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Colon cancer needs better screening and treatment options. Its incidence in the young population is rising. Recent changes in guidelines recommend beginning screening for colon cancer at the age of 45. Circulating tumor DNA presents an opportunity to select patients for administration of adjuvant chemotherapy. Immunotherapy is an option for patients with a deficiency in mismatch repair proteins. However, its efficacy outside of this group of patients remains a challenge. Targeted therapies such as BRAF inhibitors are an option for patients with poor prognosis, for whom cytotoxic chemotherapy is not as effective. This review presents the recently published evidence regarding screening and treating patients with colon cancer.

Purpose of the Study: The purpose of the study was to investigate whether the risks of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Additionally, we conducted subgroup analysis to assess potential effect modification by race/ethnicity. The role of body composition in cancer outcomes is of great clinical interest, and measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. Methods: Participants included 1682 adult cancer survivors who had undergone dual-energy x-ray absorptiometry (DXA) examination to measure body composition, gathered from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass (weight of fat in the body) was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was defined by appendicular skeletal muscle mass index (females < 5.45kg/m2 and males < 7.26kg/m2). Multivariable Cox proportional hazards models were performed to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI); we also stratified by race. In addition, we performed a restricted cubic spline analysis to assess the potential non-linear association between fat mass and all-cause mortality. Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. Overall, sarcopenia was present in 304 (25.0%), and 561 (33.4%) of the participants had high total fat mass. Participants with higher fat mass had 30% increased risk of all-cause mortality (aHR=1.30, 95% CI=1.06-1.61) compared to participants with low-fat mass, while participants with sarcopenia had a 51% higher risk (aHR=1.51, 95% CI=1.22-1.88) than participants with no sarcopenia. A restricted cubic spline analysis revealed a J-shaped association between fat mass and all-cause mortality. Further, sarcopenia was also associated with a higher risk of cancer-specific mortality (aHR=1.74, 95% CI=1.23-2.29) compared to non-sarcopenia. The association between sarcopenia and all-cause mortality was twice as strong in Non-Hispanic Blacks (aHR=2.99, 95% CI=1.39-6.06) compared to Non-Hispanic Whites (aHR=1.53, 95% CI=1.19-1.95). Conclusion: Our findings show opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors. Citation Format: Livingstone Aduse-Poku, Shama D. Karanth, Meghann Wheeler, Danting Yang, Caretia Washington, Jesus Fabregas, Ting-Yuan David Cheng, Dejana Braithwaite. Associations of total body fat mass and skeletal muscle index with all-cause and cancer-specific mortality in cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3036.

Background: Pancreatic cancer portends a very poor prognosis. It is the third leading cause of cancer deaths in the United States. African Americans have a 50- 90% increased incidence of pancreatic cancer in comparison to other racial groups. 20% of patients with pancreatic cancer present with early-stage disease and will have a median overall survival of 2.5 years if able to undergo surgical resection. There is a desperate need to discover novel ways of treating pancreatic cancer. Understanding of the microbiome may be informative to overcoming chemotherapy resistance, toxicity and improving outcomes and disparities. The aim of this study is to (1) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment response and (2) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment toxicity in a diverse patient population. Methods: Patients with resectable or borderline resectable pancreatic cancer who are enrolled in a multi-site clinical trial (NCT03483038) receiving neoadjuvant NEO-Nali-IRI (oxaliplatin, liposomal irinotecan and 5- FU) followed by surgical resection were asked to provide stool samples and a dietary log during the following four (or five) time points: baseline, mid-therapy (after C4), at completion of chemotherapy (after C8), after radiation if applicable, and at 4-6 weeks post-operative. Participants will be given stool collection kits at clinic visits for home sample acquisition. All samples will be mailed to the University of Florida Health Cancer Center Microbiome Biorepository. Data will be collected regarding demographics, stage, medical history and concurrent medications including antimicrobics and probiotics, chemotherapy dose-reductions, delays, discontinuations, adverse events, safety adverse events, attribution of causality, and hospitalizations. Outcomes will include imaging response using RECIST criteria, CA 19-9 trend, development of metastatic disease, and the ability to proceed to definitive surgical resection. DNA will be extracted from stool and analyzed using 16S rRNA sequencing methods to determine signatures and biodiversity. Descriptive statistics and correlative analysis will be reported. Continuous and categorical variables will be compared with Student’s t-test and Chi-squared test. Multiple groups will be compared by ANOVA. Kaplan-Meier logistic regression will be performed to compare outcomes between the different microbiota groupings. Conclusion: Stool collection from a multi-site clinical trial is feasible during neoadjuvant chemotherapy for pancreatic cancer and can increase diversity of the sample population. Citation Format: Sherise Rogers, Ryan Thomas, Brain Ramnaraign, Ilyas Sahin, Jesus Fabregas, Karen Russell, Steven Hughes, Ibrahim Nassour, Kathyrn Hitchcock, Omar Kayaleh, Anita Turk, Ji-Hyun Lee, David DeRemer, Carmen Allegra, Thomas George. An exploratory analysis of the intestinal microbiome in neoadjuvant chemotherapy for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2186.

Background: Pancreatic cancer portends a very poor prognosis. It is the third leading cause of cancer deaths in the United States. African Americans have a 50- 90% increased incidence of pancreatic cancer in comparison to other racial groups. 20% of patients with pancreatic cancer present with early stage disease and will have a median overall survival of 2.5 years if able to undergo surgical resection. There is a desperate need to discover novel ways of treating pancreatic cancer. Understanding of the microbiome may be informative to overcoming chemotherapy resistance, toxicity and improving outcomes and disparities. The aim of this study is to (1) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment response and (2) identify changes in the intestinal microbiota during neoadjuvant treatment of pancreatic ductal adenocarcinoma that correlate with treatment toxicity in a diverse patient population. Methods: Patients with resectable or borderline resectable pancreatic cancer who are enrolled in a multi-site clinical trial (NCT03483038) receiving neoadjuvant NEO-Nali-IRI (oxaliplatin, liposomal irinotecan and 5- FU) followed by surgical resection were asked to provide stool samples and a dietary log during the following four (or five) time points: baseline, mid-therapy (after C4), at completion of chemotherapy (after C8), after radiation if applicable, and at 4-6 weeks post-operative. Participants will be given stool collection kits at clinic visits for home sample acquisition. All samples will be mailed to the University of Florida Health Cancer Center Microbiome Biorepository. Data will be collected regarding demographics, stage, medical history and concurrent medications including antimicrobics and probiotics, chemotherapy dose-reductions, delays, discontinuations, adverse events, safety adverse events, attribution of causality, and hospitalizations. Outcomes will include imaging response using RECIST criteria, CA 19-9 trend, development of metastatic disease, and the ability to proceed to definitive surgical resection. DNA will be extracted from stool and analyzed using 16S rRNA sequencing methods to determine signatures and biodiversity. Descriptive statistics and correlative analysis will be reported. Continuous and categorical variables will be compared with Student’s t-test and Chi-squared test. Multiple groups will be compared by ANOVA. Kaplan-Meier logistic regression will be performed to compare outcomes between the different microbiota groupings. Conclusion: Stool collection from a multi-site clinical trial is feasible during neoadjuvant chemotherapy for pancreatic cancer and can increase diversity of the sample population. Citation Format: Sherise Rogers, Ryan Thomas, Brian Ramnaraign, Ilyas Sahin, Jesus Fabregas, Karen Russell, Steven Hughes, Ibrahim Nassour, Kathryn Hitchcock, Omar Kayaleh, Anita Turk, Ji-Hyun Lee, David DeRemer, Carmen Allegra, Thomas George. An exploratory analysis of the intestinal microbiome in neoadjuvant chemotherapy for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B037.