GCC 2545- Improving Post-Radiotherapy Respiratory Function Through Sparing Serial and Parallel Components in the Lung

Decreased respiratory function is a common side effect experienced by non-small cell lung cancer (NSCLC) patients who receive radiation therapy. In current clinical practice when treating cancerous lesions in the lung, it is not standard to explicitly try and avoid excessive radiation dose and therefore radiation injury to smaller airways. However, because of this patients may obtain damage to an airway segment can cause downstream regions in the lung to lose their "supply line" and, therefore, cause patients to lose the ability to exchange oxygen with the blood. The purpose of this clinical trial is to systematically compare post-treatment lung function of those who receive regular clinical radiation therapy (standard of care \[SoC\]) versus those who receive the airway-sparing radiation therapy regimen. The investigators hope to show that, by preserving airways and connected lung regions, participants will be able to retain a larger amount of their lung function, which will have a direct, positive impact on their post-treatment quality of life.

Inclusion Criteria: * Step 1- Inclusion Criteria 1. Adult (≥18 years) patients (both sexes) with histologically diagnosed Stage III NSCLC per AJCC ver 9 2. Patients to be treated with definitive external beam photon radiotherapy with or without systemic therapy (e.g., chemothrapy, immunotherapy). 3. No restrictions on number radiotherapy fractions, or location/number of lesions 4. ECOG performance status ≤ 3 5. Ability to hold breath for ≥ 15 seconds 6. Patient has signed informed consent document and agreed to study procedures Step 2- Inclusion Criteria 1. Patient has completed 4DCT and BHCT with subsequent plans created and Radiation Oncologist has determined that patient would benefit from INSPIRE RT. Exclusion Criteria: * Step 1- Exclusion Criteria 1. Prior lung cancer-directed radiotherapy 2. Recent (\< 12 mo) or planned lung surgery (which would confound pre- and post-RT lung function measures) 3. Patients with metal implants or metal stents in the thoracic region 4. Known severe chronic obstructive pulmonary disease or interstitial lung disease 5. Women who are pregnant or trying to get pregnant Step 2- Exclusion Criteria 1\. Patient found to not benefit from INSPIRE RT after comparison of treatment plans.