Oligometastatic (oligomet) disease represents a newly proposed disease state that is hypothesized to be an intermediate state of metastatic disease that benefits from definitive local therapy. Our group was the first to show that definitive treatment of oligomet patients with radiation results in an overall survival benefit. We are currently accruing to the follow up EXTEND trial, a biomarker-heavy basket study funded by CPRIT, and the unfunded oligomet RCC trial. With this grant we aim to capitalize on our momentum to conduct unfunded tissue correlatives collected from these trials and to initiate the next investigator-initiated oligomet trial. 1.Analyze the genetic landscape of oligomet di...

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Oligometastatic (oligomet) disease represents a newly proposed disease state that is hypothesized to be an intermediate state of metastatic disease that benefits from definitive local therapy. Our group was the first to show that definitive treatment of oligomet patients with radiation results in an overall survival benefit. We are currently accruing to the follow up EXTEND trial, a biomarker-heavy basket study funded by CPRIT, and the unfunded oligomet RCC trial. With this grant we aim to capitalize on our momentum to conduct unfunded tissue correlatives collected from these trials and to initiate the next investigator-initiated oligomet trial. 1.Analyze the genetic landscape of oligomet disease from tissue samples. We will analyze collected tissue samples from EXTEND (NCT03599765) and oligomet RCC (NCT03575611) trials to identify mutations associated with the oligomet state in order to create a circulating tumor DNA (ctDNA)-based biomarker. Objectives a.Sequence serially collected tissue samples to identify genetic alterations correlated with the oligometastatic state. b.Create and test a ctDNA-based biomarker to identify patients with oligomet disease. c.Under the mentorship of Dr. Wistuba, I will work with the Departments of Translational Molecular Pathology to develop my understanding of DNA sequencing. 2.Assess changes in the peripheral immune landscape to identify novel inhibitors that augment antigen presentation and attenuates radiation-induced immune suppression. We will expand immune analyses from EXTEND and conduct analyses in oligomet RCC to investigate immune perturbations induced by radiation. Objectives a.Analyze the expression of druggable antigens that interact with the radiation-induced immune phenotype. b.Activate a clinical trial of immunotherapy and radiation for oligomet disease. c.Under the mentorship of Dr. Hong, conduct a 2-4 week externship with a pharmaceutical company and/or the Cancer Therapy Evaluation Program.

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