使用Y-90树脂微球进行选择性内照射（SIRT）治疗对酪氨酸激酶抑制剂（TKI）治疗耐药的胃肠道间质瘤（GIST）肝转移灶
Selective internal radiation with Y-90 resin microspheres (SIRT) for liver metastases of gastro-intestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy.
作者信息
Hohenberger Peter, Rathmann Nils, Büsing Karen, Menge Franka, Jakob Jens, Pink Daniel, Wardelmann Eva, Schoenberg Stefan O, Diehl Steffen J
机构信息
Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany.
Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany.
出版信息
Br J Cancer. 2025 May;132(8):716-724. doi: 10.1038/s41416-025-02952-3. Epub 2025 Mar 5.
BACKGROUND
Hepatic metastases of GIST might be the dominant site of progression and resistant to available tyrosine kinase inhibitors (TKIs). Selective internal radiation therapy (SIRT) offers treatment by intratumoral radiation up to 200 Gy. We analyzed the hepatic progression-free survival (H-PFS) in a consecutive patient cohort.
METHODS
Twenty-six patients (median age 57.6 years) with biopsy proven liver metastases of GIST were treated by SIRT. All had RECIST documented tumor progression, and 24/26 patients had up to four lines of pretreatment. Mutational status was 'quadruple wildtype' (q-wt, n = 5), KIT exon 11/9/13 in n = 15/4/1 cases and PDGFRα (n = 1). Median follow-up of this retrospective analysis of a prospectively kept database is 33.6 months.
RESULTS
Median H-PFS was 16 months (range, 4-54+ months, 95% CI 6.5-25.4 months) and OS after SIRT was 28 months (95% CI 17.2-28.7 months). Best H-PFS was observed in patients with 'q-wt' at 25 months (range, 6+-54 months, 95% CI 16.2-33.8 months). The worst outcome was for KIT exon 11 mutations plus secondary mutations with 7 months (range, 4-33 months, 95% CI, 4.2-9.8 months).
CONCLUSIONS
90Y-SIRT is a potent treatment for patients with liver metastases of GIST resistant to TKI therapy. In patients with 'q-wt' GIST, SIRT is an option for first-line use.
背景
胃肠道间质瘤（GIST）的肝转移可能是疾病进展的主要部位，且对现有的酪氨酸激酶抑制剂（TKIs）耐药。选择性内照射治疗（SIRT）可通过瘤内照射提供高达200 Gy的治疗剂量。我们分析了一组连续患者队列的肝无进展生存期（H-PFS）。
方法
26例经活检证实为GIST肝转移的患者（中位年龄57.6岁）接受了SIRT治疗。所有患者均有根据实体瘤疗效评价标准（RECIST）记录的肿瘤进展，24/26例患者接受过最多四线的预处理。突变状态为“四重野生型”（q-wt，n = 5），KIT外显子11/9/13突变分别为15/4/1例，血小板衍生生长因子受体α（PDGFRα）突变1例（n = 1）。对前瞻性保存数据库的这项回顾性分析的中位随访时间为33.6个月。
结果
中位H-PFS为16个月（范围4 - 54 +个月，95%置信区间6.5 - 25.4个月），SIRT后的总生存期（OS）为28个月（95%置信区间17.2 - 28.7个月）。“q-wt”患者的最佳H-PFS为25个月（范围6 + - 54个月，95%置信区间16.2 - 33.8个月）。KIT外显子11突变加继发突变患者的预后最差，为7个月（范围4 - 33个月，95%置信区间4.2 - 9.8个月）。
结论
90Y-SIRT是治疗对TKI治疗耐药的GIST肝转移患者的有效方法。对于“q-wt”GIST患者，SIRT可作为一线治疗选择。
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