Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death. Methods: This multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome. Results: Of 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 ( P < 0.0001 and P = 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression ( P = 0.012 and P = 0.027, respectively). Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.

Local therapies replaced systemic chemotherapy for ocular preservation in retinoblastoma. In middle income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncologia Pediatrica (GALOP developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except those with less advanced disease or age younger than 6 months. OAC allowed for the elimination of the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for advanced eyes.

The ongoing COVID-19 pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. Four cross-sectional surveys were electronically distributed among pediatric onco-hematologist 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. 453 pediatric onco-hematologists from 20 countries responded 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 on-going 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 (OR:1.84, 95%C: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. 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.

CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare entity recently described. Thirteen CNS HGNET-MN1 patients were identified using genome wide methylation arrays/RT-PCR across 7 institutions and were correlated with treatment and outcome. All patients had surgery (GTR:9/STR:4) as initial management followed by radiotherapy (focal:5/craniospinal:2/CyberKnife:1) and systemic chemotherapy in 3 patients. Seven patients relapsed; 5 local and 2 metastatic despite complete resection and radiotherapy. Three patients died due to their tumor relapse after 24 months despite upfront radiotherapy. Treatment of CNS HGNET-MN1 remains a major challenge with multiple failures, despite aggressive surgical resections and upfront radiotherapy.