Nickerson H J, Matthay K K, Seeger R C, Brodeur G M, Shimada H, Perez C, Atkinson J B, Selch M, Gerbing R B, Stram D O, Lukens J
Department of Pediatrics, Marshfield Clinic, Marshfield, WI, USA.
J Clin Oncol. 2000 Feb;18(3):477-86. doi: 10.1200/JCO.2000.18.3.477.
Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy.
Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined.
Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age </= 3 months at diagnosis was significant for EFS (P =. 043), it was less significant for survival (P =.077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival.
This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.
IV-S期神经母细胞瘤是一种伴有自发消退且生存率良好的转移性疾病，但10%至20%的婴儿死于早期并发症。本研究的目的是评估仅接受支持性治疗或对有症状的患者采用低剂量细胞毒性疗法进行前瞻性治疗的IV-S期神经母细胞瘤婴儿的预后及预后因素。
对80例符合条件的婴儿进行研究，观察其接受支持性治疗后的反应和生存情况，对于有症状的患者，给予环磷酰胺5mg/kg/d，连用5天，同时或不同时在3天内给予4.5Gy的肝脏放疗。分期由中心进行复查，并测定MYCN基因拷贝数、岛田组织病理学分类、血清铁蛋白水平和骨髓免疫细胞检查结果。
IV-S期与国际神经母细胞瘤分期系统4S期的一致性为98%。在所检测的任何肿瘤中（n = 58），MYCN均未扩增，96%（n = 68/71）的肿瘤岛田组织病理学分类为良好。所有婴儿的5年无事件生存率（EFS）为86%，生存率为92%。80例婴儿中有44例（55%）仅接受了支持性治疗，其5年生存率为100%，而因症状需要细胞毒性治疗的婴儿生存率为81%（P = 0.005）。6例死亡病例中有5例是诊断时年龄小于2个月的婴儿，死于广泛腹部受累伴呼吸功能不全或弥散性血管内凝血的并发症。尽管诊断时年龄≤3个月对EFS有显著意义（P = 0.043），但对生存率的意义较小（P = 0.077）。唯一其他预测生存率提高的显著因素是岛田组织病理学分类良好。转移受累部位（肝脏、皮肤或骨髓）及原发肿瘤的手术切除对生存率无显著影响。
本研究证实了IV-S期神经母细胞瘤婴儿具有良好的生物学特征，采用最小化治疗时生存率良好。诊断时年龄小于2个月且腹部疾病进展迅速的婴儿可能从更早、更强化的治疗中获益。
