Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection

Tomoro Hishiki¹, Kohmei Ida², Kenichiro Watanabe³, Makiko Mori⁴, Junya Fujimura⁵, Yuki Nogami⁶, Tomoko Iehara⁷, Ken Hoshino⁸, Akiko Yokoi⁹, Shohei Honda¹⁰, Takuro Kazama¹¹, Masahiro Sekiguchi¹², Norihiko Kitagawa¹³, Risa Matsumura¹⁴, Motonari Nomura¹⁵, Yohei Yamada⁸, Ryo Hanaki¹⁶, Hide Kaneda¹⁷, Yuichi Takama¹⁸, Takeshi Inoue¹⁹, Yukichi Tanaka²⁰, Osamu Miyazaki²¹, Hiroki Nagase²², Tetsuya Takimoto²³, Kenichi Yoshimura²⁴, Eiso Hiyama^{25

26}

Affiliations

¹ Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
² Department of Pediatrics, Teikyo University Mizonokuchi Hospital, Kawanagawa, Japan.
³ Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
⁴ Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
⁵ Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
⁶ Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
⁸ Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
⁹ Department of Pediatric Surgery, Kobe Children's Hospital, Kobe, Japan.
¹⁰ Department of Gastroenterological Surgery I, Hokkaido University Hospital, Hokkaido, Japan.
¹¹ Department of Pediatric Surgery, Tohoku University Hospital, Sendai, Japan.
¹² Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
¹³ Department of Surgery, Children's Cancer Center, Kanagawa Children's Medical Center, Yokohama, Japan.
¹⁴ Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
¹⁵ Department of Pediatric Surgery, Osaka University, Osaka, Japan.
¹⁶ Department of Pediatrics, Mie University Hospital, Tsu, Japan.
¹⁷ Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan.
¹⁸ Department of Pediatric Surgery, Osaka City General Hospital, Osaka, Japan.
¹⁹ Department of Pathology, Osaka City General Hospital, Osaka, Japan.
²⁰ Department of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
²¹ Department of Radiology, National Center for Child Health and Development, Tokyo, Japan.
²² Graduate School of Medicine, Diagnostics and Therapeutics of Intractable Diseases, Juntendo University, Tokyo, Japan.
²³ Department of Childhood Cancer Data Management, National Center for Child Health and Development, Tokyo, Japan.
²⁴ Innovative Clinical Research Center (iCREK), Nagoya City University, Nagoya, Japan.
²⁵ Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
²⁶ Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan.

PMID: 40346753
DOI: 10.1002/pbc.31770

Clinical Trial

Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection

Tomoro Hishiki et al. Pediatr Blood Cancer. 2025 Aug.

. 2025 Aug;72(8):e31770.

doi: 10.1002/pbc.31770. Epub 2025 May 9.

Authors

Affiliations

¹ Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
² Department of Pediatrics, Teikyo University Mizonokuchi Hospital, Kawanagawa, Japan.
³ Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
⁴ Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
⁵ Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
⁶ Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
⁸ Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
⁹ Department of Pediatric Surgery, Kobe Children's Hospital, Kobe, Japan.
¹⁰ Department of Gastroenterological Surgery I, Hokkaido University Hospital, Hokkaido, Japan.
¹¹ Department of Pediatric Surgery, Tohoku University Hospital, Sendai, Japan.
¹² Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
¹³ Department of Surgery, Children's Cancer Center, Kanagawa Children's Medical Center, Yokohama, Japan.
¹⁴ Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
¹⁵ Department of Pediatric Surgery, Osaka University, Osaka, Japan.
¹⁶ Department of Pediatrics, Mie University Hospital, Tsu, Japan.
¹⁷ Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan.
¹⁸ Department of Pediatric Surgery, Osaka City General Hospital, Osaka, Japan.
¹⁹ Department of Pathology, Osaka City General Hospital, Osaka, Japan.
²⁰ Department of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
²¹ Department of Radiology, National Center for Child Health and Development, Tokyo, Japan.
²² Graduate School of Medicine, Diagnostics and Therapeutics of Intractable Diseases, Juntendo University, Tokyo, Japan.
²³ Department of Childhood Cancer Data Management, National Center for Child Health and Development, Tokyo, Japan.
²⁴ Innovative Clinical Research Center (iCREK), Nagoya City University, Nagoya, Japan.
²⁵ Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
²⁶ Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan.

PMID: 40346753
DOI: 10.1002/pbc.31770

Abstract

Background: Complete resection of the primary tumor is critical for the survival of children with hepatoblastomas (HBs). This prospective clinical study aimed to clarify the outcome of a chemotherapy regimen comprising cisplatin and doxorubicin (PLADO) followed by definitive surgery conducted at the appropriate time in patients with intermediate-risk HB.

Methods: Intermediate-risk HB was defined as patients without evidence of metastatic disease who met any of the following criteria: age ≥3 years; PRETEXT IV disease; presence of more than one PRETEXT annotation factor. The study protocol consisted of four preoperative and two postoperative courses of PLADO. The appropriate surgeries were conducted at optimized timings via real-time central surgical reviews.

Results: The 3-year progression-free and overall survivals of the 33 intermediate-risk patients included were 78.7% and 87.9%, respectively. Preoperative PLADO resulted in a partial response in 83.9% of the patients. Microscopic complete resection was ultimately obtained in 31 (94%) patients. No patient required more than six preoperative courses before surgery or liver transplantation (LTx). Two patients never had surgery due to tumor progression.

Conclusions: The outcome for patients with intermediate-risk HB was satisfactory. PLADO, combined with surgery (including LTx) conducted at the optimal time, appeared to cure most patients in this study.

Keywords: cisplatin; doxorubicin; hepatoblastoma; pediatric liver tumor.

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References

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Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection

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Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection

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