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High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan

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Abstract

Objective

The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or relapsed neuroblastoma (NBL) in Japan.

Methods

We retrospectively analyzed 20 patients with refractory or relapsed high-risk NBL who underwent 131I-MIBG therapy with an administration dose ranging from 444 to 666 MBq/kg at Kanazawa University Hospital, Japan, between September 2008 and September 2013. We focused on measurements regarding their initial responses, prognostic factors, survivals, and toxicities following 131I-MIBG therapy using our hospital data and questionnaires from the hospitals that these patients were initially referred from. Furthermore, we performed Kaplan–Meier survival analysis to evaluate event-free survival (EFS) and overall survival (OS).

Results

In 19 patients with complete follow-up data, the median age at first 131I-MIBG treatment was 7.9 years (range 2.5–17.7 years). Following 131I-MIBG therapy, 17 of the 19 patients underwent stem-cell transplantations, and their treatment response was either complete (CR) or partial (PR) in three and two cases, respectively. The EFS and OS rates at 1 year following 131I-MIBG therapy were 42% and 58%, respectively, and those at 5 years following 131I-MIBG therapy were 16% and 42%, respectively. Using the two-sample log-rank test, the OS time following 131I-MIBG therapy was significantly longer for < 3-year time interval between the initial diagnosis and 131I-MIBG therapy (p = 0.017), Curie score < 16 just before 131I-MIBG therapy (p = 0.002), without pain (p = 0.002), without both vanillylmandelic acid (VMA) and homovanillic acid (HVA) elevation (p = 0.037) at 131I-MIBG therapy, and with CR or PR following 131I-MIBG therapy (p = 0.015). Although severe hematological toxicities were identified in all 19 patients, severe nonhematological toxicity was not recorded in any patient, except for one patient with grade 3 anorexia and nausea.

Conclusions

High-dose 131I-MIBG therapy in patients with refractory or relapsed high-risk NBL can provide a favorable prognosis without severe nonhematological toxicities. Better prognosis may be anticipated in patients with the initial good response, no pain at 131I-MIBG therapy, no VMA and HVA elevation at 131I-MIBG therapy, low Curie score (< 16) just before 131I-MIBG therapy, and short time interval (< 3 years) between the initial diagnosis and 131I-MIBG therapy.

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References

  1. Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Mattay KK, et al. Children's Oncology Group's 2013 blueprint for research: neuroblastoma. Pediatr Blood Cancer. 2013;60:985–93.

    Article  Google Scholar 

  2. Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6:649–58.

    Article  CAS  Google Scholar 

  3. Mueller S, Matthay KK. Neuroblastoma: biology and staging. Curr Oncol Rep. 2009;11:431–8.

    Article  Google Scholar 

  4. Treuner J, Klingebiel T, Feine U, Buck J, Bruchelt G, Dopfer R, et al. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Pediatr Hematol Oncol. 1986;3:205–16.

    Article  CAS  Google Scholar 

  5. Kayano D, Kinuya S. Iodine-131 metaiodobenzylguanidine therapy for neuroblastoma: reports so far and future perspective. Sci World J. 2015;2015:189135.

    Article  Google Scholar 

  6. Matthay KK, DeSantes K, Hasegawa B, Huberty J, Hattner RS, Ablin A, et al. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol. 1998;16:229–36.

    Article  CAS  Google Scholar 

  7. Matthay KK, Yanik G, Messina J, Quach A, Huberty J, Cheng SC, et al. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. J Clin Oncol. 2007;25:1054–60.

    Article  CAS  Google Scholar 

  8. Wakabayashi H, Taki J, Inaki A, Nakamura A, Kayano D, Fukuoka M, et al. Prognostic values of initial responses to low-dose 131I-MIBG therapy in patients with malignant pheochromocytoma and paraganglioma. Ann Nucl Med. 2013;27:839–46.

    Article  CAS  Google Scholar 

  9. Yoshinaga K, Oriuchi N, Wakabayashi H, Tomiyama Y, Jinguji M, Higuchi T, et al. Effects and safety of 131I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry. Endocr J. 2014;61:1171–80.

    Article  CAS  Google Scholar 

  10. Giammarile F, Chiti A, Lassmann M, Brans B, Flux G. EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy. Eur J Nucl Med Mol Imaging. 2008;35:1039–47.

    Article  CAS  Google Scholar 

  11. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  Google Scholar 

  12. Ady N, Zucker JM, Asselain B, Edeline V, Bonnin F, Michon J, et al. A new 123I-MIBG whole body scan scoring method–application to the prediction of the response of metastases to induction chemotherapy in stage IV neuroblastoma. Eur J Cancer. 1995;31:256–61.

    Article  Google Scholar 

  13. Matthay KK, Shulkin B, Ladenstein R, Michon J, Giammarile F, Lewington V, et al. Criteria for evaluation of disease extent by 123I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer. 2010;102:1319–26.

    Article  CAS  Google Scholar 

  14. Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006;24:500–6.

    Article  CAS  Google Scholar 

  15. DuBois SG, Chesler L, Groshen S, Hawkins R, Goodarzian F, Shimada H, et al. Phase I study of vincristine, irinotecan, and 131I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial. Clin Cancer Res. 2012;18:2679–86.

    Article  CAS  Google Scholar 

  16. DuBois SG, Allen S, Bent M, Hilton JF, Hollinger F, Hawkins R, et al. Phase I/II study of 131I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma. Br J Cancer. 2015;112:644–9.

    Article  CAS  Google Scholar 

  17. Genolla J, Rodriguez T, Minguez P, Lopez-Almaraz R, Llorens V, Echebarria A. Dosimetry-based high-activity therapy with 131I-metaiodobenzylguanidine (131I-mIBG) and topotecan for the treatment of high-risk refractory neuroblastoma. Eur J Nucl Med Mol Imaging. 2019;46:1567–75.

    Article  CAS  Google Scholar 

  18. Lumbroso J, Hartmann O, Schlumberger M. Therapeutic use of 131I-metaiodobenzylguanidine in neuroblastoma: a phase II study in 26 patients: "Societe Francaise d'Oncologie Pediatrique” and Nuclear Medicine Co-investigators. J Nucl Biol Med. 1991;35:220–3.

    CAS  PubMed  Google Scholar 

  19. Weyl Ben-Arush M, Ben Barak A, Bar-Deroma R, Ash S, Goldstein G, Golan H, et al. Targeted therapy with low doses of 131I-MIBG is effective for disease palliation in highly refractory neuroblastoma. Isr Med Assoc J. 2013;15:31–4.

    PubMed  Google Scholar 

  20. Modak S, Zanzonico P, Carrasquillo JA, Kushner BH, Kramer K, Cheung NK, et al. Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study. J Nucl Med. 2016;57:231–7.

    Article  CAS  Google Scholar 

  21. Hishiki T, Matsumoto K, Ohira M, Kamijo T, Shichino H, Kuroda T, et al. Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG). Int J Clin Oncol. 2018;23:965–73.

    Article  Google Scholar 

  22. Zhou MJ, Doral MY, DuBois SG, Villablanca JG, Yanik GA, Matthay KK. Different outcomes for relapsed versus refractory neuroblastoma after therapy with 131I-metaiodobenzylguanidine (131I-MIBG). Eur J Cancer. 2015;51:2465–72.

    Article  CAS  Google Scholar 

  23. Bleeker G, Schoot RA, Caron HN, de Kraker J, Hoefnagel CA, van Eck BL, et al. Toxicity of upfront 131I-metaiodobenzylguanidine (131I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis. Eur J Nucl Med Mol Imaging. 2013;40:1711–7.

    Article  CAS  Google Scholar 

  24. Kayano D, Kinuya S. Current Consensus on I-131 MIBG Therapy. Nucl Med Mol Imaging. 2018;52:254–65.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank all staffs of East 2 Ward at Kanazawa University Hospital, Japan, for supporting 131I-MIBG therapy.

Funding

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Authors and Affiliations

  1. Department of Nuclear Medicine, Kanazawa University Hospital and Department of Nuclear Medicine, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Daiki Kayano, Hiroshi Wakabayashi, Anri Inaki, Ayane Toratani, Norihito Akatani, Takafumi Yamase, Yuji Kunita, Tomo Hiromasa, Aki Takata, Hiroshi Mori, Shintaro Saito, Junichi Taki & Seigo Kinuya

  2. Department of Functional Imaging and Artificial Intelligence, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Kenichi Nakajima & Satoru Watanabe

  3. Department of Pediatrics, Kanazawa University Hospital and Department of Pediatrics, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Rie Kuroda

  4. Department of Radiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa, 920-0293, Japan

    Takafumi Yamase

  5. Department of Pediatrics, Ishikawa Prefectural Central Hospital, 2-1 Kuratsuki-Higashi, Kanazawa, Ishikawa, 920-8530, Japan

    Raita Araki

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  1. Daiki Kayano
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  2. Hiroshi Wakabayashi
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Corresponding author

Correspondence to Daiki Kayano.

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Conflict of interest

S. K. has a funded research collaboration with FUJIFILM Toyama Chemical Co., Ltd. The remaining authors declare that there is no conflict of interest regarding the publication of this article.

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Kayano, D., Wakabayashi, H., Nakajima, K. et al. High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan. Ann Nucl Med 34, 397–406 (2020). https://doi.org/10.1007/s12149-020-01460-z

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  • DOI: https://doi.org/10.1007/s12149-020-01460-z

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