Abstract：
OBJECTIVE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity.
METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications.
RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%].
CONCLUSIONS: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.
METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications.
RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%].
CONCLUSIONS: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.
摘要：
目的：高危神经母细胞瘤患者的生存率是不可接受的。日本已经开发了一种时间强化治疗策略，即延迟局部治疗以控制全身性疾病。我们在全国范围内进行了一次，prospective,延迟局部治疗的单臂临床试验。这项研究评估了延迟手术以增加治疗强度的安全性和有效性。
方法：2011年5月至2015年9月，75例高危神经母细胞瘤患者纳入本研究。延迟的局部治疗包括五个疗程的诱导化疗（顺铂，吡柔比星,长春新碱,和环磷酰胺）和清髓性高剂量化疗（美法仑，依托泊苷,和卡铂)，随后通过手术和放疗进行局部肿瘤切除。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS），响应率,不良事件,和手术并发症。
结果：纳入75例患者，64个可评估(第3阶段，n=8；第4阶段，n=56)。估计的3年PFS和OS率(95%置信区间[CI])分别为44.4%[31.8%-56.3%]和80.7%[68.5%-88.5%]。具体而言。完成治疗方案后INRC的反应率为66％（42/64;95％CI：53％-77％;23CR[完全反应]，10VGPR[非常好的部分响应]，和九个公关[部分响应])。没有患者在方案治疗期间或完成后30天内死亡。4级不良反应,排除血液学不良反应，48%的患者发生[31/64；95%CI：36%-61%]。在25％的患者中观察到主要的手术并发症[13/51;95％CI：14％-40％]。
结论：这项研究表明，延迟局部治疗是可行的，并显示出有希望的疗效，提示在对高危神经母细胞瘤的比较研究中，应进一步考虑这种治疗方法。
方法：2011年5月至2015年9月，75例高危神经母细胞瘤患者纳入本研究。延迟的局部治疗包括五个疗程的诱导化疗（顺铂，吡柔比星,长春新碱,和环磷酰胺）和清髓性高剂量化疗（美法仑，依托泊苷,和卡铂)，随后通过手术和放疗进行局部肿瘤切除。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS），响应率,不良事件,和手术并发症。
结果：纳入75例患者，64个可评估(第3阶段，n=8；第4阶段，n=56)。估计的3年PFS和OS率(95%置信区间[CI])分别为44.4%[31.8%-56.3%]和80.7%[68.5%-88.5%]。具体而言。完成治疗方案后INRC的反应率为66％（42/64;95％CI：53％-77％;23CR[完全反应]，10VGPR[非常好的部分响应]，和九个公关[部分响应])。没有患者在方案治疗期间或完成后30天内死亡。4级不良反应,排除血液学不良反应，48%的患者发生[31/64；95%CI：36%-61%]。在25％的患者中观察到主要的手术并发症[13/51;95％CI：14％-40％]。
结论：这项研究表明，延迟局部治疗是可行的，并显示出有希望的疗效，提示在对高危神经母细胞瘤的比较研究中，应进一步考虑这种治疗方法。
