Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Predictive Factors for Gram-negative Versus Gram-positive Bloodstream Infections in Children With Cancer.

BACKGROUND: Identifying potential predictive factors for the type of bacteremia (Gram-negative vs. Gram-positive) in children with cancer would be crucial for the timely selection of the appropriate empiric antibiotic treatment. MATERIALS AND METHODS: Demographic, clinical, and laboratory characteristics of children with cancer and a bacterial bloodstream infection (BSI) (February 1, 2011 to February 28, 2018) in a tertiary pediatric oncology department were retrospectively examined and were correlated with the type of isolated bacteria. RESULTS: Among 224 monomicrobial bacterial BSI episodes, Gram-negative and Gram-positive bacteria were isolated in 110 and 114 episodes, respectively. Gram-negative bacteria were isolated significantly more frequently in girls (Gram-negative/Gram-positive ratio 1.7:1) versus boys (Gram-negative/Gram-positive ratio 0.72:1), P=0.002, in patients with previous BSI episodes (1.4:1) versus those without (0.8:1), P=0.042, and in children with hematologic malignancy (1.3:1) versus those who suffered from solid tumors (0.52:1), P=0.003. Gram-negative BSI episodes were more frequently correlated with a lower count of leukocytes, P=0.009, neutrophils, P=0.009 and platelets, P=0.002, but with significantly higher C-reactive protein (CRP) levels, P=0.049. Female sex, hematologic malignancy, and higher CRP levels remained independent risk factors for Gram-negative BSI in the multivariate analysis. Among neutropenic patients, boys with solid tumors and a recent central venous catheter placement appear to be at increased risk for Gram-positive BSI in the multivariate analysis. CONCLUSIONS: Although Gram-negative and Gram-positive BSIs are close to balance in children with cancer, Gram-negative bacteria are more likely to be isolated in girls, children with hematologic malignancies and those with higher CRP level at admission. In contrast, neutropenic boys with solid tumors and a recently placed central venous catheter may be at increased risk for Gram-positive BSI indicating probably the need for initially adding antibiotics targeting Gram-positive bacteria.