Exercise Therapy and Radiation Therapy (EXERT) for Metastatic Prostate Cancer

Summary

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Description

In 2018, 30,000 patients were diagnosed metastatic prostate cancer in the US. Short-course radiation therapy (RT) is a mainstay of treatment for symptomatic metastases, and it stimulates an immune response against the tumor. However, RT also decreases systemic interleukin-1 receptor antagonist (IL-1...

In 2018, 30,000 patients were diagnosed metastatic prostate cancer in the US. Short-course radiation therapy (RT) is a mainstay of treatment for symptomatic metastases, and it stimulates an immune response against the tumor. However, RT also decreases systemic interleukin-1 receptor antagonist (IL-1Ra), placing the body in a pro-inflammatory state, and increasing fatigue and reducing quality of life (QOL). Fatigue and QOL are surrogates of the limited 2-20 month survival time. If fatigue and quality of life are improved, then toxicity and survival will follow. Our long-term goal is to identify the potential for exercise therapy (ET) to improve RT treatment toxicities and outcomes among metastatic cancer patients. The mechanistic hypothesis is that adding ET training to RT decreases long-term systemic inflammation, mitigating toxicity thereby widening the therapeutic window. Aim 1. Quantify the potential of ET to mitigate RT toxicities and physical function decline. The hypothesis is that ET mitigates patient-reported QOL and toxicities of RT. Our approach in 1A will be to use standardized questionnaires and assessment tools: toxicity is measured using the NIH Patient-Reported Outcomes Measurement Information System library + Common Terminology Criteria for Adverse Events. In 1B, we will use 30-second chair stand and timed up-and-go. Pre vs post difference scores for each variable would be compared with a generalized estimating equations (GEE) model with an ordinal logistic link function. Aim 2. Characterize the immunologic mechanism by which ET mitigates RT toxicity. The hypothesis is that ET training mitigates toxicity of RT (measured in aim 1) by increasing serum interleukin-1Ra. Our approach will be to measure IL-1Ra pre-RT and 1 month post-RT±ET. We will similarly measure exploratory pro-inflammatory (IL-1B, IL-6, TNF-?, IL-8, IL-15, CRP) and anti-inflammatory (IL-10) markers using a GEE model with ordinal logistic link function. Aim 3. Evaluate the ability of ET to improve survival. Since physical function is a surrogate of survival, the hypothesis is that adding ET to RT will improve overall survival, measured from the date of random assignment to date of death. This pilot work is essential for the development of a full scale randomized trial, to be funded by an R01 application to NCI, planned for submission within 1 year of pilot study completion.

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