BRIEF REPORT
Racial, Ethnic, and Socioeconomic Characteristics
Independently Predict for Cachexia Risk and
Associated Survival Outcomes in Stage IV NSCLC: A
Brief Report
Santiago Olaechea, MS,a
Alison Liu, BA,a
Brandon Sarver, BS,b
Linda Anne Gilmore, PhD,a
Christian Alvarez, BS,a
Kayvon Yazdanbakhsh, MPH,c
Rodney Infante, MD, PhD,a,
** Puneeth Iyengar, MD, PhDd,
*
a
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas
b
McGovern Medical School, University of Texas Health Science Center, Houston, Texas
c
Rush Medical College, Rush University Medical Center, Chicago, Illinois
d
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas
Received 26 September 2022; revised 2 March 2023; accepted 6 March 2023
Available online - 11 March 2023
ABSTRACT
Introduction: Cancer cachexia, found in more than a third
of patients with NSCLC, directly leads to functional and
survival detriments. As screening and interventions for
cachexia and NSCLC improve, deﬁcits in health care access
and quality among patients disadvantaged by racial-ethnic
and socioeconomic factors must be addressed.
Methods: We retrospectively evaluated 957 patients diagnosed
with having stage IV NSCLC between 2014 and 2020 in
Dallas, Texas. Cachexia was retrospectively assessed by
applying criteria for substantial unintentional weight loss in
the time leading up to cancer diagnosis. Nonparametric, parametric,
multivariate logistic regression, and Kaplan-Meier analyses
were conducted to evaluate for variables potentially
associated with cachexia incidence and survival.
Results: In multivariate analysis including age, sex, comorbidities,
body mass index, risk behaviors, and tumor characteristics,
Black race and Hispanic ethnicity were
independently associated with more than a 70% increased
risk of presenting with cachexia at the time of NSCLC diagnosis
(p < 0.05). When private insurance status was included
as a covariate, this association was diminished for Hispanic
patients only. Black patients presented with stage IV disease at
an average of approximately 3 years younger than White
patients (Kruskal-Wallis p ¼ 0.0012; t test p ¼ 0.0002).
Cachexia status at diagnosis consistently predicted for survival
detriments, further highlighting the importance of addressing
differential cachexia risk across racial-ethnic groups.
Conclusions: Fundamentally, our ﬁndings reveal elevated
cachexia risk in Black and Hispanic patients with stage IV
NSCLC with associated survival detriments. These differences
are not fully accounted for by traditional determinants
of health and suggest novel avenues for
addressing oncologic health inequities.
Ó 2023 The Authors. Published by Elsevier Inc. on behalf of
the International Association for the Study of Lung Cancer.
This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/
4.0/).
Keywords: Cachexia; Health inequities; Palliative care; Lung
neoplasms; Mass screening
*Corresponding author.
Disclosure: Mr. Olaechea has a research grant from the American Society
of Clinical Oncology. Dr. Infante’s laboratory has received
funding from Pﬁzer unrelated to this work. Dr. Iyengar has worked
with AstraZeneca in an advisory capacity unrelated to this work. The
remaining authors declares no conﬂict of interest.
Cite this article as: Olaechea S, Liu A, Sarver B, et al. Racial, ethnic,
and socioeconomic characteristics independently predict for cachexia
risk and associated survival outcomes in stage IV NSCLC: a brief report.
JTO Clin Res Rep. 2023;4:100496.
Address for correspondence: Puneeth Iyengar, MD, PhD, Department of
Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
75390. E-mail: Puneeth.Iyengar@UTSouthwestern.edu.
**Address for correspondence: Rodney Infante, MD, PhD, Center for
Human Nutrition, University of Texas Southwestern Medical Center,
Dallas, TX 75390. E-mail: Rodney.Infante@UTSouthwestern.edu
ª 2023 The Authors. Published by Elsevier Inc. on behalf of the
International Association for the Study of Lung Cancer. This is an
open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
ISSN: 2666-3643
https://doi.org/10.1016/j.jtocrr.2023.100496
JTO Clinical and Research Reports Vol. 4 No. 4: 100496
Introduction
NSCLC is a leading cause of cancer-related mortality in
the United States, as most patients present with late-stage
disease and limited treatment options. It is estimated that
36% of patients with NSCLC have cachexia,1
a clinically
challenging multifactorial syndrome characterized by substantial
loss of muscle and adipose stores.2
Cancer cachexia
is associated with decreased quality of life, reduced
response to cancer therapies, and poor overall prognosis.3
Racial, ethnic, and socioeconomic status (SES) outcome
disparities are prevalent in NSCLC, as higher incidence and
mortality are consistently observed in marginalized
groups.4
Patients with NSCLC who are Black, Hispanic,
uninsured, or residing in low-income areas have been found
to be less likely to receive guideline-concordant care.5
Although the importance of race, ethnicity, and SES in
NSCLC is well established and encourages targeted
research, the relationship is poorly deﬁned within the
context of cachexia. In this study, we reviewed a 7-year
data set of patients diagnosed with having stage IV
NSCLC in Dallas, Texas, to investigate associations between
cachexia and clinical, demographic, and SES factors.
Materials and Methods
Cohort Characteristics and Cachexia Incidence
at Diagnosis
Retrospective tumor data extraction and electronic
medical record review were conducted through an institutional
review board–approved study at a tertiary care
center in Dallas, Texas. Demographic information, comorbid
conditions, treatment information, longitudinal weight
data, survival time, pertinent health behaviors, and tumor
characteristics were collected for patients diagnosed with
having stage IV NSCLC between 2014 and 2020.
Comorbidities were quantitatively assessed by the
Charlson comorbidity index. Patients were classiﬁed as
not having private insurance if they were uninsured or
entirely dependent on government-associated coverage
(Medicare, Medicaid, and veteran programs).
The international consensus deﬁnition2
of cachexia
was applied to determine cachexia status at diagnosis.
For patients with body mass index (BMI) greater than or
equal to 20, unintentional weight loss exceeding 5%
from baseline in the 6-month period leading to the
diagnosis met the criteria for cachexia at cancer diagnosis.
A cutoff of 2% was applied for patients with BMI
less than 20 per consensus deﬁnition.
Statistical Evaluation
With the classiﬁcation of cachexia incidence at cancer
diagnosis as the binary dependent variable, multivariate
logistic regression was conducted, including the
following covariates: age at diagnosis, sex, pretreatment
BMI, alcohol history, tobacco history, Charlson comorbidity
value, tumor cell morphology, and racial-ethnic
group.
Independent-sample Kruskal-Wallis testing was conducted
with pairwise comparisons to determine whether
any statistically signiﬁcant difference existed based on
age at cancer diagnosis across racial-ethnic groups of the
cohort. Statistically signiﬁcant comparison groups were
further evaluated with independent-sample t testing.
Survival was evaluated through Kaplan-Meier estimators
and Cox regression analysis for non-Hispanic (NH)
White and Black patients stratiﬁed by cachexia status at
diagnosis, as these groups had sufﬁcient (n > 100) representation
within the overall cohort. Survival was evaluated
as time in days from cancer diagnosis date to the
date of death or last contact, with appropriate censoring.
All statistical analyses, tables, and ﬁgures were
created or carried out on IBM SPSS Statistics for
Macintosh, Version 28.0. (Armonk, NY). Tests were
conducted at the 5% signiﬁcance level.
Results
Cachexia Incidence at Diagnosis
The total cohort consisted of 957 patients, with
42.95% (n ¼ 411) meeting the criteria for cachexia at
diagnosis. Table 1 displays frequencies of patient and
tumor characteristics within our cohort along with
cachexia incidence by category. More speciﬁc payor information
for patients without private insurance can be
found in Supplementary Table 1.
Multivariate Analyses
In multivariate analysis including private insurance
as a binary covariate, Black patients had an OR of 1.558
(95% conﬁdence interval [CI]: 1.051–2.309, p ¼ 0.0272)
toward cachexia at diagnosis. Hispanic ethnicity was not
associated with an elevated risk of cachexia incidence at
diagnosis (p ¼ 0.03937). Private insurance had a protective
association toward cachexia incidence, with an
OR of 0.692 (95% CI: 0.496–0.964, p ¼ 0.0298; Table 2).
Repeated analysis excluding the private insurance
covariate revealed signiﬁcant elevations of cachexia risk
at diagnosis greater than 70% for Black (OR ¼ 1.748,
95% CI: 1.205–2.535, p ¼ 0.0033) and Hispanic (OR ¼
1.717, 95% CI: 1.005–2.932, p ¼ 0.0477; Supplementary
Table 2) patients.
Comparing Age at Diagnosis
Pairwise comparisons between racial-ethnic groups
on Kruskal-Wallis testing detected a signiﬁcant difference
in age at diagnosis solely between NH White and
Black patients (p ¼ 0.0012; Supplementary Table 3).
Independent-sample t testing between these groups
2 Olaechea et al JTO Clinical and Research Reports Vol. 4 No. 4
again revealed a signiﬁcant difference of age at diagnosis
(p ¼ 0.0002; Supplementary Table 4). NH White and
Black patients presented with mean ages of 65.64 and
62.60 years at diagnosis, respectively.
Survival
Figure 1 illustrates Kaplan-Meier curves for NH
White and Black patients stratiﬁed by cachexia status at
diagnosis. Within the cohort of patients who did not
present with cachexia at diagnosis, there was no significant
difference between survival time between NH
White and Black patients detected on log-rank testing
(p ¼ 0.5121). Similar analysis within the cohort of
patients with cachexia at diagnosis also found no signiﬁcant
difference between NH White and Black patients
(p ¼ 0.2744). Signiﬁcant survival differences were found
for all groups with opposing cachexia status at diagnosis
(p < 0.05). Supplementary Tables 5 and 6 display median
survival times and log-rank comparisons.
Simultaneous interpretation of survival inﬂuence of
Black race—compared with NH White patients—and
cachexia status was performed by means of Cox
regression. Black race was associated with a hazard ratio
of 1.044 (95% CI: 0.860–1.268, p ¼ 0.6633), whereas
cachexia status was associated with a hazard ratio of
1.416 (95% CI: 1.187–1.690, p ¼ 0.0001).
Table 1. Population Characteristics and Cachexia Incidence
Category Characteristics n Cachexia Incidence (%)
Patient information Median age at diagnosis (y), IQR 65, 57–72
Sex
Male 524 252 (48.09)
Female 432 158 (36.57)
Race
Non-Hispanic White 579 228 (39.38)
Black 216 118 (54.63)
Asian 72 23 (31.94)
Hispanic 90 42 (46.67)
Insurance
No private insurance 437 223 (51.03)
Any private insurance 475 175 (36.84)
Risk factors Median Charlson comorbidity score, IQR 11, 9–13
Median pretreatment BMI (kg/m2
), IQR 24.80, 21.98–28.62
Alcohol history
None 575 250 (43.48)
Current or prior 334 141 (42.22)
Tobacco history
None 211 70 (33.18)
Current or prior 698 321 (45.99)
Tumor characteristics Cellular morphology
Adenocarcinoma 705 283 (40.14)
Squamous 137 71 (51.82)
Large cell 16 8 (50)
Mixed or NOS 99 49 (49.49)
Total 957 411 (42.95)
BMI, body mass index; IQR, interquartile range; NOS, not otherwise speciﬁed.
Table 2. Multivariate Analysis of Cachexia Incidence at Cancer Diagnosis
Category Parameter OR (95% CI) p value
Patient information Age at diagnosis (y) 1.005 (0.989–1.021) 0.5618
Female sex 0.719 (0.520–0.994) 0.0457
Race
Non-Hispanic White - 0.1575
Black 1.558 (1.051–2.309) 0.0272
Asian 0.982 (0.470–2.050) 0.9606
Hispanic 1.285 (0.722–2.288) 0.3937
Private insurance 0.692 (0.496–0.964) 0.0298
Risk factors Charlson comorbidity score 1.005 (0.954–1.058) 0.8620
Pretreatment BMI 0.981 (0.954–1.008) 0.1641
Alcohol history 1.045 (0.751–1.453) 0.7948
Tobacco history 1.606 (1.027–2.510) 0.0377
Tumor characteristics Cell morphology
Adenocarcinoma - 0.4141
Squamous cell 1.326 (0.867–2.027) 0.1929
Large cell 1.117 (0.373–3.345) 0.8427
Mixed or NOS 1.414 (0.834–2.399) 0.1983
BMI, body mass index; CI, conﬁdence interval; NOS, not otherwise speciﬁed.
April 2023 Race, Ethnicity, SES in NSCLC Cachexia 3
Discussion
Development of cachexia is common among patients
with cancer, associated with reduced function, decreased
response to anticancer therapy, and increased mortal-
ity.3
Despite the prevalence and impact of cancer
cachexia, weight loss in patients with cancer is rarely
actively monitored.2
Although cachexia research has
progressed in the past decade, our understanding of
racial-ethnic disparities in cachexia is limited. One study
found that an increased risk of cachexia among Black
patients contributed to outcome disparities in pancreatic
cancer.6
To our knowledge, this is the ﬁrst study evaluating
racial-ethnic disparities regarding cachexia risk in
patients with NSCLC.
Health Inequity in Stage IV NSCLC Cachexia
Prior studies have revealed that Black patients with
NSCLC consistently present with more advanced disease
at diagnosis, undergo prolonged diagnosis-to-treatment
times, and are less likely to receive recommended
care.7,8
Hispanic ethnicity, lower household income, and
a lack of private insurance have similarly been observed
to associate with worsened outcomes and survival.9
Development of cachexia is clinically important in
NSCLC care, especially in advanced stages, where pretreatment
weight loss independently predicts for survival
outcomes.10
In this study, we further characterize
associations between cachexia with race, ethnicity, and
private insurance in NSCLC.
Multivariate analysis without a private insurance
covariate found a signiﬁcantly increased risk of cachexia
at diagnosis exceeding 70% for Black and Hispanic
patients. This indicates an oncologic outcome inequity
independent of underlying patient and tumor characteristics
including prior comorbidities and risk behaviors—
representing generally conceived determinants of health.
Cachexia risk in multivariate analysis was attenuated for
Hispanic patients after adjusting for access to private insurance.
This suggests a contributory role of increased
dependence on public insurance toward cachexia burden
in Hispanic populations. Despite the consideration of this
measure, Black patients had a 55.8% greater cachexia
risk, revealing racial inequities persisting beyond this
surrogate measure of health care access.
In survival analysis of NH White and Black patients,
race was not found to signiﬁcantly predict for survival
within groups of equivalent cachexia status at diagnosis.
Cachexia incidence, however, was consistently associated
with pronounced survival detriment. This observation,
in conjunction with the differential cachexia
incidence we observed, suggests that the decreased
survival observed in Black and Hispanic patients with
NSCLC may depend on cachexia or factors contributing
to the progression of cachexia. This was further substantiated
in our Cox regression analysis, which found no
association between Black race and survival risk when
considered simultaneously with cachexia status at
diagnosis.
Advanced disease is an important risk factor for
development of cancer cachexia.2
The increased frequency
of late-stage NSCLC presentation for Black patients
has been supported to result from delayed
detection and inadequate quality and consistency of
screening.7,11
Although all patients in this study presented
with stage IV NSCLC, the elevated incidence of
cachexia in Black patients at time of diagnosis suggests a
within-stage delay in cancer detection compared with
NH White patients. Important factors contributing to
delayed detection in Black patients are inadequacies of
lung cancer screening protocols and utilization. Current
U.S. Preventive Services Task Force recommendations
Figure 1. Two-year Kaplan-Meier survival curves for non-Hispanic White and Black patients stratiﬁed by cachexia status at
cancer diagnosis.
4 Olaechea et al JTO Clinical and Research Reports Vol. 4 No. 4
are predominantly based on the National Lung Screening
Trial,12
whose participants were disproportionately
White and of higher SES compared with the general
population, and the Nederlands-Leuvens Longkanker
Screenings Onderzoek,13
which did not report on
participant race, ethnicity, or SES. In our cohort, we
found that Black patients presented signiﬁcantly
younger than NH White patients at diagnosis, by
approximately 3 years. This ﬁnding is consistent with
prior literature revealing that race-speciﬁc adjustment of
age requirements in U.S. Preventive Services Task Force
guidelines would result in more equitable lung cancer
screening.7,14
Importantly, of the individuals eligible
under current guidelines, Black patients and those with
low SES are still less likely to obtain recommended
screening.7
Early detection is crucial in preventing and
palliating cachexia.3
This highlights the necessity for efforts
in health policy to mitigate further barriers in
health care access in parallel to the revision of screening
criteria.
The greater cachexia risk observed in minority or
socioeconomically disadvantaged groups might also
depend on environmental or pathophysiological mechanisms
not evaluated in this study. A key risk factor for
cachexia development is poor nutrition status,2
which is
well known to correlate with racial-ethnic background
and SES. Our cohort received care in Texas, which has
consistently revealed poor health equity measures and
ranks in the bottom quartile nationally when assessed by
access to, quality of, and utilization of health care services
among minority populations.15
Conclusion
Marked disparities persist in cachexia risk at time of
stage IV NSCLC diagnosis, even after controlling for
several demographic and clinical characteristics. Hispanic
patients have an increase in cachexia risk that is at
least partially attributable to decreased access to private
insurance. Black patients have increased cachexia risk
irrespective of insurance status. As the ﬁeld of cancer
cachexia sees improvements in diagnostic and interventional
strategy, future research must simultaneously
expand to further characterize the speciﬁc mechanisms
behind outcome disparities to substantiate targeted and
equitable reform to health policy.
CRediT Authorship Contribution
Statement
Santiago Olaechea: Conceptualization, formal analysis,
investigation, methodology, visualization, writing—
original draft, writing—review and editing.
Alison Liu: Writing—original draft, writing—review
and editing.
Brandon Sarver: Writing—review and editing.
Linda Anne Gilmore: Data curation.
Christian Alvarez: Data curation.
Kayvon Yazdanbakhsh: Writing—review and
editing.
Rodney Infante: Project administration, supervision.
Puneeth Iyengar: Data curation, project administration,
supervision, writing—review and editing.
Acknowledgments
This work was supported by the National Institutes of
Health (P30 CA142543); Burroughs Wellcome Fund
Career Awards for Medical Scientists (1019692); American
Cancer Society grant (133889-RSG-19-195-01-TBE);
Cancer Prevention and Research Institute of Texas
(RP200170); and the Conquer Cancer Medical Student
Rotation for Underrepresented Populations Award. Any
opinions, ﬁndings, and conclusions expressed in this
material are those of the author(s) and do not necessarily
reﬂect those of the American Society of Clinical
Oncology or Conquer Cancer.
Supplementary Data
Note: To access the supplementary material accompanying
this article, visit the online version of the JTO
Clinical and Research Reports at www.jtocrr.org and at
https://doi.org/10.1016/j.jtocrr.2023.100496.
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