Cancer survival among

children and adolescents in a

brazilian reference service

Estrabão

Vol(4):13 – 21

©The Author(s) 2023

Reprints and permission:

DOI: 10.53455/re.v4i.2

Jane Kelly Oliveira Friestino

, Mendonça Denisa

, Oliveira Pedro

, Luis

Antunes

, Rosemeire Olanda Ferraz

, Priscila Maria Stolses Bergamo

Francisco

and Djalma Carvalho Moreira Filho

Abstract

Few studies have been found that report cancer survival in children and adolescents in Brazil

over the years due to limited information. We aim to analyse the cancer survival time of children

and adolescents (0-19 years) residents in Campinas, Southeastern Brazil diagnosed in 1996-

2005, attended in the reference service of childhood cancer. This is a cohort retrospect study and

the follow-up censored date was December 31, 2011. Cancers were classified according to the

International Classification of Childhood Cancer Groups. By design, just the 4 most common groups

were studied: Group I, Group II, Group III and Group IX. Kaplan-Meier estimation methods, log-rank

test and Cox regression were used for survival analysis. A total of 180 cases were diagnosed during

the study period. Significant differences in survival times were found by diagnostic groups adjusted

for age and sex (p=0.001). In conclusion, five-year survival was higher in children than in adolescents

similar to the findings reported in the literature.

Keywords

Neoplasms, survival, child health, adolescent’s health

Introduction

Cancer is the name of group over than one hundred diseases with disorder cells grow (maligned) spread

cells to organ and tissues (metastasis) for different body parts. The causes of cancer are variant, can be

extern or intern related (Amador 2011).

1 University of Campinas, Campinas, São Paulo, Brazil

2Institute of Public Health, University of Porto, Porto, Portugal

Corresponding author:

Jane Kelly Oliveira Friestino, University of Campinas, Campinas, São Paulo, Brazil

Email: jane.friestino@uffs.edu.br

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Childhood cancers (age at diagnosis 0–19 years) comprise a variety of malignancies, with

incidence varying worldwide by age, sex, ethnicity and geography, which provide insights into cancer

etiology (Gatta et al. 2014; Steliarova-Foucher 2017).

In developed countries, over the last four decades, advances in cancer treatment and in diagnostic

techniques have resulted in an increased survival for children (ages 0-14 years) and adolescents (ages

15-19 years). It has been reported that in developed countries the 5-year survival increased from less than

30% in the 60s to approximately 80% in the 2000s for all childhood cancers (Gatta et al. 2014; Stiller

et al. 2012).

In developing countries, the mortality rates are higher in Brazil, neoplasms corresponded to the

second leading cause of death in children only surpassed by external causes INCA (2016).

Few studies have been found that report cancer survival in children and adolescents in Brazil over the

years due to limited information on the date of death and the lack of active monitoring Silva et al. (2016)

. Only from the historical knowledge about the occurrence of events will it be possible to implement care

policies in order to understand the survival rates in specific regions.

In Brazil, the childhood cancer statistics have been less studied in the national medic literature, despite

the existence of database liked by the Mortality Information System (SIM) from Health of Ministry and

the Population Based-cancer registries (PBPCR) Morais De (2017).

For implementation of a qualified cancer registry, providing the access to care information as

identification of epidemiological profile, providing comprehensive and accurate management.5

Epidemiological studies about the childhood cancer are rare in Brazil. This is resulted from

the insufficient number of primary notice and registry that difficult to describe the clinical and

epidemiological characteristics from these cases Grabois et al. (2011).

It is known that for cases of malignant neoplasms, the use of information about death is not enough to

know the problem impact, because there are different types of cancer, and each of them has a different

lethality and survival (Gatta et al. 2005). The knowledge respect of the and the profile of the incidence,

clinical characteristics and survival depend of the

In the same way, some rare diseases, such as childhood cancer, need to be monitored. Although they

have a low occurrence, their incidence can negatively affect the quality of life of children and adolescents,

and a worse prognosis is found when there is no structured care network based on the needs population’s.

Thus, the production of information about the cancer survival and improvement of cancer registries

contributes to the formulation of public health policies consistent with reality.

Therefore, this study analyses survival among children (0–14 years) and adolescents (15–19 years)

residents in a Brazilian city, attended in the reference service of childhood cancer.

Material and methods

An observational retrospective study of a longitudinal cohort of children and adolescents (0 - 19 years),

diagnostic with the Leukemias, Lymphomas, Central Nervous System tumors and soft tissue and other

extra osseous sarcomas was conducted in Campinas, São Paulo, Brazil. This is an industrial city with

approximately 1.1 million inhabitants IBGE (2022), located in the State of São Paulo. About 30% of the

population living in Campinas is aged less than 19 years.

Friestino et al.

This retrospective coorth was conducted in the High Complexity Care Unit for Pediatric Oncology

in Campinas, that is a main cancer care for children and adolescents, and was conducted with cases

diagnosed in the period of 1996-2005, and mortality identified between 1996 and 2011.

Case definition

Data were retrieved of all children and adolescents residing in Campinas, aged 0–19 years who were

diagnosed between January 1st, 1996 and December 31st 2005. Confirmed diagnosis of cancer was

obtained from medical records, using the date of diagnoses of first primary tumors.

Cancers were classified according to the International Classification for Childhood Cancer, third

edition (ICCC-3) (Inca, 2016). Benign tumors were excluded. By design, just the most common 4 groups

were studied: Group I – Leukemias, myeloproliferative diseases, and myelodysplastic diseases, Group II

Lymphomas and reticuloendothelial neoplasms, Group III - CNS and miscellaneous intracranial and

intraspinal neoplasms and, Group IX - Soft tissue and other extraosseous sarcomas.

Survival Analysis

Mortality data from 1996 to 2011 were confirmed, by examining the medical records linked to

the Campinas’s Mortality Registry and Health Mortality Information System, Department of Data and

Information Technology, the information and statistics office of the Unified National Health System

(SUS), representing the Ministry of Health (DATASUS, 2021).

The survival time was calculated as the difference between the date of diagnosis and the date of death

or loss to follow-up. The analysis was performed with all cases followed until December 31, 2011. The

follow-up for vital status was collected from the hospital medical records.

To calculate the lower and upper limits of the 95% confidence interval for a proportion. Survival in

each group was analysed using Kaplan-Meier estimation methods. Log rank test was used to compare

the survival curves (Kaplan 1958). The probability of five-year survival was estimated by Kaplan Meier

method. Cox regression models were used for the uni and multivariable analyses, and assumptions of

proportionality of hazards was verified by inspection of the log-hazard plots versus time (Kleinbaum

1995).

The analyses were performed using the software SPSS and R version 2.14.1 (Project for Statistical

Computing).

Ethics approval and consent to participate

The study was conducted in accordance with the Resolution 466/2012 of the Brazilian National Health

Council and was approved by CAAE number 0566.0.000.144-11 from Research Human Research Ethics

Committee.

Results

A total of 180 cases were diagnosed, 85.6% children (n=154) and 14.4% adolescents (n=26). The

median follow-up time in the cohort was 7.5 years (percentile 25:1.3; percentile 75: 11.5). Death was

observed for 68 cases (37.8%). Figure 1 shows the cumulative survival of children and adolescents by

ICCC-3 and age groups. Statistically significant differences in the probability of survival were observed

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according to diagnostic Group (p = 0.001), but not to age groups (p = 0.071). Group IX and

Group III showed lowest survival rates with median estimated survival 2.89 years and 2.91

years, respectively.

Figure 1. Estimates of survival probabilities by diagnostic and age groups among children and

adolescents between 1996-2011 in Campinas, São Paulo, Brazil.

Overall, 5-year survival was 65.6% (95% CI: 57.4% - 72.9%) among children and 53.8% (95%

CI: 33.7% - 72.8%) among adolescents (Table I).

Friestino et al.

The 5-year survival was higher than 80% for Group II, both in children and adolescents. The

most favourable prognosis was observed for those with non-Hodgkin lymphomas except Burkitt

lymphoma, with 91.7 % of children and 100% of adolescents alive 5 years after the diagnosis. The 5-

year survival was lower than 40% among children for the diagnostic Group - IX, and among adolescents

for the diagnostic Group III.

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Table 2 shows the main results of Cox Regression models. The probabilities of overall survival

for girls, adolescents, mother’s and father’s profession not specified, private health service, white ethnic

group, were higher than those for other categories of these covariates, but not statistically different (p >

0.05).

Regarding the survival time, statistically significant differences were observed according to the

diagnostic Groups adjusted for age and sex (p=0.001), with lower survival in the Group IX (HRadj =6.38

-Group IX vs Group II) followed by Group III (HRadj =6.27 Group III vs Group II) (Table 2).

Table 2. Cox Regression Analysis for Survival among children and adolescents residing in

Campinas, São Paulo, Brazil: 1996-2011.

Friestino et al.

Discussion

This study analysed the childhood cancer survival in Campinas, São Paulo, Brazil, showing that

adolescents survive less than children. The most frequent childhood cancer adjusted by age was Group I

–Leukaemia (28.8 per million), followed by Group III - CNS and miscellaneous intracranial and

intraspinal neoplasm (11.9 per million).

Considering that characteristics such as frequency and cancer type distribution in children and

adolescents are unique and different from those observed at any other age-group, it has been

recommended that epidemiological studies of childhood cancer are performed separately from other age

groups (Carreira et al, 2012).

In Campinas, similarly to results from previous European Registries reports, the most frequent

childhood cancer is Group I, representing standardized incidence rates lower than those of the majority

of European countries but similar to Portugal (28.0 per million), Poland (29.9 per million) and Romania

(28.3 per million) (Who, 2014). In addition, the distribution of cases among sex, age and the four most

common Groups of disease are similar to those found in other Brazilian studies and reported by 14

Brazilian Population-based Cancer Registries – PBCRs (Oliveira et al, 2020; Saraiva, Santos &

Monteiro, 2018).

Acute lymphoblastic - ALL, Acute non-lymphoblastic, Astrocytomas, Hodgkin lymphomas were

the most frequent diagnoses in Campinas, both in children and adolescent’s studies, findings already

reported in the literature (Oliveira et al, 2020; Steliarova-Foucher et al, 2018).

Compared to European countries, the largest differences in incidences were observed for Group

III and Group IX, besides might indicate a deceleration in the increase of cancer incidence, although the

registry datasets included differ somewhat between the studies (Steliarova-Foucher et al, 2018). In other

hand, that’s lower rate could suggest the reduced reporting discipline or other factors. For the knowledge

reference on epidemiological profile of incidence and cancer survival is important to improve the studies

for populations of smaller sizes, as been done in Europe (Steliarova-Foucher et al, 2018).

These differences may be explained by the type of tumour (solid) affecting mainly adolescents,

who could have been treated elsewhere or confounded as young adult cases and not referred to the High

Care Unit complexity in Pediatric Oncology.

Although incidence rates in the four diagnostic groups studied differs from the observations of

PBCRs from developed countries, they are similar to those found in the literature for developing

countries, including Brazil (Oliveira et al, 2020; Steliarova-Foucher et al, 2018).

A limitation of the study is the data source because a single childhood oncology service was

used, and even though it had an 85% coverage of the cases of city dwellers, there were still other

possible individuals who were not included in the analysis.

The creation of efficient monitoring system for cancer, in particular for rare cases of childhood

cancer, is necessary across the healthcare networks and would greatly potentiate the value of spatial

analysis permitting for more precise results. When investigated the cancer Incidence rates and the

Standardized Morbidity Rates (SMR) spatial patterns in the same Brazilian city, the showed that results

are agreement with previous reports from other cancer study and can be paramount in the definition of

intervention programs for the region (Oliveira-Friestino et al, 2018).

Data from the EUROCARE-5 (Gatta et al, 2005; Gatta et al, 2009; Gatta et al, 2014), involving

children under 15 years diagnosed with cancer between 1978 and 2007, pointed slightly higher Five-year

survival. Nevertheless, in our study, the 5-year survival of children diagnosed with ALL (79.3%) and

Non-Hodgkin lymphomas (87.5%), were substantially higher than those reported for the Eastern Europe

countries (69.7% and 64.2%, respectively) and for all Group III not much different from those observed

in the present study (Gatta et al, 2014).

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In the Cox Regression analysis for survival of these four major groups significant differences in

survival time were found in terms of diagnostic Groups adjusted for age and sex (p=0.001), similar to

studies in developing countries (Gatta et al, 2014; Zouain-Figueiredo, Zandonade & Amorim, 2013).

It is known that for cases of malignant neoplasms, the use of information about death is not

enough to know the problem impact, because there are different types of cancer, and each of them has a

different lethality and survival (Inca, 2016). Thus, early diagnosis and initiation of immediate treatment

can influence cancer patients' survival, as it is often possible that the outcome of treatment may lead to a

good prognosis (Lima, 2018).

However, the inclusion of children and youth cancer in Public Health becomes a useful strategy

to improve Health Information Systems, seeking to assess health conditions in different cancer groups,

as well as contributing to early diagnosis and also to monitor the survival of existing cases (Silva, 2016).

In conclusion, incidence in the majority diagnostic groups in Campinas was similarly to previous

reports from other Cancer Registries. The Five-year survival estimated for adolescents was higher than in

children. The study of the cancer incidence rates can be used as baseline indicators of the quality of the

healthcare system and as a framework for future improvements and health planning.

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38292013000400006

Credits: Jane Kelly Oliveira Friestino: Conceptualization and Writing draft , Mendonça Denisa:

Investigation, Oliveira Pedro: Writing draft, Luis Antunes: Writing draft , Rosemeire Olanda

Ferraz: Writing draft , Priscila Maria Stolses Bergamo Francisco: Writing – review & editing,

Djalma Carvalho Moreira Filho: Review & editing