Mortality Patterns of Synchronous Uterine and Ovarian Cancers: A SEER Registry Analysis.

BACKGROUND: The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns similar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. METHODS: The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchronous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endometrioid cancers, and stage IA cancers. RESULTS: Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers. CONCLUSIONS: We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy. IMPACT: The possible misdiagnosis associated with clinicopathologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level.

Real-World Outcomes of Patients With BRAF-Mutated Metastatic Colorectal Cancer Treated in the United States.

BACKGROUND: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Whether these patients may benefit from more aggressive frontline chemotherapy with a triplet regimen such as FOLFOXIRI remains unclear. We used real-world data from a cohort of patients in the United States to assess the BRAF testing rate, determine the prevalence of FOLFOXIRI use, and compare survival outcomes in mCRC, stratified by BRAF mutation status and first-line therapy. METHODS: A nationwide electronic health record-derived deidentified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Those with documented BRAF mutation testing who received standard first-line therapy were included. Kaplan-Meier estimates with corresponding log-rank tests and Cox proportional hazards modeling compared survival outcomes stratified by BRAF status and first-line therapy. RESULTS: Of 4,457 included patients, 3,991 (89.5%) had BRAF wild-type (BRAFwt) and 466 (10.5%) had BRAF-mutated (BRAFmt) mCRC. Median overall survival (OS) was 15.4 months in the BRAFmt group versus 28.1 months in the BRAFwt group (hazard ratio [HR], 0.48; 95% CI, 0.41-0.56; P<.001). Only 3% of patients with BRAF mutations received first-line FOLFOXIRI ± bevacizumab, with a median OS of 13.8 months compared with 15.5 months in those treated with doublet chemotherapy ± bevacizumab (P=.38). In patients with BRAF mutations, propensity-weighted analysis did not detect a significant improvement in OS with FOLFIRI + bevacizumab (HR, 0.90; 95% CI, 0.58-1.39; P=.63) or FOLFOX/CAPEOX + bevacizumab (HR, 0.81; 95% CI, 0.52-1.26; P=.35) versus doublet chemotherapy alone. In 2018, only 56% of patients diagnosed with mCRC had documented BRAF testing at any time. CONCLUSIONS: This real-world data analysis confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the United States. The proportion of patients with documented BRAF testing in this real-world population was low at 56%. We were unable to show any significant difference in OS of patients with BRAFmt mCRC based on the first-line therapy received.

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States.

BACKGROUND: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. METHODS: A nationwide electronic health record (EHR)-derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. RESULTS: A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8-32.3), 27.5 months with bevacizumab (95% CI, 25.8-28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). CONCLUSIONS: This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

Second primary breast cancer after unilateral mastectomy alone or with contralateral prophylactic mastectomy.

BACKGROUND: An increasing number of patients undergo contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. However, the benefit of CPM has not been quantified in the setting of contemporary breast cancer therapy. METHODS: We performed an analysis of 180 068 patients in the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with unilateral ductal breast carcinoma between 1998 and 2013 and treated with unilateral mastectomy (UM) or CPM. UM was performed in 146 213 patients (81.2%); CPM was performed in 33 855 patients (19.8%). Primary outcome of interest was cumulative incidence of a second primary breast cancer in the ipsilateral or contralateral breast greater than 3 months after initial diagnosis. Cumulative incidence analysis was based on a Cox proportional model to generate curves of second primary breast cancer in any breast, ipsilateral breast only, or contralateral breast only. RESULTS: Patients who underwent CPM had a significantly reduced incidence of second primary breast cancer 10 and 15 years after surgery (CPM 0.93% [0.73%, 1.12%] vs UM 4.44% [4.28%, 4.60%]). Patients who underwent CPM had significantly lower adjusted hazard of second primary breast cancer when compared with UM (HR 0.38 vs 1.0, P < .0001). CONCLUSIONS: CPM offers some protection from a second primary breast cancer, attributable to a reduced incidence in the contralateral breast. These findings provide additional information to providers and patients as they make decisions regarding surgical management. They should also be interpreted in the context of the absolute incidence of second primary breast cancer after UM and previous literature demonstrating no survival benefit.

Enhancing Capacity of Community-Academic Partnerships to Achieve Health Equity: Results From the CBPR Partnership Academy.

Community-based participatory research (CBPR) is an equitable partnership approach that links academic researchers, community organizations, and public health practitioners to work together to understand and address health inequities. Although numerous educational materials on CBPR exist, few training programs develop the skills and knowledge needed to establish effective, equitable partnerships. Furthermore, there are few professional development opportunities for academic researchers, practitioners, and community members to obtain these competencies in an experiential co-learning process. In response, the Detroit Community-Academic Urban Research Center developed the CBPR Partnership Academy, an innovative, yearlong capacity-building program facilitated by experienced community and academic partners, involving an intensive short course, partnership development, grant proposal preparation and funding, mentoring, online learning forums, and networking. Three diverse cohorts (36 teams) from 18 states and 2 tribal nations have participated. We describe the rationale and components of the training program and present results from the first two cohorts. Evaluation results suggest enhanced competence and efficacy in conducting CBPR. Outcomes include partnerships established, grant proposals submitted and funded, workshops and research conducted, and findings disseminated. A community-academic partner-based, integrated, applied program can be effective for professional development and establishing innovative linkages between academics and practitioners aimed at achieving health equity.

US oral health students' willingness to train and administer the HPV vaccine in dental practices.

HPV oropharyngeal cancers have now surpassed cervical cancer rates in the US. Dental providers' engagement in HPV education and vaccination efforts may help reduce the burden of HPV oropharyngeal cancers. We examined factors associated with oral health students' willingness to train and administer the human papillomavirus (HPV) vaccine in dental settings. US students in 15 oral health programs participated in an online survey in 2016. Unadjusted and adjusted multivariable logistic regression were conducted and odds ratios (OR) and 95% confidence intervals (CI) were reported. Analyses were conducted in SAS Version 9.4. Data from a total of N = 306 students were analyzed to examine sociodemographic, educational, practice, and attitudinal factors associated with willingness to train and administer the HPV vaccine. Majority of the participants were female (70.3%), non-Hispanic/Latino (90.8%), and White (62.1%). Perceiving that HPV vaccination recommendation (OR = 1.95, 95% CI = 1.14-3.35) and administration (OR = 3.79, 95% CI = 1.63-8.81) was in the dental professional's scope was positively associated with outcome measures when other factors were held constant. Students with greater patient contact time (OR = 4.47, 95% CI = 1.14-17.58) and lower role conflict (agreed that HPV vaccine administration was in the dental professional's scope) had higher odds of willingness to administer the HPV vaccine when other factors were held constant (OR = 5.9, 95% CI = 2.27-15.3). The major barrier to engaging oral health students in HPV vaccination efforts was role conflict. Professional organizations and oral health programs should strongly support the role of oral health professionals in HPV oropharyngeal prevention.

Clinical and Molecular Features of Post-Colonoscopy Colorectal Cancers.

BACKGROUND & AIMS: Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy). METHODS: Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Archived specimens were retrieved and tested for microsatellite instability (MSI), CpG island methylation, and mutations in KRAS and BRAF. There were 2659 cases of CRC diagnosed within the study window; 6% of these (n = 159) were defined as PCCRCs; 84 of these cases had tissue available and were matched to 84 subjects with detected CRC. RESULTS: Higher proportions of PCCRCs than detected CRCs formed in the proximal colon (64% vs 44%; P = .016) and were of an early stage (86% vs 69%; P = .040). MSI was observed in 32% of PCCRCs compared with 13% of detected CRCs (P = .005). The other molecular features were found in similar proportions of PCCRCs and detected CRCs. In a multivariable logistic regression, MSI (odds ratio, 4.20; 95% CI, 1.58-11.14) was associated with PCCRC. There was no difference in 5-year survival between patients with PCCRCs vs detected CRCs. CONCLUSION: In this population-based cross-sectional study of incident CRC cases in Utah, we found PCCRCs to be more likely to arise in the proximal colon and demonstrate MSI, so PCCRCs and detected CRC appear to have different features or processes of tumorigenesis. Additional studies are needed to determine if post-colonoscopy cancers arise through a specific genetic pathway.

The Epidemiology of Cancer Among Homeless Adults in Metropolitan Detroit.

BACKGROUND: Homeless individuals suffer and die disproportionately from chronic diseases and disorders. We describe the epidemiology of cancer among homeless persons in metropolitan Detroit. METHODS: A retrospective cohort study was performed using 1973-2014 data from the Metropolitan Detroit Cancer Surveillance System, a population-based cancer registry and member of the National Institutes of Health-National Cancer Institute's Surveillance, Epidemiology, and End Results program. Homeless adults were identified through address at diagnosis listed as a homeless shelter, hospital, or supplemental field indicating homelessness. Age-adjusted, sex-specific proportional incidence ratios (PIR) compared cancer incidence proportions by primary tumor site of homeless patients to the nonhomeless referent population. Kaplan-Meier curves depicted unadjusted survival differences in a propensity score matched sample. Differences in 10-year survival were assessed using the score test with a sandwich estimator accounting for matched cluster effects. Statistical tests were two-sided. RESULTS: A total of 388 individuals experienced homelessness at first primary invasive cancer diagnosis. Statistically significantly higher proportions of respiratory system (PIR = 1.51; 95% confidence interval = 1.28 to 1.79) and female genital system (PIR = 1.83; 95% confidence interval = 1.31 to 2.55) cancers were observed among homeless men and women, respectively. Homeless persons had poorer overall and cancer-reported survival compared with a propensity score matched referent population (median: overall survival, 20.0 vs 38.0 months, respectively, P < .001; cancer-reported survival, 38.0 vs 64.0 months, respectively, P < .001). CONCLUSION: Disparities in disease burden exist between adults who are experiencing homelessness compared with the nonhomeless population at cancer diagnosis. These findings provide clinically relevant information to understand the cancer burden in this medically underserved population and suggest an urgent need to develop cancer prevention and intervention programs to reduce disparities and improve the health of homeless persons.

Family History Associates With Increased Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing colorectal cancer (CRC). Although family history of CRC is a well-established risk factor in healthy individuals, its role in patients with IBD is less clear. We aimed to estimate the risk of CRC in a cohort of patients with IBD from Utah and the significance of family history of CRC in a first-degree relative (FDR). METHODS: We identified Utah residents with IBD, using the Intermountain Healthcare and University of Utah Health Sciences databases, from January 1, 1996, through December 31, 2011. CRCs were identified using the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. CRC incidence was compared with that of the state population by standardized incidence ratios (SIRs). RESULTS: A cohort of 9505 individuals with IBD was identified and 101 developed CRC during the study period. The SIR for CRC in patients with Crohn's disease was 3.4 (95% CI, 2.3-4.4), and in patients with ulcerative colitis was 5.2 (95% CI, 3.9-6.6). Patients with IBD and a concurrent diagnosis of primary sclerosing cholangitis had the greatest risk of CRC (SIR, 14.8; 95% CI, 8.3-21.2). A history of CRC in a FDR was associated with a nearly 8-fold increase in risk of CRC in patients with IBD (SIR, 7.9; 95% CI, 1.6-14.3), compared with the state population. CONCLUSIONS: Patients with IBD have a 3- to 5-fold increase in risk of CRC, and those with CRC in a FDR have an almost 8-fold increase in risk. Family history may act as a simple measure to identify individuals with IBD at highest risk for CRC and indicates the need for enhanced surveillance in this population.

Histone Deacetylase Inhibition Has Targeted Clinical Benefit in ARID1A-Mutated Advanced Urothelial Carcinoma.

Histone deacetylase (HDAC) inhibition has sporadic clinical efficacy in urothelial carcinoma; the genomic basis for clinical response is not known. In two separate phase I clinical trials testing pharmacokinetic aspects of HDAC inhibitors in advanced solid tumors, we identified one patient with advanced urothelial carcinoma who had a complete response to belinostat, and one patient with advanced urothelial carcinoma who had a partial response to panobinostat. The archived tumors of the responders were genomically characterized in comparison to others with urothelial carcinoma on the trials. Urothelial carcinoma cell lines treated with panobinostat and belinostat were studied to elucidate the mechanisms of benefit. Notably, the urothelial carcinoma tumors that responded to HDAC inhibition had ARID1A mutations. ARID1A mutations were also noted in the tumors of three patients who had stable disease as their best response to HDAC inhibition. Corroborating the basis of sensitivity, transcriptional profiling of platinum-resistant ARID1A-mutated HT1197 cells treated with panobinostat reveals negative enrichment for both cyto-proliferative (MYC and E2F targets) and DNA repair gene sets, and positive enrichment for TP53 and inflammatory gene sets. Our study identifies ARID1A loss as a basis for clinical response to pan HDAC inhibition and offers avenues for potential rational therapeutic combinations with HDAC inhibitors in advanced urothelial carcinoma.

A functional assay-based procedure to classify mismatch repair gene variants in Lynch syndrome.

PURPOSE: To enhance classification of variants of uncertain significance (VUS) in the DNA mismatch repair (MMR) genes in the cancer predisposition Lynch syndrome, we developed the cell-free in vitro MMR activity (CIMRA) assay. Here, we calibrate and validate the assay, enabling its integration with in silico and clinical data. METHODS: Two sets of previously classified MLH1 and MSH2 variants were selected from a curated MMR gene database, and their biochemical activity determined by the CIMRA assay. The assay was calibrated by regression analysis followed by symmetric cross-validation and Bayesian integration with in silico predictions of pathogenicity. CIMRA assay reproducibility was assessed in four laboratories. RESULTS: Concordance between the training runs met our prespecified validation criterion. The CIMRA assay alone correctly classified 65% of variants, with only 3% discordant classification. Bayesian integration with in silico predictions of pathogenicity increased the proportion of correctly classified variants to 87%, without changing the discordance rate. Interlaboratory results were highly reproducible. CONCLUSION: The CIMRA assay accurately predicts pathogenic and benign MMR gene variants. Quantitative combination of assay results with in silico analysis correctly classified the majority of variants. Using this calibration, CIMRA assay results can be integrated into the diagnostic algorithm for MMR gene variants.

Patterns of family communication and preferred resources for sharing information among families with a Lynch syndrome diagnosis.

OBJECTIVES: To explore patterns of communication among families with a Lynch syndrome diagnosis and understand what resources could facilitate family communication. METHODS: 127 probands (i.e., first person in family with identified mutation) and family members participated in semi-structured interviews about: how they learned about the Lynch syndrome diagnosis, with whom they shared genetic test results, confidence in sharing results with other family members, and helpfulness of educational resources. RESULTS: Both probands and family members were most likely to share genetic test results with parents and siblings, and least likely to share results with aunts, uncles, and cousins. Most participants felt very confident sharing their test results with family members, but reported that certain topics such as cancer risk were challenging to convey. Probands reported the most helpful resources to be access to a specialty clinic or website, while family members described general printed materials as most helpful. CONCLUSIONS: Families affected by Lynch syndrome may experience barriers to communication with more distant relatives, and may benefit from receiving specific resources (e.g., websites about Lynch syndrome, print materials) to facilitate family communication. PRACTICE IMPLICATIONS: Providers could emphasize the need to share information with more distant family members and provide appropriate supportive resources.

Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous polyposis patients.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) frequently undergo colectomy to reduce the 70 to 90% lifetime risk of colorectal cancer. After risk-reducing colectomy, duodenal cancer and complications from duodenal surgeries are the main cause of morbidity. Our objective was to prospectively describe the duodenal and gastric polyp phenotype in a cohort of 150 FAP patients undergoing pre-screening for a chemoprevention trial and analyze variables that may affect recommendations for surveillance. METHODS: Individuals with a diagnosis of FAP underwent prospective esophagogastroduodenoscopy using a uniform system of mapping of size and number of duodenal polyps for a 10 cm segment. Gastric polyps were recorded as the total number. RESULTS: The distribution of the count and sum diameter of duodenal polyps were statistically different in two genotype groups, those with APC mutations associated with classic FAP had a greater count (median 17) and sum diameter of polyps (median 32 mm) than those with APC mutations associated with attenuated FAP (median count 4 and median sum diameter of 7 mm) (p < 0.0001). The number of gastric polyps did not differ based on genotype (p = 0.67) but advancing age correlated with severity of gastric polyposis (p = 0.019). Spigelman (modified) staging of II or greater was found in 88% of classic FAP patients and 48% attenuated FAP patients. Examples of severe and mild upper GI phenotype are observed in patients with identical APC mutations, showing that the APC mutation location is not absolutely predictive of an upper GI phenotype. CONCLUSIONS: Most FAP patients have duodenal and gastric polyps which become more prevalent and advanced with age. Standard upper endoscopic surveillance is recommended based on personal history independent of APC mutation location. TRIAL REGISTRATION: NCT 01187901 registered August 24, 2010, prospective to enrollment.

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. Objective: To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Design, Setting, and Participants: Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. Interventions: Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. Main Outcomes and Measurements: The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. Results: Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009). Conclusion and Relevance: In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum. Trial Registration: clinicaltrials.gov Identifier: NCT01187901.

A statewide investigation of geographic lung cancer incidence patterns and radon exposure in a low-smoking population.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in Utah despite having the nation's lowest smoking rate. Radon exposure and differences in lung cancer incidence between nonmetropolitan and metropolitan areas may explain this phenomenon. We compared smoking-adjusted lung cancer incidence rates between nonmetropolitan and metropolitan counties by predicted indoor radon level, sex, and cancer stage. We also compared lung cancer incidence by county classification between Utah and all SEER sites. METHODS: SEER*Stat provided annual age-adjusted rates per 100,000 from 1991 to 2010 for each Utah county and all other SEER sites. County classification, stage, and sex were obtained from SEER*Stat. Smoking was obtained from Environmental Public Health Tracking estimates by Ortega et al. EPA provided low (< 2 pCi/L), moderate (2-4 pCi/L), and high (> 4 pCi/L) indoor radon levels for each county. Poisson models calculated overall, cancer stage, and sex-specific rates and p-values for smoking-adjusted and unadjusted models. LOESS smoothed trend lines compared incidence rates between Utah and all SEER sites by county classification. RESULTS: All metropolitan counties had moderate radon levels; 12 (63%) of the 19 nonmetropolitan counties had moderate predicted radon levels and 7 (37%) had high predicted radon levels. Lung cancer incidence rates were higher in nonmetropolitan counties than metropolitan counties (34.8 vs 29.7 per 100,000, respectively). Incidence of distant stage cancers was significantly higher in nonmetropolitan counties after controlling for smoking (16.7 vs 15.4, p = 0.02*). Incidence rates in metropolitan, moderate radon and nonmetropolitan, moderate radon counties were similar. Nonmetropolitan, high radon counties had a significantly higher incidence of lung cancer compared to nonmetropolitan, moderate radon counties after adjustment for smoking (41.7 vs 29.2, p < 0.0001*). Lung cancer incidence patterns in Utah were opposite of metropolitan/nonmetropolitan trends in other SEER sites. CONCLUSION: Lung cancer incidence and distant stage incidence rates were consistently higher in nonmetropolitan Utah counties than metropolitan counties, suggesting that limited access to preventative screenings may play a role in this disparity. Smoking-adjusted incidence rates in nonmetropolitan, high radon counties were significantly higher than moderate radon counties, suggesting that radon was also major contributor to lung cancer in these regions. National studies should account for geographic and environmental factors when examining nonmetropolitan/metropolitan differences in lung cancer.

Pilot Test of Survey to Assess Dental and Dental Hygiene Student Human Papillomavirus-Related Oropharyngeal Cancer Knowledge, Perceptions, and Clinical Practices.

This was the first study to develop and pilot test an assessment tool for the examination of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) knowledge, perceptions, and clinical practices of oral health students. An interdisciplinary team developed the tool using surveys that examined this topic in other populations. The tool was then pilot tested at two different dental programs. Results from the pilot informed revisions to the final version of the tool. Of the 46 student participants, 18 were first-year dental hygiene and 28 were first-year dental students. The majority of participants were female (N = 29, 63%) and ages 18 to 29 years old (N = 41, 89%). Four scales used in the questionnaire were analyzed for reliability. Of these, the HPV and HPV-OPC knowledge and the HPV vaccination knowledge scales had Cronbach alphas of 0.71 and 0.79, respectively. Questions assessing HPV and the role of dental professionals had a correlation coefficient of 0.71. Questions assessing willingness to administer vaccines in the dental office had a correlation coefficient of 0.85. Assessing oral health students' HPV-OPC knowledge, perceptions, and clinical practices are important for future assessment of possible HPV-OPC cases. Dental professionals may be optimally positioned to provide HPV patient education. The tool developed and pilot tested in this study can help schools assess their students' knowledge and guide their dental curriculum to address deficiencies. Since this topic has not been effectively examined with dental health students, the results could help improve dental education and dental care.

Improvements in Colorectal Cancer Incidence Not Experienced by Nonmetropolitan Women: A Population-Based Study From Utah.

PURPOSE: Little is known about disparities in colorectal cancer (CRC) incidence and mortality by community-level factors such as metropolitan status. METHODS: This analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) program from Utah. We included patients diagnosed with CRC from 1991 to 2010. To determine whether associations existed between metropolitan/nonmetropolitan county of residence and CRC incidence, Poisson regression models were used. CRC mortality was assessed using multivariable Cox regression models. FINDINGS: CRC incidence rates did not differ between metropolitan and nonmetropolitan counties by gender (males: 46.2 per 100,000 vs 45.1 per 100,000, P = .87; females: 34.4 per 100,000 vs 36.1 per 100,000, P = .70). However, CRC incidence between the years of 2006 and 2010 in nonmetropolitan counties was significantly higher in females (metropolitan: 30.4 vs nonmetropolitan: 37.0 per 100,000, P = .002). As compared to metropolitan counties, the incidence of unstaged CRC in nonmetropolitan counties was significantly higher in both males (1.7 vs 2.8 per 100,000, P = .003) and females (1.4 vs 1.6 per 100,000, P = .002). Among patients who were diagnosed between 2006 and 2010, metropolitan counties were found to have significantly increased survival among males and females, but nonmetropolitan counties showed increased survival only for males. CONCLUSIONS: While we observed a decreasing incidence of CRC among men and women in Utah, this effect was not seen in women in nonmetropolitan areas nor among those with unstaged disease. Further studies should evaluate factors that may account for these differences. This analysis can inform interventions with a focus on women in nonmetropolitan areas.

Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia.

To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months (P < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy. Ten FAP patients on placebo and 10 on sulindac and erlotinib were selected for analysis. Purity of biopsied polyp tissue was calculated from RNA expression data. RNAs differentially expressed between endpoint polyp and paired baseline normal were determined for each group and mapped to biological pathways. Key genes in candidate pathways were further validated by quantitative RT-PCR. RNA expression analyses of endpoint polyp compared with paired baseline normal for patients on placebo and drug show that pathways activated in polyp growth and proliferation are blocked by this drug combination. Directly comparing polyp gene expression between patients on drug and placebo also identified innate immune response genes (IL12 and IFNγ) preferentially expressed in patients on drug. Gene expression analyses from tissue obtained at endpoint of the trial demonstrated inhibition of the cancer pathways COX2/PGE2, EGFR, and WNT. These findings provide molecular evidence that the drug combination of sulindac and erlotinib reached the intended tissue and was on target for the predicted pathways. Furthermore, activation of innate immune pathways from patients on drug may have contributed to polyp regression. Cancer Prev Res; 11(1); 4-15. ©2017 AACRSee related editorial by Shureiqi, p. 1.

Utah Cancer Survivors: A Comprehensive Comparison of Health-Related Outcomes Between Survivors and Individuals Without a History of Cancer.

Assessments of cancer survivors' health-related needs are often limited to national estimates. State-specific information is vital to inform state comprehensive cancer control efforts developed to support patients and providers. We investigated demographics, health status/quality of life, health behaviors, and health care characteristics of long-term Utah cancer survivors compared to Utahans without a history of cancer. Utah Behavioral Risk Factor Surveillance System (BRFSS) 2009 and 2010 data were used. Individuals diagnosed with cancer within the past 5 years were excluded. Multivariable survey weighted logistic regressions and computed predictive marginals were used to estimate age-adjusted percentages and 95 % confidence intervals (CI). A total of 11,320 eligible individuals (727 cancer survivors, 10,593 controls) were included. Respondents were primarily non-Hispanic White (95.3 % of survivors, 84.1 % of controls). Survivors were older (85 % of survivors ≥40 years of age vs. 47 % of controls). Survivors reported the majority of their cancer survivorship care was managed by primary care physicians or non-cancer specialists (93.5 %, 95 % CI = 87.9-99.1). Furthermore, 71.1 % (95 % CI = 59.2-82.9) of survivors reported that they did not receive a cancer treatment summary. In multivariable estimates, fair/poor general health was more common among survivors compared to controls (17.8 %, 95 % CI = 12.5-23.1 vs. 14.2 %, 95 % CI = 12.4-16.0). Few survivors in Utah receive follow-up care from a cancer specialist. Provider educational efforts are needed to promote knowledge of cancer survivor issues. Efforts should be made to improve continuity in follow-up care that addresses the known issues of long-term survivors that preclude optimal quality of life, resulting in a patient-centered approach to survivorship.

White, affluent, educated parents are least likely to choose HPV vaccination for their children: a cross-sectional study of the National Immunization Study - teen.

BACKGROUND: Human Papillomavirus (HPV) vaccination coverage is below national goals in the United States. Research is needed to inform strategically designed interventions that target sociodemographic groups with underutilization of HPV vaccination. METHODS: Secondary data analysis of the National Immunization Survey-Teen 2013 measured association of sociodemographic factors (e.g., ethnicity/race, insurance) with HPV vaccination among females and males ages 13-17 (N = 18,959). Chi-square and multivariable Poisson regressions were conducted using survey-weighted statistics. RESULTS: Having a mother ≥35 years, a mother with some college, being of "Other" ethnicity/race, and having no providers who order vaccines from health departments was negatively associated with females initiating HPV vaccination. Having a mother with some college, being of Non-Hispanic White or "Other" ethnicity/race, and having some or no providers who order vaccines from health departments was negatively associated with males initiating HPV vaccination. These same factors were negatively associated with males completing HPV vaccination with the exception of "Other" ethnicity/race. In contrast, having an unmarried mother, being ages 15-17, having a hospital based provider, and receiving other adolescent vaccinations were positively associated with females initiating and completing HPV vaccination. Having an unmarried mother, health insurance that is not employer or union sponsored, and influenza and meningitis vaccinations was positively associated with male's initiating HPV vaccination. For males, being 15 or 17 years old and having other adolescent vaccinations was positively associated with vaccine completion. All findings p ≤ 0.05. CONCLUSIONS: Future HPV vaccination interventions may benefit from targeting certain sociodemographic groups that were negatively associated with HPV vaccination in this study.