Research Projects: Cancer Prevention and Control Program

Rural Cancer Survivors/Health Disparities

Prevalence and Health Status of Cancer Survivors in the Rural US (R03CA156641; PI: Weaver, Co-Is: Case) is a study that used data from the National Health Interview Survey to generate the first population-based estimate of the number of US cancer survivors who reside in rural areas and to describe their socio-demographic and cancer characteristics, health behaviors, health care utilization, and health status (self-reported health, psychological distress, non-cancer comorbidities, and unemployment due to health).

Cancer-related Follow-up Care Experiences of Rural Cancer Survivors (R03CA157211; PI: Weaver; Co-Is: Avis, Tooze). This study surveyed breast, prostate, and colorectal cancer survivors (n=174) who were two to five years post-diagnosis and resided in rural areas. Key topics of interest included characteristics of post-treatment follow-up care received, barriers to follow-up care, health-related information needs, and adherence to screening and surveillance guidelines.

End of Treatment Transition to Follow-Up Care among Early Stage Lung Cancer Survivors (R03CA179019;PI: Weaver, PhD, Co-Is: Tooze, Petty, Ruiz) This mixed-methods study focuses on an understudied, but growing population, early stage lung cancer survivors, and gathered novel data on their follow-up care transition experiences and needs. This study recruited patients diagnosed with localized lung cancer who completed primary treatment within the past 3-24 months to explore lung cancer survivors' experiences in the two years after initial treatment, focusing on their health needs, communication with treatment team, and psychosocial concerns using both semi-structured interview and survey research strategies.

A Primary Care Multilevel mHealth Colorectal Cancer Screening (mCRC) (R01CA178941; PI: D. Miller, Co-I: Weaver)  This project is evaluating the efficacy of an innovative multilevel mHealth colorectal cancer (CRC) screening intervention (mCRC) designed for primary care practices that incorporates a tablet computer CRC screening decision aid and text messaging support. This randomized clinical trial will evaluate: 1) the ability of the mCRC system to increase receipt of CRC screening within 24 weeks of enrollment, 2) potential mechanisms of change by which the mCRC system facilitates screening, and 3) the additional cost of the mCRC system per patient screened.

Tobacco Control

Smokeless Tobacco Use in College Students (R01CA141643; Co-PIs: Wolfson and Spangler;  Co-Is: Reboussin, Sutfin). The goal of this study is to better understand trajectories and correlates of smokeless tobacco (SLT) use among college students. The study team measured trajectories of SLT use among undergraduate college students over the course of their college careers and are analyzing data collected to identify environmental and individual-level correlates of trajectories of SLT use. The research team is also examining patterns of use of different SLT products, including chewing tobacco, dry and moist snuff (including snus and other flavored products), and alternative products (including lozenges, strips, orbs, and sticks).

Dissolvable Tobacco Perceptions and Use among Young Adults in Test Markets (R01CA141643-04S2, Co-PIs: Wolfson and Spangler,  Co-Is: Reboussin, Sutfin, Wagoner) A new generation of dissolvable tobacco products has been introduced into test markets in the U.S. This study assesses perceptions and use of these products in three test markets where they are currently available (Denver, CO, Charlotte, NC and various cities in Kansas).  This information will better enable the Food and Drug Administration to fulfill its responsibilities regarding regulation of these products under the Family Smoking Prevention and Tobacco Control Act of 2009.

Tobacco Use Trajectories and Surgical Outcomes in Newly Diagnosed Head and Neck Cancer Patients in North and South Carolina (Joint Pilot Grant between Wake Forest Baptist Comprehensive Cancer Center and Hollins Cancer Center, Medical University of South Carolina; Co-PIs: Weaver and  Sterba; Co-Is: Janet Tooze)  The goal of this observational pilot study was to understand the influence of smoking status on surgical outcomes in head and neck cancer patients (n=109) and to gather preliminary data that can be used to translate study findings into future clinic-based interventions for head and neck cancer patients.

Effective Communication on Tobacco Product Risk and FDA Authority (P50CA180907, PI: Ribisl, PD: Sutfin, Co-Is: Reboussin, Wolfson, Wagoner). The Center for Regulatory Research on Tobacco Communication is a partnership with UNC Lineberger Comprehensive Cancer Center and one of 14 NIH/FDA-funded Tobacco Regulatory Research Centers. The goal of this center grant is to advance regulatory science by using communication science to improve messages about cigarette smoke constituents, emerging tobacco products, and the FDA's regulatory authority over tobacco. The Center aims to conduct three integrated research projects among vulnerable populations and across the lifespan to inform regulatory science.  

Large Epidemiologic Studies/Resources Covering Multiple Content Areas

Wake Forest NCI Community Oncology Research Program (NCORP) Research Base  (UG1CA189824; PI: Lesser; Co-Is: Weaver, Danhauer, Rapp, Vitolins). NCORP research bases serve as a conduit for community-based research through its 837 practices.The WF NCORP Research Base is the only NCI-designated Comprehensive Cancer Center Research Base. The Wake Forest NCORP supports research on neurocognitive deficits, cardiotoxicity, symptom management, and cancer care delivery research, with an emphasis on survivorship care. The Wake Forest NCORP represents a key inter-programmatic collaboration between the Cancer Prevention and Control Program and the Clinical Research Program.

Women's Health Initiative and WHIMS (N01WH44221; PI: Shumaker).The Women's Health Initiative (WHI) was initiated in the early 1990s, and was comprised of an observational cohort study of approximately 93,000 healthy women ages 50-79 at study entry. There were also three clinical trials in WHI:  1) low fat dietary modification (intervention vs. placebo group) of approximately 46,000 women;  2) post-menopausal hormone therapy study (n=26,000 women) comparing estrogen only (CEE) vs. placebo for those women with a uterus, or estrogen plus progesterone (CEE/MPA) vs. estrogen for those women who had not had a hysterectomy, and 3)  a study of Calcium and vitamin D supplements vs. placebo, which was open to women in either the dietary modification and/or the hormone trials.  In all, approximately 162,000 women were enrolled in either the observational or clinical trial components of WHI.  Women were recruited into WHI from 1993 - 1999. The study was extended from 2005-2010, and then received a second extension from 2010-2015, enrolling approximately 93,000 of the original WHI participants. During the second extension, regional coordinating centers for WHI were created.  Wake Forest University houses the center for the Southeastern Region of the United States, overseeing medical outcomes data collection and the production of papers and ancillary study proposals from WHI data. Dr. Shumaker is the PI of our Southeastern Region Coordinating Center.             

Symptom Management and Quality of Life

Acupuncture for the Treatment of Hot Flashes (R01AT005854; PI:Avis). A recently completed trial, "Acupuncture Treatment for Menopausal Hot Flashes" (R21CA104427; PI: Avis) randomized women to one of three groups: true acupuncture, sham acupuncture, or usual care. The research team found a significant decrease in mean frequency of hot flashes, but no difference between the two acupuncture groups, but both showing a significantly greater decrease in hot flashes compared to the usual care group (Avis et al. Menopause, 2008). These results suggest either a strong placebo effect or that both traditional and sham acupuncture significantly reduce hot flash frequency.  A subsequent study is currently underway to provide greater insight into the effectiveness of acupuncture for hot flashes (R01AT005854, "Acupuncture for Hot Flashes" PI: Avis). This study is randomizing 200 women to examine real world effectiveness of acupuncture for hot flashes among cancer survivors and menopausal women.

Reducing Lung Cancer Survivor Anxiety (RELAX) with Brief Device-Guided Breathing (R21CA182111; PI: Danhauer). Lung cancer is the second-most common cancer diagnosed in the US, yet little "survivorship" research has focused on this population. As the number of early stage lung cancer (ESLC) survivors increases because of uptake in low dose computerized tomography lung cancer screening, it will be increasingly important to develop interventions to improve their well-being. The goal of study is to determine feasibility of a device-guided breathing intervention versus a music control group and to obtain preliminary data on effects on anxiety, dyspnea, pulmonary function, and functional fitness in ESLC survivors. This study will enroll 60 post-treatment ESLC survivors with clinically meaningful anxiety symptoms through two sites of the Wake Forest NCI Community Oncology Research Program Research Base (WF NCORP RB). Participants will be randomly assigned to one of three groups: low-dose (15 minutes, once per day) RESPeRATE device-guided breathing (n=20), high-dose (15 minutes, twice per day) RESPeRATE (n=20), and music control (15 minutes, once per day) (n=20). The results of this study will provide outstanding preliminary data for a planned R01 application for a larger randomized controlled trial that will be run through the WF NCORP RB that can better elucidate the impact of the proposed simple intervention for anxious, post-treatment ESLC survivors, that can be easily disseminated.

Investigating Mechanisms to Explain Age Associated Differences in Quality of Life among Breast Cancer Patients (PI:Avis, Co-I: Naughton). The purpose of this study is to better understand why younger women have greater psychological morbidity following a breast cancer diagnosis than older women and to examine age-related differences in treatment. This prospective observational cohort study has enrolled over 650 women and followed them for 2 years post diagnosis and provides a rich resource for manuscripts related to cancer survivorship.

Lifestyle Interventions

Prosocial Behavior and Volunteerism to Promote Physical Activity in Older Adults (R01HL109429; PI: Foy, Co-Is: Vitolins, Tooze) is a 5-year randomized controlled trial that compares the effect of a "healthy aging" control intervention (n=150) vs. that of a physical activity intervention (N=150) which embeds prosocial behavior and volunteerism upon physical activity at 12 months. Three hundred men and women aged 55 to 80 years are being randomized into the two interventions. This study involves administration of questionnaires, direct measures of blood pressure, body weight and size, and direct measures of physical performance. In addition, survivors of cancer are eligible for this study, which may provide opportunities for qualitative interviews and assessments which address cancer survivorship.

Taking Health Realization into Valued Eating and Exercise (THRIVE): A Feasibility Study of an Intervention to Prevent Weight Gain for Breast Cancer Survivors during Chemotherapy. (PI:Mihalko, Danhauer). The goal of the THRIVE pilot study is to demonstrate the feasibility of conducting a randomized clinical trial to test the effectiveness of an intervention to prevent weight gain for breast cancer survivors during chemotherapy. This study tests the efficacy of the intervention as a springboard to a short-term healthy lifestyle program.

A Feasibility Study of a Physical Activity Intervention in Older Adult Inpatients with Acute Leukemia  (Intramural grant; PI: Mihalko; Co-Is: Danhauer, Klepin).  Acute myelogenous leukemia (AML) is a disease of older adults characterized by disproportionately worse survival associated with increasing age. Adults undergoing intensive treatment for AML frequently experience substantial physical deconditioning, treatment-related symptoms and emotional distress.  Development of evidence based treatment guidelines for older adults will depend upon targeted interventions designed to minimize the impact of therapy in this population on physical function and quality of life.  The goal of this pilot study is to demonstrate the feasibility of conducting a randomized clinical trial to test the effectiveness of a physical activity intervention for older adult patients with acute leukemia who are undergoing induction or reinduction chemotherapy on physical and psychological health.

Omega-3 PUFA-Gene Interaction in Prostate Cancer (R01CA163273; PI: Chen). The goal of this research is to study the interaction between dietary PUFA and their metabolic enzymes in prostate cancer. This research team has previously shown that I3 PUFA reduced prostate cancer (PCa) growth, slowed histopathological progression and increased survival, whereas I6 PUFA had the opposite effects. They hypothesize that I3 PUFA is primarily metabolized by Cox1 in vivo and that the anti-proliferative effect of I3 PUFA is, in part, mediated by Cox1 metabolite(s). Furthermore, I6 PUFA is metabolized by Cox1, Cox2 and Lox5, and the corresponding metabolites play important roles in stimulating PCa growth. To test this hypothesis, three specific aims are proposed: (1) Study the cellular mechanism(s) of PUFA-gene interaction on PCa growth, (2) Identify metabolite(s) of I3 and I6 PUFA important in PCa and (3) Examine metabolite signaling in PCa cell proliferation and apoptosis.

Late Effects of Cancer Treatment

Resonance Imaging Trial for Heart bioMarkers (RITHM) in AYA Cancer Survivors  (R21CA159557; PI: Castellino; Co-I: Hundley). Treatment of childhood cancer has been one of the resounding successes of medicine in the last half of the 20th century, as 1 in 640 young adults in the US is a survivor of childhood cancer. With increased person-years of life impacted, cardiovascular (CV) disease is now the leading cause of non-cancer death in childhood cancer survivors. Anthracycline chemotherapy is a major risk for this CV morbidity and mortality. A lack of functional markers of CV risk has limited cardioprotection and secondary prevention strategies. Cardiac magnetic resonance imaging (CMR) provides precise measures of aortic and cardiac function, making it ideal for establishing surrogate markers of subclinical disease in smaller populations. This project is an observational clinical trial with a cross-sectional and longitudinal design to evaluate the application of CMR in detecting subclinical markers of cardiac injury after anthracycline therapy. The research team is using CMR to measure aortic stiffness and myocardial wall strain in adolescent/young adult survivors of childhood cancer off therapy in comparison to a control group without cancer. In addition they are evaluating the ability of CMR to detect and follow changes in aortic function in newly diagnosed adolescent patients receiving anthracycline chemotherapy. The trial at two childhood cancer programs will lead to: novel CMR biomarkers of subclinical anthracycline cardiotoxicity, an understanding of previously unexplored concepts of aortic stiffness and myocardial strain in the pathophysiology, and the establishment of a young anthracycline exposed cohort who can be followed with CMR for future studies of the technology and targeted interventions. 

Early Imaging Detection of CV Injury after Cancer (R01CA167821; PI: Hundley).  In collaboration with Siemens Medical Solutions, this project develops a new magnetic resonance imaging (MRI) scanner for detecting early subclinical vascular toxicity secondary to cancer chemotherapy. This technical and methodological solution for cancer investigations establishes an innovative methodology to detect the risk for early cardiovascular disease, and thereby enable timely new preclinical therapy guidelines designed to reduce potential cardiovascular events and thus improve the overall survival of those treated for cancer.

Cognition

Cognitive functioning is an important area of cancer survivorship as researchers are increasingly finding cognitive deficits following cancer treatment. More research needs to be done on the exact nature of these deficits, identification of risk factors for cognitive deficits, and possible interventions to prevent or slow these deficits. Cognition is a strong area at WFUSM in population sciences, basic sciences, and radiation oncology and several multidisciplinary groups are already addressing these issues. 

Women's Health Initiative Memory Study (PI: Shumaker). A long standing ancillary study to WHI is the Women's Health Initiative Memory (WHIMS) suite of studies. These studies were developed by Dr. Shumaker and colleagues and the WHIMS coordinating center is also located at WFSM.  Beginning in 1996, the WHI included a unique and detailed assessment of global cognitive functioning, mild cognitive impairment, and dementia  on a subset of women (aged 65 and older) who were enrolled in the WHI hormone trials  (N=7,450).  Follow-up of about 3,700 of these women still continues.  The Women's Health Initiative Study of Cognitive Aging (WHISCA) and the Women's Health Initiative Magnetic Resonance Imaging (WHIMS-MRI) study were conducted on subsets of WHIMS participants.  In addition, the Women's Health Initiative Memory Study of Younger Women (WHIMS-Y) began in 2008. 

This study is designed to assess the long-term impact of random assignment to postmenopausal hormone therapy among women who were 50-54 years of age at the time they were initially enrolled into the WHI hormone trials.  Hormone therapy continues to be widely prescribed for the treatment of menopausal symptoms.  There remains a strong belief among basic and clinical scientists that hormone therapy begun during the peri- or immediate post-menopausal periods may bestow cognitive benefits and that the cognitive harm associated with hormone therapy in the post-menopausal woman occurs only when there is some pre-existing, sub-clinical disease and/or the aging brain is more vulnerable to the possible negative effects of hormones.  This specific issue was not addressed within the original WHIMS cohort, and WHIMS-Y takes advantage of the rich WHI cohort by adding critical information on the clinical treatment of peri-menopausal and early post-menopausal women and on potential mechanisms of action for how HT may affect cognition.

Both WHI and WHIMS provide a wealth of opportunities to study factors related to cancer prevention and control, as well as survivorship, due to rich data on dietary habits, exercise, social support, comorbidities, quality of life and health disparities.   

Gene-Hormone Interaction and Risk of Breast Cancer (R01CA149135; Co-PIs: Sun, Vitolins). The overall hypothesis of this study is that common genetic variants can be used to classify women into low or neutral risk groups for developing breast cancer due to HT use (gene-hormone interaction). The research team specially hypothesize that 1) a subset of genetic variants account for individual differences in risk of developing breast cancer upon HT use (E+P or E only) on breast cancer risk, 2) those SNPs may or may not alter the risk of developing CVD upon HT use. We will identify the genetic variants using data and samples from the Hormone Therapy Trial (HT) of the Women's Health Initiative (WHI) study, a large randomized, double-blind, placebo-controlled clinical trial, and perform a replication study in the WHI Observational Study (OS). To test these hypotheses, we have four specific aims. Aim 1 is to identify SNPs that account for individual differences in risk of developing breast cancer upon HT use (SNP-HT interactions). Aim 2 is to confirm the top significant SNPs identified in Aim 1 among women in the OS arm. Aim 3 is to evaluate the SNP-HT interaction with other phenotypes (primarily CVD) among women in the OS arm. Aim 4 is to estimate the individual absolute risk of developing breast cancer upon HT use among women in the OS arm. The identified genetic variants will be used to create a risk-benefit profile for HT treatment and may potentially improve clinical decision making for HT use.

The Study of Women's Health Across the Nation (SWAN) (U01AG12546; Wake Forest PI: Avis) is a large multi-site, multi-ethnic 15-year study of mid-aged women as they transition through menopause. The dataset includes psychosocial factors, health risks and health behaviors, physiological measures, and disease outcomes.  The data provide the opportunity to prospectively examine cancer survivorship among those women who develop cancer over the course of the study and to compare health status to healthy controls. An ancillary study focused on cancer survivors is planned for the Fall.