The proposed project is in the field of thoracic oncology. Lung cancer patients that get treated with radiotherapy and immunotherapy are at risk of developing serious lung side-effects, and in particular, pneumonitis. Pneumonitis results in cough, shortness of breath, and can be fatal. Pneumonitis, is a serious, overlapping toxicity that can results as a function of both radiotherapy and immunotherapy. Pneumonitis has a significant impact on patient quality of life and limits the aggressive combinations of therapies that can be evaluated in clinical trials. Strategies are needed that can reduce pneumonitis rates for patients treated with aggressive combinations of radiotherapy and immunotherapy in clinical trials. A novel lung function imaging modality has been developed that uses data acquired as part of routine clinical care for lung cancer patients along with software techniques to innovatively calculate lung function maps. The novel lung function imaging modality has been incorporated into radiotherapy through a personalized, functional avoidance radiation treatment paradigm. The idea of functional avoidance is to design radiation treatment plans that reduce dose to functional portions of the lung with the hypothesis that reduced dose to functional lung will lead to decreased side-effects from treatment and improved quality of life. Imaging-based functional avoidance provides a promising method for significantly reducing toxicity for lung cancer patients who get treated with combinations of radiotherapy and immunotherapy. The problem is that the novel lung function imaging methods have not been developed and evaluated with immunotherapy added to the treatment paradigm. The purpose of our project is to develop novel methods that enable the evaluation of imaging-based functional avoidance for patients enrolled in radiotherapy and immunotherapy clinical trials. Our study will develop methods that provide a complete picture of lung function (perfusion imaging in addition to ventilation), evaluate the most stable and clinically relevant form of lung function imaging, and perform a sensitivity analysis of how various functional parameters effect radiation treatment plans for patients treated with radiotherapy and immunotherapy. Our study will use data from 4 clinical trials to evaluate whether the proposed imaging framework can reduce toxicity for lung cancer patients in the setting of immunotherapy added to the treatment paradigm. More aggressive combinations of radiotherapy and immunotherapy are going to continue to evolve and be investigated in clinical trials. Pulmonary toxicity will be a serious clinical limitation for these studies. Our project proposes a convenient, inexpensive imaging modality to reduce toxicity and has the potential to significantly improve quality of life of lung cancer patients treated with radiotherapy and immunotherapy. The impact of our imaging framework is that it can 1) reduce treatment-related side-effects for pa...