葡萄膜黑色素瘤患者巩膜外敷贴放射治疗反应模式及治疗效果

Response patterns and treatment outcomes of uveal melanoma patients treated with external scleral plaque radiotherapy

目的:观察并分析葡萄膜黑色素瘤(UM)患者巩膜外敷贴放射治疗(PRT)的不同临床反应模式以及治疗失败后行二期眼球摘除手术的危险因素。方法:单中心回顾性研究。2011年3月至2017年9月于北京同仁医院眼科检查确诊并接受 125I巩膜外PRT的465例UM患者纳入研究。其中,男性217例,女性248例;年龄(46.7±12.1)岁。均为单眼。二期眼球摘除原因包括局部肿瘤治疗失败、青光眼、巩膜坏死和患者要求等。肿瘤分级参照美国癌症联合委员会(AJCC)制定的分级标准。依据文献标准将PRT后肿瘤反应模式分为消退型、增长型、稳定型、其他型。治疗后中位随访时间59个月,观察肿瘤变化情况。465例患者中,有3次及以上彩色多普勒超声成像(CDI)检查完整随访记录245例。治疗前患者年龄、眼压、最佳矫正视力、肿瘤厚度及最大基底直径比较行 t检验;患者性别、肿瘤AJCC T分级、是否累及睫状体、是否存在视网膜下液、视盘侵犯、玻璃体积血以及瘤体形状、位置等因素比较行 χ^(2)检验。采用Kaplan-Meier生存分析预估PRT后二期眼球摘除的累积概率;采用单变量和多变量Cox比例风险回归分析评价肿瘤特征与PRT后二期眼球摘除的关系。 结果:465例患者中,随访期间行二期眼球摘除(保眼失败)78例(16.8%,78/465 ),其中1、3、5年眼球摘除率分别为5.4%、9.3%、17.1%;保眼成功387例(83.2%,387/465)。与保眼成功者比较,保眼失败者肿瘤最大基底直径更大,肿瘤不规则状及弥散状形态百分比、肿瘤累及黄斑百分比、AJCC T分级更高,差异均有统计学意义( P<0.05 )。有3次及以上完整CDI检查记录的245例患者中,消退型、稳定型、增长型、其他型分别为115、76、27、27例。增长型、其他型患者肿瘤厚度明显小于消退型、稳定型,差异有统计学意义( P<0.05 );增长型患者保眼失败率明显高于消退型、稳定型、其他型,差异有统计学意义( P<0.05 )。单因素Cox分析结果显示,肿瘤最大基底直径( HR=1.19 )、肿瘤厚度( HR=1.08)、AJCC T分级( HR=1.90)、增长型反应模式(相对于消退型反应模式)( HR=4.20)与保眼失败相关( P<0.05 )。多因素Cox分析结果显示,肿瘤最大基底直径( HR=1.24 )、增长型反应模式(相对于消退型反应模式)( HR=4.59)仍与保眼失败相关( P<0.05 )。 结论:PRT后增长型、其他型反应模式UM患者治疗前的肿瘤厚度更小;肿瘤最大基底直径、增长型反应模式是PRT失败后进行二期眼球摘除的独立危险因素。

Objective To observe the different clinical response patterns of uveal melanoma(UM)patients after external scleral plaque radiotherapy(PRT),and to investigate the risk factors of secondary enucleation after treatment failure.Methods A single-centre retrospective study.Demographic baseline characteristics and clinical data were collected from 465 UM patients treated with 125I external scleral PRT at Beijing Tongren Hospital from March 2011 to September 2017.Among them,217 were male and 248 were female,tumor all occurred monocularly.The mean age of subjects was 46.7±12.1 years.Reasons for secondary enucleation included local tumor treatment failure,glaucoma,scleral necrosis and patient request.Tumor grading was based on the grading standards established by the American Joint Committee on Cancer(AJCC).The pattern of tumor response after PRT was classified as degenerated type,growth type,stable type or other types according to literature criteria.The median follow-up time after PRT was 59 months to observe tumor changes.Complete follow-up records of 3 or more color doppler ultrasound imaging(CDI)was available in 245 cases.A t-test was performed to compare the patient's age,intraocular pressure,best corrected visual acuity,tumor thickness and maximum basal diameter before treatment;a chi-square test was performed to compare the patient's gender,AJCC T classification of the tumor,whether the ciliary body was involved,presence of subretinal fluid,optic disc invasion and vitreous hemorrhage,tumor shape and location.Kaplan-Meier survival analysis was used to estimate the cumulative probability of secondary enucleation after extra-scleral PRT.Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the relationship between tumor characteristics and secondary enucleation after extra-scleral PRT.Results Among 465 patients,eecondary enucleation was performed on 78(16.8%,78/465)patients during the follow-up period.The 1,3 and 5 year secondary enucleation rates were 5.4%,9.3%and 17.1%,respectively.Eye preservation was successful in 387 cases(83.2%,387/465).Patients treated by secondary enucleation had a larger maximum basal diameter of tumor,a higher proportion of irregular and diffuse morphology,a cumulative macular involved and a higher AJCC T classification,the difference was statistically significant(P<0.05).There were 115,76,27,and 27 cases of degenerated type,stable type,growth type,and other type,respectively.The tumor thickness of the growth type and other types was significantly smaller than that of the degenerated type and the stable type,and the difference was statistically significant(P<0.05).Univariate Cox analysis showed that the maximum basal diameter of the tumor(HR=1.19),tumor thickness(HR=1.08),AJCC T classification(HR=1.90),growth type response pattern(relative to degenerated type response pattern)(HR=4.20)was associated with failure of eye preservation(P<0.05).In the multivariate Cox analysis,the largest tumor basal diameter(HR=1.24)and the growth type response pattern(relative to the degenerated type response pattern)(HR=4.59)were still associated with failure of eye preservation(P<0.05).Conclusions The tumor thickness of UM patients with growing and other response patterns after PRT is smaller before treatment;the maximum basal diameter of the tumor and the growing response pattern are independent risk factors for secondary enucleation.