Investigating Therapeutic Response Disparities in Locally Advanced Rectal Cancer
Abstract
This proposal addresses a critical problem in the fiscal year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Area of colorectal cancer. Rectal cancer (RC) is growing in incidence in the United States (44,850 cases in 2022), especially an increased incidence has been observed in younger people (<50 years of age). This application proposes to address the gaps in treatment of individuals with rectal cancer (both military and civilian population) which prevent them from becoming better (such as better response to therapy, improved survival, reduced chances of tumor recurrence). Most (~60%) rectal cancer cases are identified at the advanced stages (i.e., locally advanced rectal cancer LARC), which means that the primary tumor has spread to the lymph nodes or even further in the individual s body. There is a significant difference (i.e., a disparity) in outcomes of African American LARC patients when compared to European American LARC patients, with African American patients ~40% more likely to die of RC. The causes for worse outcomes in African American patients are complex and include socioeconomic factors (e.g., income level, poverty, education), and other barriers to patient care (e.g., lack of health insurance, transportation access, language barriers). However, recent work suggests that these factors by themselves cannot fully explain the worse outcome in African American LARC patients. Thus, there is a critical gap in our understanding of the worse outcomes in African American LARC patients. An explanation for the worse outcome in African American LARC patients is poor response to therapy. A patient with LARC is treated with chemotherapy drugs and radiation prior to surgical removal of their tumor. This is called neoadjuvant chemoradiation therapy (nCRT) and is the standard of care. Recently, there have been several new advances in treatment for LARC patients and these present new ways to treat patients who do not respond well to standard nCRT. However, the clinical trials establishing nCRT and the new treatment strategies included either very few or did not report race/ethnic data. Hence, this study aims to investigate biological differences in response to LARC therapies among African American and European American LARC patients. In this proposal, we will address the gaps in treatment and outcomes of African American LARC patients by identifying predictive biomarkers that can help predict who will benefit or not benefit from nCRT. I will work closely with a multidisciplinary team that will provide expertise in various aspects of this project and will be key in addressing cancer health disparities. I predict that it will take 2 years to complete our proposed work and another ~2-3 years to validate findings in prospective clinical studies. This validation would develop a biomarker that could be deployed clinically. A prospective study would be conducted as a correlate to a study already underway, so as to quicken the timeline. The successful completion of these studies will particularly benefit the U.S. Military and Veterans community. The main risk factors for rectal cancer, such as smoking and radiation exposures, are over-represented within this community. Also, our active-duty members are a of a younger age (<50 years); the incidence of rectal cancer is rising in this age group. I anticipate that our project findings will identify a novel biomarker to select which African American LARC patients will benefit from nCRT. This will ensure better outcomes for these individuals. For those who will not respond, they will not be exposed to toxic effects of chemoradiation and could be candidates for other new LARC. The results will shed light on a critically understudied area of therapeutic response in African American LARC patients, with an overall goal to improve treatment and patient outcomes. Thus, this proposal would impact mission readiness by increasing our understanding
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310840
Entities
People
- Sanjeevani Arora
Organizations
- United States Army