Hero Barbara, Simon Thorsten, Spitz Ruediger, Ernestus Karen, Gnekow Astrid K, Scheel-Walter Hans-Guenther, Schwabe Dirk, Schilling Freimut H, Benz-Bohm Gabriele, Berthold Frank
Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
J Clin Oncol. 2008 Mar 20;26(9):1504-10. doi: 10.1200/JCO.2007.12.3349.
The excellent prognosis of localized neuroblastoma in infants, the overdiagnosis observed in neuroblastoma screening studies, and several case reports of regression of localized neuroblastoma prompted us to initiate a prospective cooperative trial on observation of localized neuroblastoma without cytotoxic treatment.
For infants with localized neuroblastoma without MYCN amplification, chemotherapy was scheduled only in cases with threatening symptoms; otherwise, the tumor was either resected or observed by ultrasound and magnetic resonance imaging (MRI).
Of 340 eligible participants, 190 underwent resection, 57 were treated with chemotherapy, and 93 were observed with gross residual tumor. Of those 93 patients with unresected tumors, spontaneous regression was seen in 44, local progression in 28, progression to stage 4S in seven, and progression to stage 4 in four. Time to regression was quite variable, with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life. So far, complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis. Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression. Overall survival (OS; 3-year OS, 0.99 +/- 0.01) and metastases-free survival (rate at 3 years, 0.94 +/- 0.03) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy.
Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life. A wait-and-see strategy is justified in those patients.
婴儿局限性神经母细胞瘤的预后良好、神经母细胞瘤筛查研究中观察到的过度诊断以及几例局限性神经母细胞瘤消退的病例报告促使我们启动一项关于观察未经细胞毒性治疗的局限性神经母细胞瘤的前瞻性合作试验。
对于无MYCN扩增的局限性神经母细胞瘤婴儿，仅在出现威胁症状的情况下安排化疗；否则，肿瘤要么切除，要么通过超声和磁共振成像（MRI）观察。
在340名符合条件的参与者中，190人接受了切除，57人接受了化疗，93人观察到有肉眼可见的残留肿瘤。在这93例未切除肿瘤的患者中，44例出现自发消退，28例局部进展，7例进展为4S期，4例进展为4期。消退时间差异很大，诊断后1至18个月出现消退的最初迹象，44例患者中有15例甚至在1岁以后出现。迄今为止，44例患者中有17例在诊断后4至20个月观察到完全消退。已知的临床风险因素无法区分出现消退与局部或转移进展的患者。未切除肿瘤患者的总生存率（OS；3年OS，0.99±0.01）和无转移生存率（3年时的比率，0.94±0.03）极佳，与接受手术或化疗的患者无差异。
局限性神经母细胞瘤婴儿中经常出现自发消退，且不限于1岁以内。对这些患者采取观望策略是合理的。
