Abstract 5281: An exercise intervention for pancreas cancer patients increases tumor vascularity
Authors: Florez Claudia Alvarez , Parker Nathan , Katz Matthew , Ngo-Huang An , Cardoso Carol Ferreira , Wang Huamin , Petzel Maria , Fogelman David , Schadler Keri 
Published: August 2018

Abstract
We and others have demonstrated in mice that moderate aerobic exercise remodels tumor vasculature and improves chemotherapy delivery. The sparse, dysfunctional vasculature in pancreatic ductal adenocarcinoma (PDAC) is one major barrier to delivering chemotherapy to the tumor. Improved vascular function and chemotherapy delivery could substantially improve patient survival over the current 7% rate. We first evaluated whether exercise might improve survival for patients with PDAC using a patient-derived xenograft (PDX) mouse model and moderate treadmill running. Treatment of PDX-bearing mice with gemcitabine or gemcitabine plus exercise caused tumor regression. However, gemcitabine was more effective when combined with exercise and excitingly, regrowth of tumors after treatment cessation was significantly delayed in mice treated with exercise combined with gemcitabine compared to gemcitabine alone. Our animal data suggests that exercise may be beneficial for patients with pancreatic cancer. However, it is unclear whether a sufficient level of exercise can be performed by patients with advanced cancers to achieve improved vascular function as predicted by animal studies. Recently, we completed a pilot study delivering a home-based aerobic and strength training exercise program (EP) to patients with potentially operable pancreas cancer. Fifty-eight patients (48% female, median age 66) completed the EP concurrent with chemotherapy or chemoradiation over a mean duration of 15 weeks prior to pancreatectomy. Participants completed a mean of 145.8 minutes of weekly moderate to vigorous physical activity. Surgical tumor specimens were obtained from 28 patients who participated in the EP, and were evaluated for the total number of vessels, vessel density, average number of open lumens, and number of elongated vessels. We found that tumors of patients who participated in the EP had significantly increased vessel density and a significantly increased number of elongated vessels compared to tumors from control patient, similar to our observations in mice. This is the first demonstration that an EP is feasible during the chemotherapy/ chemoradiation phases for pancreatic cancer patients, and importantly, that moderate exercise changes human tumor vascular biology. There was also a trend toward increased immune cell infiltration in tumors from patients who exercised. Cell death in tumors is being evaluated. This data suggests that exercise is a low-cost, low risk way to remodel human tumor vasculature and therefore may be an adjuvant to chemotherapy. Remodeled vasculature may increase chemotherapy delivery to the tumor, improving survival, as predicted in animal models. Further studies evaluating the impact of exercise on patient outcome as well as angiogenic biomarkers are underway.
Citation Format: Claudia Alvarez Florez, Nathan Parker, Matthew Katz, An Ngo-Huang, Carol Ferreira Cardoso, Huamin Wang, Maria Petzel, David Fogelman, Keri Schadler. An exercise intervention for pancreas cancer patients increases tumor vascularity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5281.