The standard of care (SOC) for locally advanced cervical cancer, pelvic radiation (RT) with concurrent cisplatin, is associated with a 30-50% failure rate, and there is no cure for recurrent disease. Our preliminary data suggests that a complex interaction between macrophages, dendritic cells, and T-cells within the tumor microenvironment (TME), as remodeled by radiotherapy, may limit the development of anti-tumor immunity and promote development of treatment resistance in these tumor types. The Washington University (WU) ROBIN Center
(MicroEnvironment Tumor Effects Of Radiotherapy (METEOR)), will create a resource for in tandem single cell and spatially resolved omics that will be used to study how the immune system co-evolves with tumors during RT, which will be combined with well-annotated clinical, dosimetric, and imaging data to paint a detailed picture of RT/TME interactions. Specifically, we will study how standard of care chemotherapy, radiation and combined chemoradiation remodels TME, and how this contributes to tumor relapse and the development of radiation resistance. A molecular characterization trial (Comprehensive Radiobiology Assessment TRial (METEOR-CRATR)) will be initiated to support detailed studies in this space within the context of our two METEOR Center Projects and lay a foundation for future studies (trans-ROBIN pilot studies, additional inter/intra- Network collaboration, future P01/R01). We hypothesize that a dynamically adaptable Trial design focused on deep characterization of small patient cohorts, coupled with a robust infrastructure to enable rapid provision of samples for analysis, will enable generation of new radiobiological concepts related to changes in the TME in response to standard of care radiotherapy. We will prospectively evaluate changes in the TME through collection of longitudinal biospecimen and multimodal clinical data for patients with locally advanced cervical and pancreatic cancer undergoing standard of care chemoradiotherapy. To allow for optimal collection of data to support comparisons within and across groups, METEOR-CRATR will be initiated in patient populations where the standard of care therapy includes radiotherapy and cytotoxic chemotherapy, and where various opportunities for acquisition of both biopsy and surgical samples during a patient’s treatment course naturally exists. We will also enable a robust iterative infrastructure to support rapid provision of samples and clinical data to enable near real-time processing and analysis within the Center Shared Resource Cores (SRCs) and Research Projects. We have developed a responsive system between METEOR-CRATR, SRCs, and Research Projects to enable efficient specimen and data capture and analysis. Such a system will also support dynamic Trial iteration and refinement based on new data and evolving challenges.