Introduction Hepatoblastoma has a low annual incidence (1.7/1,000,000 children) posing a barrier to studying epidemiologic risk factors in its development. Current accepted associations include low birthweight and overgrowth syndromes. Neonatal intensive care unit (NICU) interventions were evaluated for the relationship with subsequent development of hepatoblastoma. Methods Pediatric Health Information System data between 2016-2022 was queried for all NICU admissions. From this set, patients with a diagnosis code for hepatoblastoma were identified. Pharmacy billing information was used to calculate total number of days of total parenteral nutrition (TPN) and mechanical ventilation exposure during NICU hospitalization. Results 293,681 patients met inclusion, with 51 patients diagnosed with hepatoblastoma. Logistic regression demonstrated that every 10 additional days of TPN (OR 1.10, 95% CI 1.00-1.13) or mechanical ventilation (OR 1.08, 95% CI 1.06-1.09) was correlated with increased likelihood of development of hepatoblastoma. The dataset was partitioned into two samples, one for training and the other for validation. TPN and duration of mechanical ventilation were the retained predictors within the training sample following least absolute shrinkage and selection operator analysis. Using these retained predictors within the validation sample, there were 773 patients with a predicted probability of developing hepatoblastoma greater than 0.05%, with 6 patients who developed hepatoblastoma (0.78%). Discussion A cohort of infants were identified as having a risk for the subsequent development of hepatoblastoma, similar to that of patient with known associated syndromes. A predictive model was created to assist in identifying patients who may benefit from screening based upon specific NICU exposures.

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers (EXPeRT) and the Children’s Oncology Group (COG) fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g. pleuropulmonary blastoma, desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g. thyroid, melanoma, gastrointestinal stromal tumor). [1](#ref-0001) Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14.[1](#ref-0001) This article highlights several of the most common rare tumor types.

The Children’s Oncology Group (COG) Rare Tumor committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that don’t fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.