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Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma

Received: 13 March 2021     Accepted: 27 March 2021     Published: 7 April 2021
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Abstract

Background: High-risk Neuroblastoma (N. B) patients have a poor outcome with 5-year survival rates of 50%. Patients with stage 4 disease or MYC-N amplification showed post-progression 5y O. S. of 7% to 8%. Other studies proved the same dismal outcome in high-risk relapsed patients. This study aimed to detect the O. S. and EFS of N. B patients post-progression. Secondary to explore, if initial prognostic factors, high-intensity salvage therapy and other treatment modalities could improve the outcome of progressive /refractory disease. Methods: Seventy patients of high-risk Neuroblastoma needed salvage therapy, either due to refractory/progressive disease or irresectability of the primary tumor. Initial prognostic factors and different treatment strategies were collected and correlated with the outcome. Results: Fifty-seven (57 /70) patients died from progressive disease with a median survival of 20.6 months with three y EFS and O. S. of 9.5% and 35.7%, respectively. Objective response (CR/VGPR/PR) post-induction, consolidation by HSCT, radiotherapy, and maintenance therapy; affected survival significantly post salvage therapy. Multivariate analysis revealed that the only independent factor that significantly affected O. S was maintenance therapy. The independent factors that affected the EFS negatively were the presence of liver metastases, poor response post-induction, and not administering radiotherapy. Conclusion: Response to induction had a significant impact on the outcome post salvage. Salvage therapy did not improve the outcome for those with inadequate induction response. Initial front-line targeted therapy like antiGD2 is needed to improve the outcome, especially for chemo-resistant ones.

Published in Cancer Research Journal (Volume 9, Issue 2)
DOI 10.11648/j.crj.20210902.11
Page(s) 85-91
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Salvage, Neuroblastoma, High Risk-Low Middle, Income Countries

References
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[3] Parikh NS, Howard SC, Chantada G, et al (2015). SIOP-PODC adapted risk stratification and treatment guidelines: Recommendations for Neuroblastoma in low-and-middle-income settings. Pediatric blood cancer, 62, 1305-6.
[4] Greengard E, Hill KC, Bagatell R, (2013). Treatment of high-risk Neuroblastoma in children: recent clinical trial results. Clinical. Invest, 3, 1071–1.
[5] Kushner H B, Modak S, Kramer K, et al (2013). High-dose salvage regimen and review of the literature. Cancer, 119, 665-1.
[6] Lau L, Tai D, Weitzman S, et al (2004). Factors influencing survival in children with recurrent Neuroblastoma. J Pediatr Hematol Oncol, 26, 227–2.
[7] Santana VM, Furman WL, McGregor LM, Catherine A Billups, (2008). Disease control intervals in high-risk Neuroblastoma. Cancer, 112, 2796–1.
[8] Garaventa A, Parodi S, De Bernardi B, et al (2009). The outcome of children with Neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry, Eur J Cancer 45, 2723-2.
[9] Zhou JM, Doral YM, Du Bois SG, et al (2015). Different outcomes for relapsed vs. refractory Neuroblastoma after therapy with 131I-metaiodobenzylguanidine (131I-MIBG). Eur J Cancer, 51, 2465–2.
[10] Bergeron C, Dubourg L, Chastagner P, et al (2005). Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: Results of the SFOP NBL90 study. Pediatr Blood Cancer, 45, 32–6.
[11] Fischer J, Pohl A, Volland R, et al (2017). Complete surgical resection improves outcome in INRG high-risk patients with localized Neuroblastoma older than 18 months. BMC Cancer, 17,520Kubota M, Yagi M, Kanada S, et al (2004). Long-term follow-up status of patients with Neuroblastoma after undergoing either aggressive surgery or chemotherapy—a single institutional study. J. Pediatr. Surg, 39, 1328-2.
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[13] Seeger RC, Reynolds CP, Gallego R, et al (2000). Quantitative tumor cell content of bone marrow and blood as a predictor of outcome in stage IV neuroblastoma: a Children's Cancer Group Study. J Clin Oncol, 18, 4067–6.
[14] Jennifer M., Irene IP, Benjamin AF, et al (2016). Salvage Rates after Progression of High-Risk Neuroblastoma with a Soft Tissue Mass. J Pediatric Surg, 51, 285–8.
[15] Basta ON, Halliday GC, Makin G, et al (2016). Factors associated with recurrence and survival length following a relapse in patients with Neuroblastoma. Br J Cancer, 115, 1048 –7.
[16] Pinto N, Naranjo A, Hibbitts E, et al (2019). Predictors of differential response to induction therapy in high-risk Neuroblastoma: A report from the Children's Oncology Group (COG). Eur J Cancer, 112, 66–9.
[17] Abdel Rahman H, Moussa EA, Zekri WK, et al (2011). Did Salvage ICE Chemotherapy Improve the Outcome in Primary Resistant/Relapsing Stage III/IV Neuroblastoma? J. Egypt. Nat. Cancer Inst, 23, 47–3.
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    Ahmed Elhemaly, Ahmed Fathalla, Mahmed Elhusseny, Mohamed Fawzy. (2021). Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma. Cancer Research Journal, 9(2), 85-91. https://doi.org/10.11648/j.crj.20210902.11

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    ACS Style

    Ahmed Elhemaly; Ahmed Fathalla; Mahmed Elhusseny; Mohamed Fawzy. Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma. Cancer Res. J. 2021, 9(2), 85-91. doi: 10.11648/j.crj.20210902.11

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    AMA Style

    Ahmed Elhemaly, Ahmed Fathalla, Mahmed Elhusseny, Mohamed Fawzy. Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma. Cancer Res J. 2021;9(2):85-91. doi: 10.11648/j.crj.20210902.11

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  • @article{10.11648/j.crj.20210902.11,
      author = {Ahmed Elhemaly and Ahmed Fathalla and Mahmed Elhusseny and Mohamed Fawzy},
      title = {Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma},
      journal = {Cancer Research Journal},
      volume = {9},
      number = {2},
      pages = {85-91},
      doi = {10.11648/j.crj.20210902.11},
      url = {https://doi.org/10.11648/j.crj.20210902.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20210902.11},
      abstract = {Background: High-risk Neuroblastoma (N. B) patients have a poor outcome with 5-year survival rates of 50%. Patients with stage 4 disease or MYC-N amplification showed post-progression 5y O. S. of 7% to 8%. Other studies proved the same dismal outcome in high-risk relapsed patients. This study aimed to detect the O. S. and EFS of N. B patients post-progression. Secondary to explore, if initial prognostic factors, high-intensity salvage therapy and other treatment modalities could improve the outcome of progressive /refractory disease. Methods: Seventy patients of high-risk Neuroblastoma needed salvage therapy, either due to refractory/progressive disease or irresectability of the primary tumor. Initial prognostic factors and different treatment strategies were collected and correlated with the outcome. Results: Fifty-seven (57 /70) patients died from progressive disease with a median survival of 20.6 months with three y EFS and O. S. of 9.5% and 35.7%, respectively. Objective response (CR/VGPR/PR) post-induction, consolidation by HSCT, radiotherapy, and maintenance therapy; affected survival significantly post salvage therapy. Multivariate analysis revealed that the only independent factor that significantly affected O. S was maintenance therapy. The independent factors that affected the EFS negatively were the presence of liver metastases, poor response post-induction, and not administering radiotherapy. Conclusion: Response to induction had a significant impact on the outcome post salvage. Salvage therapy did not improve the outcome for those with inadequate induction response. Initial front-line targeted therapy like antiGD2 is needed to improve the outcome, especially for chemo-resistant ones.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Impact of Initial Prognostic Factors and Intensity of Salvage Therapy on the Outcome of Progressive / Refractory High-Risk Neuroblastoma
    AU  - Ahmed Elhemaly
    AU  - Ahmed Fathalla
    AU  - Mahmed Elhusseny
    AU  - Mohamed Fawzy
    Y1  - 2021/04/07
    PY  - 2021
    N1  - https://doi.org/10.11648/j.crj.20210902.11
    DO  - 10.11648/j.crj.20210902.11
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 85
    EP  - 91
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20210902.11
    AB  - Background: High-risk Neuroblastoma (N. B) patients have a poor outcome with 5-year survival rates of 50%. Patients with stage 4 disease or MYC-N amplification showed post-progression 5y O. S. of 7% to 8%. Other studies proved the same dismal outcome in high-risk relapsed patients. This study aimed to detect the O. S. and EFS of N. B patients post-progression. Secondary to explore, if initial prognostic factors, high-intensity salvage therapy and other treatment modalities could improve the outcome of progressive /refractory disease. Methods: Seventy patients of high-risk Neuroblastoma needed salvage therapy, either due to refractory/progressive disease or irresectability of the primary tumor. Initial prognostic factors and different treatment strategies were collected and correlated with the outcome. Results: Fifty-seven (57 /70) patients died from progressive disease with a median survival of 20.6 months with three y EFS and O. S. of 9.5% and 35.7%, respectively. Objective response (CR/VGPR/PR) post-induction, consolidation by HSCT, radiotherapy, and maintenance therapy; affected survival significantly post salvage therapy. Multivariate analysis revealed that the only independent factor that significantly affected O. S was maintenance therapy. The independent factors that affected the EFS negatively were the presence of liver metastases, poor response post-induction, and not administering radiotherapy. Conclusion: Response to induction had a significant impact on the outcome post salvage. Salvage therapy did not improve the outcome for those with inadequate induction response. Initial front-line targeted therapy like antiGD2 is needed to improve the outcome, especially for chemo-resistant ones.
    VL  - 9
    IS  - 2
    ER  - 

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Author Information
  • Pediatric Oncology, National Cancer Institute (NCI)-Cairo University and Children Cancer Hospital of Egypt (CCHE), Cairo, Egypt

  • Surgical Oncology, National Cancer Institute, Cairo, Egypt

  • Pediatric Oncology, Children cancer Hospital of Egypt, Cairo, Egypt

  • Pediatric Oncology, National Cancer Institute (NCI)-Cairo University and Children Cancer Hospital of Egypt (CCHE), Cairo, Egypt

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