Background: Neoadjuvant imatinib therapy plays a crucial role in the management of gastrointestinal stromal tumors (GISTs), but its impact across various mutational profiles remains uncertain. Objective: The aim of this study is to describe the clinicopathological features and to assess the response and surgical outcomes of neoadjuvant imatinib in GIST patients exhibiting diverse mutational profiles. Methods: We conducted a retrospective study, extracting data from the Dutch GIST Registry, including patients treated with neoadjuvant imatinib. Response rate was the primary outcome, and secondary outcomes were the time on neoadjuvant treatment and resection margins (R0 vs. R1/R2), respectively. Results: Between 2009 and 2021, 326 patients were treated with neoadjuvant imatinib, of which 264 (80.9%) underwent resection. A total of 197 (74.6%) of them had aKIT-exon 11 mutation, 19 (7.3%) had otherKITmutations, 10 (3.8%) had PDGFRA D842 mutations, 21 (6.8%) had other PDGFRA mutations, 2 (0.7%) had NTRK mutation, 1 (0.4%) had an SDH mutation, and 17 (6.4%) had WT GISTs. Patients withKIT-exon 11 mutations demonstrated a higher rate of partial response to imatinib (60.5% vs. 33.3%;p= 0.00). A positive resection margin (R1 or R2) was observed in 14 (21.2%) patients with a non-KITexon 11 mutations and in 11 (5.5%) patients with aKIT-exon 11 mutation (p= 0.00). Moreover, non-KITexon 11 mutation patients had a shorter median duration of neoadjuvant therapy (5.3 months, range 0.5–21.0) compared to patients with aKITexon 11 mutation (8.8 months, range 0.2–31.3;p< 0.001). Conclusions: Our study highlights the variability in treatment response associated with different GIST mutational profiles. Patients with aKIT-exon-11 mutation tended to respond more favorably to neoadjuvant imatinib in terms of partial response and surgical outcomes.
背景：新辅助伊马替尼治疗在胃肠道间质瘤（GIST）的治疗中起着关键作用，但其对不同突变谱的影响尚不明确。目的：本研究旨在描述具有不同突变谱的GIST患者的临床病理特征，并评估新辅助伊马替尼的治疗反应及手术结果。方法：我们开展了一项回顾性研究，数据来源于荷兰GIST登记库，纳入接受新辅助伊马替尼治疗的患者。主要结局指标为治疗反应率，次要结局指标分别为新辅助治疗持续时间和手术切缘状态（R0对比R1/R2）。结果：2009年至2021年间，共有326例患者接受新辅助伊马替尼治疗，其中264例（80.9%）接受了手术切除。在手术患者中，197例（74.6%）携带KIT外显子11突变，19例（7.3%）为其他KIT突变，10例（3.8%）为PDGFRA D842突变，21例（6.8%）为其他PDGFRA突变，2例（0.7%）为NTRK突变，1例（0.4%）为SDH突变，17例（6.4%）为野生型GIST。KIT外显子11突变患者对伊马替尼的部分缓解率更高（60.5%对比33.3%；p=0.00）。非KIT外显子11突变患者中14例（21.2%）出现阳性切缘（R1或R2），而KIT外显子11突变患者中仅11例（5.5%）出现阳性切缘（p=0.00）。此外，非KIT外显子11突变患者的中位新辅助治疗持续时间（5.3个月，范围0.5-21.0）短于KIT外显子11突变患者（8.8个月，范围0.2-31.3；p<0.001）。结论：我们的研究揭示了不同GIST突变谱与治疗反应之间的差异性。在部分缓解率和手术结果方面，携带KIT外显子11突变的患者对新辅助伊马替尼治疗往往表现出更好的反应。
Impact of Mutation Profile on Outcomes of Neoadjuvant Therapy in GIST
肿瘤(癌症)患者之家