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Long-Term Survival Trends in Pediatric Patients with Solid Tumors in the State of São Paulo, Brazil (2000-2022): An Analytical Descriptive Epidemiological Study

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02 July 2024

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03 July 2024

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Abstract
(1) Background: São Paulo, Brazil, exhibits high mortality rates from pediatric solid tumors. This study analyzed the survival trends of patients aged 0-19 diagnosed with the state's five most prevalent solid tumors between 2000-2022. (2) Methods: An epidemiological, descriptive study utilized data from the Oncocentro Foundation of São Paulo, classified according to the International Classification of Childhood Cancer. The time between the first consultation and diagnosis, between diagnosis and treatment initiation, and patient survival were assessed using the Pe-to-Peto test. (3) Results: Analysis involved 11,067 cases: 53.5% male, with 89.6% diagnosed via microscopic confirmation. Tumor distribution comprised 34.3% central nervous system, 21.1% bone, 18.6% soft tissue, 14.2% germ cell, and 11.9% retinoblastomas. Main treatments included surgery with chemotherapy (26.5%), surgery alone (20.5%), and chemotherapy alone (15.6%). The average time between consultation and diagnosis was 22.94 ± 69.93 days, significant for treatments and recurrences, except for germ cell tumors (p=0.0178). The time between diagnosis and treatment was 25.46 ± 39.71 days, not significant for germ cell tumor treatments (p=0.0793). (4) Conclusions: Survival curves varied among neoplasm groups, with patients experiencing delays beyond recommended times, despite advanced healthcare services in the state.
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Subject: Public Health and Healthcare  -   Public Health and Health Services

1. Introduction

Childhood cancer is the second leading cause of death among children aged 0 to 19 in developed countries and in Latin America and the Caribbean [1]. In Brazil, it is the leading cause of death (accounting for 8.0% of the total) among children and adolescents aged 1 to 19 years due to disease [2].
However, the literature indicates that the burden of cancer in this population remains unknown and disregarded in many low socioeconomic countries, which hampers the efficient collection and statistical analysis of data on incidence, prevalence, and survival [3].
Among the malignant solid tumors most commonly affecting children and adolescents are those of the central nervous system, which are the most common in childhood with a peak incidence between one and four years, accounting for about 8.0% to 15.0%, making them the second or third most common neoplasms; neuroblastoma, primarily affecting children under 10 years; Wilms tumor, the most common renal tumor; retinoblastoma, representing 2.5% to 4.0% of intraocular tumors, most commonly occurring in children under five years; germ cell tumors, which represent 3.3% of pediatric tumors; osteosarcoma, accounting for 3.0% to 5.0% of neoplasms with a peak incidence between ten and 19 years; and sarcomas, where rhabdomyosarcomas represent about 4.0% to 5.0% of pediatric malignant tumors [2].
Over the past 50 years, there has been a significant improvement in the overall survival curve of these patients, reaching 80.0% in 2021, compared to around 30.0% in the 1960s [4]. This change is closely related to the improvement in the treatment of leukemias, the most common malignant neoplasms in this age group, a trend not observed for other neoplasms or in different countries [5,6].
Nonetheless, critical points such as the recognition of early signs and symptoms by patients and their families, leading to seeking health services; early detection, faster diagnostic confirmation, and timely treatment need to be analyzed. Each stage of this timeline, with its different actors and levels of system complexity, has implications for cancer statistics [7].
In Brazil, several strategies are employed to improve these statistics and mobilize society. Campaigns and symbolic dates are widely used to inform the population about warning signs and symptoms, thus contributing to health literacy and faster seeking of health services. Additionally, to enhance the efficiency of the health system itself, professional societies promote discussions about the quality and speed of services, culminating in the establishment of legal frameworks such as Law No. 12,732 of November 22, 2012, which mandates a maximum of 60 days for the start of the first treatment in the Unified Health System (SUS) [8]. This was amended by Law No. 13,896 of October 30, 2019, further limiting the timeframe by establishing a 30-day period for conducting tests related to the diagnosis of malignant neoplasms [9].
Moreover, investments are being made in the training of human resources (specializations, residencies), organization, and accreditation of High Complexity Oncology Care Centers (CACON) and High Complexity Oncology Care Units (UNACON), as well as isolated services to enhance the agility, specificity, and resolution of oncological treatment [10].
In this context, the State of São Paulo stands out, accounting for 24.0% of the estimated cases and 12.0% of the total deaths in the country. In absolute numbers, it is the state with the highest morbidity and mortality rates due to cancer in this age group [11], which is the focus of this research. It is a state with significant technological density and accredited services in all 17 Regional Health Districts (DRS).
Given the above, the objective of this research was to analyze long-term survival trends in pediatric patients of both sexes diagnosed with the five most prevalent solid tumors in the State of São Paulo, Brazil, between 2000 and 2022.

2. Materials and Methods

2.1. Ethical Aspects

The project was not submitted to the Research Ethics Committee (CEP) involving human subjects of the proposing institution because it is a study using secondary data, which are publicly available, with unrestricted access, and without individual identification. However, the international principles of data handling in research involving human subjects were duly respected [4].

2.2. Study Design

This is a descriptive epidemiological study based on data obtained and extracted from the Fundação Oncocentro do Estado de São Paulo (FOSP), covering the period from January 2000 to December 2022.

2.3. Population and Sample

All patients up to 19 years of age recorded in the database of the Fundação Oncocentro do Estado de São Paulo (FOSP) were considered, sourced from 77 registered institutions in the state. The malignant neoplasms analyzed were selected according to the International Classification of Childhood Cancer (ICCC) [12], classified as follows: III – Central Nervous System (CNS) and miscellaneous intracranial and intraspinal neoplasms; V – retinoblastoma; VIII – malignant bone tumors; IX – soft tissue and other extraosseous sarcomas; X – germ cell tumors, trophoblastic tumors, and gonadal neoplasms.

2.4. Data Collection Procedure

The data were extracted from the FOSP database on February 7, 2023, and exported in Data Base File (DBF) format for analysis using the R program, version 4.1.2 [13]. It is important to note that, according to FOSP, the years 2017, 2018, 2019, 2020, 2021, and 2022 still had ongoing cases.

2.5. Data Analysis

The outcome variables assessed were the time elapsed between the medical consultation and the oncological diagnosis, as well as the time between diagnosis and the start of oncological treatment. To study these periods, a survival analysis was performed [13,14], where the event of interest (considered as a failure) is the occurrence of cancer-related death. To standardize, times exceeding 180 days were considered censored (three times the period to start treatment after diagnosis according to current legislation). Independent variables included the type of treatment, either alone or in combination (surgery, surgery + chemotherapy, surgery + radiotherapy + chemotherapy, surgery + radiotherapy + chemotherapy + hormonal therapy, surgery + radiotherapy, no treatment, other treatment combinations, chemotherapy, radiotherapy, radiotherapy + chemotherapy), gender (male, female), and recurrence (yes, no). Analyses were stratified by group. Additionally, the Federation Unit (UF) of birth and residence and the Regional Health Departments (DRS) of treatment were analyzed.
For the descriptive analysis of outcome variables, measures of central tendency such as mean and median, and measures of dispersion such as standard deviation, minimum, and maximum were used. Additionally, for the independent variables, frequency and percentage of the data were considered. To compare survival periods among treatments, gender, and recurrence, the Peto-Peto test was used [15]. The variance of the Peto statistic (non-parametric estimation) is equal to the variance of the log-rank, where each time interval is weighted by the square of the survival function. Greater weight is given to differences (or similarities) at the beginning of the curve, where there is a higher concentration of data, hence more informative. A weight S(t) is used in the estimator, incorporating censoring without assuming time distribution. The Peto statistic follows approximately a χ2 distribution with k - 1 degrees of freedom.
The outcome variables assessed were the time elapsed between the medical consultation and the oncological diagnosis, as well as the time between diagnosis and the start of oncological treatment. To study these periods, a survival analysis was performed [13,14], where the event of interest (considered as a failure) is the occurrence of cancer-related death. To standardize, times exceeding 180 days were considered censored (three times the period to start treatment after diagnosis according to current legislation). Independent variables included the type of treatment, either alone or in combination (surgery, surgery + chemotherapy, surgery + radiotherapy + chemotherapy, surgery + radiotherapy + chemotherapy + hormonal therapy, surgery + radiotherapy, no treatment, other treatment combinations, chemotherapy, radiotherapy, radiotherapy + chemotherapy), gender (male, female), and recurrence (yes, no). Analyses were stratified by group. Additionally, the Federation Unit (UF) of birth and residence and the Regional Health Departments (DRS) of treatment were analyzed.
For the descriptive analysis of outcome variables, measures of central tendency such as mean and median, and measures of dispersion such as standard deviation, minimum, and maximum were used. Additionally, for the independent variables, frequency and percentage of the data were considered. To compare survival periods among treatments, gender, and recurrence, the Peto-Peto test was used [15]. The variance of the Peto statistic (non-parametric estimation) is equal to the variance of the log-rank, where each time interval is weighted by the square of the survival function. Greater weight is given to differences (or similarities) at the beginning of the curve, where there is a higher concentration of data, hence more informative. A weight S(t) is used in the estimator, incorporating censoring without assuming time distribution. The Peto statistic follows approximately a χ2 distribution with k - 1 degrees of freedom.
For cases where there were differences between the evaluated groups, in the case of the treatment variable, the Benjamini-Hochberg multiple comparison procedure was used [16]. All analyses were conducted considering a 5.0% significance level and using R, version 4.1.2 [13].

3. Results

3.1. Sample Characteristics

A total of 11,067 cases (100.0%) were analyzed, with 5,926 (53.5%) male and 5,141 (46.5%) female patients. Of these, 3,792 cases (34.3%) were Central Nervous System (CNS) and miscellaneous intracranial and intraspinal neoplasms (ICCC - III), 2,337 cases (21.1%) were malignant bone tumors (ICCC - VIII), 2,055 cases (18.6%) were soft tissue and other extraosseous sarcomas (ICCC - IX), 1,566 cases (14.2%) were germ cell, trophoblastic, and gonadal tumors (ICCC - X), and 1,317 cases (11.9%) were retinoblastomas (ICCC - V). The age range of the analyzed cases, according to each type of malignant neoplasm, is presented in (Table 1).
Neoplasms of the central nervous system (CNS) and the miscellaneous category of intracranial and intraspinal neoplasms were most prevalent between five and ten years (29.8%), followed by the age group between one and five years (27.2%); those of soft tissue and other extraosseous sarcomas between ten and 15 years (24.3%), followed by 15 to 19 years (24.1%); retinoblastomas in infants under one year (61.6%), followed by one to five years (35.5%); malignant bone tumors between ten and 15 years (42.8%), followed by 15 to 19 years (30.8%); and germ cell tumors, trophoblastic tumors, and gonadal neoplasms between 15 and 19 years (40.4%), followed by ten to 15 years (25.8%) (Table 1).
Of these, 7,457 (67.4%) had no prior diagnosis or treatment, and 3,610 (32.6%) had a diagnosis but no prior treatment; in 9,905 (89.6%), confirmation was made by microscopic examination, 51 (0.5%) by clinical examination, and 1,101 (10.0%) through non-microscopic auxiliary resources.
(Table 2) presents the Federation Units (UF) of birth and residence of the patients and the Regional Health Departments (DRS) of care.
The birth Federation Units (UF) with the most cases were São Paulo with 7,870 (71.1%), Minas Gerais with 647 (5.8%), and Bahia with 315 (2.8%); meanwhile, the main Residence UF were São Paulo with 8,958 (80.9%) cases, Minas Gerais with 595 (5.4%), and Mato Grosso with 151 (1.4%). The main Regional Health Departments (DRS) of care were DRS 01 (Greater São Paulo) with 4,122 (46.0%), DRS 07 (Campinas) with 1,028 (11.5%), and DRS 17 (Taubaté) with 612 (6.8%) (Table 2).
The average time between consultation and diagnosis was 22.94 days (SD ± 36.94), considering the 180-day cutoff. However, when analyzing the entire period, the average time between consultation and diagnosis was 27.79 days (SD ± 69.50), with a maximum of 996 days.
The median times between consultation and diagnosis and the survival probabilities for patients who waited 31 days, for each of the solid tumor groups were: 52 days and 0.5805 [95% CI; (0.6016; 0.5600)] for central nervous system (CNS) and miscellaneous intracranial and intraspinal neoplasms; 53 days and 0.5952 [95% CI; (0.6235; 0.5682)] for soft tissue and other extraosseous sarcomas; more than 180 days and 0.8799 [95% CI; (0.9089; 0.8518)] for retinoblastomas; 32 days and 0.5158 [95% CI; (0.5444; 0.4887)] for malignant bone tumors; more than 180 days and 0.8233 [95% CI; (0.8498; 0.7977)] for germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
There was statistical significance of the waiting time between consultation and diagnosis in relation to treatment for all neoplasm groups (p <0.001). Regarding local recurrences, this time was also significant for all, with four of them (p <0.001) and for retinoblastomas (p = 0.005). However, this significance was observed only for germ cell tumors, trophoblastic tumors, and gonadal neoplasms in relation to gender (p = 0.0178).
(Figure 1) shows the survival curves, considering the time patients waited between consultation and establishment of the oncological diagnosis and between diagnosis and initiation of treatment, for both sexes.
The curves are quite similar for both sexes, with overall survival appearing to be slightly lower in males. The median survival for females is 53 days and for males is 51 days. However, a small difference is notable when it comes to germ cell tumors, trophoblastic tumors, and gonadal neoplasms, where the curves are slightly more pronounced in males, and in retinoblastoma, there was an inversion around 100 days, with better survival for males in both periods analyzed (Consultation_Diagnosis and Diagnosis_Treatment) (Figure 1). The average time between diagnosis and initiation of oncological treatment, in days, was 25.46 (± 39.71), considering the cutoff for a maximum time of 180 days, and 30.40 (± 70.27), maximum of 985 days.
The median times between diagnosis and treatment and the survival probabilities for patients who waited approximately 61 days, for each of the solid tumor groups were: 43 days and 0.43715 [95% CI; (0.4633; 0.4124)] for central nervous system (CNS) and miscellaneous intracranial and intraspinal neoplasms; 62 days and 0.5064 [95% CI; (0.5386; 0.4761)] for soft tissue and other extraosseous sarcomas; more than 180 days and 0.8405 [95% CI; (0.8806; 0.8022)] for retinoblastomas; 42 days and 0.4443 [95% CI; (0.4755; 0.4152)] for malignant bone tumors; more than 180 days and 0.7172 [95% CI; (0.7605; 0.6764)] for germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
The waiting time between diagnosis and initiation of treatment of patients revealed statistical significance when analyzing the implemented treatment, except for the group of germ cell tumors, trophoblastic tumors, and gonadal neoplasms (p = 0.0793) and local recurrences for retinoblastomas (p = 0.0697). Regarding gender, significance was only observed for germ cell tumors, trophoblastic tumors, and gonadal neoplasms (p = 0.0054).
The treatments performed, in descending order of presentation, were: 2,930 (26.5%) surgeries combined with chemotherapy, 2,264 (20.5%) surgeries, 1,721 (15.6%) chemotherapies, 1,430 (12.9%) surgeries combined with radiotherapy and chemotherapy, 882 (8.0%) radiotherapies combined with chemotherapy, 871 (7.9%) other treatment combinations, 351 (3.2%) with no treatment performed in the period, 259 (2.3%) radiotherapies, and 5 (0.0%) combinations of surgery, radiotherapy, chemotherapy, and hormonal therapy. The average time between diagnosis and initiation of oncological treatment, in days, was 25.46 (± 39.71), considering the cutoff for a maximum time of 180 days, and 30.40 (± 70.27), maximum of 985 days.
The median times between diagnosis and treatment and the survival probabilities for patients who waited approximately 61 days, for each of the solid tumor groups were: 43 days and 0.43715 [95% CI; (0.4633; 0.4124)] for central nervous system (CNS) and miscellaneous intracranial and intraspinal neoplasms; 62 days and 0.5064 [95% CI; (0.5386; 0.4761)] for soft tissue and other extraosseous sarcomas; more than 180 days and 0.8405 [95% CI; (0.8806; 0.8022)] for retinoblastomas; 42 days and 0.4443 [95% CI; (0.4755; 0.4152)] for malignant bone tumors; more than 180 days and 0.7172 [95% CI; (0.7605; 0.6764)] for germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
The waiting time between diagnosis and initiation of treatment of patients revealed statistical significance when analyzing the implemented treatment, except for the group of germ cell tumors, trophoblastic tumors, and gonadal neoplasms (p = 0.0793) and local recurrences for retinoblastomas (p = 0.0697). Regarding gender, significance was only observed for germ cell tumors, trophoblastic tumors, and gonadal neoplasms (p = 0.0054).
The treatments performed, in descending order of presentation, were: 2,930 (26.5%) surgeries combined with chemotherapy, 2,264 (20.5%) surgeries, 1,721 (15.6%) chemotherapies, 1,430 (12.9%) surgeries combined with radiotherapy and chemotherapy, 882 (8.0%) radiotherapies combined with chemotherapy, 871 (7.9%) other treatment combinations, 351 (3.2%) with no treatment performed in the period, 259 (2.3%) radiotherapies, and 5 (0.0%) combinations of surgery, radiotherapy, chemotherapy, and hormonal therapy.
Overall, the medians and survival probabilities for patients who waited approximately 61 or 180 days, for each type of treatment were: more than 180 days, 0.8411 [95% CI; (0.8594; 0.8233)] and 0.7175 [95% CI; (0.7576; 0.6796)] for surgeries; 92 days, 0.5469 [95% CI; (0.5735; 0.5215)] and 0.3015 [95% CI; (0.3494; 0.2601)] for the combination of surgery and chemotherapy; 42 days, 0.4314 [95% CI; (0.4692; 0.3966)] and 0.2219 [95% CI; (0.2712; 0.1816)] for the combination of surgery, chemotherapy, and radiotherapy; 178 days, 0.6984 [95% CI; (0.7283; 0.6697)] and 0.4281 [95% CI; (0.4976; 0.3684)] for other treatment combinations; 43 days, 0.4366 [95% CI; (0.4664; 0.4087)] and 0.2003 [95% CI; (0.2453; 0.1637)] for chemotherapy alone; 48 days, 0.4447 [95% CI; (0.5154; 0.3837)] and 0.2521 [95% CI; (0.3420; 0.1858)] for radiotherapy alone; and 38 days, 0.3813 [95% CI; (0.4195; 0.3465)] and 0.1369 [95% CI; (0.1846; 0.1016)] for the combination of radiotherapy and chemotherapy. The treatments implemented, by neoplasms, considering the clinical stages at diagnosis, are presented in (Table 3).
In stages I, II, and III, surgery alone or combined with chemotherapy was performed for most patients with soft tissue neoplasms and other extraosseous sarcomas, malignant bone tumors, and germ cell tumors, trophoblastic tumors, and gonadal neoplasms. The combination of surgery, chemotherapy, and radiotherapy was used for patients with soft tissue neoplasms and other extraosseous sarcomas in stage III (Table 3).
Chemotherapy alone stands out in the treatment of patients with malignant bone tumors and germ cell tumors, trophoblastic tumors, and gonadal neoplasms in stage IV. When the neoplasms could be properly staged, surgery combined with chemotherapy was used for most patients with malignant bone tumors, followed by chemotherapy alone (Table 3).
In cases where staging was done during or after treatment, surgery alone was most used for central nervous system (CNS) tumors and miscellaneous intracranial and intraspinal neoplasms, as well as for germ cell tumors, trophoblastic tumors, and gonadal neoplasms. Surgery combined with radiotherapy was used for retinoblastoma, soft tissue tumors, other extraosseous sarcomas, and malignant bone tumors (Table 3).
(Figure 2) illustrates the survival curves of patients, within a 180-day timeframe, considering the time they waited between the oncological diagnosis and the commencement of various treatments.
In (Figure 2), the analysis of the 50.0% survival curve reveals significant variations among the analyzed neoplasms. Considering the different therapeutic options offered, the curves indicate lower survival probabilities for patients with bone tumors. Patients with retinoblastomas (CICIGRUP V) treated with surgery combined with radiotherapy and chemotherapy had a survival of 70 days, while those with radiotherapy combined with chemotherapy showed 100 days of survival.
The last recorded information of the patients showed that 3,304 (29.9%) died due to cancer, and 299 (2.7%) from other causes, 1,935 (17.5%) were alive with cancer, and 5,529 (50.0%) were alive. However, there was a loss of follow-up for 3,497 (31.6%) of the patients.

4. Discussion

Overall, the prevalence of solid neoplasms in the studied age groups aligns closely with national and international statistics [1,2,16]. Central nervous system (CNS) tumors were the most prevalent, followed by malignant bone tumors, soft tissue tumors, and other sarcomas, and germ cell, trophoblastic, and gonadal tumors. Notably, the prevalence of retinoblastoma, ranking fifth in the state of São Paulo, stands out. This could be related to what the literature terms overdiagnosis [7], due to the law that established the National Day for Retinoblastoma Awareness and Early Diagnosis [17], or patient migration to São Paulo for treatment after identifying initial signs and symptoms.
Regarding age groups, two peaks of CNS tumors were observed: one clustering from zero to five years (38.1%), but with significant prevalence between five and ten years (29.8%) and ten to fifteen years (20.7%). This differs from the literature, which indicates a peak incidence between one and four years [18].
For soft tissue tumors and other extraosseous sarcomas, the age groups with the most cases were ten to fifteen years (24.3%) and fifteen to nineteen years (24.1%), though there were significant numbers between one and five years (19.5%) and five to ten years (18.6%). This result also differs from the literature, where the peak incidence is around five years [7]. For retinoblastoma, the results show that 97.1% of cases were in children under five years old, aligning with reported statistics [18].
For germ cell tumors, the peak number of cases was in the fifteen to nineteen age group (40.4%), with a significant number between ten and fifteen years (25.8%). These tumors are heterogeneous and present with gonadal or extragonadal clinical manifestations depending on the age group [18].
Bone tumors were more prevalent in the ten to fifteen age group (42.8%), but if we group the ten to nineteen age range, the cases sum up to 93.8%, consistent with the literature, which indicates a peak incidence between ten and nineteen years [18].
The data shows a higher prevalence of neoplasms in males, which is consistent with literature findings indicating a slightly higher incidence in males. However, the underlying mechanisms are not well understood, as in adults [19]. Evidence suggests that males tend to have higher average birth weights, are more susceptible to infections in childhood, have a faster pubertal growth rate, and exhibit different hormonal expressions during childhood [20]. This difference is also associated with the type of neoplasia, as in the cases of osteosarcomas and germ cell tumors [21], where incidences are relatively higher in males.
Regarding diagnostic confirmation, the majority (89.6%) was via microscopic examination, which is expected. However, for CNS tumors and retinoblastoma, due to access difficulties, diagnosis is made through clinical exams and non-microscopic auxiliary resources [22].
Regarding the states of birth and residence of the patients, the data shows that the majority were born (71.1%) and reside (80.9%) in the state of São Paulo (Table 1). However, there is patient migration, though the causes were not studied, which may be related to seeking treatment. States like Minas Gerais, Bahia, and Mato Grosso are important for analyzing this flow, given their geographical proximity [23].
In terms of healthcare regions (DRS) for care, DRS 01 (Greater São Paulo) was notable, with 46.0% of cases, followed by DRS 07 (Campinas) with 11.5%, and DRS 17 (Taubaté) with 6.8% (Table 2). This is important for analyzing the Oncology Care Network, technological infrastructure, and oncology services accredited for treating children and adolescents with neoplasms in each region.
Considering the analysis period of these cases (2000 to 2022) and the current legislation since 2019 [9], which sets a limit of 30 days for performing exams related to the diagnosis of malignant neoplasms, 50.0% of patients still had a median wait time of over 50 days.
These numbers are significant when analyzing the influence of this period on the treatments implemented (p<0.001) and the occurrence of recurrences (p<0.001). As the factors responsible for the emergence of pediatric and adolescent neoplasms are still not well understood [24], including in relation to gender, this waiting period can be crucial for some types of tumors, such as germ cell tumors, trophoblastic tumors, and gonadal neoplasms, where the wait time was significant in relation to gender (p=0.0178).
When analyzing the probability of survival for these patients, around 31 days between consultation and diagnosis, only 58.05% of those with CNS tumors, 59.52% with soft tissue tumors and other extraosseous sarcomas, and 51.58% with malignant bone tumors were alive. In contrast, the survival of patients, beyond the 180-day analysis interval, was 87.99% for those with retinoblastoma and 82.33% for those with germ cell tumors, trophoblastic tumors, and gonadal neoplasms. Statistics from developed countries indicate an overall survival rate above 80.0% for patients [25], which can be observed for some types of neoplasms in São Paulo, indicating the need for a focused approach for each type of neoplasm.
The importance of these data, in general, even without separation by histological type, presence of metastases, tumor size, among others, lies in the need to improve services for this population and the presence of trained professionals for early recognition of clinical signs and symptoms. Additionally, there is a need to improve the infrastructure for establishing early diagnosis and proper referral, which can change the course of these diseases with such distinct behaviors [26].
Regarding the wait time between diagnosis and treatment, also considering the analysis period of these cases (2000 to 2022) and the current legislation since 2012 [8], the data showed greater agility in the treatment of CNS tumors and malignant bone tumors, with a median wait time of 43 days and 42 days, respectively. For the others, the median wait time was 62 days for soft tissue tumors and other extraosseous sarcomas, and over 180 days for retinoblastomas and germ cell tumors, trophoblastic tumors, and gonadal neoplasms. It is noteworthy that treatments are still not performed in a timely manner.
The implications of this delay can be seen when analyzing the treatment implemented and local recurrences for most of these neoplasm groups. Again, it is notable that for germ cell tumors, trophoblastic tumors, and gonadal neoplasms, the wait time was only significant in relation to gender (p=0.0054).
Regarding the probabilities of survival around a 61-day wait time, they were 43.71% for patients with CNS tumors and miscellaneous intracranial and intraspinal neoplasms, 50.64% with soft tissue tumors and other extraosseous sarcomas, and 44.43% with malignant bone tumors. About 84.05% of patients with retinoblastoma and 71.72% with germ cell tumors, trophoblastic tumors, and gonadal neoplasms were alive after 180 days of analysis. These data align with the literature, showing that the survival of these patients is still a subject of analysis and investment, despite the introduction of new therapies or their combinations, as in the case of bone and soft tissue tumors [25].
The most implemented treatments were surgery combined with chemotherapy (26.5%), surgeries (20.5%), and chemotherapy (15.6%). Chemotherapy alone stands out in the treatment of patients with malignant bone tumors and germ cell tumors, trophoblastic tumors, and gonadal neoplasms in stage IV.
Analyzing overall, the treatments are multimodal. CNS tumors are treated with surgery, chemotherapy, and radiotherapy; bone tumors are also treated with chemotherapy, before or after surgery; retinoblastomas may require surgery (enucleation), chemotherapy, radiotherapy, and, in certain cases, bone marrow transplant; germ cell tumors are primarily treated surgically, though chemotherapy may be necessary before or after surgery; for sarcomas, chemotherapy, surgery, and radiotherapy may be employed [18].
The median wait time for treatments was over 180 days for surgeries; 92 days for the combination of surgery and chemotherapy; 42 days for the combination of surgery, chemotherapy, and radiotherapy; 178 days for other treatment combinations; 43 days for chemotherapy alone; 48 days for radiotherapy alone; and 38 days for the combination of radiotherapy and chemotherapy. These data indicate a longer wait time for surgeries, surgery with chemotherapy, and other treatment combinations, which may be related to oncology care services, specialties, and capacity, important issues for discussion in the Oncology Care Network.
Despite the wait time, the best survival was observed in patients who underwent surgery alone, highlighting the importance of this treatment modality [27]. When surgery alone was implemented, 71.75% of patients were alive after 180 days of analysis; in other treatment combinations, 42.81%, and in the combination of surgery and chemotherapy, 30.15%. The worst survival probability was observed in the combination of radiotherapy and chemotherapy, reaching 13.69%.
In this study, according to the latest information in the FOSP database, 17.5% of registered patients were alive with cancer and 50.0% were alive, but about 31.6% of patients had no updated information. This fact may alter the survival and cancer mortality statistics, leaving doubts about the accuracy of the information.

4.1. Study Limitations

The present study is characterized by certain limitations inherent to its nature, susceptible to various biases. Some institutions enter information with about a one-year delay, which can lead to errors in interpreting the presented data, such as the type of treatment performed, thereby affecting survival curves. The possibility that families might relocate to be near the pediatric treatment center introduces a potential source of bias. Additionally, the geographical distribution of technological resources and the system's capacity to address this issue may have significantly influenced the results. Inaccuracies in residence addresses can impact the reliability of the data, especially regarding patient care.

4.2. Clinical Implications

This study provides important insights into the clinical implications by highlighting the critical need for improvements in the diagnosis and treatment of pediatric solid tumors in the State of São Paulo. By understanding the survival of young patients with malignant neoplasms, the research highlights significant gaps in the response time between the initial consultation, diagnosis, and the start of treatment, even in a state with extensive healthcare infrastructure. These findings suggest that despite the availability of resources, there are systemic barriers delaying timely treatment, negatively impacting patient survival.
Clinically, this points to the urgency of implementing strategies that expedite the diagnosis and initiation of treatment, including continuous training of healthcare professionals to recognize early signs and symptoms of malignant neoplasms in children and adolescents. Furthermore, the study underscores the importance of a personalized approach in oncological treatment, considering variations in treatment responses and survival rates among different types of tumors.
Health policies should therefore focus on targeted interventions that improve the efficiency of clinical workflows and ensure that all patients receive high-quality treatment equitably. The research also suggests the need for better health data management, enabling more precise and continuous patient follow-up, which can facilitate rapid adjustments in treatment as needed.
In summary, this study serves as a call for integrated and coordinated actions among hospitals, research centers, and policymakers to enhance pediatric oncological care, reduce critical treatment delays, and improve survival prospects and quality of life for young patients.

5. Conclusions

This study allowed for the analysis of the survival of patients diagnosed with the five most prevalent solid malignant neoplasms in the 0 to 19 age group, of both sexes, in the State of São Paulo, between 2000 and 2022. The data revealed significant differences in the survival curves of patients with different types of neoplasms, highlighting the need for individualized analysis for each type of neoplasm.
Despite the high concentration of services and high technological density in the State of São Paulo, the waiting time for diagnosis and the start of treatment remains a concerning issue. This delay can negatively impact the survival and quality of life of pediatric patients.
It is urgent to implement measures to regulate patient flow according to the severity and need for early intervention. Ensuring timely diagnosis and treatment is essential to improve survival rates and the quality of life of patients. Additionally, continuous investments in infrastructure, professional training, and public health policies are necessary to address these disparities and ensure more efficient and equitable oncological care.
Thus, this study highlights the importance of health policies aimed at reducing the time to diagnosis and initiation of treatment, as well as the need to personalize oncological care to improve survival outcomes in pediatric patients with solid malignant neoplasms.

Public Involvement Statement

Not applicable.

Use of Artificial Intelligence

Not applicable.

Author Contributions

ACCO, PEGP, PJC, JBL, CMZ led the study design, data collection, analysis and interpretation, and drafted the manuscript. ACCO, PEGP, PJC, JBL, CMZ significantly contributed to study design, data collection, and data analysis and interpretation. ACCO, PEGP, PJC, JBL, CMZ participated in study design. All authors contributed to manuscript preparation and approved the final manuscript.

Funding

This work was supported by the National Council for Scientific and Technological Development (CNPq), Project Code: 2022-3138.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

To the Ribeirão Preto School of Nursing at the University of São Paulo (EERP-USP). To Senior Professor/Doctor Emília Campos de Carvalho for her contributions and criticisms to improve this scientific study.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Time elapsed between consultation and diagnosis; between diagnosis and oncological treatment initiation, for both sexes. Note: CICIGRUP III – Central Nervous System (CNS) and miscellaneous intracranial and intraspinal neoplasms; CICIGRUP IX - Soft tissue and other extraosseous sarcomas; CICIGRUP V - Retinoblastoma; CICIGRUP VIII - Malignant bone tumors; CICIGRUP X - Germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
Figure 1. Time elapsed between consultation and diagnosis; between diagnosis and oncological treatment initiation, for both sexes. Note: CICIGRUP III – Central Nervous System (CNS) and miscellaneous intracranial and intraspinal neoplasms; CICIGRUP IX - Soft tissue and other extraosseous sarcomas; CICIGRUP V - Retinoblastoma; CICIGRUP VIII - Malignant bone tumors; CICIGRUP X - Germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
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Figure 2. Time elapsed between diagnosis and treatment, according to the implemented therapies. Note: CICIGRUP III - Central Nervous System and miscellany of intracranial and intraspinal neoplasms; CICIGRUP IX - Soft tissues and other extraosseous sarcomas; CICIGRUP V - Retinoblastoma; CICIGRUP VIII - Malignant bone tumors; CICIGRUP X - Germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
Figure 2. Time elapsed between diagnosis and treatment, according to the implemented therapies. Note: CICIGRUP III - Central Nervous System and miscellany of intracranial and intraspinal neoplasms; CICIGRUP IX - Soft tissues and other extraosseous sarcomas; CICIGRUP V - Retinoblastoma; CICIGRUP VIII - Malignant bone tumors; CICIGRUP X - Germ cell tumors, trophoblastic tumors, and gonadal neoplasms.
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Table 1. Most prevalent solid malignant neoplasms by age group (n = 11,067). Ribeirão Preto, São Paulo, Brazil, 2024.
Table 1. Most prevalent solid malignant neoplasms by age group (n = 11,067). Ribeirão Preto, São Paulo, Brazil, 2024.
CICI 0 ┤ 1
N(%)		 1 ┤ 5
N(%)		 5 ┤ 10
N(%)		 10 ┤ 15
N(%)		 15 ┤ 19
N(%)
III - Central Nervous System (CNS) and miscellaneous intracranial and intraspinal neoplasms 412
(10,9%)		 1.033
(27,2%)		 1.131
(29,8%)		 784
(20,7%)		 432
(11,4%)
IX - Soft tissue and other extraosseous sarcomas 278
(13,5%)		 400
(19,5%)		 382
(18,6%)		 499
(24,3%)		 496
(24,1%)
V – Retinoblastoma 811
(61,6%)		 468
(35,5%)		 33
(2,5%)		 4
(0,3%)		 1
(0,1%)
VIII - Malignant bone tumors 25
(1,1%)		 120
(5,1%)		 473
(20,2%)		 1.000
(42,8%)		 719
(30,8%)
X - Germ cell tumors, trophoblastic tumors, and gonadal neoplasms 204
(13,0%)		 125
(8,0%)		 200
(12,8%)		 404
(25,8%)		 633
(40,4%)
Source: FOSP, 2024.
Table 2. Birth Federation Units (UF), Residence UF, and Regional Health Departments (DRS) of care. Ribeirão Preto, São Paulo, Brazil, 2024.
Table 2. Birth Federation Units (UF), Residence UF, and Regional Health Departments (DRS) of care. Ribeirão Preto, São Paulo, Brazil, 2024.
Variable N % Variable N % Variable N %
Federation Unit of Birth Federation Unit of Residence Regional Department of Health
São Paulo 7.840 71,1 São Paulo 8.958 80,9 DRS 01 - São Paulo 4.122 46,0
Minas Gerais 647 5,8 Minas Gerais 595 5,4 DRS 07 - Campinas 1.028 11,5
No Information 415 3,7 Mato Grosso 151 1,4 DRS 17 -Taubaté 612 6,8
Bahia 315 2,8 Rondônia 129 1,2 DRS 16 - Sorocaba 451 5,0
Mato Grosso 161 1,5 Mato Grosso do Sul 125 1,1 DRS 06 - Bauru 389 4,3
Paraná 151 1,4 Amazonas 110 1,0 DRS 13 – Ribeirão Preto 342 3,8
Mato Grosso do Sul 132 1,2 Bahia 105 0,9 DRS 15 – São José do Rio Preto 342 3,8
Amazonas 121 1,1 Paraná 105 0,9 DRS 10 - Piracicaba 322 3,6
Rondônia 126 1,1 Goiás 93 0,8 DRS 04 - Santos 239 2,7
Goiás 99 0,9 Distrito Federal 72 0,7 DRS 09 - Marília 232 2,6
Pará 88 0,8 Espírito Santo 72 0,7 DRS 03 – Araraquara 204 2,3
Alagoas 76 0,7 Pará 82 0,7 DRS 14 – São João da Boa Vista 167 1,9
Dsitrito Federal 80 0,7 Tocantins 65 0,6 DRS 08 – Franca 132 1,5
Espírito Santo 73 0,7 Rio de Janeiro 60 0,5 DRS 02 – Araçatuba 113 1,3
Maranhão 83 0,7 Maranhão 43 0,4 DRS 05 - Barretos 119 1,3
Pernambuco 75 0,7 Santa Catarina 49 0,4 DRS 11 – Presidente Prudente 112 1,3
Rio de Janeiro 70 0,6 Acre 38 0,3 DRS 12 - Registro 32 0,4
Santa Catarina 64 0,6 Alagoas 28 0,3
Ceará 54 0,5 Roraima 35 0,3
Tocatins 58 0,5 Amapá 25 0,2
Acre 42 0,4 Ceará 21 0,2
Another Country 44 0,4 Rio Grande do Sul 20 0,2
Paraíba 36 0,3 Sergipe 25 0,2
Roraima 34 0,3 Paraíba 11 0,1
Sergipe 37 0,3 Piauí 15 0,1
Amapá 22 0,2 Rio Grande do Norte 16 0,1
Rio Grande do Norte 27 0,2 Anather Country 02 0,0
Rio Grande do Sul 27 0,2
Piauí 40 0,4
Source: FOSP, 2024.
Table 3. Treatments performed, by type of neoplasm, according to clinical staging at diagnosis (n=11,067). Ribeirão Preto, São Paulo, Brazil, 2024.
Table 3. Treatments performed, by type of neoplasm, according to clinical staging at diagnosis (n=11,067). Ribeirão Preto, São Paulo, Brazil, 2024.
Staging Treatment III* IX† V‡ VIII§ X||
0 Surgery 0 (-) 0 (-) 0 (-) 0 (-) 3 (60,0%)
0 Surgery + Chemotherapy 0 (-) 0 (-) 0 (-) 0 (-) 0 (0,0%)
0 Surgery + Radiotherapy + Chemotherapy 0 (-) 0 (-) 0 (-) 0 (-) 0 (0,0%)
0 No treatment performed 0 (-) 0 (-) 0 (-) 0 (-) 0 (0,0%)
0 Other treatment combinations 0 (-) 0 (-) 0 (-) 0 (-) 1 (20,0%)
0 Chemotherapy 0 (-) 0 (-) 0 (-) 0 (-) 1 (20,0%)
0 Radiotherapy 0 (-) 0 (-) 0 (-) 0 (-) 0 (0,0%)
0 Radiotherapy + Chemotherapy 0 (-) 0 (-) 0 (-) 0 (-) 0 (0,0%)
I Surgery 0 (0,0%) 27 (27,%) 0 (-) 45 (14,2%) 108 (39,1%)
I Surgery + Chemotherapy 2 (100,0%) 15 (15,5%) 0 (-) 156 (49,1%) 92 (33,3%)
I Surgery + Radiotherapy + Chemotherapy 0 (0,0%) 21 (21,6%) 0 (-) 15 (4,7%) 2 (0,7%)
I No treatment performed 0 (0,0%) 0 (0,0%) 0 (-) 11 (3,5%) 4 (1,4%)
I Other treatment combinations 0 (0,0%) 22 (22,7%) 0 (-) 39 (12,3%) 29 (10,5%)
I Chemotherapy 0 (0,0%) 7 (7,2%) 0 (-) 44 (13,8%) 40 (14,5%)
I Radiotherapy 0 (0,0%) 1 (1,0%) 0 (-) 2 (0,6%) 1 (0,4%)
I Radiotherapy + Chemotherapy 0 (0,0%) 4 (4,1%) 0 (-) 6 (1,9%) 0 (0,0%)
II Surgery 0 (-) 9 (17,3%) 0 (-) 14 (4,8%) 5 (8,2%)
II Surgery + Chemotherapy 0 (-) 13 (25,0%) 0 (-) 159 (55,0%) 33 (54,1%)
II Surgery + Radiotherapy + Chemotherapy 0 (-) 11 (21,2%) 0 (-) 19 (6,6%) 4 (6,6%)
II No treatment performed 0 (-) 2 (3,8%) 0 (-) 4 (1,4%) 0 (0,0%)
II Other treatment combinations 0 (-) 9 (17,3%) 0 (-) 43 (14,9%) 13 (21,3%)
II Chemotherapy 0 (-) 3 (5,8%) 0 (-) 40 (13,8%) 5 (8,2%)
II Radiotherapy 0 (-) 2 (3,8%) 0 (-) 0 (0,0%) 0 (0,0%)
II Radiotherapy + Chemotherapy 0 (-) 3 (5,8%) 0 (-) 10 (3,5%) 1 (1,6%)
Continued
Staging Treatment III* IX† V‡ VIII§ X||
Continuation
III Surgery 0 (0,0%) 7 (8,9%) 0 (-) 3 (4,1%) 13 (9,9%)
III Surgery + Chemotherapy 1 (100,0%) 17 (21,5%) 0 (-) 47 (63,5%) 84 (64,1%)
III Surgery + Radiotherapy + Chemotherapy 0 (0,0%) 26 (32,9%) 0 (-) 3 (4,1%) 4 (3,1%)
III No treatment performed 0 (0,0%) 1 (1,3%) 0 (-) 2 (2,7%) 2 (1,5%)
III Other treatment combinations 0 (0,0%) 11 (13,9%) 0 (-) 3 (4,1%) 11 (8,4%)
III Chemotherapy 0 (0,0%) 7 (8,9%) 0 (-) 9 (12,2%) 16 (12,2%)
III Radiotherapy 0 (0,0%) 2 (2,5%) 0 (-) 0 (0,0%) 0 (0,0%)
III Radiotherapy + Chemotherapy 0 (0,0%) 8 (10,1%) 0 (-) 7 (9,5%) 1 (0,8%)
IV Surgery 0 (0,0%) 3 (2,2%) 0 (-) 8 (2,4%) 2 (7,1%)
IV Surgery + Chemotherapy 0 (0,0%) 23 (17,0%) 0 (-) 167 (49,3%) 7 (25,0%)
IV Surgery + Radiotherapy + Chemotherapy 1 (33,3%) 31 (23,0%) 0 (-) 26 (7,7%) 2 (7,1%)
IV No treatment performed 0 (0,0%) 2 (1,5%) 0 (-) 3 (0,9%) 3 (10,7%)
IV Other treatment combinations 2 (66,7%) 8 (5,9%) 0 (-) 16 (4,7%) 3 (10,7%)
IV Chemotherapy 0 (0,0%) 37 (27,4%) 0 (-) 81 (23,9%) 11 (39,3%)
IV Radiotherapy 0 (0,0%) 0 (0,0%) 0 (-) 1 (0,3%) 0 (0,0%)
IV Radiotherapy + Chemotherapy 0 (0,0%) 31 (23,0%) 0 (-) 37 (10,9%) 0 (0,0%)
X Surgery 0 (0,0%) 47 (12,5%) 0 (-) 56 (5,2%) 38 (30,2%)
X Surgery + Chemotherapy 1 (100,0%) 55 (14,6%) 0 (-) 569 (52,5%) 45 (35,7%)
X Surgery + Radiotherapy + Chemotherapy 0 (0,0%) 85 (22,6%) 0 (-) 92 (8,5%) 4 (3,2%)
X No treatment performed 0 (0,0%) 10 (2,7%) 0 (-) 21 (1,9%) 2 (1,6%)
X Other treatment combinations 0 (0,0%) 11 (2,9%) 0 (-) 28 (2,6%) 10 (7,9%)
X Chemotherapy 0 (0,0%) 80 (21,3%) 0 (-) 228 (21,0%) 27 (21,4%)
X Radiotherapy 0 (0,0%) 6 (1,6%) 0 (-) 4 (0,4%) 0 (0,0%)
X Radiotherapy + Chemotherapy 0 (0,0%) 82 (21,8%) 0 (-) 86 (7,9%) 0 (0,0%)
y** Surgery 1.091 (28,8%) 231 (17,6%) 210 (15,9%) 62 (26,6%) 282 (30,0%)
Continued
Staging Treatment III* IX† V‡ VIII§ X||
End
y** Surgery + Chemotherapy 472 (12,5%) 255 (19,4%) 385 (29,2%) 66 (28,3%) 266 (28,3%)
y** Surgery + Radiotherapy + Chemotherapy 699 (18,5%) 186 (14,1%) 91 (6,9%) 23 (9,9%) 85 (9,1%)
y** No treatment performed 130 (3,4%) 123 (9,3%) 11 (0,8%) 4 (1,7%) 19 (2,0%)
y** Other treatment combinations 528 (13,9%) 133 (10,1%) 217 (16,5%) 13 (5,6%) 77 (8,2%)
y** Chemotherapy 306 (8,1%) 213 (16,2%) 368 (27,9%) 51 (21,9%) 147 (15,7%)
y** Radiotherapy 208 (5,5%) 14 (1,1%) 6 (0,5%) 3 (1,3%) 9 (1,0%)
y** Radiotherapy + Chemotherapy 351 (9,3%) 161 (12,2%) 29 (2,2%) 11 (4,7%) 54 (5,8%)
Note: *: III – Central Nervous System (CNS) and miscellany of intracranial and intraspinal neoplasms; †: IX - Soft tissue and other extraosseous sarcomas; ‡: V - Retinoblastoma; §: VIII - Malignant bone tumors; ||: X- Germ cell tumors, trophoblastic tumors, and gonadal neoplasms; : X - category cannot be properly assessed; **: y - staging is done during or after treatment. Source: FOSP, 2024.
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