European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Clin Oncol (R Coll Radiol). 2018 Jul;30(7):448-454. doi: 10.1016/j.clon.2018.02.065. Epub 2018 Mar 15.
Epithelioid sarcoma is a soft tissue sarcoma associated with a high rate of local recurrence after wide resection and high incidence of distant metastasis. Little is known about the clinical course and response to systemic treatments in epithelioid sarcoma patients. We carried out a retrospective analysis of clinical data from epithelioid sarcoma patients to provide a reference for the design of future epithelioid sarcoma-specific studies.
Data from patients with epithelioid sarcoma entered in prospective multi-sarcoma phase II/III trials were pooled: EORTC trial 62012 (doxorubicin versus doxorubicin/ifosfamide), 62043 (pazopanib), 62072 (pazopanib versus placebo) and 62091 (doxorubicin versus trabectedin). Patients had either a local or a centrally confirmed diagnosis of epithelioid sarcoma, had inoperable/metastatic disease at study entry and were eligible for the according trial. Response was assessed according to RECIST 1.1. Progression-free survival (PFS) and overall survival were calculated from date of entry.
Among 976 patients with advanced sarcomas, 27 epithelioid sarcoma patients (2.8%) were eligible for the analysis (17 men, median age at diagnosis 50 years, range 19-72). Eighteen (66.7%) received chemotherapy as first-line treatment (five doxorubicin, eight doxorubicin/ifosfamide, two pazopanib, three trabectedin) and nine (33.3%) received pazopanib as second line or later. The primary tumour was located in the lower extremity (n = 8; 29.6%), upper extremity (n = 5; 18.5%), retro/intra-abdominal (n = 4; 14.8%) and in other locations (n = 10; 37.0%). At entry, metastases were mainly found in lung (n = 17; 63%), lymph nodes (n = 9; 33.3%), bone (n = 8; 29.6%) and soft tissue (n = 7; 25.9%). The best response for first-line patients was four partial responses (22.2%), 10 stable disease (55.6%) and four progressive disease (22.2%). In subsequent lines, pazopanib achieved one partial response (11.1%), four stable disease (44.4%) and four progressive disease (44.4%). All patients but one progressed on treatment. The median PFS and overall survival were 3.8 (95% confidence interval 2.2-4.8) and 10.8 months (95% confidence interval 8.1-21.3), respectively. Five patients were still alive at the time of the according trial analysis.
With all limitations of such a rare disease and small data set, objective response and survival outcomes are similar in epithelioid sarcoma to non-selected sarcoma populations. The clinical testing of novel systemic treatments for epithelioid sarcoma remains an unmet medical need and a high priority.
上皮样肉瘤是一种软组织肉瘤，广泛切除后局部复发率高，远处转移发生率高。对于上皮样肉瘤患者的临床病程和对全身治疗的反应知之甚少。我们对上皮样肉瘤患者的临床数据进行了回顾性分析，为未来上皮样肉瘤特异性研究的设计提供了参考。
纳入前瞻性多肉瘤 II/III 期试验中的上皮样肉瘤患者的数据进行汇总：EORTC 试验 62012（多柔比星与多柔比星/异环磷酰胺）、62043（帕唑帕尼）、62072（帕唑帕尼与安慰剂）和 62091（多柔比星与拓扑替康）。患者的局部或中心确认诊断为上皮样肉瘤，在研究入组时有不可切除/转移性疾病，符合相应试验的条件。根据 RECIST 1.1 评估反应。无进展生存期（PFS）和总生存期从入组日期开始计算。
在 976 例晚期肉瘤患者中，27 例上皮样肉瘤患者（2.8%）符合分析条件（男性 17 例，中位诊断年龄 50 岁，范围 19-72 岁）。18 例（66.7%）接受化疗作为一线治疗（多柔比星 5 例，多柔比星/异环磷酰胺 8 例，帕唑帕尼 2 例，拓扑替康 3 例），9 例（33.3%）接受帕唑帕尼作为二线或更后线治疗。原发肿瘤位于下肢（n=8；29.6%）、上肢（n=5；18.5%）、腹膜后/腹腔内（n=4；14.8%）和其他部位（n=10；37.0%）。入组时，转移主要发生在肺部（n=17；63%）、淋巴结（n=9；33.3%）、骨骼（n=8；29.6%）和软组织（n=7；25.9%）。一线患者的最佳反应是 4 例部分缓解（22.2%）、10 例稳定疾病（55.6%）和 4 例进展疾病（22.2%）。在后续治疗中，帕唑帕尼取得 1 例部分缓解（11.1%）、4 例稳定疾病（44.4%）和 4 例进展疾病（44.4%）。所有患者均进展。中位 PFS 和总生存期分别为 3.8 个月（95%置信区间 2.2-4.8）和 10.8 个月（95%置信区间 8.1-21.3）。截至相应试验分析时，有 5 例患者仍存活。
尽管存在所有这些罕见疾病和小数据集的局限性，但上皮样肉瘤的客观反应和生存结果与非选择性肉瘤人群相似。上皮样肉瘤的新型全身治疗的临床检测仍然是一个未满足的医疗需求，应优先考虑。
