除了幼年纤维肉瘤（IFS）外，关于NTRK重排间质肿瘤（NMT）的了解非常少。本研究的目的是描述NMT的分布、特征、自然史和预后。该研究作为一项转化性研究计划进行，回顾性地从500例软组织肉瘤（STS；除IFS外）的队列中进行，同时在例行实践和RNASARC分子筛选计划中进行前瞻性研究（N = 188; NCT03375437）。利用RNA测序，在16例诊断为STS的患者肿瘤中检测到NTRK融合：简单基因组学的肉瘤样本有8个（4个NTRK重排的纺锤细胞肿瘤、3个ALK/ROS野生型炎性肌纤维母细胞瘤和1个四重野生型胃肠道平滑肌肉瘤），复杂基因组学的肉瘤样本有8个（分化不良脂肪肉瘤、内皮肉瘤、平滑肌肉瘤、未分化多形性肉瘤、高级别子宫肉瘤、恶性周围神经鞘瘤）。在8个简单基因组学患者中，有4个在不同阶段接受了酪氨酸受体激酶抑制剂（TRKi）治疗，并且所有患者从治疗中受益，其中一个完全缓解。在另外8名患者中，有6名发生了转移扩散，转移生存中位数为21.9个月，这与这些肿瘤类型的典型报告相符。其中两人接受了第一代TRKi，但没有明显疗效。我们的研究证实了NTRK融合在STS中的低频率和组织类型多样性。尽管简单基因组学NMT中TRKi的活性得到了确认，但我们的临床数据鼓励随后进行关注NTRK融合在复杂基因组学Sarcomas中的生物学相关性，以及TRKi在这种人群中的疗效的研究。Copyright © 2023 The Author(s). Published by Elsevier Ltd. All rights reserved.

Apart for infantile fibrosarcoma (IFS), very little is known about NTRK-rearranged mesenchymal tumors (NMTs). The objective of this study is to describe the distribution, characteristics, natural history, and prognosis of NMT.This study was carried out as a translational research program, retrospectively from a cohort of 500 soft tissue sarcoma (STS; excluding IFS) and prospectively both in routine practice and from the RNASARC molecular screening program (N = 188; NCT03375437).Using RNA-sequencing, NTRK fusion was detected in 16 patient tumors diagnosed as STS: 8 samples of sarcoma with simple genomics (4 NTRK-rearranged spindle cell neoplasm, 3 ALK/ROS wild-type inflammatory myofibroblastic tumor, and 1 quadruple Wild-type gastrointestinal stromal tumor) and 8 samples of sarcomas with complex genomics (dedifferentiated liposarcoma, intimal sarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, high-grade uterine sarcoma, malignant peripheral nerve sheath tumor). Among the eight patients with simple genomics, four were treated with tyrosine receptor kinase inhibitor (TRKi) at different stages of the disease and all benefited from the treatment, including one complete response. Among the eight other patients, six evolved with metastatic spreading and the median metastatic survival was 21.9 months, as classically reported in these tumor types. Two of them received a first-generation TRKi without objective response.Our study confirms low frequency and histotype diversity of NTRK fusion in STS. While the activity of TRKi in simple genomics NMT is confirmed, our clinical data encourage subsequent studies focusing on the biological relevance of NTRK fusions in sarcomas with complex genomics together with the efficacy of TRKi in this population.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.