全身化学药物治疗对晚期视网膜母细胞瘤患儿肿瘤浸润和眼外转移及特定疾病生存率的影响

Effect of systemic chemotherapy on conditions of tumor infiltrating, metastasis and disease-specific survival for advanced retinoblastoma

目的 观察全身化学药物治疗（化疗）对晚期视网膜母细胞瘤（RB）患儿肿瘤浸润和眼外转移以及特定疾病生存率（DSS）的影响。方法 行眼球摘除的41例晚期RB患儿纳入研究。其中，男性26例，女性15例。诊断年龄2~72个月，平均诊断年龄23.08个月。单眼25例，双眼16例。D期13例，E期28例。眼球摘除手术前曾接受过全身化疗25例（化疗组），首选治疗为眼球摘除手术者（手术组）16例。两组患者性别、诊断年龄、单双眼发病比例、RB分期比较，差异均无统计学意义（P＞0.05）。对每例患儿的病理组织学报告进行手术后病理分期（pTNM）风险性评估，确定肿瘤在视神经、脉络膜和前房侵犯程度，并将其分为低风险、中等风险、高风险3个等级。41例患儿中，因颅内转移或眼外转移最终死亡5例；均为化疗组E期患儿。采用R软件生存分析软件包的survfit函数，应用Kaplan-Meier估计方法，测算E期患儿自诊断之日到随诊结束或死亡时间为止的DSS。对比分析化疗组、手术组E期患儿以及诊断后眼球摘除时间超过3个月和3个月以内E期患儿的DSS差异。结果 化疗组高风险比例较手术组明显降低。但两组总体风险性分级比较，差异无统计学意义（χ2=3.130，P=0.077）。化疗组D期患儿的总体风险性较手术组更低，两组比较差异有统计学意义（χ2=5.870，P=0.015）。两组E期患儿总体风险性比较，差异无统计学意义（χ2=0.019，P=0.889）。化疗组、手术组E期患儿DSS分别为0.71和1.00；两组E期患儿DSS比较，差异有统计学意义（χ2=3.700，P=0.050）。诊断后眼球摘除时间超过3个月及3个月以内的E期患儿DSS分别为0.64和1.00；两者DSS比较，差异有统计学意义（χ2=4.800，P=0.028）。结论 全身化疗并不能降低晚期RB患儿肿瘤浸润和眼外转移的风险，反而会降低E期患儿的DSS。

Objective To observe the effect of systemic chemotherapy on conditions of tumor infiltrating,metastasis and disease-specific survival （DSS） for advanced retinoblastoma （RB）. Methods Forty-one patients with advanced RB who received enucleation were enrolled in this study. There were 26 males and 15 females, age at diagnosis was ranged from 2 to 72 months, with a mean of 23.08 months. There were 16 bilateral patients and 25 unilateral patients; 13 group D eyes and 28 group E eyes. 16 patients received enucleation as the primary treatment （operation group）, 25 eyes received chemotherapy before enucleation （chemotherapy group）. There was no significant statistical difference between two groups for the gender, unilateral and bilateral, international staging or diagnostic age （P〉0.05）. The histopathology report was performed to assess the risk of postoperative tumor-node-metastasis staging （pTNM） in each patient, and the extent of tumor invasion in the optic nerve, choroid and anterior chamber was divided into 3 levels of low risk, medium risk and high risk. Five deaths were all in the group E with chemotherapy before enucleation. Using R software survival analysis software package survfit function, the application of Kaplan-Meier estimation method, DSS of RB children was calculated from the time of diagnosis, up to the date of the death of patient. DSS differences between chemotherapy, operation group and eye removal time （more than 3 months, less than 3 months） in group E RB children were analyzed. Results The proportion of high risk pTNM stage in chemotherapy group was significantly lower than the operation group. But there was no significant difference between the two groups in the overall risk classification （χ2=3.130,P=0.077）. For group D eyes, the overall risk classification in chemotherapy group was significantly lower than the operation group （χ2=5.870,P=0.015）. There was no significant difference between the two groups in the overall risk of group E eyes （χ2=0.020,P=0.889）. The DSS in chemotherapy group and operation group were 0.71 and 1.00, respectively; the difference was significant （χ2=3.700,P=0.05）. The DSS in children whose enucleation delayed for more than 3 months and children whose enucleation performed within 3 months were 0.64 and 1.00, respectively; the difference was significant （χ2=4.800,P=0.028）. Conclusion Systemic chemotherapy did not reduce the risk of tumor invasion and metastasis in patients with advanced RB. Instead, it will reduce the DSS in group E eyes of RB.