Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Type 1 Insulin-Like Growth Factor Receptor Nuclear Localization in High-Grade Glioma Cells Enhances Motility, Metabolism, and In Vivo Tumorigenesis.

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility and metabolism without affecting their proliferation. In vivo, IGF1R has the capacity to translocate to the nucleus and allows not only a higher proliferation rate and the earlier development of tumors but also renders the cells sensitive to OSI906 therapy. With this work, we provide evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization.

Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome.

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

Diffuse hyperplastic perilobar nephroblastomatosis.

Nephroblastomatosis is a rare preneoplastic lesion defined as the presence of diffuse or multifocal nephrogenic rests. They are divided into 4 categories: perilobar, intralobar, combined, and universal. The aim of this report is to describe a case of diffuse hyperplastic perilobar nephroblastomatosis. A 1-year-old boy presented with an abdominal mass on the left side. Computed tomography scan showed a homogeneous, isointense enlarged left kidney. A fine needle aspiration cytology was reported as Wilms tumor. After chemotherapy, the left kidney was excised. Nephrectomy specimen presented a thick cortical rim of hyperplastic nephrogenic tissue, well delineated from preserved renal parenchyma without pseudocapsule. Nephroblastomatosis is a rare condition affecting renal parenchyma. Diagnosis is based on imaging studies, such as ultrasound, computed tomography scan, and magnetic resonance imaging. Fine needle aspiration cytology is of limited value. Therapeutic management is controversial. Chemotherapy is used preoperatively, and surgical excision may be an alternative for refractory cases.

No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas.

In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.

Colorectal carcinoma in children, adolescents, and young adults.

The authors conducted a retrospective evaluation of patients younger than 30 years with colorectal carcinoma in Argentina. Patients were divided into group 1 (patients treated at pediatric institutions from 0 to 20 years of age, n = 14) and group 2 (patients from 21 to 30, n = 7, treated at adult centers). Group 1 had significantly more advanced disease and a poorer prognosis. Six patients (2/14 in group 1 and 4/7 in group 2) survive disease-free. Thirteen patients died of progressive disease, 1 died of a non-tumor-related cause, and 1 is still on treatment. Patients younger than 20 years have a poorer prognosis, probably because of advanced disease on presentation.