Background: Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Methods: Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Results: Thirty-eight patients were identified. Median age at diagnosis of HB was 16 months (range: 3 to 168 months). All patients had received a platinum agent, and almost all had anthracycline exposure. Of 12 patients with a known history of liver transplantation for primary resection of their HB, the majority had post-transplant lymphoproliferative disorder (PTLD) (n=7). The most common SMNs reported were non-PTLD hematopoietic malignancies (n=19). Solid tumors were seen in 12 patients: peripheral neuroectodermal tumor/Ewing sarcoma (3); and one each for renal cell carcinoma, nephroblastoma, colorectal carcinoma, thyroid carcinoma, medulloblastoma, clear cell sarcoma-like tumor, hepatocellular carcinoma, osteosarcoma, and malignant schwannoma. Of 36 patients with data, nineteen survived. Conclusions: SMNs following HB treatment were seen in patients with anthracycline (and cisplatin) exposure, hereditary tumor predisposition syndromes, and/or history of liver transplantation. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data via a companion late effects study or international registry could be used to further evaluate rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB.

Purpose: Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt Phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks we aimed to evaluate if additional transarterial embolization is of benefit for children with KHE and KMP. Methods: 17 patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding rate as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by Magnetic Resonance Imaging (MRI), time to response of KMP defined as thrombocyte increase >150 x 103/µl, as well as rebound rates of both after cessation of sirolimus were compared. Results: N= 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N=9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months, however tumor response as well as rebound rates were similar between both groups. Conclusion: Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.