Background: The JPLT3-S (Japanese study group for Pediatric Liver Tumors) 3 study, conducted cisplatin (CDDP) monotherapy for young children (< 3 years old) with standard risk hepatoblastoma (HB) evaluated central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT classification (standard risk HB) showed favorable outcomes by the therapies consisted of CDDP and pirarubicin, but showed toxicities and late complications. In this JPLT3-S trial, less intensity regimen consisted of CDDP alone were evaluated in the young children (< 3 years old) with standard risk HB. Methods: Patients who were less than three years of age, who had PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, we introduced central radiological and pathological reviews of all patients. The primary outcome was 3-year progression-free survival (PFS). Results: A total of 38 patients (23 female) were included. The median patient age was 12 (range, 2-34) months. Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3- year PFS rate was 93.9% (95% confidence interval [CI], 86.4 to 100). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (confidence interval, 100). There were no cases with late complication without ototoxicity. Conclusion: CDDP monotherapy regimen is feasible in young patients with localized HB classified by central review.

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.