Eiso Hiyama1,2, Tomoro Hishiki3,4, Kenichiro Watanabe5, Kohmei Ida6, Yuka Ueda2, Sho Kurihara2, Michihiro Yano7, Ken Hoshino8, Akiko Yokoi9, Yuichi Takama10, Yuki Nogami4, Tomoaki Taguchi11, Makiko Mori12, Kentaro Kihira13, Osamu Miyazaki3, Hiroshi Fuji3, Shohei Honda14, Tomoko Iehara15, Takuro Kazama16, Junya Fujimura17, Yukichi Tanaka18, Takeshi Inoue19, Tatsuro Tajiri20, Satoshi Kondo21, Takaharu Oue22, Kenichi Yoshimura23. 1. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan. 2. Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan. 3. Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan. 4. National Cancer Center Hospital, Tokyo, Japan. 5. Shizuoka Children's Hospital, Shizuoka, Japan. 6. Department of Pediatrics, Teikyo University Mizonokuchi Hospital, Kawasaki, Japan. 7. Department of Pediatrics, Akita University School of Medicine, Akita, Japan. 8. School of Medicine, Keio University, Tokyo, Japan. 9. Department of Pediatric Surgery, Kobe Children's Hospital, Kobe, Hyogo, Japan. 10. Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 11. Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 12. Departments of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan. 13. Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan. 14. Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 15. Department of Pediatrics, Graduate School of Medicine, Tohoku University, Sendai, Japan. 16. Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan. 17. Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan. 18. Department of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan. 19. Department of Pathology, Osaka City General Hospital, Osaka, Japan. 20. Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan. 21. Division of Pediatric Surgery and Transplant Surgery, Nagoya City University Medical School, Nagoya, Japan. 22. Department of Pediatric Surgery, Hyogo College of Medicine, Hyogo, Japan. 23. Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima, Japan.
Abstract
PURPOSE: We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS: From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) or received low-dose CITA, followed by surgery and postoperative chemotherapy (stratum 2). In the remaining patients, after 2 cycles of CITA, responders received the CITA regimen before resection (stratum 3), and nonresponders were switched to ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC; stratum 4). Intensified chemotherapeutic regimens with autologous hematopoietic stem-cell transplantation (SCT) after resection were an optional treatment for patients with refractory/metastatic disease. RESULTS: The 5-year event-free and overall survival rates of HB patients were 74.2% and 89.9%, respectively, for stratum 1, 84.8% and 90.8%%, respectively, for stratum 2, 71.6% and 85.9%%, respectively, for stratum 3, and 59.1% and 67.3%%, respectively, for stratum 4. The outcomes for CITA responders were significantly better than those for nonresponders, whose outcomes remained poor despite salvage therapy with a second-line ITEC regimen or SCT. The late effects, ototoxicity, cardiotoxicity, and delayed growth, occurred in 61, 18, and 47 patients, respectively. Thirteen secondary malignant neoplasms (SMNs), including 10 leukemia, occurred, correlating with higher exposure to pirarubicin and younger age at diagnosis. CONCLUSION: The JPLT-2 protocol achieved up-front resectability in PRETEXT I/II patients with no annotation factors, and satisfactory survival in patients who were CITA responders in the remaining patients. However, outcomes for CITA nonresponders were unsatisfactory, despite therapy intensification with ITEC regimens and SCT. JPLT-2 had a relatively low incidence of cardiotoxicity but high rates of SMNs.
PURPOSE: We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS: From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) or received low-dose CITA, followed by surgery and postoperative chemotherapy (stratum 2). In the remaining patients, after 2 cycles of CITA, responders received the CITA regimen before resection (stratum 3), and nonresponders were switched to ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC; stratum 4). Intensified chemotherapeutic regimens with autologous hematopoietic stem-cell transplantation (SCT) after resection were an optional treatment for patients with refractory/metastatic disease. RESULTS: The 5-year event-free and overall survival rates of HB patients were 74.2% and 89.9%, respectively, for stratum 1, 84.8% and 90.8%%, respectively, for stratum 2, 71.6% and 85.9%%, respectively, for stratum 3, and 59.1% and 67.3%%, respectively, for stratum 4. The outcomes for CITA responders were significantly better than those for nonresponders, whose outcomes remained poor despite salvage therapy with a second-line ITEC regimen or SCT. The late effects, ototoxicity, cardiotoxicity, and delayed growth, occurred in 61, 18, and 47 patients, respectively. Thirteen secondary malignant neoplasms (SMNs), including 10 leukemia, occurred, correlating with higher exposure to pirarubicin and younger age at diagnosis. CONCLUSION: The JPLT-2 protocol achieved up-front resectability in PRETEXT I/II patients with no annotation factors, and satisfactory survival in patients who were CITA responders in the remaining patients. However, outcomes for CITA nonresponders were unsatisfactory, despite therapy intensification with ITEC regimens and SCT. JPLT-2 had a relatively low incidence of cardiotoxicity but high rates of SMNs.
Authors: Simone de Campos Vieira Abib; Chan Hon Chui; Sharon Cox; Abdelhafeez H Abdelhafeez; Israel Fernandez-Pineda; Ahmed Elgendy; Jonathan Karpelowsky; Pablo Lobos; Marc Wijnen; Jörg Fuchs; Andrea Hayes; Justin T Gerstle Journal: Ecancermedicalscience Date: 2022-02-17