背景：高剂量化疗和自体干细胞移植（HDCT/auto-SCT）和131I-间碘苄基胍（131I-MIBG）治疗在高危神经母细胞瘤中显示出积极的结果。然而,仍需要更优化的治疗策略。
方法：NB-2014研究是非随机的，前瞻性试验检查转移性高危神经母细胞瘤患者使用响应适应巩固治疗的生存结局。我们使用转移部位的诱导后残留123I-MIBG状态作为治疗反应标记。在转移部位实现MIBG摄取完全消退的患者经历了减少的第一次HDCT/auto-SCT,HDCT剂量减少20%。在第一次HDCT/自动SCT之后，MIBG摄取剩余的患者接受剂量递增(18mCi/kg)131I-MIBG治疗.相比之下,转移部位MIBG完全消退的患者接受标准剂量(12mCi/kg)的131I-MIBG.我们将生存和毒性结果与NB-2009的历史对照组进行了比较。
结果：在接受治疗的65例患者中，63%的人在诱导化疗后转移部位获得MIBG摄取的完全缓解，而29%的患者在首次HDCT/auto-SCT后仍在转移部位摄取MIBG。3年无事件生存率（EFS）和总生存率（OS）分别为68.2％±6.0％和86.5％±4.5％，分别。与NB-2009相比，EFS相似(p=.855)；然而，NB-2014具有更高的OS（p=.031），治疗相关死亡率的累积发生率较低（p=.036），和较少的急性和晚期毒性。
结论：我们的结果表明，基于转移部位化疗反应的反应适应性巩固治疗有利于更好的治疗剪裁，对于转移性高危神经母细胞瘤患者似乎很有希望。
BACKGROUND: Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed.
METHODS: The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18 mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009.
RESULTS: Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB-2009, EFS was similar (p = .855); however, NB-2014 had a higher OS (p = .031), a lower cumulative incidence of treatment-related mortality (p = .036), and fewer acute and late toxicities.
CONCLUSIONS: Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.
