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