^125I粒子植入术联合化疗治疗72例不可切除晚期胰腺癌临床观察

Clinical effectiveness of I radioactive particle implantation combined with chemotherapy in the treatment for unresectable advanced pancreatic carcinoma

目的胰腺癌发病率逐年递增,死亡率居高不下,而晚期胰腺癌的治疗一直以来都是临床面临的难点。本研究通过对比观察分析^125I粒子植入术联合吉西他滨+顺铂(GP方案)化疗治疗不可切除晚期胰腺癌的疗效,探讨该方法的可行性。方法纳入2013-09-01-2018-09-01潍坊医学院附属医院收治的143例不可切除晚期胰腺癌患者资料进行回顾性分析,依据治疗方案不同分为对照组(n=71)和观察组(n=72)。对照组予以GP方案化疗(吉西他滨1000mg/m^2,静脉滴入>30min,d1、d8;顺铂30mg/m^2,静脉滴入,d2~d4。治疗3周为1个周期,连续治疗3~4个周期。观察组先行^125I粒子植入术,术后5~10d内给予GP方案化疗。比较2组治疗后糖类抗原19-9(carbohydrate antigen 19-9,CA19-9)下降情况、黄疸改善情况、疼痛缓解情况和不良反应发生率,随访无进展生存期(progression-free survival,PFS)及总生存期(overall survival,OS)。结果观察组和对照组CA19-9下降率分别为48.6%(35/72)和26.8%(19/71),差异有统计学意义,χ^2=7.262,P=0.007;黄疸缓解率分别为46.3%(19/41)和23.1%(9/39),差异有统计学意义,χ^2=4.755,P=0.036;疼痛缓解率分别为80.6%(58/72)和45.1%(32/71),差异有统计学意义,χ^2=19.298,P<0.001。2组患者不良反应比较,恶心呕吐(χ^2=0.168,P=0.682)、腹胀(χ^2=1.376,P=0.241)、腹泻(χ^2=0.193,P=0.660)、便秘(χ^2=0,643,P=0.423)、白细胞减少(χ^2=0.186,P=0.666)、血小板减少(χ^2=0.081,P=0.776)和肝损害(χ^2=0.286,P=0.592)的发生率差异均无统计学意义。观察组6和12个月PFS分别为80.5%(58/72)和34.7%(25/72),生存率分别为93.1%(67/72)和77.8%(56/72);对照组6和12个月PFS分别为59.1%(42/71)和2.8%(2/71),生存率分别为74.6%(53/71)和60.6%(43/71)。观察组与对照组中位PFS(mPFS)分别为9.5和5.2个月,中位OS(mOS)为12.5和10.1个月,观察组mPFS和mOS均较对照组延长。^125I放射性粒子植入术联合化疗患者的死亡风险低于单纯GP方案化疗的患者(HR=0.475,95%CI:0.253~0.892,P=0.021)。结论^125I粒子植入术联合GP方案化疗用于不可切除晚期胰腺癌,在不增加不良反应的前提下,对缓解梗阻性黄疸以及降低CA19-9水平有一定疗效,同时显著缓解疼痛,提高患者的生活质量,延长生存时间。

OBJECTIVE For a long time,the therapy for advanced pancreatic cancer is a clinical difficulty.The aim of this study was to assess the feasibility and long-term effect of^125 I radioactive particle implantation combined with GP chemotherapy in the treatment of advanced stage of pancreatic cancer.METHODS In this study,treated in Affiliated Hospital of Weifang Medical University,one hundred and forty-three patients with advanced pancreatic cancer were involved.We divided our patients into control group(n=71)and experimental group(n=72).In control group,Gemcitabine(1000 mg/m^2)and Cisplatin(30 mg/m^2)were administered on d1,d8,and d2-d4 every 21 days for 3 or 4 cycles,whereas the experimental group received implantation of^125 I radioactive particles within 5-10 days following Gemcitabine and Cisplatin chemotherapy.After these treatments,we compared reduction rate of CA19-9,remission rate of jaundice,pain relief rate,incidence of adverse reactions,progression free survival time(PFS)and the overall survival(OS)between the two groups.RESULTS The reduction rate of CA19-9 of the experimental group was 48.6%(35/72)and that of the controlled group was 26.8%(19/71).The difference was statistically significant,χ^2=7.262,P=0.007.The remission rate of jaundice of the experimental group was 46.3%(19/41)and that of the controlled group was 23.1%(9/39).The difference was statistically significant,χ^2=4.755,P=0.036.The pain relief rate of the experimental group was 80.6%(58/72)and that of the controlled group was 45.1%(32/71).The difference was statistically significant,χ^2=19.298,P<0.001.The adverse reactions of the two groups are nausea and vomiting,abdominal distension,diarrhoea,constipation,leucocytopenia,thrombocytopenia and liver injury.The incidence of adverse reactions in experimental group were similar to that in control group.The difference was not statistically significant.The rates of progression free survival in experimental group were 80.5%(58/72)and 34.7%(25/72)at 6,12 months,respectively,which were significantly higher than59.1%(42/71)and 2.8%(2/71)of the control group.The rates of overall survivall in experimental group were 93.1%(67/72)and 77.8%(56/72)at 6,12 months,and those of the control group were 74.6%(53/71)and 60.6%(43/71).The median of PFS(mPFS)in experimental group and controlled group were 9.5 months and 5.2 months.The median of OS(mOS)in experimental group and control group were 12.5 months and 10.1 months.To summarize,we observed significant extensions of mPFS and mOS in experimental group compared with control group.Patients with implantation of^125 I radioactive particles combined with Gemcitabine and Cisplatin chemotherapy had a lower risk of death than those with Gemcitabine and Cisplatin chemotherapy(HR=0.475,95%CI:0.253-0.892,P=0.021).CONCLUSIONS The therapy of advanced stage of pancreatic cancer,^125 I radioactive particle implantation combined with GP chemotherapy is a safe and effective treatment.Without increasing adverse reactions,it exerts a certain effect on relieving obstructive jaundice and reducing CA19-9 rate,while significantly relieving pain.These improve the life quality of patients and prolong the patients’survival time.