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Breast Cancer Survivorship and Level of Institutional Involvement Utilizing Integrative Oncology

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Objective: Integrative oncology is widely used by patients with breast cancer. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in integrative oncology at the institutions treating them. Methods: Claims-based data were used to find 4,815 newly diagnosed breast cancer patients treated between January 2013 and December 2014 for survival analysis. A scoring system was developed by asking oncologists about their institutions' efforts to educate, support, and provide funding for 12 complementary and lifestyle approaches. Cohort analysis using two-tailed chi-square and a separate multivariate model using SMOTE and lasso regression were used. Nine variables across patient and institutional profiles were included. The model coefficients were exponentiated and presented as odds ratios. Results: 173 patients mapped to 103 institutions and 103 oncologists. The median patient age was 51, and 8% were metastatic. Institutions were scored for integrative oncology involvement and placed into four cohorts. Low-scoring institutions showed less effort to educate, support, and provide integrative therapies compared to others. The 5-year survival of patients in the low cohort was directionally but not significantly lower than others. In the multivariate model, a composite integrative oncology score was shown to increase 5-year survival odds three times for institutions in the low-mid cohort and 48% in the mid-high, compared to the low. Conclusion: Crossing the threshold beyond 'low' involvement in integrative oncology represents a new path to incremental survival benefit for many cancer patients. Entities invested in the survival of breast cancer patients should increase education, access, and funding for a core set of six therapies: nutrition counselling, exercise counselling, patient support groups, spiritual services, meditation, and psycho-oncology support.
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Research Article
Breast Cancer Survivorship and Level of Institutional Involvement
Utilizing Integrative Oncology
Terri Crudup ,
1
Linna Li ,
2
Jennifer Wright Dorr ,
3
Elizabeth Lawson ,
1
Rachel Stout ,
1
Pedram Vazifeh Niknam ,
1
Judi Jones ,
1
Robert G. Steen ,
4
Susan Casner ,
4
Lynn L. Lu ,
5
Yi Wang ,
5
James Scott ,
1
Shelby Zanine ,
1
Stacey Robertshaw ,
1
Gabriella Broderick ,
1
Simarpreet Singh ,
6
Jingsong Lu ,
5
Li Zhou ,
5
Vaishali Palommella ,
1
Tye Harris ,
1
Michael Hanamirian Jr. ,
1
Mula Shivani Reddy ,
7
Bruce Cowgill ,
1
Jen Rice ,
1
Avinash Nagaraja ,
7
and Wayne Jonas
3
1
Primary Intelligence, IQVIA, Plymouth Meeting, PA, USA
2
Radiation Oncology, Bryn Mawr Hospital, Bryn Mawr, PA, USA
3
Integrative Health Programs, Samueli Foundation, Alexandria, VA, USA
4
Real World Oncology, IQVIA, Plymouth Meeting, PA, USA
5
Advanced Analytics, IQVIA, Plymouth Meeting, PA, USA
6
Primary Intelligence, IQVIA, Gurgaon, Haryana, India
7
Primary Intelligence, IQVIA, Bengaluru, Karnataka, India
Correspondence should be addressed to Terri Crudup; terri.crudup@iqvia.com
Received 23 August 2021; Accepted 25 November 2021; Published 18 December 2021
Academic Editor: Faisal Raza
Copyright ©2021 Terri Crudup et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. Integrative oncology is widely used by patients with breast cancer. is study aims to investigate the relationship between
the survival outcomes of breast cancer patients and the level of involvement in integrative oncology at the institutions treating them.
Methods. Claims-based data were used to find 4,815 newly diagnosed breast cancer patients treated between January 2013 and
December 2014 for survival analysis. A scoring system was developed by asking oncologists about their institutions’ efforts to educate,
support, and provide funding for 12 complementary and lifestyle approaches. Cohort analysis using two-tailed chi-square and a
separate multivariate model using SMOTE and lasso regression were used. Nine variables across patient and institutional profiles
were included. e model coefficients were exponentiated and presented as odds ratios. Results. 173 patients mapped to 103 in-
stitutions and 103 oncologists. e median patient age was 51, and 8% were metastatic. Institutions were scored for integrative
oncology involvement and placed into four cohorts. Low-scoring institutions showed less effort to educate, support, and provide
integrative therapies compared to others. e 5-year survival of patients in the low cohort was directionally but not significantly lower
than others. In the multivariate model, a composite integrative oncology score was shown to increase 5-year survival odds three times
for institutions in the low-mid cohort and 48% in the mid-high, compared to the low. Conclusion. Crossing the threshold beyond
‘low’ involvement in integrative oncology represents a new path to incremental survival benefit for many cancer patients. Entities
invested in the survival of breast cancer patients should increase education, access, and funding for a core set of six therapies:
nutrition counselling, exercise counselling, patient support groups, spiritual services, meditation, and psycho-oncology support.
1. Introduction
Cancer impacts the whole person affecting all dimensions of
the individual—mind, body, and spirit. Care for the cancer
patient is correspondingly complex and increasingly
individualized. While the oncology community relies on
conventional medicine as the backbone of therapy, many
patients combine complementary and lifestyle therapies in
an approach known as integrative oncology. Integrative
oncology is defined as “a patient-centered, evidence-
Hindawi
Journal of Oncology
Volume 2021, Article ID 4746712, 8 pages
https://doi.org/10.1155/2021/4746712
informed field of cancer care that utilizes mind-body
practices, natural products, and/or lifestyle modifications
from different traditions alongside conventional cancer
treatments” [1]. Integrative approaches encompass nu-
merous modalities including patient support groups, mas-
sage, and nutritional and exercise counselling. While well-
known and often recommended, they have variable avail-
ability in cancer treatment. ere is a growing body of
evidence that adding complementary and lifestyle ap-
proaches to conventional oncology treatment benefits pa-
tients by helping them manage the side effects of treatment
[2], improving patient-reported outcomes [3], and con-
tributing to improved overall survival [4, 5]. is study
aimed to investigate the relationship between institutional
involvement in integrative oncology and survival in breast
cancer patients.
2. Materials and Methods
is study used data from US breast cancer patient claims,
paired with a survey among 103 US oncologists, to inves-
tigate the relationship between 5-year survival outcomes of
breast cancer patients and the level of education, support,
and funding across 12 complementary and lifestyle therapies
in the institutions treating those patients.
2.1. Claims Data and Survey Analytics. e IQVIA
PharMetrics®Plus database was used to meet the study
objectives. PharMetrics Plus includes longitudinal, adjudi-
cated administrative claims for more than 190 million
unique health plan members across the United States [6].
Data include inpatient and outpatient diagnoses and pro-
cedures, retail and mail order prescription records, phar-
macy and medical benefit information, inpatient stay and
provider details, demographic variables, product type, payer
type, health plan enrolment dates, and payments.
Patients diagnosed with breast cancer between January
01, 2013, and December 31, 2014 (identification period) were
selected (Figure 1). Codes from the international classifi-
cation of diseases (both ICD-9 and ICD-10) were used to
identify breast cancer diagnosis at any stage. Patients were
required to have at least one confirmatory inpatient claim, or
two confirmatory outpatient claims for breast cancer on
different days during the identification period. e first
claim with the diagnosis code was termed the index date.
e following exclusion criteria were applied: (1) age 17
or younger at the index date; (2) did not have two years of
continuous enrolment before the index date; (3) had a breast
cancer claim or diagnosis in the two-year preindex period
(“newly diagnosed” only); (4) were high-risk based on a
diagnosis of HIV (human immunodeficiency virus) or
secondary cancer; and (5) did not have five years of con-
tinuous enrolment following the index date.
e PharMetrics Plus database lacks a variable for
mortality, a discharge status of “expired,” and does not
detect mortality in the community. Instead, a previously
established claims death proxy method used by Joyce et al.
and Pelletier et al. was applied to identify and quantify
mortality. is method used a qualifying medical event and
the absence of claims within 180 days following the event
date to signify patient death [7, 8].
Additional profiling of the patients’ conventional
medical treatments was conducted using treatment and
procedural codes from claims data.
Treating oncologists were defined as those with at least
five medical claims from the same patient on different days
during the postindex period. e treating oncologists were
assigned to their “best affiliation” practice setting address
using the IQVIA OneKey®database. e process to define
“best affiliation” pulls physician physical addresses from
several professional sources, weights each address to provide
a confidence ranking, and then selects the professional lo-
cation (healthcare organization) with the most evidence as
the primary practice location.
Oncologists from the “best affiliation” institutions were
invited to take part in a 20-minute survey about the inte-
grative oncology involvement of their institutions in
2013–2014 to match the patient identification period.
Screening criteria was required which are as follows: (1)
currently a full-time practicing oncologist; (2) practicing at
one of the institutions where the study pool patients were
treated, both currently and in 2013–2014; (3) comfortable
responding to questions about “complementary and lifestyle
therapies offered or supported at their institution in 2013-
2014”; and (4) currently treat at least 10 breast cancer pa-
tients in a typical 3-month period. Only one oncologist from
each institution was allowed to take the survey.
ere are currently no standard scoring systems for
measuring level of involvement in integrative oncology. To
construct a measurement system, IQVIA partnered with the
Samueli Foundation, a leader in the field of integrative
medicine. Following a targeted literature review on the use of
complementary therapies by breast cancer patients, 12
therapies were chosen to be measured and relabelled as
“complementary and lifestyle therapies” (see Results
section).
By adapting the principles of awareness, interest, desire,
and action in the consumer purchase funnel [9], each of
these 12 therapies was measured across three constructs:
educate, support, and provide. To measure how well in-
stitutions “educate” about the 12 therapies, questions were
asked about efforts to increase patient awareness and
knowledge (see Table 1). To measure “support,” questions
were asked about efforts to offer or otherwise recommend
across the 12 therapies. To measure “provide,” questions
were asked about the institution covering the cost in part or
in full of the 12 therapies. Each response was assigned
points, as shown in Table 1, with higher points indicating
stronger involvement. Finally, two additional questions
were asked about the on-site oncology support staff and the
efforts of the institution to handle patient questions about
herbs and supplements. All questions were asked relative to
the 20132014 timeframe to match the patient treatment
period.
e composite integrative oncology involvement score
was calculated by adding the total number of points based on
responses to the five survey questions (shown in Table 1).
2Journal of Oncology
2.2. Statistical Analysis. e final set of patients for analysis
was limited by the number of oncologists who completed the
survey (see Results). e patient mortality marker was
checked for the final breast cancer patient cohort and
subsequent 5-year overall survival was calculated. To
compare survival rates between cohorts with different levels
of integrative oncology involvement, a chi-square test was
used.
To fully analyse the impact of the integrative approaches,
a multivariate model was constructed from the claims data
with 5-year survival as the dependent variable. Due to the
limited sample available to analyse, SMOTE and lasso re-
gression were combined [10, 11]. SMOTE is a validated
oversampling technique to adjust for low event rates (in our
case, deceased), and lasso regression has been shown to
include relevant variables when the number of variables is
high relative to the sample size [12]. Numerous categorical
independent variables were included. From patient claims
data, the following are obtained: age at index date, US
geographic region, metastatic status, and type of patient
insurance health plan. From the survey data representing
each institution, the following are obtained: composite in-
tegrative oncology score, NCCN (National Comprehensive
Cancer Network) designation, NCI (National Cancer In-
stitute) designation, ACO (Accountable Care Organization)
affiliation, and practice setting. Each of these variables is
present in the final output.
3. Results
3.1. Claims Data and Survey Analytics. Within the two-year
identification period, 241,726 unique breast cancer patients
were identified in PharMetrics Plus claims data using the
definition of breast cancer diagnosis. After applying ex-
clusion criteria, the study set of newly diagnosed adult breast
cancer patients was 4,815. Among these, 475 (9.9%) were
diagnosed as metastatic. Applying the mortality algorithm
yielded a 5-year survival rate of 89.8%. After being mapped
to treating institutions, a total of 2,758 oncologists repre-
senting 2,543 institutions were available for the survey
research.
Of the 2,430 oncologists invited to take the survey, 675
attempted the screener (27.8% response rate). Of these, 401
did not meet the screener requirements, 96 did not complete
the full survey, 61 were turned away due to the survey quota
being filled, and two were removed after survey completion
due to poor data quality. During the process of linking
surveyed oncologists back to patients in the claims data, 12
oncologists were unable to be mapped using classification
rules and were also removed. erefore, a final sample of
n103 oncologists representing 103 unique institutions was
analysed. Most oncologists had between 1 to 2 patients in the
claims data, producing a final study sample of 173 breast
cancer patients.
e sample of 173 breast cancer patients had the fol-
lowing profile: the median age was 51 (range: 32–76), 14 of
the patients (8%) were identified as metastatic, and 153
(88%) had a preferred provider organization (PPO) for plan
type, compared to 20 (12%) with either a health maintenance
organization (HMO), indemnity, or point of service. Using
the definition of the census regions in the US, 15.6% resided
in the Northeast, 40.5% resided in the South, 36.4% resided
in the Midwest, and 7.5% resided in the West.
3.2. Statistical Analysis. Among the 103 institutions, there
was a wide distribution of integrative involvement scores,
indicating a wide variety of integrative oncology practices
circa 2013–2014 (see Figure 2). Based on this distribution,
institutions were divided into four quartiles for integrative
involvement, indicated by black lines.
Considering individual components of the composite
score, most points were awarded based on “educate” and
“support” across the 12 therapies; the levels for “provide”
across the 12 were notably lower in all but the high inte-
grative score category. Table 2 shows the average points
awarded from each category across the 12 modalities, cut by
the institutions’ integrative score.
Using “educate” as a leading indicator, some modalities
emerge as more prevalent than others. Table 3 is aggregated
across the four components of the “educate” definition to
show how the education levels varied across the integrative
score. e therapies with the most efforts made by institutions
to raise awareness and knowledge are nutrition consultations
(76100%), exercise consultations (68100%), patient support
groups (80100%), spiritual services (48100%), and psycho-
31 December 2014
31 January 2020
Index date
Identification period
01 January 2013
Study period
01 January 2011– 31 January 2020
01 January 2011
2-year pre-index period
>=5-year post index period
Figure 1: Breast cancer patients claim data study timeframes. e full study period is from January 01, 2011, through January 31, 2020. e
identification period for breast cancer diagnosis was between January 01, 2013, and December 31, 2014. A 2-year preindex period (from
January 01, 2011, through the index date) was used to apply exclusion criteria. A 5-year postindex period (from the index date through
December 31, 2019) was used to assess survival.
Journal of Oncology 3
Table 1: Survey questions and response points used to develop a composite integrative involvement score
Survey
question
construct
Question phrasing Response instructions Response options
Integrative
score
points
Maximum
points
possible
Educate
Efforts by the institution to raise patient
awareness and knowledge of 12 integrative
modalities
Choose all that apply; asked for each of the 12 modalities
Flyers or other printed information posted in-office
or online for patients to see 1
60
Written or printed information provided to the
patient 1
Proactive discussion had with the patient (by
oncologist or member of cancer team) 2
Other methods of raising awareness 1
Unsure/not promoted 0
Support Efforts taken by the institution to offer or
otherwise recommend 12 integrative modalities
Choose one (with the exception of the first two responses,
which could both be chosen); asked for each of the 12
modalities
Offered at my primary practice institution (my
location) 3
60
Offered at my primary practice institution (another
affiliated location) 2
Not offered, but patients are referred to places that
offer 1
Not offered, but may be recommended 1
Unsure/not supported 0
Provide Institution in part or full covering the costs of 12
integrative modalities Choose one; asked for each of the 12 modalities
Yes, costs covered fully 4
48
Yes, costs covered in part 3
No, patient responsible for all costs 0
Unsure/did not offer 0
Staffing Institution keeping specific roles on staff as part
of cancer patient care team Choose one; asked in isolation
Social worker, oncology patients 3
51
Patient navigator, oncology patients 3
Financial assistant, oncology patients 3
Leader or director of integrative services 12
Credentialed acupuncturist or acupressurist 6
Credentialed massage therapist 6
Credentialed nutritionist 6
Pain specialist, oncology patients 3
Physical therapist, oncology patients 3
Psychologist, oncology patients 3
Patient liaison 3
Supplements
Efforts taken by the institution to help patients
address the use of herbal and plant-based
supplements
Choose one; asked in isolation
Yes, offered at my primary practice institution (main
location or satellite locations in-network) 3
3
No, not offered, but would refer patients to other
resources (for example, Memorial Sloan Kettering
website)
2
No, not offered, but I or my staff would help patients
with questions on a case-by-case basis 1
No, was not offered 0
Unsure 0
e range of total points possible is 0-222.
4Journal of Oncology
oncology support groups (5697%). Patients were offered
some form of awareness-raising for these core modalities in
all but the lowest quartile of institutions, being offered in
4880% of institutions in the low group compared to
97100% in the high group.
Table 4 illustrates the percentage of patients receiving
conventional medical treatment at any point during the 5
years after diagnosis. As the timeframe for diagnosis was
January 2013 to December 2014, the use of immuno-on-
cology agents and targeted therapies was minimal.
e patient mortality marker analysis of the integrative
cohorts showed a directional finding (Table 5). ough there
is no statistical significance at p<0.05, institutions in the low
cohort have a notably lower 5-year overall survival rate
(89%) compared to institutions in the low-mid (96%), mid-
high (96%), and high (95%) cohorts.
Based on multivariate modelling, older age at diagnosis
(66–76), having a PPO insurance plan, being treated in an
academic setting, and being treated by an institution with a
low-mid or mid-high integrative involvement score were
predictors of increased odds of 5-year survival; see Table 6.
Several other factors lowered the odds of 5-year survival,
including metastatic positive, being treated at a location that
is not NCCN designated, being treated in the Midwest or
0
2
4
6
8
10
12
14
16
18
20
Percent of institutions (%)
Composite integrative oncology involvement score total points
0-50a51-75b76-100c100-187d
0-15
16-30
31-45
46-60
61-75
76-90
91-105
106-120
121-135
136-150
151-165
166-180
181-195
196-210
211-222
Figure 2: Distribution of 103 institutions by their composite integrative oncology involvement score. (a) e score of 0–50 indicates “low”
integrative oncology involvement (n25). (b) 51–75 indicates the “low-mid” level (n26). (c) 76–100 indicates “mid-high” level (n23).
(d) 101–187 indicates a “high” level (n29).
Table 2: Integrative score from 2013 to 2014, average points across 12 complementary and lifestyle modalities.
Survey construct
measured
Maximum points
possible
Low integrative
score
Low-mid integrative
score
Mid-high integrative
score
High integrative
score
Educate 60 10 17 23 33
Support 60 10 18 22 29
Provide 48 4 8 14 27
Table 3: Percentage of institutions educating patients in any way about select complementary and lifestyle therapies circa 2013–2014.
Low integrative score
(n25) (%)
Low-mid integrative
score (n26) (%)
Mid-high integrative
score (n23) (%)
High integrative score
(n29) (%)
Nutrition consultation or
program 76 96 100 100
Exercise consultation or program 68 85 87 100
Patient support groups or
patient-survivor pairings 80 96 96 100
Spiritual services 48 85 83 100
Psycho-oncology support 56 92 78 97
Massage therapy 32 69 87 97
Meditation or mindfulness 20 77 91 97
Yoga 24 73 87 97
Acupuncture or acupressure 20 69 78 93
Music or art therapy 24 58 74 93
Reiki or therapeutic/healing
touch 16 35 48 72
Tai chi or qi gong 12 31 44 72
Journal of Oncology 5
West regions, being aged 55–65 at diagnosis, and being
treated at a location that is contracted or employed by an
ACO.
An odds ratio of greater than one is expressed directly
in relation to 5-year survival. Using the “low-mid” inte-
grative score as an example, a patient treated at an insti-
tution with a “low-mid” integrative score is three times
more likely to survive over the 5-year period, compared to a
patient treated at an institution with a “low” score. On the
contrary, an odds ratio of less than one indicates lower
survival. Using “metastatic positive” as an example, a pa-
tient who is metastatic positive is 50 times more likely to die
in the 5-year period compared to a patient who is “met-
astatic negative.”
4. Discussion
Many cancer institutions support a wide array of integrative
oncology services, from core supportive services such as
nutrition and psycho-oncology to less common services
such as acupuncture, massage, and reiki. However, about
one-quarter of institutions score low in these types of ser-
vices. Low-scoring institutions raised awareness of common
services less than 80% of the time, whereas all other insti-
tutions raised awareness of such services near or over 80% of
the time. Low-scoring institutions also did less to provide
access and funding to integrative oncology than all other
institutions. Compared to low-scoring institutions, the odds
of 5-year survival for breast cancer patients treated at
Table 4: Percentage of patients receiving conventional medical treatments in any line of therapy postdiagnosis, circa 2013–2014.
Conventional medical treatment Low integrative score
(n35) (%)
Low-mid integrative
score (n48) (%)
Mid-high integrative
score (n26) (%)
High integrative score
(n64) (%)
Chemotherapy (monotherapy) 43 50 42 27
Chemotherapy + immuno-oncology
agent 9 17 12 9
Chemotherapy + targeted therapy 0 0 0 2
Immuno-oncology agent
(monotherapy) 3 4 4 0
Targeted therapy (monotherapy) 0 2 0 5
Hormone therapy (monotherapy or in
combination) 51 67 88 73
Surgery (excluding diagnostic
procedures) 91 98 85 94
Radiation 69 56 69 48
Table 5: 5-year survival across varying levels of institutional integrative involvement.
Institution integrative oncology score Oncologist sample Patient sample Survival rate (%)
Low 25 35 89
Low-mid 26 48 96
Mid-high 23 26 96
High 29 64 95
Total 103 173 94
Table 6: Lasso regression of 5-year survival: variable coefficients and odds ratios.
Variables Coefficient Odds ratio Variable comparison
Metastatic positive 3.99 0.02 Relative to metastatic negative
Not NCCN designated 1.74 0.18 Relative to NCCN designated
Midwest region 1.70 0.18 Relative to Northeast region
West region 1.60 0.20 Relative to Northeast region
Age 56–65 0.74 0.48 Relative to age 32–45
ACO contracted or employed 0.08 0.92 Relative to no ACO relationship
High integrative score 0 1.00
Neutral
South region 0 1.00
Age 46–55 0 1.00
Not NCI designated 0 1.00
Mid-high integrative score 0.39 1.48 Relative to low score
Academic setting 0.96 2.61 Relative to community setting
Low-mid integrative score 1.13 3.10 Relative to low score
PPO patient insurance 1.20 3.32 Relative to “other insurance” (HMO/indemnity/POS)
Age 66–76 1.36 3.90 Relative to age 32–45
NCCN, National Comprehensive Cancer Network; ACO, Accountable Care Organization; NCI, National Cancer Institute; PPO, preferred provider or-
ganization; HMO, health maintenance organization; POS, point of service.
6Journal of Oncology
institutions with low-mid and mid-high integrative in-
volvement were three times and 48% higher, respectively.
e magnitude of this survival advantage is comparable to
being treated at an academic medical centre or an NCCN-
designated centre.
e study has some limitations which are as follows: the
sample is limited to patients filing under commercial in-
surance; patients may not all be de novo due to a two-year
lookback period; oncologist recall from 6–7 years prior may
be subject to error; the scoring system is based on the au-
thors’ understanding of methods used by institutions to
educate, support, and provide access to complementary and
lifestyle therapies but has not been validated; the multi-
variate model is limited to the variables included and could
benefit from additional patient characteristics; and con-
ventional medical treatments were shown to be similar
across the integrative cohorts, but no adjustments were
made to the model to account for treatment variation.
Regarding the role of the integrative score, there are no
secondary sources to directly compare the results. e main
finding is that patients’ survival odds increase at either the
low-mid or mid-high level of integrative involvement, but
survival odds are neutral at the high level. One possible reason
is that patients treated at high-scoring institutions may be
correlated with patients who are more severe and/or have had
cancer longer and are therefore looking for institutions that
offer “more” through whole-person approaches. Additional
patient variables would need to be included to test this hy-
pothesis. Validation of the composite score calculation as a
representation of involvement in integrative oncology prac-
tice and repetition of the experiment are needed.
When going through cancer treatment, patients rely
heavily on the information provided to them by their on-
cologist and the larger healthcare team. Patients cannot use
complementary or lifestyle therapies if they are not aware of
them, and they may be hesitant to change current practices if
these therapies are not supported at their treating institution.
Convenience also plays a role; patients may not be willing or
able to travel to other locations if additional modalities are not
offered at their main location for cancer treatment. Finally,
cost is one of the known barriers to more patients’ use of
integrative approaches. If a minimal threshold of integrative
involvement is all that is needed to increase the odds of
survival, as shown in this study, then this is important to
patients, to institutions, to healthcare professionals that treat
them, and to pharmaceutical companies providing conven-
tional treatments. Increasing the odds of survival through
whole-person integrative oncology is an endeavour worthy of
additional investigation and investment by the treating in-
stitutions and pharmaceutical companies. In particular, there
are national charitable organizations, such as Unite for HER,
that have a proven model to provide education and funding of
complementary and lifestyle therapies and represent a path to
increasing integrative access for patients. In addition, the
Samueli Foundation, the SIO (Society of Integrative Oncol-
ogy), and ASCO (American Society of Clinical Oncologists)
are working to increase the ability of oncologists to discuss
and assist patients to learn about and access such services in
appropriate ways.
Showing the benefit of adding specific integrative
therapies to breast cancer patients is the basis of the SIO
guidelines published in 2017 and approved by ASCO [13]. In
these guidelines, specific modalities are recommended to
address anxiety and mood disorders (meditation, yoga, and
relaxation with imagery) or to address stress reduction,
anxiety, depression, fatigue, and quality of life (stress
management, yoga, massage, music therapy, energy con-
servation, and meditation). Many of these modalities can be
facilitated by trained psychologists, further highlighting the
importance of access to psycho-oncology services for cancer
patients. Additional joint guidelines from SIO and ASCO for
pain and fatigue are in development.
Although 12 modalities were researched in this study,
five are highlighted in the results that are more commonly
adopted. ese are exercise counselling, nutrition counsel-
ling, psycho-oncology support, chaplain services, and pa-
tient support groups. When checking the SIO guidelines,
meditation is listed for both mood disorder management
and general stress reduction. We recommend adding
meditation as a sixth key “core modality.” ese six rep-
resent an attractive bundle that addresses patients’ needs
physically, mentally, socially, and spiritually, is often ac-
cepted as part of usual care, and provides some degree of
choice for patients. Treating institutions can cross the
threshold into low-mid involvement in numerous ways; one
specific plan to do so is as follows: (1) educating patients
about the core six complementary and lifestyle modalities in
print, on the website, and in discussion during a treatment
visit. (2) Offering a path to access three on-site (for example,
nutrition counselling, exercise counselling, and psycho-
oncology support) and the other three at a referred location
(patient support groups, chaplain services, and meditation).
(3) Covering the costs of the three offered on-site. (4) In-
cluding on-site staffing of a nutritionist, exercise consultant/
physical therapist, and psychologist. is requires resources
and training and should be planned for accordingly.
Finally, this study concludes that institutional support
for complementary and lifestyle therapies increases the odds
of patient survival, which may initially seem to contradict a
2018 study published in the Journal of the National Cancer
Institute. e 2018 study suggests that patients who choose
alternative treatments and eschew conventional medical
treatments have significantly worse survival than patients
who receive conventional treatment only [14]. e difference
is in the use of conventional medical treatments as a basis;
the 2018 study used alternative modalities, while the as-
sumption in this study is that patients are using comple-
mentary and lifestyle therapies in addition to their medical
treatments, supported by “integrative involvement” being
derived from actions taken by the institution and the
medical team treating the patient. Both studies point to the
importance of oncologists to address behavioural, lifestyle,
and psychosocial issues with patients as well as alternative
modalities to assure that all beneficial services—conven-
tional and complementary—are properly provided in patient
care. Proper “integration” of these services can improve both
quality of life and survival and must become the standard of
care for all cancer patients.
Journal of Oncology 7
5. Conclusion
Institutions crossing the threshold beyond “low” involve-
ment in integrative oncology represent a survival benefit for
many cancer patients. Treating institutions should invest in
six core complementary and lifestyle therapies and integrate
them with conventional medical treatments. Other entities
that support patients on their cancer treatment jour-
ney—such as pharmaceutical companies and national or
regional payers—should also investigate the socioeconomic
benefits of providing education and access to these six core
therapies. Once these modalities are made more widely
available and accessible to all cancer patients, the survival
benefit can be realized.
Data Availability
e data underlying this article that is HIPAA-compliant
will be shared on reasonable request to the corresponding
author.
Disclosure
e abstract for this study was included in the online ab-
stract library at the Annual ASCO 2021 meeting.
Conflicts of Interest
e authors have no conflicts of interest to disclose.
Authors’ Contributions
Terri Crudup was responsible for the conceptualization
and supervision of the full study. Wayne Jonas, Jennifer
Wright Dorr, Linna Li, Rachel Stout, Pedram Vazifeh
Niknam, Judi Jones, Robert G. Steen, Susan Casner, Lynn
L. Lu, Yi Wang, Simarpreet Singh, Jingsong Lu, Li Zhou,
Avinash Nagaraja, Bruce Cowgill, and Jen Rice were re-
sponsible for methodological input. Robert G. Steen,
Susan Casner, Lynn L. Lu, Yi Wang, Jingsong Lu, and Li
Zhou curated the data. Lynn L. Lu, Yi Wang, Simarpreet
Singh, Jingsong Lu, Li Zhou, James Scott, Shelby Zanine,
Stacey Robertshaw, Gabriella Broderick, and Vaishali
Palommella performed formal analysis. Elizabeth Lawson
(lead), James Scott, Shelby Zanine, Stacey Robertshaw,
Gabriella Broderick, and Vaishali Palommella investi-
gated the data. James Scott, Shelby Zanine, Stacey Rob-
ertshaw, Gabriella Broderick, and Vaishali Palommella
visualized the study. Tye Harris, Michael Hanamirian Jr.,
and Mula Shivani Reddy provided administrative aid
through desk research. Terri Crudup, Wayne Jonas, and
Linna Li drafted the manuscript. Simarpreet Singh, Bruce
Cowgill, and Jen Rice contributed to the critical review
and revision of the manuscript.
Acknowledgments
e authors thank Alyssa McManamon, MD, and Doug
Cavarocchi from Samueli Foundation for their support. e
authors also thank those from IQVIA who supported the
research: Chris Nickum, Dan Winkelman, Harneet Bhogal,
and Mitchell DeKoven. is study was funded by IQVIA and
the Samueli Foundation which each provided personnel to
conduct the survey research and data analytics. IQVIA
provided honoraria to survey respondents.
References
[1] C. M. Witt, L. G. Balneaves, M. J. Cardoso et al., “A com-
prehensive definition for integrative oncology,” Journal of the
National Cancer Institute Monographs, vol. 2017, no. 52, 2017.
[2] D. L. Hershman, J. M. Unger, H. Greenlee et al., “Effect of
acupuncture vs sham acupuncture or waitlist control on joint
pain related to aromatase inhibitors among women with
early-stage breast cancer,” Journal of the American Medical
Association, vol. 320, no. 2, pp. 167–176, 2018.
[3] C. M. Witt, O. Außerer, S. Baier et al., “Effectiveness of an
additional individualized multi-component complementary
medicine treatment on health-related quality of life in breast
cancer patients: a pragmatic randomized trial,” Breast Cancer
Research and Treatment, vol. 149, no. 2, pp. 449–460, 2015.
[4] R. A. Cannioto, A. Hutson, S. Dighe et al., “Physical activity
before, during, and after chemotherapy for high-risk breast
cancer: relationships with survival,” Journal of the National
Cancer Institute, vol. 113, no. 1, pp. 54–63, 2021.
[5] C. M. Friedenreich, L. S. Cook, Q. Wang et al., “Prospective
cohort study of pre-and postdiagnosis physical activity and
endometrial cancer survival,” Journal of Clinical Oncology,
vol. 38, no. 34, pp. 4107–4117, 2020.
[6] IQVIA, US Claims—IQVIA PharMetrics Plus, Durham, NC,
USA, 2020.
[7] A. T. Joyce, J. M. Iacoviello, S. Nag et al., “End-stage renal
disease-associated managed care costs among patients with
and without diabetes,” Diabetes Care, vol. 27, no. 12,
pp. 2829–2835, 2004.
[8] E. M. Pelletier, B. Shim, S. Goodman, and M. M. Amonkar,
“Epidemiology and economic burden of brain metastases
among patients with primary breast cancer: results from a US
claims data analysis,” Breast Cancer Research and Treatment,
vol. 108, no. 2, pp. 297–305, 2008.
[9] Oxford Reference, AIDA Overview—A Dictionary of Mar-
keting, Oxford University Press, Oxford, UK, 2021.
[10] N. V. Chawala, K. W. Bowyer, L. O. Hall, and
W. P. Kegelmeyer, “SMOTE: synthetic minority over-sam-
pling technique,” Journal of Artificial Intelligence Research,
vol. 16, pp. 321–357, 2002.
[11] R. Tibshirani, “Regression shrinkage and selection via the
lasso,” Journal of the Royal Statistical Society: Series B, vol. 58,
no. 1, pp. 267–288, 1996.
[12] J. D. Lee, D. L. Sun, Y. Sun, and J. E. Taylor, “Exact post-
selection inference, with application to the lasso,” Annals of
Statistics, vol. 44, no. 3, pp. 907–927, 2016.
[13] H. Greenlee, M. J. DuPont-Reyes, L. G. Balneaves et al.,
“Clinical practice guidelines on the evidence-based use of
integrative therapies during and after breast cancer treat-
ment,” CA: A Cancer Journal for Clinicians, vol. 67, no. 3,
pp. 194–232, 2017.
[14] S. B. Johnson, H. S. Park, C. P. Gross, and J. B. Yu, “Use of
alternative medicine for cancer and its impact on survival,”
Journal of the National Cancer Institute, vol. 110, no. 121–124,
2018.
8Journal of Oncology
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