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目的在进展期的胃肠间质瘤(GIST)患者中,大约有5%到7%的患者存在血小板衍生生长因子α(PDGFRα)基因突变的情况。此文旨在评估此类亚组患者使用伊马替尼治疗的效果。方法我们进行了一项国际调查,依据在胃肠间质瘤转诊中心的资料,收集伴有PDGFRα基因突变的进展期胃肠间质瘤患者使用伊马替尼治疗的临床数据进行分析。结果总共有58例患者资料被收集,其中34例男性,24例女性,开始接受治疗时的中位年龄61岁(年龄范围,19～ 83岁)。在这些患者中,原发肿瘤在胃部的有40例(69%)。32例(55%)患者是PDGFRα-D842V替代突变,17例(29%)患者是外显子18的密码子突变,还有9例(16%)患者是其它外显子的突变。治疗后57例患者接受了疗效评估,其中2例(4%)患者完全缓解,8例(14%)患者部分缓解,23例(40%)患者疾病稳定。31例D842V替代突变被评估的患者中,没有1例在治疗后得到缓解,反而21例(68%)患者出现进展。对于D842V替代突变的患者无进展生存期的中位时间是2.8个月(95%CI=2.6-3.2),而PDGFRα其它部位突变的患者,无进展生存期的中位时间是28.5个月(95%CI=5.4-51.6)。经过46个月的随访,D842V替代突变患者总生存期的中位时间是14.7个月,比非D842V替代突变患者的总生存期要短。结论本研究是目前最大宗的对伴有PDGFRα突变的进展期胃肠间质瘤患者使用伊马替尼治疗的疗效研究。结果证实,伊马替尼对于外显子18中D842V替代突变这一亚组的患者疗效不佳,对于其它突变的患者伊马替尼治疗敏感。
Objectives In patients with advanced gastrointestinal stromal tumors (GISTs), approximately 5% to 7% of patients have mutations in the platelet-derived growth factor alpha (PDGFRα) gene. This article aims to assess the efficacy of imatinib therapy in this subset of patients. Methods We conducted an international survey to analyze clinical data on the use of imatinib in patients with advanced gastrointestinal stromal tumors with mutations in the PDGFRα gene based on data from a referral center for gastrointestinal stromal tumors. RESULTS A total of 58 patient data were collected, 34 of them were males and 24 were females. The median age at onset of treatment was 61 years (range, 19-83 years). Of these patients, 40 (69%) had primary tumors in the stomach. 32 (55%) patients were PDGFRα-D842V substitution mutations, 17 (29%) were exon 18 codon mutations, and 9 (16%) were other exon mutations. Fifty-seven patients were evaluated for efficacy after treatment, with 2 (4%) patients completely relieved, 8 (14%) partially relieved, and 23 (40%) stable. Of the 31 patients evaluated for D842V substitution mutation, none of them was relieved after treatment, whereas 21 patients (68%) experienced progression. The median progression-free survival was 2.8 months (95% CI = 2.6-3.2) for patients with the D842V substitution mutation, while the median progression-free survival was 28.5 months for patients with other mutations in PDGFRα % CI = 5.4-51.6). After a 46-month follow-up, the median overall survival was 14.7 months for D842V surrogate mutants and shorter overall survival than for non-D842V surrogate mutants. Conclusions This study is currently the largest study of the efficacy of imatinib in patients with advanced gastrointestinal stromal tumors with the PDGFRα mutation. The results confirm that imatinib is ineffective in patients with the subgroup of D842V substitution mutations in exon 18 and is sensitive to imatinib treatment in other mutated patients.