伴MYCN扩增的婴儿神经母细胞瘤临床特征及预后分析

Clinical features and prognosis of infantile neuroblastoma with MYCN amplification

目的总结伴MYCN扩增的婴儿神经母细胞瘤(NB)临床特征及预后分析。方法回顾性分析2010年1月1日—2021年12月31日在我院诊断并规律治疗的年龄≤12个月,同时伴有MYCN扩增的13例婴儿NB的临床资料,总结临床特征及评估预后,并以13例MYCN无扩增的婴儿NB做对照,随访截止2022年4月30日。结果(1)MYCN基因扩增的婴儿NB占同期本单位收治婴儿NB总数的5.5%(13/235),中位诊断年龄9(4~12)个月,中位随访时间28个月(13天~130个月)。(2)13例MYCN基因扩增的婴儿NB均为高危,IV期11例,III期1例;12例肿瘤原发部位为腹膜后/肾上腺,1例为纵膈;12例发生肿瘤转移,其中10例远处骨转移、9例骨髓转移、7例肝脏转移;11例接受手术治疗,其中3例化疗前行手术治疗,8例化疗后行手术治疗,2例仅化疗,平均化疗9.6个疗程;6例放疗,中位放疗剂量为20.1Gy;3例行自体造血干细胞移植治疗;11例手术治疗患儿中,6例瘤灶完整切除,4例部分切除,1例不详;5例无事件生存,8例事件发生的中位时间为17(0.2~88)个月,6例出现肿瘤复发或进展,其中5例化疗结束后复发,复发中位时间5(2~58)个月,1例在化疗中疾病进展,13例中7例死亡。(3)单因素分析显示LDH、NSE水平显著增高的MYCN扩增NB婴儿预后不良(P<0.05);MYCN扩增组与MYCN无扩增组的预计5年无事件生存率(EFS)分别为21%和100%,具有显著性差异(P=0.0004),预计5年总生存率(OS)分别为33%和100%,具有显著差异(P=0.002);MYCN扩增组发生骨转移、骨髓转移、肝转移及LDH≥1500的比例显著较高(P<0.05)。结论伴MYCN扩增的婴儿NB预后明显不良,且LDH、NSE水平显著增高者预后更差。

Objective To summarize the clinical features and prognosis of infantile neuroblastoma(NB)with MYCN amplification.Methods The clinical data of 13 NB infants with MYCN amplification who were diagnosed and regularly treated in Beijing Children′s Hospital,Capital Medical University from January 1,2010 to December 31,2021 were retrospectively analyzed to summarize the clinical features and evaluate the prognosis.Follow-up ended April 30,2022.Results(1)MYCN gene amplified infant NB accounted for 5.5%(12/235)of the total number of infants treated in our unit in the same period.The median diagnosis age was 9(4-12)months,and the median follow-up time was 28 months(13d-130m).(2)13 cases were high-risk,12 cases in stage IV and 1cases in stage III.The primary site of tumor was retroperitoneal/adrenal gland in 12 cases and mediastinum in 1 case.Tumor metastasis occurred in 12 cases,including 10 cases of distant bone metastasis,9 cases of bone marrow metastasis and 7 cases of liver metastasis.11 cases received surgical treatment,of which 3 cases received surgical treatment before chemotherapy,8 cases received surgical treatment after chemotherapy,and 2 case received chemotherapy only,with an average of 9.6 courses of chemotherapy.The median radiation dose was 20.1Gy.3cases were treated with autologous stem cell transplantation.Among the 11 children who underwent surgery,6 cases underwent complete resection,4 cases underwent partial resection,and 1 case was unknown.Among the 11 children who underwent surgical treatment,6 cases were completely resected,4 cases were partially resected,and 1 case was unknown.A total of 5 patients survived without an event,and 8 patients developed an event within 17(0.2-88)months.Among them,6 patients had tumor recurrence or progression,5 patients had recurrence after chemotherapy,and the median time of recurrence was 5(2-58)months,and 1 patient had disease progression during chemotherapy.Of the 13 cases,7 were fatal.(3)Compared with 1:1 matched infants of the same age and sex without MYCN amplification,NB of infants with MYCN amplification had a significantly poorer prognosis,with the predicted 5-year EFS of 100%vs.21%,P=0.0004.The projected 5-year OS is 100%vs.33%,P=0.002.Conclusions MYCN amplified infants have a poor prognosis of NB,and high LDH and NSE levels suggest a worse prognosis.The levels of bone and bone marrow metastasis,liver metastasis and LDH in the MYCN amplified group are significantly higher than those in the MYCN non-amplified group.