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Walking Forward:
The South Dakota Native American Project
DANIEL G. PETEREIT, MD, DEBORAH ROGERS,
LINDA BURHANSSTIPANOV, JUDITH KAUR, FRANK GOVERN,
STEVE P. HOWARD, CHRISTEN H. OSBURN, C. NORMAN COLEMAN,
JACK F. FOWLER, RICHARD CHAPPELL, MINESH P. MEHTA
Abstract—Background. The “Walking Forward” program is a scientific collaborative program be
-
tween Rapid City Regional Hospital, the University of Wisconsin, the Mayo Clinic, and partner
-
ships with the American Indian community in western South Dakota—3 reservations and 1 urban
population. The purpose is to increase participation of health disparities populations on National
Cancer Institute clinical trials as part of the Cancer Disparities Research Partnership program. Clin
-
ical practice suggests that Native American cancer patients present with more advanced stages of
cancer and hence have lower cure rates and higher treatment-related morbidities. It is hypothesized
that a conventional course of cancer treatment lasting 6 to 8 weeks may be a barrier. Methods.
Therefore, innovative clinical trials have been developed to shorten the course of treatment. A mo
-
lecular predisposition to treatment side effects is also explored. Results and Conclusions. All of these
clinical endeavors will be performed in conjunction with a patient navigator program. Research
metrics include analysis of process, clinical trials participation, treatment outcome, and access to
cancer care at an early stage of disease. J Cancer Educ. 2005; 20:65-70.
T
hat there are differential trends in cancer detection,
treatment, clinical trials participation, and treat-
ment outcomes between various US subpopulations
has long been recognized.
1-4
The National Cancer Institute
(NCI) has recently initiated a unique research program to
evaluate and potentially redress this situation through com-
munity-based hospitals partnering with comprehensive can
-
cer centers to target underserved populations. We describe
the basic structure of this important program, “Walking For
-
ward,” which focuses on the Native American population in
the region surrounding Rapid City, SD.
CANCER DISPARITIES
The burden of cancer is not borne equally by all popula-
tion groups in the United States. The unequal burden is ex-
emplified by differences in cancer morbidity and mortality as
a function of gender, ethnicity, and socioeconomic status.
Colorectal cancers among Alaska Native men and kidney
cancer among southwestern American Indian men are high
-
er than those for any other racial or ethnic group.
4
In addi
-
tion to significant differences in morbidity and mortality,
there are variables in treatment and patient comorbidities
that influence outcome.
Barriers to Quality Cancer Care
There are numerous well-documented barriers that may
influence the type of cancer care a patient receives: (1) lack
of knowledge about state-of-the-art cancer care; (2) fear and
distrust of the health care system; (3) lack of access to cancer
care (not referred or unable to access due to finances, lack of
child care, etc); (4) geographic isolation (travel distances);
(5) socioeconomic factors such as age, education, income,
family status, and lack of insurance; (6) gender and race
(sexism and racism); (7) fear of diagnostic tests, treatment,
and side effects (disfigurement, pain, nausea, etc); and (8)
differing cultural views of health and disease processes.
5-7
These barriers and/or factors include structural factors
that influence physician recommendations and patient deci
-
65
Received from John T. Vucurevich Cancer Care Institute, Rapid City,
South Dakota (DGP, DR); Department of Human Oncology, University of
Wisconsin Comprehensive Cancer Center, Madison, Wisconsin (DGP,
SPH, JFFMPM); Native American Cancer Research Corporation Pine,
Colorado (LP); Mayo Clinic Comprehensive Cancer Center, Rochester,
Minnesota (JK); Radiation Research Program, National Cancer Institute
(FG, CNC); SAIC-Frederick, Inc., A Subsidiary of Science Applications
International Corporation (CHO); Department of Biostatistics and Medi
-
cal Informatics, University of Wisconsin Comprehensive Cancer Center,
Madison, Wisconsin (RC).
Supported by National Institutes of Health Grant RFA
1U56CA99010-01. This project has been funded in part with Federal funds
from the National Cancer Institute, National Institutes of Health under
contract no. N01-CO-12400.
Address correspondence and reprint requests to: Daniel G. Petereit,
MD; John T. Vucurevich Cancer Care Institute, 353 Fairmont Boulevard,
Rapid City, SD 57701; phone: (605) 719-2360; fax: (XXX) XXX-XXXX;
e-mail: <dpetereit@rcrh.org>.
sion making.
8
Estimates suggest that access to care accounts
for about 10% of the variability in health status of popula
-
tions, health behaviors account for 50% of the discrepancy,
the environment another 20%, and genetics 20%.
1
Health
behaviors and health status are further influenced by cul
-
tural norms and patterns of interaction with family, the com
-
munity, and health care systems.
9
Those barriers affect eth
-
nic minority participation in clinical trials and access to
experts and high-technology care. In particular, cancer
treatment trials, prevention trials, and surveillance programs
suffer from a disproportionately low rate of accrual and a
high rate of dropouts of ethnic minorities. Therefore, ethnic
and minority populations do not adequately access or benefit
from the rapid progress being made in cancer research. In ad
-
dition, data confirm lower rates of cancer screening and early
detection, differential treatment patterns, and greater fre
-
quency of a number of chronic diseases with similar risk pro
-
files to cancer.
5-7
These and many other factors contribute to
more advanced disease at diagnosis, lower survival, and
higher cancer death rates among certain United States pop
-
ulation groups.
The NCI Initiative
Community and rural hospitals that provide radiation
oncology services to a large number of medically under-
served, low-income, ethnic or minority populations struggle
to maintain state-of-the-art cancer care. The increased in
-
volvement of these institutions is necessary to develop a
stronger national cancer research effort aimed at addressing
cancer health disparities. The populations served by these
community institutions tend to access the health care sys
-
tem in the advanced stages of their disease, so radiation on
-
cology represents a major treatment modality. Therefore, the
field of radiation oncology offers a unique opportunity to ex
-
plore ways to reduce cancer related health disparities. The
Cooperative Planning Grant for Cancer Disparities Re
-
search Partnership Program (CDRP) was created by the NCI
in an effort to develop stable, long-term radiation oncology
clinical research programs with the participation of institu
-
tions that serve a disproportionate number of minority pa
-
tients. The overall goal of the CDRP program is to develop
effective interventions to reduce and eventually eliminate
these disparities.
Rapid City Regional Hospital and Its Service Population
Rapid City Regional Hospital (RCRH) is the sole health
care provider located in a town of 70,000. It serves all of
western South Dakota and parts of adjacent states (espe
-
cially Wyoming and Nebraska) including 4 large Indian res
-
ervations in western South Dakota and other smaller Native
American communities in the region. Its “service basin” in-
corporates a geographic area of 250,000 square miles with a
population base of 350,000 (Figure 1). The Native Ameri-
66 PETEREIT et al.
n
Clinical Disparities in Native Americans
FIGURE 1. XXXXXXXXXXXX.
can population within the RCRH service area, estimated at
60,000, utilizes this facility for secondary and tertiary health
services.
There is not a history of academic or clinical research at
RCRH (other than participation in cooperative group tri
-
als). Consequently, the partner institution concept inherent
in this NCI project is critical to bring the necessary expertise
in protocol and survey development and implementation,
database compilation and analysis, human subjects protec
-
tion, grants administration, and public outreach regarding
the safety and desirability of the clinical trials process. The 2
partner institutions, the University of Wisconsin Compre
-
hensive Cancer Center and the Mayo Rochester Compre
-
hensive Cancer Center (Mayo), are NCI-designated com
-
prehensive cancer centers.
Although there is a good understanding of cancer barriers
nationwide, there is no hard documentation of barriers af
-
fecting the Native American population within the RCRH
service area. Geographic dislocation from the community
may represent an impediment to seeking earlier treatment,
as Native Americans live a median of 110 miles from the
cancer center in Rapid City, with a range of 5 to 215 miles
(Figure 1). Tumor registry data from RCRH show Native
Americans appear to present with more advanced stages of
cancer and suffer from higher cancer mortality rates com-
pared to the non-Native American population (Table 1).
10
Radiation Modalities to Treat Cancer
Radiation is utilized as either primary or adjuvant treat-
ment for a significant percentage of cancers. Radiation is de-
livered as either external beam radiotherapy or brachyther-
apy. External beam radiation is given from the outside and is
therefore noninvasive, whereas brachytherapy is an invasive
procedure where radioactive elements are placed inside of
the tumor. Brachytherapy can either be given slowly—called
low-dose-rate (LDR) brachytherapy and requires hospital
-
ization—or quickly with a system called high-dose-rate
(HDR) brachytherapy since the radioactive source is in the
tumor for a period of minutes. The advantages of HDR
brachytherapy include elimination of radiation exposure to
staff, very precise treatment delivery, and possible outpatient
therapy. Brachytherapy is commonly used to treat lung,
breast, gynecological, and prostate cancers. The primary
advantage of brachytherapy is that it delivers a much higher
radiation dose to the tumor while sparing the adjacent nor
-
mal tissues. This often translates into improved survival
and/or decreased morbidity since higher doses are more safe
-
ly administered compared to external beam radiotherapy.
Prostate Cancer
Whereas the majority of prostate cancer patients in the
United States are detected with organ-confined disease, this
has not been our experience for patients in western South Da
-
kota—both Native American and non-Native American
(Table 1). Effective radiation options for these patients in
-
clude permanent seed implantation and 3-dimensional con
-
formal radiotherapy. However, for patients with more ad
-
vanced stages of disease—but still nonmetastatic—more
intensive radiation doses have translated into improved out
-
comes.
11
This hasbeen accomplished through brachytherapy,
both LDR and HDR, as well as with external beam radiation.
HDR brachytherapy is being increasingly used as another
method of dose escalation. Some of these advantages include
a potential radiobiologic rationale, markedly lower acute tox
-
icities and improved dosimetry compared to a permanent seed
boost, and elimination of radiation exposure.
12-17
Androgen ablation (hormones) combined with radiation
has also improved several clinical endpoints including sur-
vival.
18
It appears that hormones sensitize prostate cancer to
radiation and may even eliminate microscopic metastatic
foci if given long enough.
Breast Cancer, Breast Brachytherapy
Breast conservation is a standard treatment option for the
majority of patients with early stage breast cancer. The data
supporting this approach comes from at least 6 randomized
trials. Five to 6 weeks of breast radiation is often an impedi
-
ment to breast conservation.
19
Patients in western South
Dakota have had some of the highest mastectomy rates in
the nation. A Medicare survey from 1992-1993 reported
that only 1.4% of Medicare patients underwent breast con
-
servation in Rapid City, SD.
20
Although the reasons are
multiple, the distance from the cancer center is presumed to
be a major impediment to breast conservation.
To address the issue of treatment prolongation with exter
-
nal beam radiation, a number of investigators have exam
-
ined accelerated, partial breast radiotherapy—using either
external beam radiation or brachytherapy. Results of 5 to 8
years from a number of institutions have strongly suggested
that partial breast radiotherapy using brachytherapy pro
-
duces comparable results to external beam radiation, with
local recurrence rates < 5%.
21-24
Radiation Toxicity
Anecdotally, the Native American patient population
appears to be acutely hypersensitive to fractionated radio
-
therapy. This manifests as more severe skin/mucosal reac
-
67 PETEREIT et al.
n
Clinical Disparities in Native Americans
TABLE 1. Stages of Disease at Presentation for Native
Americans and Whites at Rapid City Regional Hospital’s
John T. Vucurevich Cancer Care Institute, Tumor Registry
Data for 1990 Through 2000.
Site
Stage III and IV
Native American
Stage III and IV
White
Lung 72% (92/127) 68% (669/989)
Breast 16% (12/75) 10% (111/1127)
Colorectal 48% (26/54) 40% (298/739)
Prostate 44% (8/15) 26% (13/51)
Total 50% (160/321) 36% (1372/3851)
tions compared to non-Native populations. In a retrospec
-
tive analysis of Native Americans treated with curative
intent in Rapid City, 50% experienced acute Grade 2 toxici
-
ties, and 17% experienced Grade 3 toxicities. Skin toxicities
accounted for the majority of Grade 3 reactions (15% of all
61 patients). This may partially explain why treatment de
-
lays of 6 days were observed in 28% of patients, and delays of
11 days in 15% of patients.
10
Prolongation of treatment time
in several tumor sites has been associated with an adverse
outcome.
25,26
One explanation for the purported increased
toxicity is possibly an underlying genetic susceptibility. This
phenomenon has been observed in many conditions, per
-
haps most dramatically in patients with homozygous muta
-
tions of the ataxia telangiectasia (AT) gene. AT is an au
-
tosomal recessive syndrome characterized by progressive
cerebellar ataxia, oculocutaneous telangiectasia, and im
-
mune deficiency. An established hallmark of this syndrome
is hypersensitivity to ionizing radiation. Swift et al
27
esti
-
mated that approximately 1% of the general population is
heterozygous for the AT gene; other estimates suggest that
the incidence may be as high as 5%. Although phenotyp
-
ically normal and asymptomatic, AT heterozygotes carry an
excess risk for the development of cancer. The incidence of
the AT heterozygote within the Native American popula-
tion remains unknown, but it is known that there are signifi-
cant population differences in the incidence of ataxia telan-
giectasia mutation (ATM) heterozygosity.
METHODS
Walking Forward Project
The South Dakota Native American initiative at RCRH,
“Enhancing Native American Participation in RT Trials”
(NCI U56CA99010), is called the Walking Forward Pro
-
ject. The primary long-term goal of the CDRP Program at
RCRH is to lower cancer mortality rates for Native Ameri
-
cans in the region.
A patient navigator program has been created that relies
on the used of trained community research representatives
(CRRs) to serve as lay health advisors. This aspect of the
program is done in conjunction with the NCI Center to Re
-
duce Cancer Health Disparities. Specific objectives of the
program are (1) to provide culturally appropriate public edu
-
cation on cancer prevention, development, diagnosis, treat
-
ment, and follow-up; (2) to improve access to early diagnosis
and treatment; (3) to provide assistance to patients in “navi
-
gating” the health care and related insurance system; (4) to
provide patients with resources for emotional and social sup
-
port; (5) to provide logistical support for patients who must
travel to receive health care; and (6) to increase enrollment
and reduce dropout rates in clinical research trials.
General Population Survey
Native Americans do not appear to access novel cancer
therapies and clinical trials due to barriers—both real and
perceived. One recent survey found that 75% of cancer pa
-
tients in their sample were not aware of the opportunity to
participate in clinical trials.
28
Likewise, the National Native
American Cancer Survivors’ Support Network has docu
-
mented that less than 5% of Native patients were provided
information about potential clinical trials participation. To
examine the potential barriers to accessing the best cancer
treatments,
29
a culturally responsive survey has been devel
-
oped by project staff in partnership with tribal members. A
stratified sampling design will be used to ensure equitable
distribution of respondents across the 3 reservations and the
1 urban area under study. This survey will be administered to
the general population. It is anticipated that 1000 surveys
will be administered. The impact of traditional healing, ie,
medicine men and women, on western medicine will be as
-
sessed since this is a significant part of the Lakota tradition.
Results from the survey will be used to modify the proposed
education module and other project activities.
Cancer Educational Intervention
An educational module is being developed for breast
and prostate cancer, diseases that have complex treatment
choices and unique cultural connotations within Northern
Plains tribes. The goals of these modules are to provide cul-
turally relevant breast and prostate information to influence
earlier diagnoses of cancer (ie, stages I and II), thus making
the patient potentially eligible for participation in radiation
therapy clinical trials provided by RCRH. We have part-
nered with Native American Cancer Research (NACR) on
this component of the project. NACR has developed and
evaluated a culturally specific and effective “Clinical Trials
Education for Native Americans” curriculum, available on
their Web site.
30
Based on this curriculum, NACR began de-
veloping an interactive, tailored, quality of life education in
-
tervention to increase Native patients’ understanding of
clinical trials to increase opportunities for participation in
breast cancer clinical trials. The quality of life clinical trial
module is focused on the radiation therapy clinical trial be
-
ing provided by RCRH and expands an existing NACR
product, “Get on the Path to Breast Health,” which provides
basic background for the module (available on the NACR
Web page). The first 6 segments of a comparable background
module completed pretesting May 2004, “Get on the Path to
Prostate Health.” These materials will be integrated within
the project’s community education activities. NACR will
provide training on how to use the culturally and geographi
-
cally specific quality of life interactive, tailored modules for
the RCRH CRRs in 2004.
THERAPEUTIC CLINICAL TRIALS
A primary hypothesis of this project is that Native Amer
-
icans forego conventional radiation cancer treatments to re
-
main within their cultural infrastructure. This becomes even
more problematic for patients who live 2 to 3 hours away.
Therefore, a shorter treatment course with culturally compe
-
68 PETEREIT et al.
n
Clinical Disparities in Native Americans
tent navigators might be more acceptable, which could lead
to earlier treatment and better survival. To address this
potential barrier, clinical protocols have been developed
utilizing advanced radiation oncology delivery systems, ie,
brachytherapy and tomotherapy, to shorten a course of radi
-
ation of 6 to 8 weeks to 1 to 4 weeks. All clinical treatment
trials will be offered to the non-Native American population
as well.
HDR Brachytherapy as Monotherapy for Patients
With Select Stage I and II Breast Cancer
Through the Walking Forward study, Native Americans
may undergo a multiplane interstitial implant in which
HDR brachytherapy will be delivered twice a day for either 4
or 5 days. This trial will document the safety and efficacy of
this form of radiation while also documenting a number of
quality of life parameters.
A Phase II Trial of Hypofractionated External Beam
Radiation and HDR Brachytherapy
for Advanced Prostate Cancer
Through the Walking Forward study, patients with inter-
mediate- to high-risk prostate cancer will be given 6 months
of a luteinizing hormone-releasing hormone agonist either
before and/or concurrent with 3-dimensional conformal ra-
diotherapy followed by an HDR boost. The overall time to
complete radiation will be approximately 4 weeks rather
than 8 weeks.
Intensity Modulated Radiotherapy/Tomotherapy
Although external beam radiotherapy is an effective form
of radiation for many tumor sites, radiating normal tissues
can lead to complication rates. When possible, brachythera
-
py addresses this clinical dilemma. Unfortunately, many pa
-
tients are either not candidates for brachytherapy because of
location, eg, brain tumors, or patients desire a noninvasive
option.
Helical tomotherapy is a new form of radiation treatment
delivery. In essence, a conventional linear accelerator is
placed inside a computed tomographic scanner. Rather than
radiating the patient from a limited number of static fields,
tomotherapy treats patients continuously as they slowly move
inside the radiation unit. The radiation delivered is ex
-
tremely conformal since multiple metal leaflets are pro
-
grammed to turn off and on to maximize the tumor dose
while minimizing the dose to the adjacent normal tissues.
The ability to deliver larger and fewer doses of radiation
(hypofractionation) is an advantage of both brachytherapy
and tomotherapy since normal tissue doses are minimized.
Therefore, the duration of external beam radiation can be sig
-
nificantlyreducedwithtomotherapyaswithbrachytherapy.
Tomotherapy Clinical Trials
Protocols have been developed at the University of Wis
-
consin for lung, head and neck, and prostate cancer. Where
-
as the overall treatment duration is about 8 weeks when
treating prostate cancer patients with conventional external
beam radiation, the treatment duration for the initial tomo
-
therapy prostate protocol will only take 5½ weeks, with the
last dose level requiring only 3 to 4 weeks to complete.
Through the Walking Forward study, these tomotherapy
protocols are being conducted in parallel with the Univer
-
sity of Wisconsin. All patients treated in Rapid City will be
entered at dose levels that have already been safely tested
and established at the University of Wisconsin.
ATM Analysis
A genetic milieu may exist that renders Native Ameri
-
cans more sensitive to radiation. ATM testing will be offered
for Native Americans and non-Native Americans who un
-
dergo radiotherapy clinical trials to assess the baseline ATM
rate and to correlate with the association between a particu
-
lar cancer type and also with the incidence and severity of
radiation toxicity.
Program Evaluation
Parameters that will be assessed at the end of the grant cy-
cle include number of patients entered on clinical trials,
analysis of the Patient Navigator Database that documents
each patient contact/intervention, results of the ATM anal-
ysis, and results of both surveys. Interventions that will lower
cancer mortality rates are the ultimate goal of each survey.
Ultimately, the results of the initial grant will help us to re-
fine the next series of interventions for subsequent grants.
DISCUSSION
Native Americans are rarely recruited and seldom re
-
tained in clinical trials. The long distances Native cancer
patients must travel to and from cancer centers providing
cancer clinical trials averages 110 miles one way, which
makes participation in traditional radiotherapy clinical trials
unlikely. In addition, the referral protocols for most clinical
trials are time sensitive (eg, patient must present for eligibil
-
ity criteria within a few weeks of diagnosis). CRRs actively
working within the respective tribal communities are likely
to be able to identify, educate, and subsequently increase the
number of Natives who are referred to RCRH for possible in
-
clusion within the radiotherapy clinical trials. At a mini
-
mum, the Native patients who interact with the CRRs will
be better informed to make an informed choice regarding
participation in such clinical trials.
The NCI CDRP program is a unique research program
that empowers the community-based center to develop the
multifaceted research program in conjunction with the com
-
prehensive cancer centers and/or national cooperative clini
-
Special Supplement, Volume 20, Spring 2005 69
cal trials groups of the CDRP grantee’s choosing. The coop
-
erative agreement mechanism encourages and ensures that
the grantees and their partners collaborate with one another
utilizing periodic meetings and also the TELESYNERGY®
telemedicine system. Incorporating aspects of the NCI navi
-
gator program helps build research and treatment teams to
provide new insight and solutions into the helping solve the
issue of cancer health disparities in the United States.
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