Tang-Her Jaing

Background: We evaluated hypofractionated proton beam therapy (PBT) feasibility for unresectable hepatoblastoma (HBL). Observations: Six patients with residual/relapsed localized HBL received PBT (50 to 60 Gy (RBE) in 10 fractions) between April 2019 and September 2024, with follow-up through September 2025. After 55-month follow-up, 5 patients remained alive without disease. One marginal recurrence was successfully salvaged by re-irradiation, and another bridged to hepatectomy (10% viable tumor). Toxicities were minimal, with one grade 2 duodenitis. One patient died of treatment-unrelated myelodysplastic syndrome while remaining HBL-free. Conclusions: Hypofractionated PBT is a feasible, well-tolerated salvage option for refractory HBL, providing encouraging local control.

Ting-Chi Yeh, M.D., Tang-Her Jaing, M.D., Hsi-Che Liu, M.D., Shih-Hsiang Chen, M.D., Shih-Chung Wang, M.D., Chih-Cheng Hsiao, M.D., Shyh-Shin Chiou, M.D., Jen-Yin Hou, M.D., Pei-Chin Lin, M.D., Fang-Liang Huang, M.D., Shang-Hsien Yang, M.D., Ting-Yu Huang, M.S., Chao-Ping Yang, M.D., and Lee-Yung Shih, M.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0573

Background. In unresectable hepatoblastoma (HB), particularly “pre-treatment extent of tumor” (PRETEXT) IV tumors or those with positive annotation factors, standard management consists of intensive chemotherapy followed by surgical resection or orthotopic liver transplantation (OLT). Radiotherapy has traditionally been avoided because of the liver’s radiosensitivity and the risk of radiation-induced liver disease. Proton beam therapy (PBT), owing to its dosimetric advantage and ability to spare uninvolved liver parenchyma, may represent a potential local control strategy in selected pediatric patients for whom curative surgery or OLT is not feasible. Case Presentation. We describe five pediatric patients with advanced hepatoblastoma treated with proton beam therapy at our institution between February 2022 and January 2024. The cohort included three girls and two boys, with a median age of 3.0 years (interquartile range [IQR], 1.6–4.0) and a median alpha-fetoprotein level of 435,453 ng/mL (IQR: 7,668–1,276,681) at diagnosis. All patients were initially considered inoperable because of extensive hepatic involvement, inadequate future liver remnant, or multifocal disease, and OLT was not feasible owing to donor limitations or medical comorbidities. All received neoadjuvant chemotherapy using SIOPEL-based regimens, achieving partial tumor response. Tumors ranged from 5 to 12 cm and involved central hepatic segments, the portal region, or both lobes. PBT was delivered at a total dose of 50 GyE in 10–25 fractions as definitive or consolidative therapy, followed by surgical resection in three patients. Two patients additionally received targeted therapy and immunotherapy. At last follow-up, four patients were alive with no evidence of disease, while one patient died from tumor progression. Conclusions. These cases suggest that proton beam therapy may serve as a feasible liver-sparing local treatment option for selected pediatric patients with unresectable or residual hepatoblastoma when surgery or OLT is not possible. While limited by availability and cost, PBT may facilitate multimodal therapy and preserve future treatment options.

High-dose methotrexate (HD-MTX) is a cornerstone of pediatric acute lymphoblastic leukemia (ALL) treatment but poses a risk for delayed clearance and associated toxicities. While hydration is standard to enhance methotrexate (MTX) excretion, the relationship between urine output (UO) and time to MTX clearance remains underexplored. We conducted a retrospective study of pediatric ALL patients treated with HD-MTX at Chang Gung Memorial Hospital between August 2023 and February 2025. Patients were stratified into higher (H-UO) and lower urine output (L-UO) groups using a 5.0 mL/kg/hr cutoff. Clinical outcomes including time to MTX normalization, delayed MTX clearance, hospitalization duration, and use of adjunctive diuretics were analyzed. Thirty-nine patients were included. The H-UO group showed significantly faster MTX clearance (2.0 vs. 4.0 days, P = 0.0035), lower incidence of delayed clearance (18.2% vs. 70.6%, P = 0.0025), and shorter hospital stays (5.0 vs. 7.0 days, P = 0.019). Diuretic use was higher in the L-UO group, primarily as a reactive measure. No significant difference in MTX-related major toxicities was observed. Higher UO is associated with more efficient time to MTX clearance and shorter hospitalization in pediatric ALL patients receiving HD-MTX. Prospective studies are warranted to optimize supportive care protocols.