 is to conduct a pilot study to decrease toxicity by adapting therapy to the uninvolved lung and esophagus while continuing to adapt therapy to the tumor for patients with Stage II/III NSCLC cancer. We have recently completed a phase II study in which we targeted FDG avid regions midtreatment with a high dose of radiation and achieved a >20% improvement in local control over standard dose (60 Gy), although toxicity was greater. With maturing of response based predictive models for treatment toxicity, we propose a pilot study in which we will continue to adapt therapy midtreatment to intensify dose to the residual FDG avid tumor, and we will use: 1) V/Q SPECT-CT scanning to avoid functional lung;2) FDG-PET-CT to adapt the risk of esophageal injury;and 3) reduce dose in patients who are unusually sensitive to radiation (by measuring TGFbetal and IL-8). We hypothesize that by adapting radiation therapy to the uninvolved lung and esophagus, we can maintain the dose to the FDG-avid tumor while causing no greater overall toxicity than expected from standard therapy (60 Gy uniformly delivered to the tumor).
Aim 2 is to conduct a phase II randomized trial to compare standard therapy to therapy that adapts treatment to the individual patient's tumor and uninvolved tissue response.
This aim will use the methodology developed from aim 1 for the experimental arm that fully adapts treatment based on intensifying treatment to the FDG avid tumor while limiting the toxicity of uninvolved lung and esophagus to be no greater than that anticipated to be caused by standard therapy. This will be accomplished by 1) avoiding functioning lung at the start of treatment;2) by replanning midtreatment based on adapting to the response of the tumor and of the uninvolved lung and esophagus and 3) reducing dose to the most sensitive patients. This arm will be compared in a randomized phase II trial to a standard arm (60 Gy) (both arms with the same chemotherapy). We hypothesize that treating patients with adaptive radiation therapy based on the tumor and normal organ responses assessed during treatment will produce superior tumor control at no greater toxicity than the standard arm of 60 Gy uniformly delivered to the tumor. The impact o f t h i s work is that it will develop a new paradigm for radiation oncology in which treatment is optimized by adapting therapy to the individual patient response, rather than based on the """"""""average patient"""""""".

Public Health Relevance

We propose to improve the cure rate by adapting therapy to the individual patient by assessing midtreatment changes in the patient's tumor and normal tissues. These changes will reveal to us the individual patient's sensitivity to treatment so that we can give more radiation to the aggressive regions of the tumor while avoiding normal functioning lung and sensitive esophagus.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (O1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Ann Arbor
United States
Zip Code
Johansson, Adam; Balter, James M; Cao, Yue (2018) Abdominal DCE-MRI reconstruction with deformable motion correction for liver perfusion quantification. Med Phys 45:4529-4540
Tseng, Huan-Hsin; Luo, Yi; Ten Haken, Randall K et al. (2018) The Role of Machine Learning in Knowledge-Based Response-Adapted Radiotherapy. Front Oncol 8:266
Jochems, Arthur; El-Naqa, Issam; Kessler, Marc et al. (2018) A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy. Acta Oncol 57:226-230
Rosen, Benjamin S; Hawkins, Peter G; Polan, Daniel F et al. (2018) Early Changes in Serial CBCT-Measured Parotid Gland Biomarkers Predict Chronic Xerostomia After Head and Neck Radiation Therapy. Int J Radiat Oncol Biol Phys 102:1319-1329
Luo, Yi; McShan, Daniel L; Matuszak, Martha M et al. (2018) A multiobjective Bayesian networks approach for joint prediction of tumor local control and radiation pneumonitis in nonsmall-cell lung cancer (NSCLC) for response-adapted radiotherapy. Med Phys :
Simeth, Josiah; Johansson, Adam; Owen, Dawn et al. (2018) Quantification of liver function by linearization of a two-compartment model of gadoxetic acid uptake using dynamic contrast-enhanced magnetic resonance imaging. NMR Biomed 31:e3913
Mendiratta-Lala, Mishal; Masch, William; Shankar, Prasad R et al. (2018) MR Imaging Evaluation of Hepatocellular Carcinoma Treated with Stereotactic Body Radiation Therapy (SBRT): Long Term Imaging Follow-Up. Int J Radiat Oncol Biol Phys :
Ohri, Nitin; Tomé, Wolfgang A; Méndez Romero, Alejandra et al. (2018) Local Control After Stereotactic Body Radiation Therapy for Liver Tumors. Int J Radiat Oncol Biol Phys :
Mendiratta-Lala, Mishal; Gu, Everett; Owen, Dawn et al. (2018) Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 102:1063-1069
Wang, Shulian; Campbell, Jeff; Stenmark, Matthew H et al. (2018) A model combining age, equivalent uniform dose and IL-8 may predict radiation esophagitis in patients with non-small cell lung cancer. Radiother Oncol 126:506-510

Showing the most recent 10 out of 289 publications