Concurrent Radiation-therapy with Immunotherapy Based Systemic-therapy (CRIBS) (Radiation Medicine and Markey Cancer Center Collaborative Bench to Bedside pilot) (RPA Pilot / Seed Project)

"Standard of care of Her2 negative metastatic esophageal, gastroesophageal, and gastric (EGG) cancers consist of cytotoxic chemotherapy and nivolumab based upon histology and PD-L1 expression based upon the CheckMate 649 trial [1]. This regimen provides an overall survival benefit when compared to cytotoxic chemotherapy alone. Radiation therapy (RT) provides a high chance of relieving dysphagia and bleeding but is often not done with concurrent systemic therapy [2-3]. Combining both therapies may
lead to a high chance of relieving dysphagia and also treat the systemic malignancy burden. Another benefit of adding concurrent radiation to immunotherapy based systemic treatment is the abscopal effect [4]. Radiation to the treated tumor site has been hypothesized to increase the number of antigens in circulation to bind to antigen presenting cells (APCs) which then increases the CD-8 T cell immunologic response, and thus leads to secondary tumor site destruction [4]. This synergistic effect with immunotherapy-based treatment can lead to an increase in both local and distant clinical response rates as well as longer progression free survival rates. Lastly, there is randomized prospective evidence showing that localized treatment in the stage IV setting can increase both progression free and overall survival for patients with stage IV cancers [5]. Therefore, this trial is designed to show efficacy and provide progression free survival rates for stage IV EGG cancer patients receiving concurrent radiation to immunotherapy based systemic therapy."