Tomoro Hishiki1,2, Kimikazu Matsumoto3, Miki Ohira4, Takehiko Kamijo4, Hiroyuki Shichino5, Tatsuo Kuroda6, Akihiro Yoneda7, Toshinori Soejima8, Atsuko Nakazawa9, Tetsuya Takimoto10, Isao Yokota11, Satoshi Teramukai11, Hideto Takahashi12, Takashi Fukushima13, Takashi Kaneko14, Junichi Hara15, Michio Kaneko16, Hitoshi Ikeda17, Tatsuro Tajiri18, Akira Nakagawara19. 1. Children's Cancer Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. tomoro.hishiki@gmail.com. 2. Pediatric Surgical Oncology, National Cancer Center Hospital, Tokyo, Japan. tomoro.hishiki@gmail.com. 3. Children's Cancer Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 4. Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan. 5. Pediatrics, National Center for Global Health and Medicine, Tokyo, Japan. 6. Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan. 7. Pediatric Surgery, Osaka City General Hospital, Osaka, Japan. 8. Kobe Proton Center, Kobe, Japan. 9. Pathology, National Center for Child Health and Development, Tokyo, Japan. 10. Clinical Epidemiology Research Center for Pediatric Cancer, National Center for Child Health and Development, Tokyo, Japan. 11. Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan. 12. National Institute of Public Health, Saitama, Japan. 13. Pediatrics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 14. Hematology and Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 15. Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan. 16. Ibaraki Prefectural Association of Health Evaluation and Promotion, Mito, Japan. 17. Pediatric Surgery, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan. 18. Pediatric Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. 19. Saga Medical Center KOSEIKAN Hospital, Saga, Japan.
Abstract
BACKGROUND: The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. METHODS: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. RESULTS: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. CONCLUSIONS: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.
BACKGROUND: The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies. METHODS: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009. Eligible patients underwent five courses of induction chemotherapy followed by high-dose chemotherapy with hematopoietic stem cell rescue. Surgery for the primary tumor was scheduled after three or four courses of induction chemotherapy. Radiotherapy was administered to the primary tumor site and to any bone metastases present at the end of induction chemotherapy. RESULTS: The estimated 3-year progression-free and overall survival rates of the 50 patients enrolled were 36.5 ± 7.0 and 69.5 ± 6.6%, respectively. High-dose chemotherapy caused severe toxicity including three treatment-related deaths. In response to this, the high-dose chemotherapy regimen was modified during the trial by infusing melphalan before administering carboplatin and etoposide. The modified high-dose chemotherapy regimen was less toxic. Univariate analysis revealed that patients younger than 547 days and patients whose tumor showed a whole chromosomal gains / losses pattern had a significantly poor prognosis. Notably, the progression-free survival of cases with MYCN amplification were not inferior to those without MYCN amplification. CONCLUSIONS: The outcome of patients treated with the JN-H-07 protocol showed improvement over the results reported by previous studies conducted in Japan. Molecular and genetic profiling may enable a more precise stratification of the high-risk cohort.
Entities:
Keywords:
Clinical trial; Genomic signature; High-risk; Multidisciplinary treatment; Neuroblastoma; Surgery
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