Stacey A. Slone

A feasibility study of home-based contingency management with adolescent smokers of rural Appalachia.

Cigarette smoking among adolescents remains a significant public health concern. This problem is compounded in regions such as rural Appalachia where rates of smoking are consistently higher than national averages and access to treatments is limited. The current research evaluated a home-based contingency management program completed over the Internet with adolescent smokers recruited from rural Appalachia. Participants (N = 62) submitted 3 video recordings per day showing their breath carbon monoxide (CO) levels using a handheld CO monitor. Participants were assigned to either an active treatment condition (AT; n = 31) in which reductions in breath CO were reinforced or a control treatment condition (CT; n = 31) in which providing timely video recordings were reinforced with no requirement to reduce breath CO. Results revealed that participants in the AT condition reduced their breath CO levels significantly more so during treatment than participants in the CT condition. Within-group comparisons revealed that participants in both conditions significantly reduced their breath CO, self-reported smoking, and nicotine dependence ratings during treatment. However, only participants in the AT condition significantly reduced urinary cotinine levels during treatment, and only participants in this condition maintained all reductions until 6-week post treatment. Participants in the CT condition only maintained self-reported smoking reductions until posttreatment assessments. These results support the feasibility and initial efficacy of this incentive-based approach to smoking cessation with adolescent smokers living in rural locations.

Effectiveness of a primary care practice intervention for increasing colorectal cancer screening in Appalachian Kentucky

OBJECTIVE This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. METHODS Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. RESULTS A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). CONCLUSIONS Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy.

Delay discounting and self‐reported impulsivity in adolescent smokers and nonsmokers living in rural Appalachia

Background and Objectives This study evaluated whether impulsivity (delay discounting and BIS-11-A) is associated with adolescent smoking status in a region with strong environmental risk factors for smoking. Methods Forty-two adolescent smokers and nonsmokers from rural Appalachia completed discounting and self-reported impulsivity assessments. Results The BIS-11-A, but not the measure of discounting, was associated with smoking status; however, neither assessment predicted smoking status once parent/best-friend smoking variables were statistically accounted for. Discussion and Conclusions In regions with strong environmental risk factors for smoking, delay discounting may play a more limited role in risk of initiation. Scientific Significance Helps to better define impulsivity as risk factors for smoking in relation to familial and broader cultural variables.

Comprehensive evaluation of treatment and outcomes of low-grade diffuse gliomas

Background Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States. Methods We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma. Results We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most common primary site location was the cerebrum (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3% chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy + chemotherapy (6.7%). Radiation was more common in treatment of elderly patients, 1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline location. Median survival was 11 years with younger age, 1p/19q co-deletion, and cerebrum location offered survival advantage. Conclusions Tumor location, 1p/19q co-deletion, and age were the main determinants of treatment received and survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting in the majority of the patients (86.1% versus 8.1%). Survival of low-grade gliomas is higher than previously reported in the majority of clinical trials and population-based analyses. Our analysis provides a real world estimation of treatment decisions, use of molecular data, and outcomes.

Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: A multicenter study from the international lung cancer consortium

Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08–1.72, P = 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84–1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61–1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors. Clin Cancer Res; 23(24); 7550–7. ©2017 AACR.

Abstract 2248: CommonTDP1polymorphisms in relation to survival among small cell lung cancer patients in a multicenter study from the International Lung Cancer Consortium

Introduction: DNA topoisomerase inhibitors (e.g. etoposide, irinotecan, teniposide, topotecan) are commonly used for treating small cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) plays a role in repairing DNA damage caused by DNA topoisomerase inhibitors and it is believed to be responsible for resistance to this class of drugs. The purpose of this study was to determine whether common TDP1 polymorphisms are associated with overall survival among SCLC patients. Method: Two common TDP1 SNPs (rs942190 and rs2401863, r2(European)=0.63 and r2(East Asian)=0.26) were analyzed in 898 patients from 10 studies in the International Lung Cancer Consortium, conducted in the U.S., Canada, Japan, Italy, Spain and the United Kingdom. Genotype data were obtained from either the OncoArray Consortium or other existing genome-wide association studies. Cox proportional hazard regression models with robust standard error were used to evaluate genotype associations for overall survival at 36 months post-diagnosis, adjusting for age, sex, race and tumor stage. Results: Patients homozygous for the minor allele (GG) of TDP1 SNP rs942190 were associated with poorer survival compared to those carrying both major alleles (AA), with a hazard ratio (HR) of 1.36 (95% confidence interval (CI): 1.07-1.72, p-value=0.01), but there was no association with survival for patients with the heterozygous genotype (HR=1.02, 95% CI: 0.83-1.27, p-value=0.83). For rs2401863, patients carrying both minor alleles (CC) tended to have better survival than patients carrying AA alleles, but this was within the limits of chance given no significant association (HR=0.79, 95% CI: 0.61-1.02, p-value=0.07). In addition, multi-tissue expression quantitative trait loci (eQTL) analyses from the Genotype-Tissue Expression Project indicated a potential effect of rs942190 on lung tissue, with higher TDP1 gene expression for the GG than AG or AA genotypes. Conclusion: We found that among SCLC patients the TDP1 rs942190 GG genotype was associated with poor overall survival. Further study could determine if this genotype can serve as a predictive marker for the treatment efficacy of DNA topoisomerase inhibitors in SCLC. Citation Format: Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. Davies, John K. Field, Eric B. Haura, Rayjean J. Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O9Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardon, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Noel S. Weiss, Chu Chen. Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients in a multicenter study from the International Lung Cancer Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2248. doi:10.1158/1538-7445.AM2017-2248

Abstract B14: Effectiveness of patient navigation for follow-up for abnormal pap tests in Appalachian Kentucky

Introduction. Residents of Appalachian Kentucky experiences significant cancer disparities. The population is characterized, in general, as largely rural with high poverty rates, high unemployment and limited access to health care. Lung and colorectal cancer incidence and mortality rates in this area are among the highest in the nation and although cervical cancer mortality has decreased over recent decades, data from the Surveillance, Epidemiology, and End Results (SEER) program reveals that mortality rates in Kentucky are substantially higher than the national average. In 2003, when this project began, the US cervical cancer mortality rate was 2.7 per 100,000 (95% confidence interval = 2.6-2.7). During the same period, the rate in Kentucky was 3.2 per 100,000 (2.9-3.6). In the 54 Appalachian counties in the state, the rate was even higher, 3.7 per 100,000 (3.5-4.0). Death from cervical cancer is preventable in nearly all cases with screening by the Pap test and adherence with recommendations to obtain follow-up care when abnormalities are detected. Methods. To address the problem of elevated cervical cancer incidence and mortality experienced by rural Appalachian women, a patient navigation intervention program was developed with the goal of increasing adherence with recommendations for follow-up for women with abnormal Pap test results. The intervention was implemented in partnership with county health departments. Intervention effectiveness was evaluated in a quasi-experimental trial that included intervention county health departments (n=13) that provided patient navigation services and a comparison group of county health departments (n=13) that provided usual care. Women with abnormal Pap test results were enrolled in the intervention group county health departments and patient navigation was tailored to the type of follow-up care recommended. Study outcome data were collected from medical records. Participants were enrolled from September 2008 through July 2010. A total of 774 medical record reviews are included in the analysis (230 women in intervention and 544 women in comparison county health departments). Recommendations for follow-up, which were based on the type of abnormality and the age of the patient, included returning to the health department to obtain a repeat Pap test or making an appointment with a community gynecologist under contract with the health department. Key Findings. The proportion of participants that received their recommended follow-up care was greater in the intervention group (91.6%) than in the comparison group (80.8%) (p=.01). The effect of the patient navigation intervention was strongest among women who received follow-up care from the health department as opposed to community gynecologists under contract with the health departments. Conclusions. The results demonstrate the effectiveness of the patient navigation intervention and also provide evidence suggesting that development of policy to promote integration of navigation with rural health care delivery systems has great potential to improve patient outcomes. Citation Format: Mark Dignan, Brent Shelton, Nancy E. Schoenberg, Carol R. White, Stacey A. Slone, Emily Van Meter, Frances J. Feltner, Gretchen Ely, Christopher DeSimone. Effectiveness of patient navigation for follow-up for abnormal pap tests in Appalachian Kentucky. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B14.

Abstract P2-14-05: A phase II study of combined fulvestrant and RAD001 (everolimus) in metastatic estrogen receptor (ER) positive breast cancer after aromatase inhibitor (AI) failure.

Background: Fulvestrant is used to treat women with metastatic ER-positive breast cancer after AI failure, but has a short duration of benefit. Pi3K/mTOR signaling has been implicated in preclinical models of fulvestrant resistance and recent trials suggest that everolimus, an oral inhibitor of mTOR, can overcome resistance to other forms of endocrine therapy. We hypothesized that everolimus may delay resistance to fulvestrant and prolong time to progression (TTP). Methods: We designed a phase II clinical trial of combined fulvestrant and everolimus in postmenopausal women with ER-positive breast cancer who relapsed or experienced metastatic disease progression within 6 months of AI use. Fulvestrant was given at 500 mg IM on day1, 250 mg d14, 250 mg d28, and monthly thereafter. Everolimus was given at 10 mg po daily. Patients were required to have measurable or evaluable disease with preserved performance status and adequate organ function. Primary endpoint is TTP, and secondary endpoints are safety, response rate, clinical benefit rate, and biomarker analysis. A sample size of 40 patients was calculated to meet a median TTP of 7.0 vs. 3.7 months for fulvestrant alone as reported in the EFECT trial. Patients were followed monthly for clinical and toxicity assessment and imaging was obtained every 2 months. Tumor blocks were collected when available and biopsies were offered if disease was accessible. Results: To date, 30 patients enrolled on study with a median age of 56 years (range 39–85). Most common metastatic disease sites were bone in 26 patients (87%), liver in 19 (63%), and lung in 16 (53%). Prior therapy included tamoxifen in 21 patients (70%), and chemotherapy in 20 (67%), of those 17 were in the adjuvant/neoadjuvant setting. 6 patients (20%) received more than one AI. 2 patients were ruled ineligible immediately after enrollment and starting study treatment, one because of a creatinine level outside the reference range and one because of the need for palliative radiation. Of the remaining 28 patients, 18 discontinued therapy because of disease progression, 3 because of toxicity, 2 upon patient request, and 1 because of unrelated intercurrent illness, with 4 patients currently on therapy. Most common adverse events reported were mucositis in 13 patients (43%) and rash in 11 (36%). Most common laboratory abnormalities were elevated ALT/AST in 18 patients (60%), elevated cholesterol in 13 (43%), and hypokalemia in 13 (43%). The majority of toxicities were grade I/II. Most common grade III toxicities, regardless of attribution, were infection requiring hospitalization in 3 patients (10%), hypokalemia in 3 (10%) and mucositis in 2 (7.4%). There was one grade 4 toxicity reported-hypokalemia. Overall, treatment was reasonably tolerated and toxicities manageable. Efficacy findings, including the primary endpoint of TTP, will be analyzed and presented at the meeting. Conclusions: Combined everolimus with fulvestrant is feasible and has manageable toxicities in this cohort of women with metastatic ER-positive breast cancer. Detailed efficacy analysis along with updated toxicity data will be presented at the meeting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-05.