北京儿童医院视网膜母细胞瘤3年诊断治疗效果总结

Treatment and short-term effect analysis of retinoblastoma in Beijing Children＇s Hospital for 3-year results

目的 建立多学科联合模式,应用全身化疗和局部治疗的综合治疗策略对眼内期视网膜母细胞瘤（RB）患儿进行诊治,评价该方法对保存RB患儿眼球、视力以及改善生存率的效果.方法 总结2009年11月至201 1年11月在首都医科大学附属北京儿童医院血液肿瘤中心诊治的全部眼内期RB患儿,分析临床资料和治疗情况,全部患儿随访至2012年12月31日.RB的诊断标准、分期、临床危险度分组、治疗方案和疗效标准均参照RB国际分类系统.化疗方案为改良的加拿大多中心RB 2003方案,同时应用810 nm及532 nm激光、冷凝技术进行局部治疗.通过随访收集患儿眼球摘除及生存质量的情况,同时在眼底镜检查下评估疗效及转移的风险.结果 共127例（180只眼）,男68例,女59例,双眼51例,单眼78例（右41例,左37例）.在双眼51例（102只眼）中,E期26只,D期52只,C期1 1只,B期11只,A期2只,D期伴视网膜脱落9只,E期伴视网膜脱落5只.单眼78例中,E期31例,D期47例,单眼中 D期伴视网膜脱落7例,E期伴视网膜脱落7例.年龄2 ～ 84个月（中位年龄17个月,其中双眼15.8个月,单眼23.2个月）.除1例患儿化疗2个疗程后死于颅内出血,随访时间为2个月外,其他患儿随访时间6 ～38个月（中位时间29.2个月）,总化疗疗程为1～11个疗程（平均5.2个疗程）.共眼球摘除76只眼,其中直接眼球摘除32只,化疗后眼球摘除44只.眼球摘除后病理显示有高危因素10例（10只眼）（13％）,其中前房种植4只眼,筛板后视神经受累（断端阴性）6只眼,葡萄膜后浸润（包括脉络膜受累）4只眼.单一危险因素3只眼,7只眼同时存在2种以上危险因素.在药物不良反应观察中,明确为卡铂致听力损伤5例,依托泊苷致皮疹3例.1例并发脓毒症.免疫指标恢复时间为停化疗至少6个月.共发生事件8例,其中失访1例为单眼患儿,化疗4个疗程后回当地医院治疗.7例死亡患儿包括2例拒绝眼球摘除者.其他死亡患儿为：单眼2例,分别为1例化疗3个疗程,眼球摘除2个月后颅内转移死亡;1例于化疗1个疗程,眼球摘除6个月后颅内进展放弃治疗,死亡.双眼2例,分别为1例停化疗11个月后出现颅内进展放弃治疗,死亡;1例在单侧眼球摘除后脏器功能衰竭死亡.其余患儿均存活至今,Kaplan-Meier进行单因素生存分析,中位随访时间29个月,生存率为93.7％.结论 肿瘤内科联合眼科,应用VEC方案（即长春新碱＋卡铂＋依托泊苷）结合激光、冷凝技术进行RB治疗,使眼内期RB患儿的近期疗效明显改善,成功保眼50只.建议对于晚期的单眼RB,眼球摘除后化疗2～4个疗程可能为预防局部和远处转移的关键.颅内转移为主要的转移部位,也是死亡的主要原因,提示治疗中的头颅影像检查很重要.

Objective To establish a multidisciplinary approach to intraocular retinoblastomas （RB） and to diagnose and treat intraocular retinoblastoma （RB） by systemic and local chemotherapy and to evaluate the curative effect of the therapy for preservation of eyes of the RB patients,eye sight,and the improvement of the survival rate.Methods We summarized the data of intraocular RB and reviewed medical records of 127 children （180 eyes） presenting with clinically and/or histologically confirmed RB and treated at Hematology oncology Centre,Beijing Children＇ s Hospital （BCH） Affiliated to Capital Medical University from Nov.2009 to Nov.2011.Eligible eyes were classified according to the International Intraocular Retinoblastoma Classification （IIRC）.Based on modified Canadian RB 2003 protocols,therapeutic modalities were enucleation,local control （810 nm and 532 nm laser therapy,cryotherapy） and chemotherapy.Chemotherapy consisted of vincristine,etoposide,and carboplatin （VEC）.All patients were followed up to Dec 31,2012.Cases of enucleation and quality of life of children were collected by follow-up,as well as to assess the efficacy and risk of transfer under the ophthalmoscopy.Results There were 127 patients （180 eyes）,68 male and 59 female,with a median age of 17 months （range 2 to 84 months）at initial diagnosis.Seventy-eight patients had unilateral RB,31 eyes of unilateral RB were classified as group E（7 eyes with detached retina）,47 eyes as group D （7 eyes with detached retina）.Fifty-one had bilateral RB（102 eyes）,26 eyes of bilateral RB were classified as group E （5 eyes with detached retina）,52 eyes as group D （9 eyes with detached retina）,group C,B and A were 11,11 and 2,respectively.With a mean chemotherapy of 5.2 cycles （range 1 to 11）,76 eyes were enucleated （42.0%）.Thirty-two eyes with advanced intraocular disease were enucleated at the time of presentation.Enucleation were then recommended for 44 of those eyes.Overall,50 eyes （42.3%） were successfully preserved without the need for enucleation.Ten enucleated eyes （13%） showed high-risk pathologic features.At the time of follow-up of 29.2 （range 6 to 38） months,event occurred in 8 cases,one patient lost follow-up,7 cases were died.One hundred and nineteen patients （93.7%） were alive.Conclusions Chemotherapy using VEC regimen was possible and effective in preventing metastasis.We were able to salvage almost half of these eyes.It is suggested that the advanced unilateral RB can be enucleated and then given chemotherapy for 2-4 courses to prevent local or distal metastasis.Intracranial site is the main site of metastasis which is also the main cause of death,so cranial imaging examination is very important during treatment.