Quantitative Lung Function Imaging to Reduce Toxicity for patients treated with Radiation and Immunotherapy

Thomas Jefferson University

Yevgeniy (Jenia) Vinogradskiy
Yevgeniy.Vinogradskiy@jefferson.edu

Emory University

Richard Castillo
richard.castillo@emory.edu

Beaumont Health System

Edward Castillo
Edward.Castillo@beaumont.edu
Grant Number: UG3 CA247605

This research 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 this project is to develop novel methods that enable the evaluation of imaging-based functional avoidance for patients enrolled in radiotherapy and immunotherapy clinical trials. This 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. This 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. This 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 patients treated with radiotherapy and immunotherapy and 2) enable the investigation of more-aggressive radiotherapy and immunotherapy treatment approaches for lung cancer patients.

List of relevant recent publications:

F Forghani, T Patton, J Kwak, D. Thomas, Q Diot, C Rusthoven, R Castillo E Castillo, I Grills, T Guerrero, M Miften, Y Vinogradskiy, “Characterizing spatial differences between SPECT- ventilation and SPECT-perfusion in patients with lung cancer undergoing radiotherapy.” Radiotherapy and Oncology , In Press
E Castillo, G Nair, D Turner-Lawrence, N Myziuk, S Emerson, S Al-Katib, S Westergaard, R Castillo, Y Vinogradskiy, T Quinn, T Guerrero, C Stevens, “Quantifying Pulmonary Perfusion from Non-Contrast Computed Tomography.” Medical Physics, 48.4 (2021): 1804-1814.
E Castillo, Y Vinogradskiy, R Castillo, “Robust HU-based CT ventilation from an integrated mass conservation formulation.” Medical Physics 46, no. 11 (2019): 5036-5046.
E Castillo, R Castillo Y Vinogradskiy, M Dougherty, D Solis, N Myzuik, A Thompson, R Guerra, G Nair, T Guerrero, “Robust CT-Ventilation from the Integral Formulation of the Jacobian.” Medical physics 46, no. 5 (2019): 2115-2125.
Y Vinogradskiy, C Rusthoven, L Schubert, B Jones, A Faught, R Castillo, E Castillo, L Gaspar, J Kwak, T Waxweiler, M Dougherty, D Gao, C Stevens, M Miften, B Kavanagh, T Guerrero, I Grills. “Interim analysis of a two institution, prospective, clinical trial of 4DCT-ventilation- based functional avoidance radiation therapy.” International journal of radiation oncology, biology, physics (2018). 102(4), pp.1357-1365