Research Projects: Cancer Prevention and Control Program
Rural Cancer
Survivors/Health Disparities
Prevalence and Health Status of Cancer Survivors in the Rural (5R03CA156641-02; PI: Kathryn Weaver, PhD,
Co-Is: L. Doug Case, PhD)
is a study using 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 (5R03CA157211-02;
PI: Kathryn Weaver, PhD; Co-Is: Nancy Avis, PhD, Janet
Tooze, PhD) 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 (R03CA179019-01A1;PI: Weaver, PhD,
Co-Is: Janet Tooze, PhD, James Urbanic, MD, William J. Petty, MD,
Jimmy Ruiz, MD) The proposed
mixed-methods study will focus on an understudied, but growing
population, early stage lung cancer survivors, and gather novel
data on their follow-up care transition experiences and needs. This
study will recruit patients diagnosed with localized lung cancer
who have 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) (R01
CA178941; PI: D. Miller, MD,
Co-I:Kathryn Weaver, PhD) 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 (5R01CA141643-04; Co-PIs: Mark Wolfson,
PhD; John Spangler, MD; Co-Is: Beth Reboussin, PhD, Erin
Sutfin, PhD). The goal of this study is to better
understand trajectories and correlates of SLT use among college
students. To do this we will measure trajectories of SLT use among
undergraduate college students over the course of their college
careers; identify environmental and individual-level correlates of
trajectories of SLT use; and examine 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 (3R01CA141643-04S2, Co-PIs: Mark
Wolfson, PhD, John Spangler, MD, Co-Is: Beth Reboussin, PhD,
Erin Sutfin, PhD, Kim Wagoner, EdD) 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 (Comprehensive Cancer Center of Wake Forest
University / Hollins Cancer Center, Medical University of South
Carolina Joint Pilot Grant; Co-PIs: Kathryn Weaver, PhD, Katherine
Sterba,PhD, Christopher Sullivan, MD, Terry Day,MD;
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 (NIDA, PI: Kurt Ribisl, PD: Erin
Sutfin, Co-Is: Reboussin, Mark Wolfson,
Wagoner) The goal of the center grant is to
advance regulatory science by using communication science to
improve messages about cigarette smoke constituents, emerging
tobacco products, and 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
Community Clinical Oncology Program (CCOP) Cancer Center Research Base (U10 CA 81851-09-13; PI: Edward Shaw, MD; Co-Is: Suzanne Danhauer, PhD, Glenn Lesser MD, Steve Rapp, PhD, Mara Vitolins, PhD, Kathryn Weaver, PhD) This program is limited to NCI-designated Comprehensive Cancer Centers. Our Community Clinical Oncology Program (CCOP) Research Base is a unique resource for the WFSM. Interventions to improve QOL of cancer patients and survivors are often conducted within major cancer centers. One of the aims of our CPC Program is to translate such interventions into community cancer centers. The CCOP Research Base mechanism provides one avenue for accomplishing this.
The CCCWFU CCOP Research Base ("Research Base") (U10 CA081851; PI:
Dr. Shaw (CR)) is one of four Cancer Center Research Bases in the
United States. Today, 25 CCOPs throughout the U.S. participate in
Research Base studies, as well as five non-CCOP institutions, which
together represent a network of over 160 community cancer centers
(plus Wake Forest) throughout the Midwest, Northeast, and Southeast
U.S. The Research Base is a multidisciplinary,
inter-programmatic effort of the Clinical Research and CPC Programs
that provides a mechanism for Cancer Center investigator-initiated
symptom management clinical trials to be conducted by a large
number of community cancer centers located across the midwestern
and eastern United States. The Research Base is led by Dr.
Shaw, a radiation oncologist who has been PI since its inception in
1998. The executive steering committee includes Drs. Naughton,
Vitolins, Weaver, Danhauer, Lesser (co-PI), and Rapp. Research Base
funding provides the infrastructure to conduct investigator
initiated trials within the CCOP system. The focus of the Wake
Forest Research Base has been on symptom management interventions
and more recently has expanded its focus to include observational
research and behavioral interventions, opening up new opportunities
for CPC members. The Research Base provides a ready population in
which to conduct cancer control research. Support for concept
and protocol development, staff training, data entry and analysis
are available to faculty.
Women's Health Initiative and WHIMS (N01-WH-4-4221; PI: Sally Shumaker, PhD).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 (1 R01
AT005854; PI:Avis,
PhD) We have studied two
alternative treatments for hot flashes in women: acupuncture and
yoga. A recently completed trial, "Acupuncture Treatment for
Menopausal Hot Flashes" (R21 CA104427; PI: Avis) randomized women
to one of three groups: true acupuncture, sham acupuncture, or
usual care. We 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 (R01 AT005854-01 "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 (R21-CA182111-01; PIs: Danhauer, PhD; Kathryn
Weaver, PhD). 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
Community Clinical Oncology Program Research Base (WF CCOP 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
our planned R01 application for a larger randomized controlled
trial that will be run through the WF CCOP 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: Nancy Avis, PhD, Co-I: Michelle
Naughton, PhD). 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 (5R01 HL109429; PI:Capri Foy,
PhD, Mara Vitolins, PhD, Janet Tooze,
PhD) 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: Shannon Mihalko,
PhD, Suzanne Danhauer, PhD). 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: Shannon Mihalko;
Co-Is: Suzanne Danhauer, Heidi
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.
Loss of fat tissue and functional responses to exercise in
older, obese adults (R01 AG020583; PI: Barbara Nicklas, PhD) The primary goal of this randomized,
clinical trial is to determine whether addition of caloric
restriction to a standardized, progressive resistance training (RT)
program enhances improvements in skeletal muscle and overall
physical function in 120 older (65-79 yrs), overweight/obese
adults. We will also examine the effects of the two
interventions on in vitro characteristics of skeletal muscle and on
systemic inflammation.
Effect of fat loss on functional and cardiovascular benefits of
aerobic exercise (R01 HL093713; PI: Barbara
Nicklas, PhD). This randomized, clinical trial will
determine whether older, obese men and women who lose more fat
during an exercise training program will experience greater
improvements in aerobic function as a result of the exercise
training. The study is designed to assess the effects of
adding moderate (-250 kcal/d deficit) or intensive (-600 kcal/d
deficit) caloric restriction to a standardized aerobic exercise
training intervention on maximal aerobic capacity (VO2max),
functional endurance (400-m walk time), CVD risk factors
(inflammatory markers, blood lipids, blood pressure, glucose
tolerance and endothelial function), and inter-muscular, abdominal
visceral and pericardial fat volumes.
Omega-3 PUFA-Gene Interaction
in Prostate Cancer (5R01CA163273-02; PI-Yong
Chen). The goal of this research is to study the
interaction between dietary PUFA and their metabolic enzymes in
prostate cancer. We have previously shown that I3 PUFA
reduced prostate cancer (PCa) growth, slowed histopathological
progression and increased survival, whereas I6 PUFA had the
opposite effects. We 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 our 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 (1R21CA159557-01A1; PI:
Sharon Castellino, MD; Greg Hundley, MD)This
study is an observational clinical trial with a cross-sectional and
longitudinal design to evaluate the cardiac MRI in detecting
subclinical markers of cardiac injury after anthracycline
therapy. 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. Our 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. We plan to use 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 we will
evaluate 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. This Quick Trial of CMR
will facilitate development of needed surrogate endpoints for
timely, targeted pharmacologic or behavioral interventions to
alleviate the burden of CV disease in this cancer population
Early Imaging Detection of CV Injury after
Cancer (5R01CA167821-02; PI: Greg Hundley, Sharon
Castellino, MD) 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:
Sally Shumaker, Co-I: Steve Rapp). A
long standing ancillary 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. Both Drs. Shumaker and Naughton have been
involved in WHI since its inception, and will assist the post-docs
in working with WHI and WHIMS data.
Phase III Study of Donepezil in the Irradiated
Brain (R01 NR009675-01A2;
PI: Steve Rapp)
This recently completed Phase III randomized,
placebo-controlled, double blind clinical trial tested the efficacy
of donepezil (5mg x 6 wks, 10 mg x 18 weeks) to improve cognitive
functioning in brain tumor survivors > 6 months
following brain radiation treatment. Data analyses are
currently underway and post-docs will be encouraged to use them for
papers and ancillary study proposals.
PPARs and Radiation-Induced Brain
Injury (5R01CA112593-10; Co-PIs Linda
Metheny-Barlow and William Blackstock). This study
examines the mechanisms by which radiation of the brain leads to
brain injury, including cognitive impairment, and evaluates the
ability of PPAR agonists to ameliorate the damage and protect
cognition in rodent models. Dr. Metheny-Barlow is also working on
the development and characterization of models to study breast
cancer brain metastasis development and treatment. As part of
a recently completed DoD pilot grant, she has developed a unique
brain metastasis-bearing rat model to study effects of therapeutic
fractionated whole brain irradiation on tumor response and
cognition; this model better represents the human condition where
damage results from a combination of tumor and therapy.
Gene-Hormone Interaction and Risk of Breast
Cancer (5R01CA149135-03; Co-PI:
Mara 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). We 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) (3U01 AG12546; Wake Forest PI:
Nancy 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.
Paricalcitol for Palliation in Advanced Prostate Cancer: A Phase
II Trial; PI: Schwartz) This ongoing Phase II clinical trial is
being conducted in men with androgen-insensitive prostate cancer
who have bony metastases and who have significantly elevated serum
parathyroid hormone (PTH). 19-nor-1,25-Dihydroxyvitamin
D2 (Zemplar, a paricalcitol capsule), is an FDA-approved
oral vitamin D analogue, being used to suppress serum PTH. We
have previously shown that this drug in intravenous form inhibits
the proliferation of prostate cancer cells in vitro. , this
research represents a translation of our laboratory and clinical
trial work to an investigator-initiated extramurally-funded,
clinical trial. The current trial is in the process of enrolling 30
men with advanced prostate cancer for 16 weeks to suppress serum
PTH levels to ≥50% of their baseline values. The Specific
Aims are to: 1) test the hypothesis that medical suppression of
serum PTH in men with metastatic prostate cancer will result in a
decrease in bone pain, a reduction in use of analgesic medications,
and improved QOL; 2) test the hypothesis that subjective
changes in bone pain and improved QOL will be associated with
objective changes in bony remodeling, as assessed by biochemical
markers of bone resorption and bone formation; and 3) use these
data to plan a blinded, placebo-controlled Phase III trial of
paricalcitol in pain reduction and QOL in metastatic prostate
cancer.