Purpose
The purpose of this study was to analyze the effect of hospital care volume on the overall survival of children with cancer in Southern Brazil.
Patients and Methods
We performed a ...retrospective cohort study of 1378 cancer patients aged 0‐19 years, diagnosed with cancer between August 1, 2009 and December 31, 2015 in Rio Grande do Sul, who received hospital treatment in institutions affiliated with the Universal Health Care System (Sistema Único de Saúde SUS).
Results
Most children and adolescents were male (56.9%) and White (75.8%). The most common types of cancer in our cohort were acute leukemia (40.7%), followed by lymphoma (15.9%) and central nervous system tumors (8.8%). Ninety‐five percent of the patients were treated in specialized pediatric oncology centers. The cumulative probability of survival at 5 years for all patients was 73.8% (95% confidence interval CI 71.4‐76.0%). Survival was significantly higher for patients younger than 4 years of age (P = .012) compared to all other age groups. Patients treated in institutions with a pediatric oncology patient volume of less than 15 patients/year were 41% more likely to die than patients treated in institutions with a volume of 60 patients/year or more (P = .029).
Conclusion
Cancer is the leading cause of death by natural causes in all age groups in Brazil, but, even so, childhood tumors are rare. This complexity makes childhood cancer care a challenge. In this study, we reiterate that pediatric cancer patients demonstrate better overall survival when treated in high‐volume hospitals.
Objectives
Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric ...cancer patients.
Methods
A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients.
Results
Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta‐analysis showed that groups submitted to high‐risk chemotherapy for OM had a 2.79‐fold increased risk of OM.
Conclusions
Identifying risk factors for OM is essential in order to allow individualized and early prevention treatment.
Ewing sarcoma (ES) is a highly aggressive pediatric cancer that may arise from neuronal precursors. Neurotrophins stimulate neuronal devlopment and plasticity. Here, we found that neurotrophins nerve ...growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as their receptors (TrkA and TrkB, respectively) are expressed in ES tumors. Treatment with TrkA (GW-441756) or TrkB (Ana-12) selective inhibitors decreased ES cell proliferation, and the effect was increased when the two inhibitors were combined. ES cells treated with a pan-Trk inhibitor, K252a, showed changes in morphology, reduced levels of β-III tubulin, and decreased mRNA expression of NGF, BDNF, TrkA and TrkB. Furthermore, combining K252a with subeffective doses of cytotoxic chemotherapeutic drugs resulted in a decrease in ES cell proliferation and colony formation, even in chemoresistant cells. These results indicate that Trk inhibition may be an emerging approach for the treatment of ES.
It has been hypothesized that a neutropenic diet has lower microbe content. Here, the microbiological and nutritional contents of regular and neutropenic diets offered to pediatric patients were ...analyzed. Microbiological contamination was detected in five of 36 of the food samples analyzed, yet there was no statistical differences between the diets (P = 1.00) or in their odds ratio (0.62) (95% CI = 0.05–6.35; P = 0.63). The strict neutropenic diet did have less fiber (P = 0.05) and vitamin C (P = 0.01). Thus, the regular diet appears safe, and possibly provides greater benefits, for pediatric patients with neutropenia.
Introduction: To assess the use of nutritional support in children and adolescents submitted to autologous hematopoietic stem cell transplantation (HSCT), and analyze changes in nutritional status at ...hospital discharge after HSCT. Methods: A retrospective observational study was conducted on pediatric oncology patients hospitalized for autologous HSCT between 2010 and 2017. Nutritional therapy was evaluated based on the duration of enteral tube feeding (ETF) and parenteral nutrition (PN), either alone or in combination. The length of hospital stay was measured in days. Nutritional status was assessed at admission and discharge, and classified according to World Health Organization criteria. Results: The sample consisted of 68 patients, 54.4% of whom were boys. Most participants (89.7%) had solid tumors. Nutritional therapy was required in over half (52.9%) of cases, with PN being the most common indication. There was a reduction in the percentage of overweight patients and an increase in the percentage of underweight patients at discharge relative to admission. Conclusions: The use of nutritional therapy is highly prevalent in this population, and HSCT has a negative impact on nutritional status at discharge.
Objectives
Methotrexate (MTX) is subject to therapeutic drug monitoring because of its high pharmacokinetic variability and safety risk outside the therapeutic window. This study aimed to develop a ...population pharmacokinetic model (popPK) of MTX for Brazilian pediatric acute lymphoblastic leukemia (ALL) patients who attended the Hospital de Clínicas de Porto Alegre, Brazil.
Methods
The model was developed using NONMEM 7.4 (Icon®), ADVAN3 TRANS4, and FOCE-I. To explain inter-individual variability, we evaluated covariates from demographic, biochemical, and genetic data (single nucleotide polymorphisms SNPs related to the transport and metabolism of drugs).
Results
A two-compartment model was built using 483 data points from 45 patients (0.33–17.83 years of age) treated with MTX (0.25–5 g/m
2
) in different cycles. Serum creatinine (SCR), height (HT), blood urea nitrogen (BUN) and a low BMI stratification (according to the z-score defined by the World Health Organization LowBMI) were added as clearance covariates. The final model described MTX clearance as
C
L
(
L
/
h
)
=
8.02
x
SCR
Median
SCR
-
0.401
x
HT
Median
HT
0.957
x
BUN
Median
BUN
-
0.181
x
1
-
0.266
LowBMI
. In the two-compartment structural model, the central and peripheral compartment volumes were 26.8 L and 8.47 L, respectively, and the inter-compartmental clearance was 0.218 L/h. External validation of the model was performed through a visual predictive test and metrics using data from 15 other pediatric ALL patients.
Conclusion
The first popPK model of MTX was developed for Brazilian pediatric ALL patients, which showed that inter-individual variability was explained by renal function and factors related to body size.
To describe survival and neurological outcomes after HSCT for these disorders.
Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic ...resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated.
Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT.
Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.
Introduction: Pediatric oncology patients have a limited number of venous access routes and need a large number of drugs during hospitalization. This study evaluates potential MI in pediatric ...oncology prescriptions and identifies possible factors associated with the risk of their occurrence. Methods: Cross-sectional study that evaluated prescriptions from a universitary and tertiary hospital from december 2014 to december 2015. The association between the variables and the risk to potential incompatibilities between drugs was determined by Student’s t test and Pearson’s chi-square, considering p<0.05 significant. Odds Ratio was calculated considering a confidence interval of 95% to each drug. Results: 385 prescriptions were evaluated. The average age from 124 patients was 9.22 years old (SD = ± 5.10), being 50.65% male. The most frequent diagnosis and reason for hospitalization were the leukemias (27.30%) and chemotherapy administration (36.10%). The fully implantable catheter was the most commonly used venous access, in 61.30% of patients. In 87.5% of prescriptions there was the possibility of MI, and a total of 2108 incompatibilities were found, considering 300 different combinations between two drugs. Age, diagnosis, reason for hospitalization and type of venous access were presented as risk factors for potential incompatibilities (p<0.05). Some of the drugs that presented higher risk to potential incompatibilities were: leucovorin, sodium bicarbonate, cefepime, diphenhydramine,dimenhydrinate,hydrocortisone and ondansetron with significant Odds Ratio. Conclusions: the possibility of MI in prescriptions of pediatric oncology patients is frequent. Thus, the identification of risk factors may contribute to patient safety and rational use of drugs.
Introduction: This study investigated the applicability of the Subjective Global Nutritional Assessment (SGNA) tool to evaluate the nutritional status of pediatric cancer patients. Methods: This was ...a multicenter, observational cohort study of infants, children, and adolescents diagnosed with malignant tumors. Participants were evaluated at the moment they were diagnosed with a malignant tumor (EV1) and at the third month of treatment (EV2). Objective data were collected and the SGNA questionnaire was applied. Correlation between the methods was performed using the Kendall test. Results: We evaluated 216 patients at EV1 and 172 patients at EV2. During EV1, 7% of patients presented with some degree of malnutrition, according to objective measures, and 35.7% according to the SGNA. During EV2, they presented 6.4% and 26.8%, respectively. The SGNA showed ability to diagnose more malnutrition than objective indicators and the agreement found between both methods was moderate and weak. We observed a significant correlation between the SGNA and the nutritional indicators (p = <0.002), thus proving its efficacy in assessing nutritional status. Conclusion: The SGNA was applicable for evaluating the nutritional status of children and adolescents diagnosed with malignant tumors, and effective in tracking malnutrition prevalence when compared to objective nutritional assessment methods.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated ...with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-2-(hexahydro-2-oxo-1H-azepin-3-yl)aminocarbonylphenyl-benzobthiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.
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