儿童恶性实体瘤发生中枢神经系统转移的临床分析

Clinical analysis of central nervous system metastasis in children with malignant solid tumor

目的提高临床医师对儿童实体瘤发生中枢神经系统(CNS)转移的认识水平。方法回顾性分析北京同仁医院2005年9月至2016年12月收治的611例儿童常见胸腹部来源恶性实体瘤中33例发生CNS转移的患者临床资料,对不同病理类型的儿童常见恶性实体瘤发生CNS转移的临床特点、治疗及预后进行统计学分析。结果611例儿童常见胸腹部来源的恶性实体瘤患者中,发生CNS转移的神经母细胞瘤15例(5.9%,15/264)、肝母细胞瘤13例(4.8%,13/274)、肾母细胞瘤2例(3.2%,2/63)、肾透明细胞肉瘤3例(3/10)。恶性实体瘤发病年龄3~189个月,中位发病年龄26.5个月;自诊断原发实体瘤到明确CNS转移诊断的时间为0~100个月,中位时间为18个月。脑转移瘤最多见,共30例;脑膜转移3例;脊髓受累5例。脑脊液细胞学检查2例阳性(2/3)。33例诊断CNS转移病例中颅内手术联合放射治疗及化学治疗者5例,单独手术者2例,单独放射治疗者3例,仅化学治疗者23例。中位随访时间36个月,33例CNS转移病例的生存时间为(16.96±3.19)个月,3年总生存率为14.7%。颅内手术联合放射治疗及化学治疗、单纯颅内手术、单纯放射治疗及单纯化学治疗患者生存时间分别为(40.50±4.32)、(3.00±0)、(35.50±5.50)及(10.35±2.84)个月;3年总生存率分别为50.0%、0、50.0%、4.3%,差异有统计学意义(χ2=15.19,P=0.002),颅内手术联合放射治疗及化学治疗组预后最好。结论儿童胸腹部来源恶性实体瘤以肾透明细胞瘤肉瘤出现CNS转移的发生率最高,出现CNS转移后预后不良,但积极给予颅内手术联合放射治疗及化学治疗的综合治疗模式,能延长生存期,改善预后。

Objective To improve the clinicians′ understanding of central nervous system (CNS) metastasis in children with solid tumors.Methods The clinical data of 33 cases of CNS metastasis among 611 children with malignant solid tumors in the chest and abdomen from September 2005 to December 2016 in Beijing Tongren Hospital, Capital Medical University were retrospectively analyzed. The clinical characteristics, treatment and prognosis of metastasis were statistically analyzed according to different pathological types of malignant solid tumors in children with CNS metastasis.Results Among the 611 children with malignant solid tumors in the chest and abdomen, 15 patients were neuroblastoma with CNS metastasis (5.9%, 15/264), 13 patients were hepatoblastoma with CNS metastasis (4.8%, 13/274), two cases were Wilms tumor with CNS metastasis (3.2%, 2/63), and three cases were clear cell sarcoma of the kidney with CNS metastasis (3/10). The onset age of the malignant solid tumors was 3-189 months, and the median age of onset was 26.5 months. The time from the diagnosis of primary malignant solid tumor to diagnosis of CNS metastasis was 0-100 months, and the median time of metastasis was 18 months. The neuroimaging features of CNS metastasis were as follows:30 cases with brain metastasis, three cases with meningeal metastasis, and five cases with spinal cord involvement. Cerebrospinal fluid cytology was positive in two cases (2/3). Of the 33 patients with CNS metastasis, five underwent intracranial tumor resection combined with radiotherapy and chemotherapy, two underwent surgery alone, three underwent radiotherapy alone, and 23 underwent chemotherapy alone. After a median follow-up of 36 months, the survival time of 33 malignant solid tumors with CNS metastasis was (16.96±3.19) months, and the overall survival rate of three years was only 14.7%. The survival time of the patients with intracranial tumor surgery combined with radiotherapy and chemotherapy, surgery alone, radiotherapy alone, and chemotherapy alone was (40.50±4.32), (3.00±0), (35.50±5.50) and (10.35±2.84) months, respectively;and the three-year overall survival rates were 50.0%, 0, 50.0% and 4.3%, respectively (χ2=15.19, P=0.002). The prognosis of the patients with intracranial tumor resection combined with radiotherapy and chemotherapy was the best.Conclusions The highest incidence of CNS metastasis in children with malignant solid tumors in the chest and abdomen was found in the clear cell sarcoma of the kidney. The prognosis of CNS metastasis was found to be poor. But the comprehensive therapy of intracranial tumor resection combined with radiotherapy and chemotherapy can prolong survival and improve prognosis.