Dong Guomin, Han Pengyu, Zhang Zhiyun, Ge Qian, Jiang Jian, Li Suoni, Ma Jiequn, Bai Jie, Wei Hui, Zhao Zheng
The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China.
Graduate School, Xi'an Medical University, Xi'an, Shaanxi, China.
Front Oncol. 2025 Aug 18;15:1588950. doi: 10.3389/fonc.2025.1588950. eCollection 2025.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase (c-kit), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha (PDGFRα) mutations are considered wild-type (WT). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. In this case report, we present a rare fusion gastrointestinal stromal tumor (GIST) in a female patient with significant response to entrectinib. The patient was initially diagnosed with a giant gastric GIST (approximately 20.6cm×12.1cm×28.0m in size) showing classic immunohistochemical features (CD117+/DOG1+) on immunohistochemistry. After neoadjuvant imatinib therapy (400 mg/day), partial response was achieved with tumor shrinkage to 14.1cm×7.6cm×15.5cm, followed by radical surgery. Postoperative pathology confirmed high-risk GIST (ypT4N0), with genetic testing revealing a KIT exon11 deletion mutation (p.K558_V560del, VAF 63.80%). Continued oral imatinib adjuvant therapy was initiated. In 2024, disease progression was observed with residual KIT mutation (VAF 1.10%) and new-onset fusion (VAF 35.29%) detected by circulating tumor DNA (ctDNA) analysis. Switching to entrectinib (600 mg/day) achieved partial imaging response within 4 weeks (tumor reduction of approximately 27%), with complete clearance of dual mutations observed in ctDNA after 3 months. The patient maintained sustained response without adverse events during final follow-up. This case highlights the breakthrough efficacy of TRK inhibitors in treating NTRK-fusion GIST and confirms the critical value of liquid biopsy in monitoring drug resistance mechanisms and guiding precision treatment.
胃肠道间质瘤（GISTs）是胃肠道最常见的间充质肿瘤，约85%的病例检测到原癌基因、受体酪氨酸激酶（c-kit）或血小板衍生生长因子受体α（PDGFRα）突变。无c-kit或血小板衍生生长因子受体α（PDGFRα）突变的GISTs被认为是野生型（WT）。最近，在极少数野生型GISTs病例中报告了一些分子改变，包括神经营养性酪氨酸受体激酶（NTRK）融合。这一新发现为在这些亚型的GIST中使用原肌球蛋白受体激酶（TRK）抑制剂治疗打开了窗口。在本病例报告中，我们展示了一名女性患者罕见的融合性胃肠道间质瘤（GIST），其对恩曲替尼有显著反应。患者最初被诊断为巨大胃GIST（大小约为20.6cm×12.1cm×28.0cm），免疫组化显示典型的免疫组化特征（CD117+/DOG1+）。新辅助伊马替尼治疗（400mg/天）后，肿瘤缩小至14.1cm×7.6cm×15.5cm，达到部分缓解，随后进行根治性手术。术后病理证实为高危GIST（ypT4N0），基因检测显示KIT外显子11缺失突变（p.K558_V560del，VAF 63.80%）。开始继续口服伊马替尼辅助治疗。2024年，通过循环肿瘤DNA（ctDNA）分析观察到疾病进展，残留KIT突变（VAF 1.10%）和新出现的融合（VAF 35.29%）。改用恩曲替尼（600mg/天）在4周内实现了部分影像学缓解（肿瘤缩小约27%），3个月后ctDNA中观察到双突变完全清除。在最后一次随访期间，患者维持持续缓解且无不良事件。该病例突出了TRK抑制剂在治疗NTRK融合GIST中的突破性疗效，并证实了液体活检在监测耐药机制和指导精准治疗中的关键价值。
