Chiusole Benedetta, Le Cesne Axel, Rastrelli Marco, Maruzzo Marco, Lorenzi Martina, Cappellesso Rocco, Del Fiore Paolo, Imbevaro Silvia, Sbaraglia Marta, Terrier Philippe, Ruggieri Pietro, Dei Tos Angelo Paolo, Rossi Carlo Riccardo, Zagonel Vittorina, Brunello Antonella
Medical Oncology 1, Istituto Oncologico Veneto IRCCS, Padova, Italy.
Medical Oncology, Insitut Gustave Roussy, Villejuif, Ile-de-France, France.
Front Oncol. 2020 Jun 16;10:828. doi: 10.3389/fonc.2020.00828. eCollection 2020.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics. This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database. 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival. In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.
骨外黏液样软骨肉瘤（EMC）是软组织肉瘤（STS）的一种罕见亚型，通常发生于四肢。它存在涉及NR4A3基因的相互易位。其生物学行为相对惰性，但长期随访研究显示局部和远处复发比例较高。对于疾病进展的转移性患者，以蒽环类药物为基础的化疗是标准的一线治疗方案，但其活性有限。有证据表明抗血管生成药物可能具有活性。这是一项在威尼斯肿瘤研究所和古斯塔夫·鲁西研究所开展的回顾性研究。从一个前瞻性维护的数据库中提取了1980年1月至2018年12月所有确诊为EMC的患者。共识别出59例患者，其中男性37例（62.7%），女性22例（37.3%），男女比例为1.7/1。我们对23例患者进行了分子分析，所有患者均携带EWSR1-NR4A3。在49例接受根治性治疗的患者中，28.6%出现局部复发，40.8%出现转移。在接受根治性切除（R0）的患者中，局部复发率为7.6%，转移率为15.4%；在接受R1手术治疗的患者中，复发率更高。20例患者因转移性疾病接受化疗；最佳反应为部分缓解，50%的患者有临床获益。14例患者接受二线化疗，疾病控制率为46.1%。8例患者接受了药物假期，平均时长为22.8个月。研究人群的中位总生存期为180个月，转移性患者为76个月。所有研究变量均未发现显著的预后作用，但观察到完整手术、原发肿瘤位于四肢以及孤立性肺转移患者有生存更好的趋势。转移性疾病的化疗与生存呈负相关。在这个大型的EMC患者回顾性队列中，原发肿瘤位置和孤立性肺转移似乎与更好的生存相关。化疗对未选择的患者生存无影响。有必要进一步开展研究以确定更有效的治疗方案，并提供临床和分子因素来选择可能延迟转移性疾病全身治疗的患者。
