How do you approach relapsed hepatocellular malignant neoplasm NOS after transplant in pediatric or AYA patients?

There exist no standards of care for patients with HCN NOS after front-line therapy has failed. Considerations include response to prior therapy, agents used front-line/not used, sites of disease, surgical options, and molecular findings of the tumor itself. Platinum/anthracycline-based therapy, carboplatin/etoposide, irinotecan, all used routinely for hepatoblastoma, tend to not work well for relapsed/progressive HCN NOS, but could be tried. Therapies designed for HCC could also be considered, such as anti-PD1 or anti-VEGF-based therapies, as the biology of HCN NOS relapsing after upfront therapy may start to mimic more closely to HCC rather than HBL. Phase 1/2 studies are worth consideration for chemorefractory cases.

It would be important to ensure this tumor has been sequenced and to know whether a TERT promoter mutation has been identified. This mutation is found at very high frequency for a subset of HCN NOS which is provisionally termed as Hepatoblastoma with HCC features. These patients are intermediate in the spectrum between Hb and HCC.

I think that there are a couple of reasonable options. Unfortunately, this patient is not eligible for CPI [we have a Phase 2 trial of pembrolizumab monotherapy currently open at the DFCI (lead site) but also in Cincinnati with Dr. @Dr. First Last and at UCSF with myself but the h/o transplant makes this not an option].
If the tumor is Glypican-3 positive, then there is an early phase trial at Memorial Sloan Ketter...