Pediatric Hematology Oncology Journal 3 (2018) 79e87

Contents lists available at ScienceDirect

Pediatric Hematology Oncology Journal

journal homepage: https://www.elsevier.com/journals/pediatric-
hematology-oncology-journal/

Childhood cancer survival disparities in a universalized health system

in Cali, Colombia*
Oscar Ramirez a, b, c, *, Paula Aristizabal e, Alia Zaidi f, Anne Gagnepain-Lacheteau g,
Raul C. Ribeiro f, Luis E. Bravo a, d, On behalf of VIGICANCER working group
a
Cali's Cancer Population-based Registry, Universidad del Valle, Cali, Colombia
b
POHEMA (Pediatric Oncologists and Hematologist) Foundation, Cali, Colombia
c
Centro M
edico Imbanaco de Cali, Colombia
d
Department of Pathology, Universidad del Valle, Cali, Colombia
e
Department of Pediatrics, Division of Pediatric Hematology/Oncology University of California San Diego/Rady Children's Hospital, Reducing Cancer
Disparities Program University of California San Diego Moores Cancer Center, La Jolla, CA, USA
f
St Jude Children's Research Hospital, Memphis, TN, USA
g
Fondation Sanofi Espoir, France

a r t i c l e i n f o a b s t r a c t

Article history: Universal healthcare has been proposed as a strategy to achieve health equity. Herein, we describe
Received 7 May 2018 childhood cancer survival disparities within a universal healthcare system in Cali, the third largest city in
Received in revised form Colombia. We prospectively included data from Cali's childhood cancer surveillance system (VIG-
25 January 2019
ICANCER) cohort (2009e2016) and adjusted the hazard ratios (aHR) for confounders using multivariate
Accepted 29 January 2019
Available online 10 February 2019
Cox regression. We included 1808 patients with a median age for children (n ¼ 1499) of 6 years and for
adolescents (n ¼ 309) of 17 years. Fifty-six percent were male, 14% were afro-descendants, 61% resided
outside of Cali, 52% had public insurance, 44% had private insurance, and 4% were uninsured. Five-year
Keywords:
Health disparities
overall survival rates for patients with private insurance, public insurance and uninsured patients were
Universal health care coverage 62% (95% CI: 58, 66), 43% (95% CI: 39, 46) and 23% (95% CI: 13, 35), respectively. Compared to private
Survival insurance, mortality among patients with public insurance (aHR ¼ 1.6; 95% CI: 1.3, 1.9) and uninsured
Childhood (aHR ¼ 2.7; 95% CI: 1.9, 4.0) was higher. We found significant disparate survival outcomes, primarily by
Epidemiology insurance and tumor type. Higher treatment abandonment, higher treatment-related mortality, and
Cancer advanced disease at diagnosis partially explained these disparities. Survival inequalities persist in
Treatment outcome Colombia despite an established universal healthcare system aimed at providing equal care for all.
© 2019 Publishing Services by Elsevier B.V. on behalf of Pediatric Hematology Oncology Chapter of Indian
Academy of Pediatrics. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction preventable, cancer control in the childhood population is depen-

Cancer in children is highly curable in approximately 80% of the
cases [1,2], but effective treatment is complex and costly, particu-
larly in low and middle income countries (LMIC), where resources
are constrained [3]. Moreover, as childhood cancer is currently not
*
Supported by the My Child Matters program of Sanofi-Espoir Foundation (O.R.,
A.Z., A.G-L.) and the POHEMA Foundation (O.R. and L.E.B.); the American Lebanese
Syrian Associated Charities (R.C.R.).
* Corresponding author.Cali's Cancer Population-based Registry, Universidad del
Valle, Cali, Colombia.
E-mail address: oramirez@pohema.org (O. Ramirez).
Peer review under responsibility of Pediatric Hematology Oncology Chapter of
Indian Academy of Pediatrics.
dent on the overall effectiveness of cancer services delivery and
health systems.
Survival disparities in children with cancer vary widely within
and between countries [4]. Cancer biology, host conditions, social
determinants, and the delivery of cancer care contribute to survival
disparities [5e7]. In high-income countries (HIC) ethnicity, race and
socioeconomic status (SES) have been associated with survival
disparities [5e7]. In LMIC, additional factors include delayed diag-
nosis, lack of training in pediatric cancer management and support,
limited access to curative care, cultural barriers, treatment aban-
donment, poor adherence to treatment, and fragmented healthcare
delivery [8,9]. In Colombia, childhood cancer survival disparities
have not been reported at the population-based level.

https://doi.org/10.1016/j.phoj.2019.01.001
2468-1245/© 2019 Publishing Services by Elsevier B.V. on behalf of Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
80 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87

Table 1
Colombia, Valle del Cauca, and Cali demographic and social-economic indicators
Abbreviations
Colombia has an average health expenditure compared to other countries in the
region and 30% lower than the OECD average (21%). It is worth pointing that during
aHR Adjusted Hazard Ratio the five year study period there was no relative increase in health expenditure.
ALL Acute Lymphoid Leukemia During the study period Valle del Cauca province was wealthier than Colombian
CNS Central nervous system average, with a lower poverty percentage, but still with high economic disparities as
measured by GINI coefficient. Cali continues to be one of the five wealthiest capital
EFS Event free survival
cities in Colombia, showing improving in health indicators such as a steady decrease
ICD-O-3 International Classification of Diseases for in infant mortality. GINI coefficient is a measure of wealth distribution of a nation's
Oncology 3rd version residents; commonly used measurement of inequality.
ICCC-3 International classification of childhood cancer
Indicator Year
3rd version
2009 2016
CI confidence interval
LMIC Low and middle income countries Colombia
HR Hazard ratio Population 44 978 832 48 747 708
Population <19 years of age 16 593 426 16 317 781
OS Overall survival Per capita gross national income 5090 6310
POSc Contributory regimen GINI coefficient 0.56 0.52
POSs Subsidized regimen Poverty (%) 40.3 28
PPNA Population with no insurance Total expenditure on health (%) 6.4 6.2
Infant mortality rate (per 1000 live births) 18.8 16.8
POU Pediatric Oncology Unit
Province of Valle del Cauca
SES Socio-economic status Population 4 338 216 4 660 741
VIGICANCER Cali's childhood cancer surveillance system Population <19 years of age 1 454 089 1 393 429
GINI coefficient 0.52 0.48
Poverty (%) 33.3 22.6
Infant mortality rate (per 1000 live births) 13.7 11.5
Province's capital city Cali
Children with cancer deserve equitable, high quality care. Uni-
Population 2 219 720 2 394 925
versal health coverage has been proposed as a strategy to achieve Population <19 years of age 716 514 696 779
health equity (defined in terms of equal use for equal need) in GINI coefficient 0.50 0.48
different countries [10e12]. Under this premise, Colombia estab- Poverty (%) 28.4 15.4
Infant mortality rate (per 1000 live births) 9.7 7.8
lished a compulsory universal health insurance system in 1993
[13e16]. This system improved universal access to healthcare, Sources: Colombian national bureau of statistics and Cali's planning office [51,52].
diagnostic resources, therapeutic technologies and availability of
chemotherapy and other medications. Additionally, financial risks
associated to catastrophic diseases, such as cancer, have been Obligatorio de Salud Subvencionado), which covers approximately
minimized, and human resources training has been optimized, as 48% of the population. A minor proportion (<15%) falls outside of
demand for services has increased inmensely [13e16]. However, these two sub-systems: those with private insurance in addition to
operational barriers had been described in the public insurance POSc, those with government insurance (police, military, or gov-
system, such as lack of institutional capacity, deficient operational ernment employees), and those who are uninsured (PPNA, Pobla-
management, lacking information systems, and delays in the flow cion Pobre No Asegurada). Third-party private and public
of resources [15]. companies are responsible of client affiliation and access to ser-
The introduction of this universal health system resulted in an vices. Insurance companies receive government funding based on
initial increase of the overall survival (OS) of children with cancer in the number of individuals insured, and payments by private em-
Cali, the third largest city in Colombia, from 31.6 ± 3.2% ployers to support the contributory sub-system. Currently, both
(1992e1996) to 54.9 ± 2.8% (2002e2007) [16]. However, Cali's sub-systems cover basic services such as diagnosis work-up,
recent survival estimates suggest stagnation, with OS of 52% for the treatment, and rehabilitation of children with cancer.
2009e2013 cohort. In the last decade in Cali, important changes in the management
Herein, we describe childhood cancer survival disparities within of childhood cancer have occurred. The most relevant is a patient
the Colombian healthcare system and the burden of childhood drift from the public hospital to two large private pediatric
cancer mortality to help public health authorities address in- oncology units (POUs). In 2009, the public hospital POU1 served
equalities in care and outcomes in our population and in other 48% of children and adolescents with cancer in the region and in
similar resource-constrained settings. 2016 served only 11% of children. In 2016, the two large private
POUsb, c served 90% of the population. Cali had five pediatric on-
cologists in 2009, and this number increased to eight in 2013.
2. Methods
Before 2011, adolescents with cancer were treated at adult oncology
units. In 2012, it was mandated by the ministry of health that ad-
2.1. Healthcare system in Colombia and Cali
olescents needed to be treated at POUs.
Colombia is categorized as an upper-middle- income country
(Table 1), with a relatively young (1993- present) compulsory 2.2. Study cohort and measurements
universal health insurance system [13,15,16,18]. This system
[15e17,19] provides coverage to the majority of the population In 2009, we established a Childhood Cancer Outcomes Surveil-
through two different sub-systems: the contributory system for lance System (VIGICANCER) in Cali, with the support of Sanofi-
employed individuals, co-financed by the employer and the Espoir Foundation's “My Child Matters” program and Cali's
employee (Spanish acronym POSc, Plan Obligatorio de Salud Con- Population-based Cancer Registry [18,20]. VIGICANCER's rationale,
tributivo), which covers approximately 40% of the population and methodology and implementation have been previously published
the subsidized system (subsidized by the government) for informal [18]. VIGICANCER collects data on children and adolescents with a
employees and the unemployed (Spanish acronym POSs, Plan new diagnosis of cancer, who are initially treated in Cali, even if
 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87
they do not reside in Cali. VIGICANCER allows registration of pa-
tients from all POUs in Cali and monitoring of their clinical out-
comes. VIGICANCER collects baseline demographic variables (date
of birth, sex, race/ethnicity, place of residence, place of diagnosis,
type of health insurance, and whether care is transferred to another
institution) and clinical variables (pathological diagnosis, tumor
location, date of diagnosis, and method of diagnosis). Transfer of
care usually is dictated by insurance contracts with the POU.
Cancer types were coded using the International Classification
of Diseases for Oncology, 3rd edition (ICD-O-3) [21]. For hemato-
logical and lymphoid tumors we used the World Health Organi-
zation version of ICD-O-3 [22]. The International Childhood Cancer
Classification version 3 (ICCC-3) was used for analyses [23]. Heath
insurance information was obtained directly from patient admis-
sion forms, medical records or pathological reports. Insurance in-
formation was then classified in one of the four insurance
categories (sub-systems) of the healthcare system. For analysis
purposes in this report, health insurance type was grouped into: a).
private insurance (POSc and private); b). public insurance (POSs
and government insurance): and c). uninsured (PPNA). VIG-
ICANCER was approved by the Institutional Review Board at the
University of the Valley and by all local POUs.
2.3. Outcomes and follow-up
The primary outcome was death. Secondary outcomes included
the following events: disease relapse, progression, development of
second malignancy, and treatment abandonment. Relapse was
defined as histopathological evidence of disease recurrence after
previously documented complete remission. Diagnosis of relapse
was made without pathologic confirmation in cases where un-
equivocal evidence of relapse was available on imaging and/or
positive tumor markers. Disease progression was defined as at least
25% increase in 2-dimension measurements of the visible tumor(s)
on relevant imaging. Second malignancy was defined as a histo-
logically distinct second cancer that developed after the first
diagnosis. Treatment abandonment was defined as an unplanned
delay of more than 4 weeks of the scheduled date to receive
curative intent therapy, that was unrelated to medical reasons and
due to the patient not returning for care [24]. All cases of treatment
abandonment were included in VIGICANCER. Treatment abandon-
ment was considered an event for survival analyses and docu-
mented in the same manner as no subsequent relapse or death.
VIGICANCER's clinical monitors gathered information every three
months from medical records and by contacting families to docu-
ment disease status (active vs. remission) and any information on
transfer of care between POUs. Lost to follow-up was defined as a
patient being non-contactable by any means for 6 months despite
of at least three phone contact attempts. After loss to follow-up was
documented, vital status of the patients was obtained from health-
insurance affiliation information, death certificates, and hospital
discharge registries (“passive surveillance”) through Cali's
Population-Based Cancer Registry.
2.4. Statistical analysis
The study period was from January 1, 2009 to December 31,
2016, with an established last follow-up as December 31, 2017.
Statistical analyses were carried out using STATA (version 13.1;
StataCorp, College Station, TX). Event-free survival (EFS) was
calculated from the date of diagnosis to the date of first event.
Overall survival (OS) was calculated from the date of diagnosis to
date of death or treatment abandonment if no vital status was
known after this event. Patients detected only by death certificate
(without diagnosis date) were excluded for survival analyses,
81
because the time to the event could not be estimated. The latest
time point to follow-up was documented from the alive patients
with no events and considered as a censored observation. Cases of
treatment abandonment were included in the analyses as events
and not as censored observations. Kaplan-Meier survival curves
were generated for EFS and OS from these survival probabilities,
and 95% confidence intervals (CIs) were calculated. We used Cox
proportional hazards regression to estimate survival hazard ratios
(HRs), adjusted hazard ratios (aHR) and associated 95% CIs to
evaluate the impact of health insurance on EFS and OS, adjusted for
the following potential confounders: age, sex, afro-descendant
ancestry [5,6], place of residence [25], year of diagnosis, treat-
ment facility (private or public) [25] and care transferred to another
institution. For extracranial and lymphoid tumors, stage [26] was
included in the model as a binary variable as metastatic vs. non-
metastatic. Collinearity was explored and was not found among
the independent variables included in the models. We evaluated
the presumption of proportional hazards using Scho €enfeld re-
siduals and logarithmically transformed survival time. No viola-
tions of the assumption were observed. All P values reported were
2-sided, and those that were 0.05 were considered to be statis-
tically significant.
3. Results
3.1. Cohort characteristics
The age-standardized annual incidence rate of childhood cancer
in Cali from 1977 to 2011 was 141 cases per million [17]. Our initial
sample included a total of 1927 cases. Fifty patients (3%) had
missing data on health insurance type and were excluded from the
analysis. Of those, 97% were followed-up using VIGICANCER during
the observation period 2009e2016. Therefore, analyses included
94% (1808 cases) of the patients included in the larger VIGICANCER
cohort. Of those, 1499 were children (<15 years of age) and 309
were adolescents (15e18.9 years of age) [Fig. 1]. Ninety-six percent
of case diagnoses had pathological confirmation.
Median age in children and adolescents at diagnosis was 6 years
(interquartile range [IQR]: 3, 11), and 17 years (IQR: 16, 18),
respectively. Fifty-six percent (95% CI: 54, 59) were male, 14% (95%
1927 children and adolescents registered
by VIGICANCER (2009 – 2016)
69 lost to follow-up
1858 in active follow-up
50 without social security
data
1808 included in analyses
790 950 68
Private Public
Uninsured
Fig. 1. Patient selection flow diagram.
82 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87

CI: 13, 16) were afro-descendants, and 61% (95% CI: 59, 63) resided
outside of Cali. Distribution of solid vs. hematological tumors was
similar (n ¼ 907 vs. n ¼ 901, respectively).
Overall, the major ICCC tumor groups were I (39%; 95% CI: 37,
42), III (18%; 95% CI: 16, 19), and II (11%; 95% CI: 9, 12). The most
frequent extra-cranial tumor in children (18% of all extra-cranial
tumors [n ¼ 463]) and adolescents (40%, [n ¼ 162]) was bone tu-
mor (ICCC group VIII). Thirty-six percent of patients with solid
extracranial tumors had metastatic disease at diagnosis.
Transfer of care among different POUs was frequent (33%; 95%
CI: 30, 35); with 53% (95% CI: 48, 57) being transferred among
private POUs, 42% (95% CI: 37, 46) from public to private POUs, and
6% (95% CI: 4, 8) to POUs outside Cali.
3.2. Disparities in outcomes by health insurance
Patient characteristics by health insurance type are described in
Table 2. During the study period, 52% of the patients had public
insurance, 44% had private insurance and 4% were uninsured. Fifty
percent of patients residing in Cali had private insurance (95% CI:
47, 54) compared to the public and uninsured groups combined
(30%; 95% CI: 27, 33). Twenty-one percent of patients with public
insurance (95% CI: 18, 24) were transferred from a public POU to a
private POU and 0.2% of patients were transferred from a private
POU to a public POU.
Metastatic extracranial solid tumors were more frequently
diagnosed in patients with public insurance (65%) compared to
patients with private insurance (35%) with an odds ratio (OR) of 1.9
(95% CI: 1.4, 2.7). Malignant bone tumors (OR 5.1; 95% CI: 1.9, 13.2)
and soft tissue sarcomas (OR 3.9; 95% CI: 1.1, 13.6) showed the
strongest association.
As of December 31, 2017, 33% (95% CI: 35, 39) of patients had
died. Proportion of deaths in hematological tumors and solid tu-
mors were 35% (95% CI: 34, 39) and 40% (95% CI: 31, 37), respec-
tively. Table 3 describes causes of death by health insurance type in
hematological and solid tumors. Overall, 2% (95% CI: 1, 2) of the
patients died prior to starting cancer treatment. Death for Mortality
during induction therapy in hematological tumors was 5% (95% CI:
4, 7) and significantly higher in uninsured patients and in those
with public insurance compared to those with private insurance
(15% vs. 6% vs. 2%, respectively; P ¼ 0.015). Among patients with
acute lymphoblastic leukemia (ALL), treatment-related post-in-
duction mortality was 9% vs. 4% in patients with public and private
insurance, respectively (P ¼ 0.04). Ten patients (0.6%; 95% CI: 0.3,
1.0) died due to a second malignancy. Treatment-related mortality
was lower for solid than for hematological tumors (2% vs. 8%;
P < 0.001).
Five-year cumulative incidence of relapse was 31% (95% CI: 28,
36) and it was lower for patients with private insurance (26%; 95%
CI: 22, 32), higher in patients with public insurance (36%; 95% CI:
30, 43), and highest in uninsured patients (54%; 95% CI: 30, 99).
Two-year cumulative incidence of treatment abandonment in
children was 12% (95% CI: 7, 14). Treatment abandonment in pa-
tients with private insurance was 3% (95% CI: 2, 5), in patients with

Table 2
Characteristics of patients by health insurance type
Since 2009, there has been a continued decrease in uninsured patients as health system coverage improves. Private vs public insurance ratio was relatively stable during this
period, and only 18% of all patients were exclusively treated in the public POU. Public insurance was twice more frequent compared to private from those patients coming for
cities different of Cali; otherwise Cali patients were almost twice more frequently private than public. Pathology confirmation was evenly distributed by insurance status. Less
frequency of infant cases were observed in the public insurance and uninsured group, which is noteworthy as demographically those groups have mayor proportion of children
compared to private group population. Ratio of hematological tumors to solid tumors was similar among the three groups. Number of cases diagnosed and treated each year
was very similar.

Characteristics Health Insurance Category P-value

Private Public *None Total

n (%) n (%) n (%) n (%)

Age group (years)

[0,1) 62 (8) 45 (5) 2 (3) 109 (6) 0.001
[1, 5) 226 (29) 257 (27) 28 (41) 511 (28)
[5,10) 180 (23) 229 (24) 19 (28) 428 (24)
[10,15) 179 (23) 257 (27) 15 (22) 451 (25)
[15,19) 143 (18) 162 (17) 4 (6) 309 (17)
Total 790 (44) 950 (53) 68 (4) 1808 (100)
Male sex 446 (56) 542 (57) 36 (53) 1024 (57) 0.797
Afro-descendants (n ¼ 1527) 86 (13) 120 (15) 13 (25) 219 (14) 0.058
Place of residence (n ¼ 1806)
Province's capital city with POU 398 (50) 277 (29) 29 (44) 704 (39) <0.001
Province's towns without POU 252 (32) 323 (34) 25 (38) 600 (33)
Other Provinces 139 (18) 349 (37) 14 (21) 502 (28)
Total 789 (44) 949 (53) 68 (4) 1806 (100)
Diagnosis with pathology confirmation 758 (96) 916 (96) 66 (97) 1740 (96) 0.817
Hematological malignancies 382 (48) 479 (50) 40 (59) 901 (50) 0.220
POU of treatment
Only private 776 (98) 452 (48) 5 (7) 1233 (68) <0.001
Public to private 0 (0) 197 (21) 19 (28) 216 (12)
Private to public 1 (0) 3 (0) 0 (0) 4 (0)
Only public 1 (0) 282 (30) 44 (65) 327 (18)
POU outside the province 12 (2) 16 (2) 0 (0) 28 (2)
Total 790 (44) 950 (53) 68 (4) 1808 (100)
Diagnosis year
2009-10 218 (28) 226 (24) 55 (81) 499 (28) <0.001
2011-12 181 (23) 234 (25) 6 (9) 421 (23)
2013-14 209 (26) 254 (27) 7 (10) 470 (26)
2015-16 182 (23) 236 (25) 0 (0) 418 (23)
Total 790 (44) 950 (53) 68 (4) 1808 (100)

n ¼ 1808 if not otherwise stated.

*Uninsured.
 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87 83

Table 3
Causes of death in solid and hematological tumors by health insurance type
In solid tumors, treatment related deaths were similar in the public and private groups, but much higher in uninsured. In hematological tumors, as compared to the private
group, induction related death was three-times more frequent in public group and seven-times in the uninsured group. Treatment related deaths after induction were similar
for both private and public, but twice higher for the uninsured. Disease related deaths were twice higher in public and the uninsured group. Unknown causes of death were
almost evenly distributed among insurance status in solid tumors, with a higher frequency in the hematological tumors.

Solid tumors Health Insurance Category

Private Public *None Total

n (%) n (%) n (%) n (%)

Alive 262 (64) 275 (58) 10 (36) 547 (60)

Death 146 (36) 196 (42) 18 (64) 360 (40)
At diagnosis prior to cancer treatment 4 (1) 11 (2) 0 (0) 15 (2)
Treatment-related 9 (2) 6 (1) 14 (50) 29 (3)
Disease related 107 (26) 141 (30) 0 (0) 248 (28)
Second neoplasm 2 (0) 2 (0) 0 (0) 4 (0)
Other 0 (0) 0 (0) 4 (14) 4 (0)
Unknown cause 24 (6) 36 (8) 1 (4) 61 (7)
Total P ¼ 0.059 408 (45) 471 (52) 28 (3) 907 (100)
Hematological tumors
Alive 288 (75) 291 (61) 18 (45) 597 (66)
Death 94 (25) 188 (39) 22 (55) 304 (34)
At diagnosis prior to cancer treatment 7 (2) 8 (2) 0 (0) 15 (2)
Treatment-related during induction 9 (2) 30 (6) 6 (15) 45 (5)
Treatment related post-induction 22 (6) 34 (7) 6 (15) 62 (7)
Disease related 36 (9) 73 (15) 9 (23) 118 (13)
Second neoplasm 5 (1) 1 (0) 0 (0) 6 (1)
Other 1 (0) 0 (0) 0 (0) 1 (0)
Unknown cause 14 (4) 42 (9) 1 (3) 57 (6)
Total ¶P < 0.001 382 (42) 479 (53) 40 (4) 901 (100)

Likelihood-ratio chi2 statistical test for the frequency distribution.

*Uninsured.

public insurance was 20% (95% CI: 16, 24) and in uninsured patients private insurance, patients with public insurance, and uninsured
was 30% (95% CI: 16, 58). patients were 72% (95% CI: 63, 79), 46% (95% CI: 38, 52) and 38%
Five-year OS rates for all patients combined, children, and ad- (95% CI: 21 19, 57), respectively. Three-year OS rates for ALL in
olescents were 51% (95% CI: 48, 53), 52% (95% CI: 50, 55) and 41% children was 65% (95% CI: 60, 69); and for patients with private
(95% CI: 33, 48), respectively. Five-year OS for solid tumors was 47% insurance was 83%(95%CI: 76, 88) compared to patients with public
(95% CI: 42, 50) and for hematological tumors was 54% (95% CI: 50, insurance which was 52% (95% CI: 46, 59). Table 4 shows EFS results
58). Fig. 2 shows OS curves by health insurance type and by tumor by insurance type and tumor type. Mortality was higher in unin-
type. Three-year OS rates for children was 57% (95% CI: 55, 60); and sured patients (aHR 2.7; 95% CI: 1.9, 4.0), and in patients with
for patients with private insurance was 70% (95% CI: 66, 74) private insurance (aHR 1.6; 95% CI: 1.3, 1.9), compared to patients
compared to patients with public insurance, which was 49% (95% with private insurance, across the three major pathological groups
CI: 45, 53). Specifically, in ALL, the 5-year OS rates in patients with (acute leukemias, extracranial lymphoid and solid tumors and

Hematological malignancies Solid tumors

1

1
.1 .2 .3 .4 .5 .6 .7 .8 .9

.1 .2 .3 .4 .5 .6 .7 .8 .9
Survival probability

Survival probability
0

0 10 20 30 40 50 60 70 80 90 0 10 20 30 40 50 60 70 80 90
Time since diagnosis (months) Time since diagnosis (months)
Number at risk Number at risk
Private 382 297 238 197 153 123 88 62 51 23 Public 408 295 226 179 134 99 67 42 24 10
Public 479 313 238 167 128 92 63 48 27 18 Private 471 274 183 130 91 67 47 27 11 1
Uninsured 40 22 18 14 12 8 8 7 4 2 Uninsured 28 13 6 4 3 2 1 1 1 1

Private Public Uninsured

Fig. 2. Overall survival graphs by tumor and health insurance type

This figure shows OS estimates for the cohort by health insurance and tumor type. In the hematological tumor group, the 5-year OS for private insurance was of 67.7% (95% CI: 61.8,
72.8), for public insurance was of 45.6% (95% CI: 40.2, 50.7), and for the uninsured group of 27.6% (95% CI: 14.5, 42.4). In the solid tumor group, the 5-year OS in patients with private
insurance patients with public insurance and uninsured patients 56.6% (95% CI: 50.8, 61.9), 39.1% (95% CI: 33.5, 44.6) and 14.1% (95% CI: 2.6, 34.8), respectively.
84 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87

Table 4
Five-year event free survival by tumor and health insurance category.

Classification (ICCC-3a) Five-year Event Free Survival

Health Insurance Category Total

Private Public

n % (95% CI) n % (95% CI) n % (95% CI)

I. Leukemias, myeloproliferative diseases, and myelodysplastic diseases 290 57 (50, 64) 384 36 (30, 42) 709 45 (41, 50)
II. Lymphomas and reticuloendothelial neoplasms 91 68 (56, 78) 95 64 (52, 73) 191 66 (58, 73)
III. CNS and miscellaneous intracranial and intraspinal neoplasms 142 42 (33, 51) 165 27 (17, 39) 316 35 (29, 42)
IV. Neuroblastoma and other peripheral nervous cell tumors 23 41 (19, 61) 18 23 (6, 46) 43 32 (16, 48)
V. Retinoblastoma 26 80 (59, 91) 45 61 (44, 75) 73 69 (56, 79)
VI. Renal tumors 34 74 (55, 86) 40 51 (33, 66) 76 62 (49, 73)
VII. Hepatic tumors 14 68 (34, 87) 11 58 (23, 82) 26 63 (39, 80)
VIII. Malignant bone tumors 57 42 (27, 57) 77 20 (10, 33) 136 30 (21, 40)
IX. Soft-tissue and other extraosseous sarcomas 42 46 (30, 61) 43 24 (11, 40) 89 36 (25, 47)
X. Germ cell tumors, trophoblastic tumors, and neoplasms of gonads 39 72 (53, 84) 38 52 (33, 68) 80 62 (49, 73)
XI. Other malignant epithelial neoplasms and malignant melanomas 25 87 (66, 96) 24 52 (27, 72) 51 72 (56, 83)
Total 783 57 (53, 61) 940 39 (35, 43) 1790 47 (45, 50)
a
ICCC-3: International classification of childhood cancer 3rd version. Total analysis time at risk ¼ 48067.8 months; Median time of follow-up in alive patients ¼ 30.6
months.

central nervous system tumors [CNS]) and after adjusting for the Table 5
confounders described in the methods section (see Table 5). Adjusted health insurance HR estimates for death from all causes.

Adolescents with CNS tumors had lower mortality (aHR 0.4; 95% Variables All-cause mortality n ¼ 1805
CI: 0.2, 0.8), whereas uninsured and public insurance patients with q
D HR (95% CI)
CNS tumors had increased mortality risk but with smaller aHR,
Health insurance
when compared with the estimates from the other two major
Private 253 1.0 ¥
histopathological types (Table 6). Residing outside Cali was strongly Public 447 1.6 (1.3,1.9)
associated with higher mortality risk in patients with CNS tumors Uninsured 46 2.7 (1.9,4.0)
(aHR 1.6; 95% CI: 1.3, 1.9). *Age group
Children 619 1.0
We found treatment center effects with worse outcomes for
Adolescents 127 1.3 (1.0,1.6)
patients who were treated in the public POU (aHR 1.6; 95% CI: 1.2, Sex
1.9). The mortality risk decreased by at least 20% (aHR 0.8; 95% CI: Female 311 1.0
0.6, 1.0) when patients were transferred from a public to a private Male 435 1.1 (0.9,1.2)
POU during treatment. We also found a 2-fold increase in mortality Afro-descendants
No 524 1.0
in patients with metastatic lymphoid and extracranial solid tumors
Yes 112 1.3 (1.1,1.6)
(aHR 2.3; 95% CI: 1.9, 4.0) (Table 6). Missing 110 1.2 (0.9,1.5)
Place of origin
4. Discussion Province's capital city with POU 271 1.0
Province's towns without POU 254 1.2 (1.0,1.4)
Other Provinces 221 1.3 (1.1,1.6)
In a comprehensive population-based analysis of childhood x
POU of treatment
cancer outcomes in a major city in Colombia, we found significant Only private 447 1.0
disparities in survival, primarily by insurance, despite universal Transfer from public to private 95 0.8 (0.6,1.0)
Only public 198 1.6 (1.2,1.9)
coverage for all children with cancer and access to uniform
Transfer to POU outside the province 6 0.6 (0.3,1.5)
chemotherapy protocols in Cali. Although we identified a treatment Period
center effect, this effect did not explain these disparities, as the aHR 2009-10 231 1.0
associated with health insurance type and treatment at public POU 2011-12 185 1.0 (0.8,1.2)
were independent. 2013-14 195 0.9 (0.8,1.2)
2015-16 135 1.0 (0.8,1.3)
Uninsured patients had inferior outcomes suggesting that uni-
Tumor classification
versal coverage did improve survival for those patients who were Hematological tumors 356 1.0
insured. However, universal coverage was insufficient to abolish VExtracranial solid tumors 235 1.0 (0.9,1.2)
survival disparities even among those with insurance, as we CNS tumors 155 1.4 (1.2,1.7)
observed a 3-fold higher risk of death in patients with public in- q D: Number of deaths.
surance compared to patients with private insurance. In adoles- ¥ Reference group.
cents and young adults in the U.S. with metastatic cancer and public *Age group: Children 0e14.9, adolescents 15e18.9 years of age.
xPOU: Pediatric oncology unit.
insurance, mortality was 50e70% higher compared to patients with
CNS: Central nervous system.
private insurance and after adjusting for sociodemographic factors
[27]. We found similar results in our cohort, where adolescents,
afro-descendants, patients who resided outside Cali, patients with population with private insurance. This could suggest barriers to
CNS tumors, and patients with metastatic disease had also higher timely diagnosis and referral to a treatment center in patients
mortality. younger than one year.
The lower proportion of patients younger than one year of age in In contrast to reports from HICs [28], we found that adolescents
our cohort among individuals with public insurance was an unex- were less frequently uninsured. Among the afro-descendant
pected finding, because the total number of infants in the popula- group, patients were more frequently uninsured or had public in-
tion covered by public insurance nationally was higher than in the surance compared to private insurance, consistent with insurance
 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87 85

Table 6
Adjusted health insurance HR estimates for death from all causes by type of tumor.

Variables All-cause mortality

¶
Acute leukemias Extracranial and lymphoid tumors CNS tumors

n ¼ 682 n ¼ 519 n ¼ 313

q
D HR (95% CI) D HR (95% CI) D HR (95% CI)

Health insurance
Private 83 1.0 ¥ 66 1.0 69 1.0
Public 195 2.0 (1.5, 2.8) 120 1.6 (1.1, 2.4) 75 1.3 (0.9, 1.9)
Uninsured 21 2.4 (1.4, 4.3) 8 6.4 (2.7, 15.1) 8 3.6 (1.5, 8.7)
Stage IV disease
No NA 101 1.0 NA
Yes 93 2.3 (1.7, 3.0)
*Age group
Children 246 1.0 166 1.0 142 1.0
Adolescents 53 1.9 (1.3, 2.9) 28 1.5 (1.0, 2.2) 10 0.4 (0.2, 0.8)
Sex
Female 122 1.0 86 1.0 61 1.0
Male 177 1.1 (0.9, 1.4) 101 1.1 (0.8, 1.4) 91 0.9 (0.7, 1.3)
Afro-descendants
No 218 1.0 155 1.0 107 1.0
Yes 48 1.5 (1.1, 2.1) 35 1.3 (0.9, 1.9) 13 0.7 (0.4, 1.2)
Missing 33 1.5 (0.9, 2.5) 4 2.0 (0.7, 5.3) 32 1.1 (0.7, 1.7)
Place of origin
Province's capital city with POU 105 1.0 68 1.0 64 1.0
Province's towns without POU 104 1.0 (0.7, 1.3) 63 1.0 (0.7, 1.5) 47 1.2 (0.8, 1.8)
Other Provinces 90 1.1 (0.8, 1.5) 63 1.3 (0.9, 1.9) 41 1.5 (1.0, 2.2)
§
POU of treatment
Only private 158 1.0 122 1.0 116 1.0
Transfer from public to private 64 0.8 (0.6, 1.5) 21 0.6 (0.3, 0.9) 2 0.3 (0.1, 1.2)
Only public 76 1.5 (1.1, 2.2) 48 1.7 (1.2, 2.7) 33 0.9 (0.6, 1.5)
Transfer to POU outside the province 1 0.3 (0.1, 2.0) 3 1.3 (0.4, 4.2) 1 0.4 (0.1, 3.1)
Period
2009-10 90 1.0 205 1.0 45 1.0
2011-12 78 1.3 (0.9, 1.7) 159 0.9 (0.6, 1.5) 36 0.7 (0.5, 1.2)
2013-14 83 1.0 (0.7, 1.4) 171 0.9 (0.6, 1.5) 43 0.7 (0.4, 1.1)
2015-16 48 0.9 (0.6, 1.3) 110 1.6 (1.0, 2.5) 28 0.7 (0.4, 1.2)

Q D: Number of deaths.
¥ Reference group.
* Age group: Children 0e14.9, adolescents 15e18.9 years of age.
x POU: Pediatric oncology unit.
CNS: Central nervous system.

disparities associated with race reported in HIC [27e30]. The pro-
portion of uninsured patients decreased over time during the study
period with no reports of uninsured patients after 2015.
We found a 2-fold increase of metastatic disease at diagnosis in
patients with public insurance and extracranial tumors, with a
strong association in patients with malignant bone and soft tissue
tumors. Stage at diagnosis is one of the determinant factors for
survival disparities in adults with cancer among different SES
groups [26]. Stage at diagnosis in extracranial solid tumors can be
used as a surrogate measurement of timely access to high quality
care because clinical outcomes are highly dependent on disease
extension in this type of tumors [31]. Advanced stage at diagnosis
implies long delays between disease suspicion by the family to
diagnostic confirmation of cancer.
In hematological tumors, treatment-related mortality during
induction was 2.5-fold higher in patients with public insurance
compared to patients with private insurance. Moreover, treatment-
related mortality post-induction in patients with ALL remained
significantly higher in patients with public insurance. Noteworthy,
both treatment-related mortality during induction and post-
induction were higher in patients with private and public insur-
ance when analyzed combined, compared to patients in HIC
[32,33]. Many of these deaths could be attributed to the limited
healthcare system infrastructure to adequately support children
with neutropenic fever, sepsis and septic shock [33,34].
We found a 6-fold increase in treatment abandonment in
patients with public insurance compared to patients with private
insurance. Treatment abandonment and refusal are the most
extreme form of lack of treatment adherence. We did not have
adherence measurements in our study, however, the role of cu-
mulative delays in chemotherapy administration could explain
survival disparities, as previously described [35]. Treatment
adherence and abandonment are complex social phenomena [36],
which involve family income, social support networks, cultural
beliefs and family values, and the ability to navigate complex
healthcare systems, such as the one in Colombia.
Event-free survival disparities were consistent among all ICCC-3
groups of tumors, with the exception of lymphomas, CNS and
epithelial tumors. Lymphomas (particularly Hodgkin lymphoma)
are highly curable with short treatments, including those with
advanced disease. Therefore, in this subgroup, the impact of time to
diagnosis, treatment-related mortality, and treatment abandon-
ment were lower and, hence, patients with public insurance had
better survival rates overall. In contrast, EFS in patients with CNS
tumors was lower in patients with both public and private insur-
ance. This is explained by the complexity of treatment for these
tumors and its reliance on very sophisticated and complex care,
which is limited in LMIC. We also found a higher OS in adolescent
patients with CNS tumors compared to younger patients. This dif-
ference could be attributed to the particular biology of CNS tumors
in infants, the avoidance of radiotherapy as a treatment strategy in
this age group, and the complexity of the care in younger patients.
86 O. Ramirez et al. / Pediatric Hematology Oncology Journal 3 (2018) 79e87
Five-year EFS for thyroid cancer -the most frequent epithelial tumor
in children and adolescents and highly curable-was lower in our
patients with public insurance than the one reported in the liter-
ature [37]. This finding could be associated to the limited avail-
ability of radioactive iodine therapy in Cali.
In patients with hematological tumors, high rates of treatment-
related mortality, particularly during induction, and treatment
abandonment explain most of the survival disparities found among
patients with different insurance types. In extracranial solid tu-
mors, advanced stages at diagnosis and treatment abandonment
seem to play a more prominent role in survival disparities than
treatment-related mortality.
At the regional level, the Argentinian hospital-based cancer
registry (ROHA) reported a three-year OS for children with all
cancer types of 62% (95% CI: 61, 63), in the 2000e2007 cohort [38].
The 57% three-year OS found on our population is comparable to
the reported by ROHA, taking into account that Argentina is a HIC
[39]. We report a 70% three-year OS in patients with private in-
surance that is very similar to the OS reported in the capital city of
Buenos Aires. However, the 49% 3-year OS in patients with
public insurance is below the lowest OS in Argentina of 55% in the
north-west region. For ALL, the five-year OS of 72% in patients with
private insurance is comparable to Argentina's (76%), higher than
the one reported in Brazil (66%), Chile (64%), Mexico (53%) and
Ecuador (50%), but lower compared to the one reported in Costa
Rica (80%) [4].
Our study has some limitations and the generalizability of the
results may be limited given that the population studied was cir-
cumscribed to one city. We were not able to directly assess the
effects of SES on clinical outcomes, although health insurance type
is inevitable linked to SES [15,16,25,28,40], and therefore could be a
mediator between the SES effect and survival [25]. Although, SES is
a multi-dimensional and complex construct [25], by including afro-
descendant ancestry and place of residence in the analyses, we
could partially adjust the health insurance effect estimate for SES.
National statistics report that afro-descendants in Colombia have
low education attainment, are more frequently unemployed and a
great majority live under the poverty line [16].
Place of residence, reflecting the distance to the treatment
center and travel time, was associated with an increased risk of
death, which was even higher if the patient resided in distant
provinces. Finally, travel time or distance to treatment center was
not available, thus we used place of residence to partially adjust for
distance to treatment center [41].
In 2014, 97% of Colombian citizens were covered by the national
compulsory health insurance system [16]. Although this universal
coverage constitutes an enormous public health achievement and
has increase access to basic care, significant survival disparities
remain. This inequity in a setting with a universal healthcare sys-
tem is, unfortunately, not only common in LMIC, such as Colombia
but also in HICs with similar health insurance systems
[25e27,42e46]. A major challenge for national health systems is
not only to ensure that all populations have adequate access to
health coverage and services [47,48], but also to create truly high-
quality care through the continuum of care [48e50]. To achieve
this purpose, itis essential to identify disparities in outcomes at the
population-based level and prioritize resources guided by data
driven-evidence; develop healthcare infrastructure and train hu-
man capital; create national cancer control plans; implement or
improve established cancer registries; support the creation of
reference, comprehensive cancer centers; define resource-
stratified evidence-based diagnosis, and treatment of common
cancers; and guarantee access to essential cancer medicines and to
palliative care [48,50].
Our findings underscore the importance of establishing
pediatric cancer registries in LMICs, to guide local health policy
decisions aimed at improving outcomes in resource-constrained
settings and help narrow the survival gap.
We hope that this data-driven report on survival disparities can
guide policy-makers and healthcare insurance leaders in our
country and other resource-strained settings in identifying gaps in
care by insurance type and plan infrastructure and system changes
to achieve equitable care and outcomes for all.
Acknowledgements
Supported by the My Child Matters program of Sanofi-Espoir
Foundation (O.R., A.Z and A.G.) and the POHEMA Foundation (O.R.
and L.E.B.); and the American Lebanese Syrian Associated Charities
(R.C.R.). We thank the Sanofi-Espoir Foundation leadership for their
support and for facilitating access to international experts who
mentored and guided this project through the My Child Matters
program. We thank Cali's population-based cancer registry staff Luz
Estela García and Paola Collazos and collaborators of the VIG-
ICANCER Group and POHEMA Foundation: Margarita Quintero,
Carlos Portilla, Viviana Lotero, Diego Medina, Ximena Castro, Luz


Angela Urcuqui, Mo
nica Lotero and Dilia Escobar.
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