DISCUSSION:
The extent of both screening and care for children with trisomy 18 is a complex, individualized and subjective discussion, unique to each patient and family. However, this emerging association between hepatoblastoma and trisomy 18, with preliminary studies estimating >1% risk of hepatoblastoma, raises questions about the potential benefits of routine screening to promote earlier diagnosis and minimize need for neoadjuvant chemotherapy. Children with Beckwith Weideman syndrome and WT1 -related overgrowth syndromes have a known predisposition for both hepatoblastoma and Wilms tumor. Tumor surveillance consisting of interval abdominal US (every 3 months until age 7) and serial AFP measurement (a baseline at birth then every 3 months until age 4) are recommended given the proven advantages of early diagnosis in prognosis.5 As AFP is a highly specific and sensitive tumor marker, secreted by over 96% of hepatoblastomas, it serves as an effective screening tool in at risk patients, as it can rise prior to tumor detection with US or other imaging modalities.6,7 In 2019 results of a literature search were released confirming a high number of reported malignancies in Trisomy 18 patients. Based on this, initial screening recommendations for abdominal malignancies were published, however this has not yet become the standard of care.1
All COG study protocols include dose modification guidelines in the event that patients experience toxicities related to chemotherapy. In AHEP0731, omission of doxorubicin is recommended in Stage III, Intermediate-Risk Hepatoblastoma only if the patient develops persistent grade 3 or 4 mucositis despite dose reduction, or for Grade 3 congestive heart failure, Grade 4 cardiac toxicity or major changes in cardiac ejection fractions attributable to doxorubicin.8Despite an initially unresectable tumor, our patient with trisomy 18 and extensive cardiac history was effectively treated for intermediate risk hepatoblastoma with modified chemotherapy without doxorubicin followed by surgical resection. This supports offering patients with Trisomy 18 and underlying cardiac abnormalities modified chemotherapy regimens as curative treatment for hepatoblastoma. Regardless, the care of individuals with trisomy 18 is not homogeneous. It should instead be family-centered, flexible, and reflect parents’ views that their children with trisomy 18 are “happy” and “enriching to their lives.”9