Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Cancer Med. 2019 Mar;8(3):1034-1043. doi: 10.1002/cam4.1994. Epub 2019 Jan 28.
The long-term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001-2007 (33.2%) and 2008-2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6-85.5) years and 51 (0-324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2. Response and disease control rates with imatinib in measurable GIST were 63.1% and 94.3%, respectively, without differences between periods. More patients in period 2 underwent surgical resection for TKI-responsive diseases within the first 2 years (24.9%, P = 0.006). With a median follow-up of 6.1 years (2.5-16.0) in survivors, median progression-free survival (PFS) was 5.4 years [95% confidence interval (CI), 4.0-6.9]. Subsequent sunitinib (P = 0.066) and regorafenib (P = 0.003) were more commonly administered in period 2. Median overall survival (OS) was 8.8 years (95% CI, 7.8-9.7). PFS with imatinib (P = 0.002) and OS (P = 0.019) were significantly longer in period 2. Young age, smaller tumor size at the initiation of imatinib, KIT exon 11 mutation, surgical intervention, and period 2 were favorable factors for PFS and OS. Patients with advanced GIST showed better prognosis with the optimal use of imatinib, along with active surgical intervention and more common use of subsequent TKIs in period 2.
评估了酪氨酸激酶抑制剂（TKI），包括伊马替尼，以及手术干预对晚期胃肠道间质瘤（GIST）的长期影响。所有 379 名患者均患有转移性或复发性 GIST，并于第 1 期和第 2 期在 Asan 医疗中心开始服用 400mg/d 伊马替尼[分别为 2001-2007 年（33.2%）和 2008-2014 年（66.8%）]。男性占 60.4%；开始服用伊马替尼时，中位患者年龄和肿瘤大小分别为 58.6（14.6-85.5）岁和 51（0-324）mm，两个时期之间无差异，除了第 2 期年龄较大和术前伊马替尼治疗较少。在可测量的 GIST 中，伊马替尼的反应率和疾病控制率分别为 63.1%和 94.3%，两个时期之间无差异。第 2 期有更多的患者因 TKI 反应性疾病在 2 年内接受手术切除（24.9%，P=0.006）。在存活者中，中位随访 6.1 年（2.5-16.0），中位无进展生存期（PFS）为 5.4 年[95%置信区间（CI），4.0-6.9]。随后，舒尼替尼（P=0.066）和瑞戈非尼（P=0.003）在第 2 期更常使用。中位总生存期（OS）为 8.8 年[95%CI，7.8-9.7]。第 2 期伊马替尼的 PFS（P=0.002）和 OS（P=0.019）明显更长。伊马替尼开始时年龄较小、肿瘤较小、KIT 外显子 11 突变、手术干预和第 2 期是 PFS 和 OS 的有利因素。晚期 GIST 患者在最佳使用伊马替尼的基础上，加上积极的手术干预和第 2 期更常使用后续 TKI，预后更好。
