不同治疗方案针对晚期或不可切除血管肉瘤的单中心研究

Single-center study of different treatment for advanced or unresectable angiosarcoma patients

目的评价不同内科方案治疗晚期或不可切除血管肉瘤的有效性和安全性。方法采用单中心回顾性研究方法,选取2005年1月至2020年8月于中山大学肿瘤防治中心治疗的晚期或不可切除的血管肉瘤患者55例,其中接受以阿霉素为主的一线联合化疗(阿霉素组)34例,接受阿霉素或脂质体阿霉素联合紫杉醇或白蛋白结合型紫杉醇方案一线化疗(联合组)12例,接受紫杉醇为主的一线化疗(紫杉醇组)4例,接受抗血管生成靶向治疗6例,接受程序性死亡受体1(PD-1)抗体联合抗血管生成靶向治疗2例。靶向和免疫联合靶向治疗包括5例一线治疗及3例二线治疗。采用实体瘤的疗效评价标准1.1标准评价疗效,药物不良反应根据常见不良反应事件评价标准4.0版本评价。生存分析采用Kaplan-Meier法和Log rank检验,影响因素分析采用Cox比例风险回归模型。结果阿霉素组34例患者中部分缓解(PR)18例,中位无进展生存时间(PFS)为4.5个月,中位总生存时间(OS)为15个月。联合组12例患者中PR 4例,中位PFS为4个月,中位OS为19个月。紫杉醇组4例患者中PR 2例,中位PFS为3个月,中位OS为9个月。抗血管生成靶向治疗6例患者中PR 1例,中位PFS为3个月,中位OS为16个月;2例PD-1抗体联合培唑帕尼或安罗替尼的患者均取得PR,PFS分别为17个月和>16个月。原发于肺、肝、脾血管肉瘤患者的中位PFS(7.5个月)优于其他原发部位患者(3.0个月,P=0.028),女性血管肉瘤患者的中位OS(20个月)优于男性患者(12个月,P=0.045)。肿瘤原发部位、性别、年龄及治疗方案均不是血管肉瘤患者预后的独立影响因素(均P>0.05)。联合组出现3~4级心脏不良反应2例。结论以蒽环类或以紫杉类为主的化疗在晚期血管肉瘤中仍是主导地位,抗血管生成靶向药物联合PD-1抗体在部分血管肉瘤中可见一定疗效,疗效维持时间长,且不良反应可控。

Objective To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma.Methods This study was a single-center retrospective clinical study.Fifty-five advanced or unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled.There were 34 patients who received first-line doxorubicin-based chemotherapy(doxorubicin group),12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy(combination therapy group),and 4 patients received first-line paclitaxel-based treatment(paclitaxel group).There were 6 patients who received anti-angiogenesis targeted therapy,another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy.Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy.The therapeutic effect was evaluated by RECIST 1.1 standard.The adverse reactions were evaluated by CTCAE4.0 standard.Kaplan-Meier survival analysis was evaluated with Log rank test.Cox proportional hazard model was used to analyze the influencing factors.Results There were 18 patients achieved partial response(PR)in 34 patients in the doxorubicin group,median progression-free survival(mPFS)was 4.5 months,and median overall survival(mOS)was 15 months.Four patients achieved PR in 12 patients in the combination therapy group,mPFS and mOS were 4 months and 19 months.Two patients achieved PR in 4 patients in the paclitaxel group,mPFS and mOS were 3 months and 9 months.However,only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy,mPFS and mOS were 3 months and 16 months.Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months.Median PFS(7.5 months)were longer in those with primary liver,lung and spleen angiosarcoma than in those with other primary site(3.0 months,P=0.028).The mOS(20 months)was longer in females than that in males(12 months,P=0.045).Primary tumor site,sex,age and treatment were not independent prognostic factors for angiosarcoma patients(P>0.05).Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group.Conclusions Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma.Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.