Strategies to improve diagnosis and access to treatment of retinoblastoma in low- and middle-income countries: A systematic review.

Retinoblastoma, the most common intraocular tumor in childhood, still faces challenges in diagnosis and treatment, particularly in low- and middle-income countries. Identifying strategies to improve the time to diagnosis and access to treatment is crucial to enhance survival rates and preserve ocular health. We conducted a systematic review to identify interventions that have demonstrated potential in addressing these challenges. We performed a comprehensive search across databases until March 2023. Out of the studies reviewed, 21 met the inclusion criteria and were categorized into five main areas: surveillance strategies, genetic counseling, education, public assistance, and international partnership. Despite the obstacles faced, the initiatives identified in this review present acts toward improving the time to diagnosis and access to treatment for retinoblastoma. Based on the extracted data, we propose a comprehensive chain of initiatives. We firmly believe that implementing this chain of initiatives can lead to improved clinical outcomes for retinoblastoma patients.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Financial hardship in families of children or adolescents with cancer: a systematic literature review.

Financial hardship in childhood cancer contributes to poor health outcomes and global disparities in survival, but the extent of the financial burden on families is not yet fully understood. We systematically reviewed financial hardship prevalence and individual components characterising financial hardship across six domains (medical, non-medical, and indirect costs, financial strategies, psychosocial responses, and behavioural responses) and compared characteristics across country income levels using an established theory of human needs. We included 123 studies with data spanning 47 countries. Extensive heterogeneity in study methodologies and measures resulted in incomparable prevalence estimates and limited analysis. Components characterising financial hardship spanned the six domains and showed variation across country income contexts, yet a synthesis of existing literature cannot establish whether these are true differences in characterisation or burden. Our findings emphasise a crucial need to implement a data-driven methodological framework with validated measures to inform effective policies and interventions to address financial hardship in childhood cancer.

Chemotherapy and Anticancer Drugs Adjustment in Obesity: A Narrative Review.

BACKGROUND: Obese individuals have higher rates of cancer incidence and cancer- related mortality. The worse chemotherapy outcomes observed in this subset of patients are multifactorial, including the altered physiology in obesity and its impact on pharmacokinetics, the possible increased risk of underdosing, and treatment-related toxicity. AIMS: The present review aimed to discuss recent data on physiology, providing just an overall perspective and pharmacokinetic alterations in obesity concerning chemotherapy. We also reviewed the controversies of dosing adjustment strategies in adult and pediatric patients, mainly addressing the use of actual total body weight and ideal body weight. METHODS: This narrative review tried to provide the best evidence to support antineoplastic drug dosing strategies in children, adolescents, and adults. RESULTS: Cardiovascular, hepatic, and renal alterations of obesity can affect the distribution, metabolism, and clearance of drugs. Anticancer drugs have a narrow therapeutic range, and variations in dosing may result in either toxicity or underdosing. Obese patients are underrepresented in clinical trials that focus on determining recommendations for chemotherapy dosing and administration in clinical practice. After considering associated comorbidities, the guidelines recommend that chemotherapy should be dosed according to body surface area (BSA) calculated with actual total body weight, not an estimate or ideal weight, especially when the intention of therapy is the cure. CONCLUSION: The actual total body weight dosing appears to be a better approach to dosing anticancer drugs in both adults and children when aiming for curative results, showing no difference in toxicity and no limitation in treatment outcomes compared to adjusted doses.

Bloodstream infection in pediatric patients with febrile neutropenia induced by chemotherapy.

INTRODUCTION: Febrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer. METHODS: This prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria. RESULTS: A total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever. CONCLUSION: A CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children.

Risk factors for catheter-related infection in children with cancer: A systematic review and meta-analysis.

RATIONALE: To understand the risk factors for catheter-related infection during treatment of pediatric cancer is essential to implement measures to prevent its occurrence. BACKGROUND: We performed a comprehensive systematic review of the literature with meta-analysis to identify and synthesize the main risk factors for catheter-related infection in children undergoing oncological treatment. METHODS: Systematic searches were conducted in Medline, Embase, Lilacs, and BVS (Biblioteca Virtual em Saúde) until January 2022, following PRISMA guidelines. The search was not limited to language or dates. Risk factors were divided into host-related, assistance-related, and catheter types. We also describe the most common pathogens. RESULTS: Thirteen studies were included in the review. Diagnosis of hematological neoplasm, the intensity of treatment, blood transfusion in the 4-7 days before the infection, type of long-term catheters (tunneled externalized catheters, double lumen, greater diameter), inpatient treatment, and a longer period of hospitalization were the most consistent risk factors. Metanalysis showed that neutropenia at the moment of catheter placement is not a risk factor for central-line-associated bloodstream infections, however, there is high heterogeneity between studies. Staphylococcus epidermidis was the most common pathogen reported. CONCLUSIONS: Understanding risk factors is an essential step to reduce morbidity and mortality of catheter-related infection. Education for preventive measures, reduction of hospitalization, wisely choosing the most adequate type of catheter, and the best moment for catheter insertion may reduce the occurrence of catheter-related infection.

Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases.

INTRODUCTION: Invasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential. OBJECTIVES: The aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses. METHODS: This was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality. RESULTS: A total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10cells/µL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia. CONCLUSION: Both confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors.

BACKGROUND: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. OBJECTIVE: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. METHODS: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were "RAS", "ACE", "Angiotensin-(1-7)", "ACE2", "Angiotensin II", "AT1 receptor", "Mas receptor", "Pediatric", "Cancer". RESULTS: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. CONCLUSION: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

Infection surveillance in pediatric hematopoietic stem cell transplantation recipients.

OBJECTIVE: To describe the profile of reported healthcare-associated infections (HAIs) in pediatric patients submitted to hematopoietic stem cell transplantation (HSCT) at a reference center. METHODS: Retrospective cohort of pediatric patients who were submitted to HSCT from 2008 to 2016. The criteria for HAI were based on those established by the National Healthcare Safety Network. Data were collected by active surveillance performed daily by professionals. This study was approved by the institutional research ethics committee. RESULTS: A total of 86 HSCTs were performed in 81 patients younger than 18 years of age (median, 10 years). Of these, 69 (85%) were males. Aplastic anemia and leukemia were the main diagnoses. A total of 140 HAIs were diagnosed with an incidence density of 28.2 infections/1000 patient-days. The most common HAI was laboratory-confirmed bloodstream infection (46), the majority of which was reported to be central venous catheter-associated (43). Gram-negative bacteria were the most prevalent microorganisms (58.5%). Almost all the infections occurred until 30 days after transplantation, and 17 deaths were observed within 180 days after the procedure. CONCLUSION: Active surveillance of HAIs in HSCT children allowed the evaluation of the incidence and profile of HAIs, which is essential for the health care of these patients.

Usefulness of positron emission tomography in the differentiation between tumor and infectious lesions in pediatric oncology: a case report.

BACKGROUND: Sometimes, in pediatric oncology, it is difficult to differentiate the relapse of primary tumor from other diagnoses such as post-ischemic lesions or fungal abscess, without performing an organ biopsy. In addition, patients frequently are not under clinical conditions to be biopsied, mainly due to febrile neutropenia. A growing number of studies has focused on the use of Positron emission tomography/computed tomography with 18 Fluorodeoxyglucose ([(18)F]FDG-PET/CT) to distinguish tumor relapse from infectious lesions in patients with febrile neutropenia. CASE PRESENTATION: This case report describes a 6 years-old girl with febrile neutropenia during the treatment of neuroblastoma. Blood culture showed Candida sp. Abdominal ultrasonography revealed multiple unspecific hypoechoic areas of variable sizes in spleen, which might be either tumor or Candida-induced abscesses. [(18)F]FDG-PET/CT was performed to help the diagnosis and revealed small splenic lesions highly suggestive of disseminated candidiasis. Patient was then treated with systemic antifungal agent. After the recovery from febrile neutropenia, a spleen biopsy was performed, confirming the diagnosis of fungal abscess. Due to the small size of lesions, modalities such as ultrasonography, CT and magnetic nuclear resonance were not able in distinguishing tumor relapse from infectious lesions. CONCLUSION: This case provides an excellent example in which the use of [(18)F]FDG-PET/CT is valuable in helping to localize potential sites of disseminated fungal infection to be diagnosed within clinical context. [(18)F]FDG-PET /CT seems to have a role in the evaluation of pediatric patients with febrile neutropenia.