192Ir近距离放疗联合外照射及胆道支架治疗不能手术切除的肝门部胆管癌的应用探索

Application of 192Ir brachytherapy combined with external beam radiation and biliary stent in the treatment of unresectable hilar cholangiocarcinoma

目的:评价 192Ir近距离放疗联合外照射治疗不能手术切除的肝门部胆管癌的疗效及安全性。 方法:回顾分析2016年2月至2018年7月河北省沧州中西医结合医院收治的26例不能手术切除的肝门部胆管癌患者的临床资料。所有患者均接受 192Ir近距离放疗联合外照射,首先给予经皮肝胆道支架置入,然后行外照射放疗(放疗剂量45 Gy,分25次),再给予 192Ir近距离放疗(放疗剂量20 Gy,分4次),并化疗4~6个周期。评价近期及远期疗效,并分析治疗前后Karnofsky功能状态(KPS)评分、CA19-9、总胆红素(TBIL)、直接胆红素(DBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平变化及经皮肝穿胆道引流(PTCD)管留置时间。根据美国肿瘤放射治疗协作组织(RTOG)损伤分级标准记录不良反应。 结果:治疗结束3个月后,完全缓解4例(15.4%),部分缓解20例(76.9%),病情稳定2例(7.7%),无疾病进展患者,客观缓解率为92.3%(24/26)。1年、2年局部控制率分别为75.0%、62.5%,1年、2年总生存率分别为57.7%、26.9%。治疗结束1个月KPS评分为70.39±10.76,较治疗前60.00±10.58明显升高( t=-27.00, P<0.001)。治疗前及治疗结束1个月、2个月、3个月CA19-9水平分别为(390.88±202.62)U/ml、(322.45±204.06)U/ml、(254.00±160.49)U/ml、(182.85±124.05)U/ml,呈现逐渐下降的趋势,差异具有统计学意义( F=126.94, P<0.001);TBIL[(250.88±80.83)μmol/L、(153.98±61.74)μmol/L、(93.45±38.12)μmol/L、(53.82±26.75)μmol/L]、DBIL[(205.82±66.68)μmol/L、(133.23±58.53)μmol/L、(64.31±36.25)μmol/L、(40.55±26.16)μmol/L]、ALT[(163.92±54.12)U/L、(68.23±28.86)U/L、(45.73±21.94)U/L、(32.66±12.88)U/L]、AST[(177.69±58.68)U/L、(79.23±32.87)U/L、(49.77±25.45)U/L、(35.54±16.10)U/L]均呈进行性下降,差异均有统计学意义( F=315.60, P<0.001;F=385.30, P<0.001;F=284.24, P<0.001;F=311.80, P<0.001),肝功能得以改善。所有患者治疗后均拔除PTCD管,拔管中位时间54 d(49~96 d)。治疗期间出现骨髓抑制、恶心呕吐、腹部胀痛、胆道感染等不良反应,给予对症治疗后均好转,未发生胆漏、胆道出血等严重并发症。 结论:192Ir近距离放疗联合外照射治疗不能手术切除的肝门部胆管癌疗效可靠,可改善患者生命质量,不良反应可耐受,为临床提供了一种可行、安全的治疗方法。

Objective To evaluate the efficacy and safety of 192Ir brachytherapy combined with external beam radiation for the treatment of unresectable hilar cholangiocarcinoma.Methods The clinical data of 26 patients with unresectable hilar cholangiocarcinoma admitted to Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine from February 2016 to July 2018 were retrospectively analyzed.All patients received 192Ir brachytherapy combined with external beam radiation.First,percutaneous hepatobiliary stent implantation was given,followed by external beam radiotherapy(radiotherapy dose 45 Gy,25 times),and then 192Ir brachytherapy(radiotherapy dose 20 Gy,4 times),a total of 4 to 6 cycles of chemotherapy.The short-term and long-term efficacy were evaluated,and the Karnofsky performance status(KPS)score,CA19-9,total bilirubin(TBIL),direct bilirubin(DBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST)level changes and percutaneous transhepatic biliary drainage(PTCD)tube indwelling time were analyzed.Adverse reactions were recorded according to the Radiation Therapy Oncology Group(RTOG)injury classification standard.Results Three months after the end of treatment,4 cases(15.4%)were completely remitted,20 cases(76.9%)were partially remitted,2 cases(7.7%)were stable,and there was no disease progression.The objective remission rate was 92.3%(24/26).The 1-year and 2-year local control rates were 75.0%and 62.5%respectively,and the 1-year and 2-year overall survival rates were 57.7%and 26.9%respectively.The KPS score was 70.39±10.76 one month after the treatment,which was significantly higher than the 60.00±10.58 before treatment(t=-27.00,P<0.001).The levels of CA19-9 before treatment and 1 month,2 months and 3 months after treatment were(390.88±202.62)U/ml,(322.45±204.06)U/ml,(254.00±160.49)U/ml,(182.85±124.05)U/ml,which showed a gradual decrease trend,and there was a statistically significant difference(F=126.94,P<0.001).TBIL[(250.88±80.83)μmol/L,(153.98±61.74)μmol/L,(93.45±38.12)μmol/L,(53.82±26.75)μmol/L],DBIL[(205.82±66.68)μmol/L,(133.23±58.53)μmol/L,(64.31±36.25)μmol/L,(40.55±26.16)μmol/L],ALT[(163.92±54.12)U/L,(68.23±28.86)U/L,(45.73±21.94)U/L,(32.66±12.88)U/L],AST[(177.69±58.68)U/L,(79.23±32.87)U/L,(49.77±25.45)U/L,(35.54±16.10)U/L]showed progressive decline,with statistically significant differences(F=315.60,P<0.001;F=385.30,P<0.001;F=284.24,P<0.001;F=311.80,P<0.001),and liver function was improved.The PTCD tube was removed after treatment in all patients,with a median time of 54 days(49-96 days).During the treatment,bone marrow suppression,nausea and vomiting,abdominal pain and biliary tract infection occurred.All of them improved after symptomatic treatment.No serious complications such as bile leakage and biliary hemorrhage occurred.Conclusion 192Ir brachytherapy combined with external beam radiation has a reliable curative effect in the treatment of unresectable hilar cholangiocarcinoma.It can improve the quality of life of patients,and the adverse reactions can be tolerated.It provides a feasible and safe treatment method for the clinic.