Clinical efficacy of combined therapy in children with stage 4 neuroblastoma

LIANG Wei-Ling, YE Xiao-Fan, ZHONG Gong, CHEN Jian-Jun, DAI Kang-Lin, CHEUK Ka Leung Daniel, MO Shu, WANG Bo-Shen, LI Chun-Yu, JIANG Xuan-Zhu, XU Zhi-Yuan, ZHOU Li, CHAN Irene, CHEN Jian-Liang, CHU Patrick., LEE Pui Wah Pamela, CHAN Chi Fung Godfrey

Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (7) : 759-764.

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Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (7) : 759-764. DOI: 10.7499/j.issn.1008-8830.2203049
CLINICAL RESEARCH

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma

  • LIANG Wei-Ling, YE Xiao-Fan, ZHONG Gong, CHEN Jian-Jun, DAI Kang-Lin, CHEUK Ka Leung Daniel, MO Shu, WANG Bo-Shen, LI Chun-Yu, JIANG Xuan-Zhu, XU Zhi-Yuan, ZHOU Li, CHAN Irene, CHEN Jian-Liang, CHU Patrick., LEE Pui Wah Pamela, CHAN Chi Fung Godfrey
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Abstract

Objective To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. Methods A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. Results The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. Conclusions Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Key words

Neuroblastoma / Hematopoietic stem cell transplantation / Ch14.18/CHO / Child

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LIANG Wei-Ling, YE Xiao-Fan, ZHONG Gong, CHEN Jian-Jun, DAI Kang-Lin, CHEUK Ka Leung Daniel, MO Shu, WANG Bo-Shen, LI Chun-Yu, JIANG Xuan-Zhu, XU Zhi-Yuan, ZHOU Li, CHAN Irene, CHEN Jian-Liang, CHU Patrick., LEE Pui Wah Pamela, CHAN Chi Fung Godfrey. Clinical efficacy of combined therapy in children with stage 4 neuroblastoma[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(7): 759-764 https://doi.org/10.7499/j.issn.1008-8830.2203049

References

1 Zhang S, Zhang W, Jin M, et al. Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing[J]. Eur J Pediatr, 2021, 180(7): 2055-2063. PMID: 33580827. DOI: 10.1007/s00431-021-03989-1.
2 Khan S, AlSayyad K, Siddiqui K, et al. Pediatric high risk neuroblastoma with autologous stem cell transplant—20 years of experience[J]. Int J Pediatr Adolesc Med, 2021, 8(4): 253-257. PMID: 34401451. PMCID: PMC8356102. DOI: 10.1016/j.ijpam.2021.02.006.
3 Applebaum MA, Vaksman Z, Lee SM, et al. Neuroblastoma survivors are at increased risk for second malignancies: a report from the International Neuroblastoma Risk Group Project[J]. Eur J Cancer, 2017, 72: 177-185. PMID: 28033528. PMCID: PMC5258837. DOI: 10.1016/j.ejca.2016.11.022.
4 张婷, 李艳华, 李珊珊, 等. 单中心儿童神经母细胞瘤4期患者临床疗效及预后分析[J]. 中国小儿血液与肿瘤杂志, 2020, 25(3): 153-158. DOI: 10.3969/j.issn.1673-5323.2020.03.007.
5 Siebert N, Zumpe M, Jüttner M, et al. PD-1 blockade augments anti-neuroblastoma immune response induced by anti-GD2 antibody ch14.18/CHO[J]. Oncoimmunology, 2017, 6(10): e1343775. PMID: 29123953. PMCID: PMC5665083. DOI: 10.1080/2162402X.2017.1343775.
6 袁晓军, 钱晓文, 李杰, 等. GD2单抗治疗中国高危及复发难治神经母细胞瘤儿童的临床研究初探[J]. 中华转移性肿瘤杂志, 2022, 5(1): 14-20. DOI:10.3760/cma.j.cn101548-20220109-00006.
7 Berthold F , Rosswog C , Christiansen H, et al. Clinical and molecular characterization of patients with stage 4(M) neuroblastoma aged less than 18 months without MYCN amplification[J]. Pediatr Blood Cancer, 2021, 68(8): e29038. PMID: 33826231. DOI:10.1002/pbc.29038.
8 Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment[J]. J Clin Oncol, 1993, 11(8): 1466-1477. PMID: 8336186. DOI:10.1200/JCO.1993.11.8.1466.
9 刘涛, 盛庆丰, 刘江斌, 等. INSS 4期神经母细胞瘤患儿3年无事件生存率的相关因素分析[J]. 临床小儿外科杂志, 2022, 21(2): 121-127. DOI: 10.3760/cma.j.cn.101785-202011036-005.
10 Li F, Zhang W, Hu H, et al. Factors of recurrence after complete response in children with neuroblastoma: a 16-year retrospective study of 179 cases[J]. Cancer Manag Res, 2022, 14: 107-122. PMID: 35023974. PMCID: PMC8747547. DOI: 10.2147/CMAR.S343648.
11 Ohira M, Nakamura Y, Takimoto T, et al. Retrospective analysis of INRG clinical and genomic factors for 605 neuroblastomas in Japan: a report from the Japan Children's Cancer Group Neuroblastoma Committee (JCCG-JNBSG)[J]. Biomolecules, 2021, 12(1): 18. PMID: 35053166. PMCID: PMC8774029. DOI: 10.3390/biom12010018.
12 Georgantzi K, Sk?ldenberg EG, Stridsberg M, et al. Chromogranin A and neuron-specific enolase in neuroblastoma: correlation to stage and prognostic factors[J]. Pediatr Hematol Oncol, 2018, 35(2): 156-165. PMID: 29737901. DOI: 10.1080/08880018.2018.1464087.
13 Sokol E, Desai AV, Applebaum MA, et al. Age, diagnostic category, tumor grade, and mitosis-karyorrhexis index are independently prognostic in neuroblastoma: an INRG project[J]. J Clin Oncol, 2020, 38(17): 1906-1918. PMID: 32315273. PMCID: PMC7280049. DOI: 10.1200/JCO.19.03285.
14 van Heerden J, Kruger M. Management of neuroblastoma in limited-resource settings[J]. World J Clin Oncol, 2020, 11(8): 629-643. PMID: 32879849. PMCID: PMC7443833. DOI: 10.5306/wjco.v11.i8.629.
15 阿衣古丽·阿巴斯, 古丽苏木汗·阿布来提, 曹静, 等. 89例小儿神经母细胞瘤的预后及影响因素分析[J]. 癌症进展, 2019, 17(24): 2984-2986, 2990. DOI: 10.11877/j.issn.1672-1535.2019.17.24.31.
16 周宇晨, 苏雁, 蒋持怡, 等. Ⅳ期高危神经母细胞瘤患儿局部放疗疗效分析[J]. 中华放射肿瘤学杂志, 2019, 28(4): 258-261. DOI: 10.3760/cma.j.issn.1004-4221.2019.04.003.
17 Uehara S, Yoneda A, Oue T, et al. Role of surgery in delayed local treatment for INSS 4 neuroblastoma[J]. Pediatr Int, 2017, 59(9): 986-990. PMID: 28643949. DOI: 10.1111/ped.13349.
18 Casey DL, Pitter KL, Kushner BH, et al. Radiation therapy to sites of metastatic disease as part of consolidation in high-risk neuroblastoma: can long-term control be achieved?[J]. Int J Radiat Oncol Biol Phys, 2018, 100(5): 1204-1209. PMID: 29439882. PMCID: PMC5934297. DOI: 10.1016/j.ijrobp.2018.01.008.
19 朱富艺, 闫杰, 曹嫣娜, 等. 血清神经元特异性烯醇化酶和尿香草扁桃酸与神经母细胞瘤临床病理特征的相关性[J]. 中国肿瘤临床, 2019, 46(22): 1160-1166. DOI: 10.3969/j.issn.1000-8179.2019.22.080.
20 赵倩, 马晓莉, 李兴军, 等. 肿瘤标记物联合检测在儿童神经母细胞瘤诊治中的意义[J].中国小儿血液与肿瘤杂志, 2013, 18(2): 65-68. DOI: 10.3969/j.issn.1673-5323.2013.02.005.
21 Zhao ZS, Shao W, Liu JK. Autologous or allogeneic hematopoietic stem cells transplantation combined with high-dose chemotherapy for refractory neuroblastoma: a protocol for systematic review and meta-analysis[J]. Medicine (Baltimore), 2021, 100(49): e28096. PMID: 34889262. PMCID: PMC8663834. DOI: 10.1097/MD.0000000000028096.
22 Johnsen JI, Dyberg C, Fransson S, et al. Molecular mechanisms and therapeutic targets in neuroblastoma[J]. Pharmacol Res, 2018, 131: 164-176. PMID: 29466695. DOI: 10.1016/j.phrs.2018.02.023.
23 GD2单抗治疗神经母细胞瘤临床应用协作组. GD2抗体达妥昔单抗β治疗神经母细胞瘤的临床应用专家共识(2021年版)[J]. 临床儿科杂志, 2022, 40(1): 14-20. DOI: 10.12372/jcp.2022.21e1685.
24 Nguyen R, Thiele CJ. Immunotherapy approaches targeting neuroblastoma[J]. Curr Opin Pediatr, 2021, 33(1): 19-25. PMID: 33315686. PMCID: PMC8818321. DOI: 10.1097/MOP.0000000000000982.
25 Ladenstein R, P?tschger U, Valteau-Couanet D, et al. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial[J]. Lancet Oncol, 2018, 19(12): 1617-1629. PMID: 30442501. DOI: 10.1016/S1470-2045(18)30578-3.
26 Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma[J]. N Engl J Med, 2010, 363(14): 1324-1334. PMID: 20879881. PMCID: PMC3086629. DOI: 10.1056/NEJMoa0911123.
27 Jazmati D, Butzer S, Hero B, et al. Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004[J]. Strahlenther Onkol, 2021, 197(8): 683-689. PMID: 33300099. PMCID: PMC8292260. DOI: 10.1007/s00066-020-01718-5.
28 Tian X, Cao Y, Wang J, et al. A single center clinical analysis of children with high-risk neuroblastoma[J]. Oncotarget, 2017, 8(18): 30357-30368. PMID: 28423674. PMCID: PMC5444748.DOI: 10.18632/oncotarget.15996.
29 朱呈光, 贺湘玲, 汤止戈, 等. 44例儿童神经母细胞瘤临床分析[J]. 中国当代儿科杂志, 2020, 22(11): 1193-1197. PMID: 33172554. PMCID: PMC7666396. DOI: 10.7499/j.issn.1008-8830.2005053.
30 苏雁, 马晓莉, 王焕民, 等. 单中心458例高危神经母细胞瘤患儿临床特征及预后分析[J]. 中华儿科杂志, 2020, 58(10): 796-801. PMID: 32987457. DOI: 10.3760/cma.j.cn112140-20200525-00540.
31 张朝霞, 钟笛箫, 李君惠, 等. 自体造血干细胞移植治疗高危神经母细胞瘤临床分析[J]. 北京医学, 2020, 42(11): 1075-1079. DOI: 10.15932/j.0253-9713.2020.11.008.
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