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中华眼科医学杂志(电子版) ›› 2023, Vol. 13 ›› Issue (01) : 18 -23. doi: 10.3877/cma.j.issn.2095-2007.2023.01.004

论著

巩膜外敷贴放射后补充经瞳孔温热疗法治疗脉络膜黑色素瘤的临床研究
王姮, 张瑞恒, 刘月明, 魏文斌†()   
  1. 100730　首都医科大学附属北京同仁医院2018级硕士研究生
    100730　首都医科大学附属北京同仁医院2020级硕士研究生
    100730　首都医科大学附属北京同仁医院　北京同仁眼科中心　眼内肿瘤诊治研究北京市重点实验室　北京市眼科学与视觉科学重点实验室　医学人工智能研究与验证工信部重点实验室
  • 收稿日期:2023-02-08 出版日期:2023-02-28
  • 通信作者: 魏文斌
  • 基金资助:
    首都卫生发展科研专项基金项目(首发2020－1－2052)

Transpupillary thermotherapy adjunctive to brachytherapy for choroidal melanoma

Heng Wang, Ruiheng Zhang, Yueming Liu, Wenbin Wei†()   

  1. Master′s degree 2018, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
    Master′s degree 2020, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
    Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology &Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing 100730, China
  • Received:2023-02-08 Published:2023-02-28
  • Corresponding author: Wenbin Wei
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引用本文：

王姮, 张瑞恒, 刘月明, 魏文斌. 巩膜外敷贴放射后补充经瞳孔温热疗法治疗脉络膜黑色素瘤的临床研究[J]. 中华眼科医学杂志(电子版), 2023, 13(01): 18-23.

Heng Wang, Ruiheng Zhang, Yueming Liu, Wenbin Wei. Transpupillary thermotherapy adjunctive to brachytherapy for choroidal melanoma[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(01): 18-23.

目的

探讨经瞳孔温热疗法(TTT)作为巩膜外敷贴放射(PRT)后补充治疗脉络膜黑色素瘤(CM)的效果及预后。

方法

收集2008年1月至2019年3月于首都医科大学附属北京同仁医院眼科中心接受碘125 PRT治疗的CM患者601例(601只眼)。其中，男性306例(306只眼)，女性295例(295只眼)，年龄13~85岁，平均(46.6±11.9)岁。对于PRT后存在瘤体血管残留的患眼，行瘤体血管残留区域TTT补充治疗。全部患者术前与术后均接受间接检眼镜、荧光素眼底血管造影(FFA)、吲哚青绿脉络膜血管造影(ICGA)、彩色多普勒超声、肝功能及腹部超声检查。记录患者的性别、年龄、治疗前眼压、肿瘤形状、肿瘤高度、肿瘤最大基底径、肿瘤与视盘关系、是否合并玻璃体积血和视网膜下液、治疗后眼球摘除、肿瘤转移及死亡情况。经检验，患者的年龄、肿瘤高度及肿瘤最大基底径等均符合正态分布，以(±s)进行描述，其比较采用独立样本t检验；患者的随访时间、眼球摘除时间、肿瘤转移时间及死亡时间等不符合正态分布，以中位数和四分位数进行描述；患者的性别、肿瘤形态、累及视盘、合并视网膜下液和玻璃体积血的眼数、眼球摘除例数、肿瘤转移例数及死亡例数以频数和百分比表示。其中，患者的性别、肿瘤形状、累及视盘、合并视网膜下液和玻璃体积血眼数的比较采用卡方检验或精确概率法；眼球摘除、肿瘤转移和归因死亡累积概率的分析采用Kaplan－Meier生存分析；眼球摘除、肿瘤转移及死亡的危险因素采用Cox比例风险回归模型进行分析。

结果

601例(601只眼)患者中存在PRT后肿瘤血管残留并接受TTT补充治疗者有60例(60只眼)，占整体的9.98%。其中，仅需要一次TTT者有51例(51只眼)，占85.0%；存在肿瘤血管残留和无残留的患者平均年龄分别为(42.3±12.1)岁和(47.1±11.8)岁，二者差异具有统计学意义(t＝3.00，P<0.05)。在接受TTT补充治疗的60例(60只眼)的患者中，3年的眼球摘除率和5年的眼球摘除率分别为6.7%[95%CI：2.6~6.8]和18.9%[95%CI：10.9~31.6]；3年的肿瘤转移率和5年的肿瘤转移率分别为3.3%[95%CI：0.8~12.7]和10.2%[95%CI：7.7~21.3]；3年的归因死亡率和5年的归因死亡率分别为1.7%[95%CI：0.2~11.2]和6.7%[95%CI：2.6~16.9]。经多因素分析，肿瘤最大基底径及肿瘤累及视盘与眼球摘除的相关性具有统计学意义(HR＝1.22，4.35；95%CI：1.11~1.34，1.84~10.23；χ2＝4.14，3.36；P<0.05)。肿瘤最大基底径及视网膜下液与肿瘤转移的相关性具有统计学意义(HR＝1.26，6.31；95%CI：1.16~1.37，1.94~20.51；χ2＝5.44，3.06；P<0.05)。肿瘤最大基底径、患者年龄及患眼眼压与患者归因死亡的相关性具有统计学意义(HR＝1.23，1.52，1.10；95%CI：1.11~1.35，1.20~1.91，1.02~1.19；χ2＝4.15，3.53，2.42；P<0.05)。

结论

FFA联合ICGA可用于评估PRT术后患眼肿瘤血管残留情况。TTT作为补充治疗可针对性应用于患眼瘤体血管残留区域。肿瘤最大基底径作为不良预后的危险因素需高度重视。

关键词: 巩膜外敷贴放射治疗, 经瞳孔温热疗法, 脉络膜黑色素瘤
Objective

To assess the efficacy and prognosis of selective transpupillary thermotherapy (TTT) adjunctive to I125 plaque radiotherapy (PRT) for choroidal melanoma.

Methods

The study retrospectively analyzed 601 patients (601 eyes) treated with I125 PRT for choroidal melanoma, collected from January 2008 to March 2019 at the Ophthalmology Department of Tongren Hospital, Capital Medical University. Among them, there were 306 males (306 eyes) and 295 females (295 eyes) with an average age of (46.6±11.9) years (ranged from 13 to 85 years). All patients underwent indirect ophthalmoscopy, fundus fluorescence angiography (FFA), indocyanine green choroidal angiography (ICGA), color Doppler ultrasound, liver function test, and abdominal ultrasound before and after PRT. Supplemental TTT was given to the tissue with tumor vasculature residue after PRT. Gender, age, pre-treatment intraocular pressure, tumor shape, tumor height, tumor maximum basal diameter, disc involvement, vitreous hemorrhage, subretinal fluid, and prognosis (enucleation, metastasis, deaths) were recorded. The age, tumor height, and maximum basal diameter, in accord with normal distribution, were represented by (±s) and compared by independent sample t-test. The time of follow-up, time to enucleation, metastasis, and death did not conform to a normal distribution and were described by median and quartiles. The gender, tumor shape, disc involvement, subretinal fluid, vitreous hemorrhage and prognosis (enucleation, metastasis, deaths) were described by cases and percentages. Among them, the differences of gender, tumor shape, disc involvement, cases with subretinal fluid and vitreous hemorrhage before and after treatment were compared by the chi-square or exact probability test; the cumulative probabilities of enucleation, metastasis, and attributed death were analyzed by Kaplan-Meier survival analysis, and risk factors were analyzed using Cox proportional hazards model.

Results

There were 60 cases (60 eyes) of 601 cases (601 eyes) with the residual tumor vasculature and treated by supplemental TTT, accounting for 9.98%. One session was required in 51 cases (51 eyes), accounting for 85.0%. The mean age of the patients with and without residual tumor vessels were (42.3±12.1) and (47.1±11.8) years with statistical significance, respectively (t=3.00, P<0.05). The 3 and 5-year enucleation rates of the 60 cases (60 eyes) treated by supplemental TTT were 6.7% (95%CI: 2.6 to 6.8) and 18.9%(95%CI: 10.9 to 31.6), respectively. The 3 and 5-year metastasis rates were 3.3% (95%CI: 0.8 to 12.7) and 10.2% (95%CI: 7.7 to 21.3), respectively. The 3-year and 5-year attributable mortality rates were 1.7% (95%CI: 0.2 to 11.2) and 6.7% (95%CI: 2.6 to 16.9), respectively. In multivariate analysis, the tumor largest basal diameter and optic disc involvement were risk factors for enucleation (HR=1.22, 4.35; 95%CI: 1.11 to 1.34, 1.84 to 10.23; χ2=4.14, 3.36; P<0.05). Tumor maximum basal diameter and subretinal fluid were risk factors for metastasis (HR=1.26, 6.31; 95%CI: 1.16 to 1.37, 1.94 to 20.51; χ2=5.44, 3.06; P<0.05). The tumor largest basal diameter, age, and intraocular pressure were risk factors for attributable death (HR=1.23, 1.52, 1.10; 95%CI: 1.11 to 1.35, 1.20 to 1.91, 1.02 to 1.19; χ2=4.15, 3.53, 2.42; P<0.05).

Conclusions

The tumor vasculature residue after PRT can be evaluated by FFA accompanied by ICGA. The supplemental TTT could be used to treat the tumor residue of the affected eyes. The tumor maximum basal diameter is a notable risk factor for poor prognosis, which should be paid attention.

Key words: Plaque radiotherapy, Transpupillary thermotherapy, Choroidal melanoma
图1 巩膜外敷贴放射后荧光素眼底血管造影及吲哚青绿血管造影　图A示荧光素眼底血管造影图像上方可见瘤体荧光着染，轻微渗漏，下方瘤体大片荧光遮蔽；图B示吲哚青绿血管造影可见残留的瘤体血管
表1 眼球摘除、肿瘤转移及患者归因死亡风险的单因素分析
相关因素 眼球摘除 肿瘤转移 归因死亡
回归系数 Wald检验值 HR[95%CI] P值 回归系数 Wald检验值 HR[95%CI] P值 回归系数 Wald检验值 HR[95%CI] P值
男性 －0.14 0.58 0.87[0.54~ 1.39] >0.05 0.18 0.79 1.20[0.76~ 1.88] >0.05 0.17 0.62 1.18[0.70~1.98] >0.05
年龄a 0.04 0.39 1.04[0.86~ 1.27] >0.05 0.10 1.07 1.11[0.92~ 1.35] >0.05 0.35 3.17 1.42[1.14~1.76] <0.05
眼压 －0.07 1.77 0.93[0.86~ 1.01] >0.05 0.02 0.53 1.02[0.95~ 1.10] >0.05 0.08 2.05 1.08[1.01~1.17] <0.05
TTT治疗 0.19 0.62 1.21[0.66~ 2.21] >0.05 －0.21 0.65 0.81[0.43~ 1.53] >0.05 0.46 －1.18 0.63[0.29~1.34] >0.05
肿瘤高度b 0.09 1.76 1.09[0.99~ 1.20] >0.05 0.07 1.50 1.07[0.98~ 1.17] >0.05 0.08 1.42 1.08[0.97~1.20] >0.05
最大基底径b 0.22 4.99 1.24[1.14~ 1.35] <0.05 0.26 6.94 1.30[1.19~ 1.38] <0.05 0.21 4.56 1.23[1.13~1.35] <0.05
视网膜下液 1.06 2.66 2.90[1.32~ 6.33] <0.05 2.06 3.49 7.81[2.46~24.79] <0.05 0.68 1.77 1.97[0.93~4.16] >0.05
累及视盘 1.49 3.46 4.44[1.91~10.33] <0.05 －0.01 0.01 0.99[0.24~ 4.03] >0.05 0.24 0.33 1.27[0.31~5.20] >0.05
玻璃体积血 －0.20 0.39 0.82[0.30~ 2.25] >0.05 －1.05 1.47 0.35[0.09~ 1.47] >0.05 0.71 －0.99 0.49[0.12~2.02] >0.05
表2 眼球摘除、肿瘤转移及患者归因死亡风险的多因素分析
相关因素 眼球摘除 肿瘤转移 归因死亡
回归系数 Wald检验值 HR[95%CI] P值 回归系数 Wald检验值 HR[95%CI] P值 回归系数 Wald检验值 HR[95%CI] P值
男性 －0.21 0.85 0.81[0.50~ 1.32] >0.05 0.16 0.67 1.17[0.74~ 1.86] >0.05 0.10 0.39 1.11[0.65~1.88] >0.05
年龄a 0.13 1.26 1.14[0.93~ 1.40] >0.05 0.18 1.81 1.20[0.99~ 1.47] >0.05 0.42 3.53 1.52[1.20~1.91] <0.05
眼压                 0.10 2.42 1.10[1.02~1.19] <0.05
TTT治疗 0.23 0.73 1.26[0.68~ 2.35] >0.05 －0.15 0.46 0.86[0.45~ 1.64] >0.05 －0.31 0.78 0.73[0.33~1.60] >0.05
肿瘤高度b 0.01 1.18 1.01[0.91~ 1.13] >0.05 －0.06 1.14 0.94[0.84~ 1.04] >0.05 0.00 0.00 1.00[0.89~1.13] >0.05
最大基底径b 0.20 4.14 1.22[1.11~ 1.34] <0.05 0.23 5.44 1.26[1.16~ 1.37] <0.05 0.21 4.15 1.23[1.11~1.35] <0.05
视网膜下液 0.68 1.63 1.98[0.87~ 4.52] >0.05 1.84 3.06 6.31[1.94~20.51] <0.05 0.52 1.28 1.68[0.76~3.71] >0.05
累及视盘 1.47 3.36 4.35[1.84~10.23] <0.05 －0.21 0.29 0.81[0.20~ 3.33] >0.05 0.11 0.16 1.12[0.27~4.65] >0.05
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