A Nutrition & Exercise Prehabilitation Intervention on Inflammatory Biomarkers in AI Cancer Patients

The purpose of this study is to assess the feasibility of a prehab intervention among American Indian (AI) patients diagnosed with obesity-related cancer and measure inflammatory biomarkers to evaluate the preliminary impact of the trial intervention. The central hypothesis is that this community-informed prehab intervention will demonstrate feasibility, patient acceptability, and modulation of host and tumor-microenvironment inflammatory biomarkers.

Aim 1: Implement the prehab translational clinical trial for AI patients with obesity-related solid tumor cancer scheduled for surgery.

Aim 2 Measure host and tumor-microenvironment (TME) biomarkers using paired serum and tissue samples to compare baseline and post-intervention levels of expression. Serum markers include CRP, IL-6, IL-10, TNFa, IGF-1, VEGF, complete blood count (CBC) with differential, comprehensive metabolic panel (CMP), and prealbumin. Tissue markers include Ki67, insulin receptor, TNFa, NFKB, NOS2, and cleaved caspase 3.

Aim 3: (optional exploratory aim): Assess differential expression of inflammatory genes in the TME using tumor tissue samples to compare baseline and post-intervention levels of expression. This will be done with a panel that analyzes inflammatory genes only.

American Indian/Alaskan Natives (AI/AN) have the worst cancer survival rates of any U.S. racial group and are 1.6 times more likely to be obese than the general population. Inflammation is a reversible mechanism through which obesity increases the risk of cancer incidence and progression. Prehabilitation (prehab) is a strategy utilizing lifestyle modifications in physical activity, nutrition, smoking cessation, and/or psychological support to optimize patients' functional capacity and improve postoperative outcomes. The proposed project is to (1) implement the prehab translational clinical trial for AI patients with obesity-related solid tumor cancer preparing for surgery and (2) measure inflammatory biomarkers pre and post-intervention to assess responsiveness. The intervention will be piloted in a sample of 30 patients with obesity-related solid tumor cancer who are enrolled tribal members, age 18-80 years, undergoing surgical resection of the tumor with at least 3 weeks until operation. Patients will eat walnuts, and exercise by walking 30 minutes daily and attending fitness sessions twice weekly during the 3 week study period. Patients will complete pre and post surveys, 6 minute walk test, 30 second sit-to-stand test, biosample collection and anthropometric measurements. These assessments will help us understand if the walnuts and exercise can mitigate inflammation in the tumor. Prior published programs have featured similar sized groups for feasibility testing. Patient reported acceptability, lifestyle behavior change, and biosample collection rates will be evaluated to assess feasibility and gain effect size estimates for a future R01 trial.

Eligibility Criteria:
Inclusion Criteria:

* Age 18-80 years
* Clinical diagnosis of obesity-related solid tumor cancer: obesity-related solid tumor cancers include thyroid, breast, liver, gallbladder, gastric, pancreatic, colorectal, ovarian, uterine, kidney, esophageal cancers.
* Preoperative status with plan to undergo an operation to remove the tumor
* Scheduled at least 3 weeks out from the operation
* Enrolled member of the San Carlos Apache nation
* Must be having cancer surgery at San Carlos Apache Healthcare Corporation or Banner University Medical Center-Tucson

Exclusion Criteria:

* Current or planned receipt of chemotherapy during the preoperative study period
* Digestive tract disease that would restrict diet modifications
* Allergy to the foods intended for the nutrition intervention
* Uncontrolled cardiac disease or other contraindications to moderate-intensity exercise