• Disparities in colon and rectal cancer queried individually between Hispanics and Whites

      Koblinski, Jenna; Jandova, Jana; Pandit, Viraj; Omesiete, Pamela; Nfonsam, Valentine; Univ Arizona, Dept Surg (PIONEER BIOSCIENCE PUBL CO, 2019-08)
      Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related deaths in the United States. Racial disparities between Hispanics and Whites exist for incidence of late-onset (LO) CRC. However, not much is known about potential disparities between colon cancer (CC) and rectal cancer (RC) incidence queried individually. Methods: Using the SEER database data from 2000 to 2010, we obtained the national estimates of CC and RC for Hispanics and Whites. We analyzed trends in incidence, mortality, gender and stage of disease for early-onset (EO) (<50 years old) and LO (>50 years old) CC and RC. Results: In Hispanics, the overall incidence of CC and RC increased by 47% and 52%, respectively; while in Whites, the overall incidence of CC and RC decreased by 13% and 2% respectively. Incidence of EO CC increased in both Hispanics and Whites by 83% and 17%, respectively, and incidence of EO RC also increased for both groups with a 76% increase in Hispanics and a 34% increase in Whites. For LO CC, the incidence increased by 37% in Hispanics while it decreased by 17% in Whites and for LO RC, the trend in incidence increased in Hispanics by 41%, but decreased in Whites by 11%. Conclusions: This study established that the incidence of CC and RC are different and there is racial disparity in incidence between Whites and Hispanics. This study, hopefully, will help in crafting public policy that might help in addressing this disparity.
    • Next generation sequencing identifies ‘interactome’ signatures in relapsed and refractory metastatic colorectal cancer

      Johnson, Benny; Cooke, Laurence; Mahadevan, Daruka; Univ Arizona, Ctr Canc (PIONEER BIOSCIENCE PUBL CO, 2017-02)
      Background: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. Methods: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms. Web-based bioinformatics tools (Reactome/Enrichr) were utilized to elucidate mutational profile linked pathways-networks that have the potential to guide therapy. Results: Pts had progressed on fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, cetuximab and/or panitumumab. Most common histology was adenocarcinoma (colon N=29; rectal N=3). Of the mutations TP53 was the most common, followed by APC, KRAS, PIK3CA, BRAF, SMAD4, SPTA1, FAT1, PDGFRA, ATM, ROS1, ALK, CDKN2A, FBXW7, TGFBR2, NOTCH1 and HER3. Pts had on average had >= 5 unique mutations. The most frequent activated signaling pathways were: HER2, fibroblast growth factor receptor (FGFR), p38 through BRAF-MEK cascade via RIT and RIN, ARMS-mediated activation of MAPK cascade, and VEGFR2. Conclusions: Dominant driver oncogene mutations do not always equate to oncogenic dependence, hence understanding pathogenic ` interactome(s)' in individual pts is key to both clinically relevant targets and in choosing the next best therapy. Mutational signatures derived from corresponding ` pathway-networks' represent a meaningful tool to (I) evaluate functional investigation in the laboratory; (II) predict response to drug therapy; and (III) guide rational drug combinations in relapsed and refractory mCRC pts.
    • Predictors of intermediate-term survival with destination locoregional therapy of hepatocellular cancer in patients either ineligible or unwilling for liver transplantation

      Ramanathan, Meera; Shroads, Michael; Choi, Myunghan; Wood, David; Seetharam, Anil; Univ Arizona, Coll Med (PIONEER BIOSCIENCE PUBL CO, 2017-10)
      Intra-arterial or percutaneous locoregional therapies (LRT) are often employed to maintain potential liver transplant (LT) recipients with hepatocellular carcinoma (HCC) within T2/Milan criteria. Predictors of survival when LRT is used as destination therapy in those who are either ineligible or unwilling for LT remain poorly defined. We evaluated predictors of 3-year survival with destination LRT in a population of cirrhotic patients diagnosed with HCC, presenting within T2 criteria, and either ineligible or unwilling for LT. The cohort surviving 3 years had a significantly lower model for end-stage liver disease (MELD) score at HCC diagnosis (9.7 vs. 11.4, P= 0.037) and MELD following initial locoregional therapy (10.7 vs. 13.3, P= 0.008) compared to those not surviving three years despite similar demographic, tumor, and treatment variables. LRT as destination therapy results in modest intermediate term survival, with liver function at presentation and immediately following initiation of LRT predicting intermediate survival with this approach.
    • Racial and gender disparities in the incidence of anal cancer: analysis of the Nationwide Inpatient Sample (NIS)

      Cruz, Alejandro; Chen, Debbie; Hsu, Paul; Pandit, Viraj; Omesiete, Pamela; Vij, Priyanka; Nfonsam, Valentine; Univ Arizona, Dept Surg; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Biostat & Epidemiol (PIONEER BIOSCIENCE PUBL CO, 2018-02)
      Background: Racial and gender disparities have been shown in other gastrointestinal cancers. However, there is a paucity of data on racial and gender disparities in anal cancer (AC). The aim of this study was to assess racial and gender disparities among patients with AC. Methods: We analyzed data from the National Inpatient Sample (NIS) 2011 database of patients diagnosed with AC with age >= 18. Demographic data including age, race and gender were assessed. Patients were stratified based on race and gender. Log binomial regression was used to generate risk ratios. Results: A total of 6,013,105 patients were assessed and 1,956 (0.03%) patients had AC. Female patients were more at risk of developing AC [relative risk (RR): 1.14, P=0.02]. Whites and Blacks had the highest incidence followed by Asians/Pacific Islanders. Black males had increased risk of AC (RR: 1.43, P<0.01). Amongst Hispanics; both males (RR: 0.69, P=0.05) and females (RR: 0.46, P<0.0001) had decreased risk of developing AC. Finally, we saw that Asian females had a much lower risk of developing AC (RR: 0.33, P<0.01). Conclusions: Racial disparities and gender differences exist in the incidence of AC. Potential causes for this disparity are disparate access to healthcare, lack of education, and lack of awareness. Greater understanding of the racial disparity in AC can help identify at risk population and eventually lead to improved preventative measures to ultimately reduce the incidence of AC.
    • Racial disparities in the incidence of colon cancer in patients with inflammatory bowel disease

      Vij, Priyanka; Chen, Debbie; Hsu, Chiu-Hsieh; Pandit, Viraj; Omesiete, Pamela; Elquza, Emad; Scott, Aaron; Cruz, Alejandro; Nfonsam, Valentine; Univ Arizona, Dept Surg, Mel & Enid Zuckerman Coll Publ Hlth; et al. (PIONEER BIOSCIENCE PUBL CO, 2019-04-01)
      Background: Studies have explored the relationship between inflammatory bowel disease (IBD) [ulcerative colitis (UC) and Crohn's disease (CD)] and colon cancer (CC). Additionally, racial disparities in the incidence of CC is well known. However, the impact of racial disparity in IBD patients who develop CC remains unclear. The aim of this study is to address the knowledge gap in this particular group of patients. Methods: A retrospective analysis was done using the National Inpatient Sample (NIS) database from 2011. We included patients with IBD over age >= 18 years with a diagnosis of CC. Patients were stratified by race, gender, age, presence of IBD and CC. Statistical analysis was performed to compare the groups. Results: A total of 57,542 patients were included (CD: 36,357, UC: 21,001). Of all patients with and without IBD, advanced age, Black and Asian race conferred an increased risk of developing CC, whereas female gender, Hispanic and Native American race conferred a protective effect. In patients with IBD, advanced age conferred an increased risk for developing CC while female gender conferred a protective effect. In this subset of patients, black race conferred a protective effect. Conclusions: Racial disparity exists in the overall incidence of CC and among patients with IBD who develop CC. Interestingly, black race conferred a protective effect for patients with IBD, contrary to what is seen in the general population. These findings could be attributed to the environmental factors and genetic makeup between racial groups. Further studies are warranted to better understand these disparities.