Abstract：
BACKGROUND: While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments.
METHODS: This is a literature review from PubMed search.
RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment.
CONCLUSIONS: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers.
CONCLUSIONS: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.
METHODS: This is a literature review from PubMed search.
RESULTS: Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment.
CONCLUSIONS: Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers.
CONCLUSIONS: International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.
摘要：
背景：虽然可用的全身治疗对晚期血管肉瘤的长期疗效不大，免疫疗法代表了一个有趣的新治疗机会。为了确定它的利益，与标准治疗相比，需要进行临床试验评估其疗效和毒性。
方法：这是PubMed检索的文献综述。
结果：目前有几种全身治疗（化疗和TKI）用于晚期血管肉瘤，ORR为12.5％至68％，PFS为2至7个月。然而,很少有随机试验，主要是第二阶段,已经进行了比较这些治疗。虽然大多数中心建议在一线或二线使用含阿霉素的方案或紫杉醇，即使在没有同意标准治疗的肉瘤专业中心中,也观察到在这种情况下给药的方案具有高度异质性.从评估单独或与抗CTLA4或TKI组合的抗PD1的若干回顾性和II期研究中，已经在血管肉瘤中报道了免疫疗法活性的令人鼓舞的信号。虽然皮肤和头部和颈部的位置似乎更受益于免疫疗法，在任何血管肉瘤亚型中都可以观察到反应。在一般的肉瘤中，特别是在AS中，尚未明确建立预测免疫治疗疗效的生物标志物:高肿瘤突变负担和三级淋巴结构的存在正在评估中.
结论：即使是必不可少的，在AS中开发一项随机临床试验与疾病的异质性作斗争，缺乏协商一致的标准方案，最佳免疫疗法给药的不确定性和缺乏已建立的预测性生物标志物。
结论：国际合作对于在晚期AS中进行随机试验和评估免疫治疗在这种罕见且异质性疾病中的疗效至关重要。
方法：这是PubMed检索的文献综述。
结果：目前有几种全身治疗（化疗和TKI）用于晚期血管肉瘤，ORR为12.5％至68％，PFS为2至7个月。然而,很少有随机试验，主要是第二阶段,已经进行了比较这些治疗。虽然大多数中心建议在一线或二线使用含阿霉素的方案或紫杉醇，即使在没有同意标准治疗的肉瘤专业中心中,也观察到在这种情况下给药的方案具有高度异质性.从评估单独或与抗CTLA4或TKI组合的抗PD1的若干回顾性和II期研究中，已经在血管肉瘤中报道了免疫疗法活性的令人鼓舞的信号。虽然皮肤和头部和颈部的位置似乎更受益于免疫疗法，在任何血管肉瘤亚型中都可以观察到反应。在一般的肉瘤中，特别是在AS中，尚未明确建立预测免疫治疗疗效的生物标志物:高肿瘤突变负担和三级淋巴结构的存在正在评估中.
结论：即使是必不可少的，在AS中开发一项随机临床试验与疾病的异质性作斗争，缺乏协商一致的标准方案，最佳免疫疗法给药的不确定性和缺乏已建立的预测性生物标志物。
结论：国际合作对于在晚期AS中进行随机试验和评估免疫治疗在这种罕见且异质性疾病中的疗效至关重要。
