Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.
目的： 探讨三氧化二砷（ATO）联合改良N7诱导方案治疗初治高危神经母细胞瘤（NB）的短期临床疗效及安全性。 方法： 前瞻性、单臂、多中心Ⅱ期临床研究。以2019年1月至2023年8月中山大学孙逸仙纪念医院、华中科技大学同济医学院附属武汉儿童医院、广西医科大学第一附属医院、海南省人民医院、广东医科大学附属医院、昆明市儿童医院、华中科技大学同济医学院附属同济医院、广东省农垦中心医院8家单位收治的67例高危NB患儿为研究对象，均予ATO联合改良N7诱导方案化疗，对诱导化疗结束时的疗效及不良反应进行评估及分析，根据疗效评估结果分为治疗有反应组及治疗无反应组，采用Fisher确切概率法比较两组患儿临床特征的差异。 结果： 67例高危NB患儿中男40例（60%）、女27例（40%）；发病年龄3.5（2.6，4.8）岁；原发灶大多在腹膜后（含肾上腺）（56/67，84%）；初诊时伴有远处淋巴结转移25例（37%）、骨转移48例（72%）、骨髓转移56例（84%）、中枢神经系统转移3例（4%）；检测出MYCN基因扩增28例（42%）。在诱导化疗结束时完全缓解33例（49%），部分缓解29例（43%），疾病稳定1例（1%），疾病进展4例（6%）；诱导化疗结束时客观缓解率为93%（62/67），疾病控制率为94%（63/67）。治疗无反应组初诊时中枢神经系统转移占比高于治疗有反应组［2/5比 2%（1/62），P=0.013］，而MYCN基因扩增情况在两组间差异无统计学意义［3/5比40%（25/62），P=0.786］。诱导化疗期间发生Ⅲ级及以上的不良反应有骨髓抑制60例（90%）、胃肠道症状33例（49%）、感染20例（30%），肝毒性4例（6%）和心血管毒性1例（2%），未出现与化疗相关的死亡。 结论： ATO联合改良N7诱导方案具有良好的疗效及安全性，值得在临床中进一步推广。.