中国实用外科杂志

中国实用外科杂志

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局限进展期胃肠间质瘤行伊马替尼术前辅助治疗23例疗效分析

陈斯乐，宋    武，彭建军，陈创奇，蔡世荣，何裕隆，詹文华，张信华   

  1. 中山大学附属第一医院，广东广州 510080
  • 出版日期:2018-05-01 发布日期:2018-04-27

  • Online:2018-05-01 Published:2018-04-27

摘要：

目的    探讨局限进展期胃肠间质瘤（GIST）行伊马替尼术前辅助治疗的有效性和安全性。方法    回顾性分析中山大学附属第一医院2008年1月至2013年12月确诊为局限进展期GIST并接受伊马替尼术前辅助治疗的23例病人的临床病理资料。结果    术前伊马替尼治疗中位时间为6（1～18）个月，22例400 mg/d，1例600 mg/d持续口服。22例获得有效的影像学评价，其中，19例（86.4%）影像学评价为部分缓解［1例术后证实病理学完全缓解（4.5%）；实际部分缓解18例（81.8%）］；疾病稳定3例（13.6%）。无原发耐药进展的病人。经过术前治疗，肿瘤缩小中位数为4（0～9）cm。伊马替尼术前停药时间为7（5～14）d。伊马替尼术前治疗期间，3级或以上不良反应发生率26.1%（6/23），其中3级粒细胞减少2例，4级药疹1例，消化道出血3例（1例死亡）。手术完整切除22例。术后发生3级以上手术相关并发症2例（9.1%），均为术后延迟性胃排空，均经保守治疗后治愈。22例病人中，KIT基因外显子11突变18例（81.8%），KIT基因外显子9突变3例（13.6%），KIT和PDGFRA野生型1例（4.5%）。20例病人术后接受辅助治疗，辅助治疗中位时间25（4～74）个月。随访中位时间为50（39～105）个月。预计术后5年无病存活率和总存活率分别为65.6%和80.5%。但单因素及多因素Cox回归分析显示，术后无进展生存及总生存时间与各种因素无相关性。结论    伊马替尼术前辅助治疗局限进展期GIST总体耐受良好，有助于缩小手术范围，严重不良反应发生率低，治疗期间应注意观察和合理处理药物副反应。伊马替尼术前辅助治疗能否改善GIST病人总生存期尚待进一步大样本研究。

关键词: 胃肠间质瘤, 辅助治疗, 伊马替尼

Abstract:

Analysis of the effectiveness of imatinib preoperative adjuvant therapy in 23 patients with locally advanced gastrointestinal stromal tumor        CHEN Si-le, SONG Wu, PENG Jian-jun, et al. The First Affiliated Hospital, SUN Yat-sen University, Guangzhou 510080, China
Corresponding author: ZHANG Xin-hua，E-mail: zhangxh_sysu@163.com
Abstract    Objective    To investigate the efficacy and safety of preoperative adjuvant therapy with imatinib for locally advanced gastrointestinal stromal tumor (GIST). Methods    The clinicopathological data of 23 patients diagnosed with locally advanced GISTs who received imatinib as preoperative adjuvant therapy in the First Affiliated Hospital, SUN Yat-sen University from January 2008 to December 2013 were analyzed retrospectively. Results    Preoperative imatinib was given for 6（1-18）months, 22 patients with 400 mg/day, and 1 with 600 mg/day, with continuous oral administration. Image study for response assessment was achieved in 22 cases, of which 19 cases(86.4%) gained partial response [18 cases (81.8%) with pathologically partial response , 1 cases providing pathologically complete response (4.5%) after operation], 3 cases(13.6%)with stable disease . The tumor size was reduced 4（0-9）cm after preoperative treatment. The mean time from imatinib withdrawal to operation was 7（5-14）days. During the preoperative treatment of imatinib, the incidence of adverse event of grade 3 or above was 26.1（6/23）, including 2 cases of neutropenia(grade 3), 1 case of rash(grade 4), and 3 cases of gastrointestinal bleeding(1 case death). Complete resection was performed in 22 cases. Postoperative complications at grade 3 or above occurred to 2 patients (9.1%), both of whom were of delayed gastric emptying and resolved with conservative therapy. There were 18 cases (81.8%) with KIT exon 11 mutation, 3 cases(13.6%) with KIT exon 9 mutation and 1 case(4.5%) with KIT and PDGFRA wild-type. Twenty out of 22 patients received adjuvant therapy after operation, and the median time of adjuvant therapy was 25(4—74) months. The median time of follow-up was 50 (39—105) months, 5-year disease-free survival rate and overall survival rate were estimated to be 65.6% and 80.5%, respectively. But univariate and multivariate Cox regression analysis showed no significant difference in progression free survival and overall survival time. Conclusion    Preoperative imatinib therapy for locally advanced GISTs is generally well tolerated, and is helpful to narrow the scope of surgery. Though the incidence of serious adverse event is low, the side effects of the treatment should be observed and treated reasonably during the preoperative imatinib therapy. Whether or not imatinib preoperative adjuvant therapy can improve the total survival of patients with GIST needs to be further studied in large samples.

Key words: gastrointestinal stromal tumor, adjuvant therapy, imatinib