Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Dipartimento di Medicina Sperimentale, Specialistica e Diagnostica, Università di Bologna, Bologna, Italy.
Eur J Cancer. 2014 Jun;50(9):1657-64. doi: 10.1016/j.ejca.2014.03.013. Epub 2014 Apr 2.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases.
From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib.
Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples.
This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.
骨外黏液样软骨肉瘤（EMC）是一种罕见的软组织肉瘤，其特征在于存在 NR4A3 重排。本文报道了一系列 10 例患者接受舒尼替尼治疗的疗效，这些患者的疗效强化了我们最初在两例患者中观察到的结果。
自 2011 年 7 月以来，连续有 10 例进展性转移性 EMC 患者接受舒尼替尼 37.5mg/天的治疗，为指定用途。为了尝试解释舒尼替尼在 EMC 中的作用，我们通过荧光原位杂交（FISH）分析进行了基因型/表型相关性研究。此外，还对一组有限的样本进行了转录组、免疫组织化学和生化分析，重点关注一些可能的舒尼替尼靶点。
10 例患者中有 8 例仍在接受治疗。6 例患者有实体瘤反应评估标准（RECIST）部分缓解（PR），2 例稳定，2 例进展。6 例可评估的病例中 PET 结果一致。1 例患者在接受舒尼替尼治疗后接受了手术，病理反应证实有效。在 8.5 个月的中位随访时间（范围 2-28 个月）内，未发现继发性耐药。中位无进展生存期（PFS）尚未达到。有趣的是，所有有反应的病例均表达典型的 EWSR1-NR4A3 融合，而耐药性病例则携带替代的 TAF15-NR4A3 融合。在推测的舒尼替尼靶点中，只有 RET 在分析样本中表达并激活。
本报告证实了舒尼替尼在 EMC 中的治疗活性。基因型/表型分析支持反应与 EWSR1-NR4A3 融合之间的相关性。RET 的参与值得进一步研究。
