侵犯视神经的视网膜母细胞瘤患儿465例预后分析

Prognostic observation of 465 patients with retinoblastoma with optic nerve invasion

目的 观察眼球摘除术后病理侵犯视神经的视网膜母细胞瘤（RB）患儿的治疗及预后情况.方法 回顾性分析北京同仁医院2006年1月至2013年12月临床确诊为单眼RB,眼球摘除后病理诊断侵犯视神经的465例患儿的病例资料,根据其病理侵犯程度分为4级：1级为肿瘤细胞侵犯视乳头;2级为侵犯筛板;3级为侵犯筛板之后,未到视神经断端;4级为侵犯视神经断端.1级和2级统称为侵犯筛板前视神经,视为病理学低风险因素;3级和4级统称为侵犯筛板后视神经,视为病理学高风险因素.其他病理学高风险因素包括侵犯大范围脉络膜、巩膜、前房、虹膜和睫状体.将患儿分为合并及不合并其他病理学高风险因素组.分别给予相应的治疗并观察其预后.随访时间6个月～7年,平均随访时间3年7个月.结果 465例患儿中男279例,女186例.右眼260例,左眼205例.从发现症状到就诊的时间为1d～2年,平均2.7个月.465例患儿中25例死亡,总生存率为94.6％.侵犯筛板前视神经的患儿有338例,2例复发死亡,生存率为99.4％ （336/338）;侵犯筛板后视神经的患儿有127例,23例复发死亡,生存率为81.9％ （104/127）;二者差异有统计学意义（χ2=52.299,P=0.000）.1～4级视神经侵犯患儿的病死率分别为0.4％、1.0％、8.7％、60.9％;465例患儿中379例不合并其他病理学高风险因素,8例死亡,病死率为2.1％;86例合并其他病理学高风险因素,17例死亡,病死率为19.8％;二者差异有统计学意义（χ2=42.955,P=0.000）.侵犯筛板前视神经的338例患儿中304例不合并其他高风险因素,复发死亡O例;34例合并其他高风险因素,2例复发死亡,病死率为5.9％;二者差异有统计学意义（P =0.010）.侵犯筛板后视神经的127例患儿中76例不合并其他高风险因素,9例复发死亡,病死率11.8％;51例合并其他高风险因素,14例复发死亡,病死率27.5％;二者差异有统计学意义（χ2 =5.014,P =0.025）.病理学高风险因素Cox回归分析显示：侵犯巩膜、视神经和视神经断端是影响预后的危险因素.结论 侵犯视神经的RB患儿总体治疗效果较好,但是侵犯视神经断端的患儿复发率高,应当积极予以辅助化疗.

Objective To observe the treatment and prognosis of optic nerve invasion in retinoblastoma （RB）.Method The children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2013 in our hospital were recruited.Tumor extension into the optic nerve were disclosed.Optic nerve involvement was classified into four grades according to the degree of invasion.Grade Ⅰ is superficial invasion of the optic nerve head only,grade Ⅱ is involvement up to and including the lamina cribrosa,grade Ⅲ is involvement beyond the lamina cribrosa,and grade Ⅳ is involvement up to and including the surgical margin.Grade Ⅰ and Ⅱ are called invasion of the optic nerve before the sieve plate.Grade Ⅲ and Ⅳ are called invasion of the optic nerve after the sieve plate.Other high-risk factors included extensive invasions of the choroid,sclera,anterior chamber,iris,and ciliary body.They were divided into two groups according to whether the merger of other high histopathologic risk factors.Treatment was delivered accordingly,and the prognosis of different degrees of optic nerve invasion was observed.The subjects were followed up for 6 months to 7 years （average：43 months）.Result There were 465 subjects in this study,including 279 boys and 186 girls.The right eye was affected in 260 patients and the left eye in 205 patients.The average time from onset of symptoms to visit was 2.7 months （range 1 day-24 months）.Twenty-five patients died,resulting in an overall survival rate of 94.6%.The mortality rate of patients with optic nerve involvement with grade Ⅰ was 0.4%,grade Ⅱ was 1.0%,grade Ⅲ was 8.7% was and grade Ⅳ was 60.9%.Of the 338 with invasion of the optic nerve before the sieve plate,two died of recurrence,with a survival rates of 99.4% （336/338）.Of the 127 patients who had invasion of the optic nerve after the sieve plate,twenty-three died of recurrence,with a survival rate of 81.9% （104/127）,the difference was statistically significant （χ2 =52.299,P =0.000）.A total of 379 patients did not have any other merged pathology high-risk factors,8 died,the mortality rate was 2.1%.Of the 86 patients who had complicated with other high-risk factors,17 died,the mortality rate was 19.8%,the difference was statistically significant （χ2 =42.955,P =0.000）.Of the 338 patients,304 had invasion of the optic nerve before the sieve plate had not merged other pathology high-risk factors,none died,of the 34 patients who had complicated with other pathology high-risk factors,2 had died,the mortality rate was 5.9%,the difference was statistically significant （P =0.010）.Of the 127 patients with invasion of the optic nerve after the sieve plate,76 had not complicated with other pathological high-risk factors,9 of whom had died,the mortality rate was 11.8%,51 had complicated with other pathological high-risk factors,14 of whom had died,the mortality rate was 27.5%,outcomes did significantly differ between the two subgroups （χ2 =5.014,P =0.025）.Cox multivariate analysis showed that invasion of the retrolaminar optic nerve,surgical margin of the optic nerve and sclera were influential factors of colorectal cancer.Conclusion Patients with optic nerve invasion have an excellent outcome with current therapy.But for those whose resection margin was invaded,which has a high incidence of recurrence,chemotherapy is recommended for patients with postlaminar optic nerve involvement.