Iwatsuki Masaaki, Harada Kazuto, Iwagami Shiro, Eto Kojiro, Ishimoto Takatsugu, Baba Yoshifumi, Yoshida Naoya, Ajani Jaffer A, Baba Hideo
Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.
Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center Houston USA.
Ann Gastroenterol Surg. 2018 Sep 27;3(1):43-49. doi: 10.1002/ags3.12211. eCollection 2019 Jan.
Gastrointestinal stromal tumors (GIST) are rare and mesenchymal in origin with a yearly incidence of 10-15 cases per million people. If it is technically resectable, surgical resection is the mainstay of therapy regardless of tumor location,. Although complete (R0) resection can be achieved in up to 85% of patients with primary disease, approximately 50% of patients experience recurrence or metastases within 5 years of primary resection. Moreover, prior to 2000, the prognosis of patients with advanced, inoperable GIST was poor because the molecular mechanism had not sufficiently been elucidated, thus effective therapy was lacking. The tyrosine kinase inhibitor imatinib, which selectively inhibits tyrosine kinase KIT, has shown substantial clinical benefit for patients with GIST. In clinical trials, imatinib treatment resulted in response rates of 40%-55% and longer progression-free survival for patients with a KIT-positive unresectable or metastatic GIST. Furthermore, recent clinical trials have shown that giving imatinib after curative resection for high-risk cases prolonged recurrence-free survival and overall survival in an adjuvant setting. Several clinical trials of imatinib treatment in a neoadjuvant setting are ongoing; however, in clinical settings, there are problems to resolve, such as optimal agents, duration of administration, and postoperative management. In this review, we discuss the application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib treatment and their potential impact on survival for patients with primary, recurrent, or metastatic GIST.
胃肠道间质瘤(GIST)较为罕见,起源于间充质,年发病率为每百万人10 - 15例。如果在技术上可切除,无论肿瘤位置如何,手术切除都是主要的治疗方法。尽管高达85%的原发性疾病患者能够实现完全(R0)切除,但约50%的患者在初次切除后5年内会出现复发或转移。此外,在2000年之前,晚期、无法手术切除的GIST患者预后较差,因为其分子机制尚未得到充分阐明,因此缺乏有效的治疗方法。选择性抑制酪氨酸激酶KIT的酪氨酸激酶抑制剂伊马替尼已显示出对GIST患者具有显著的临床益处。在临床试验中,伊马替尼治疗使KIT阳性不可切除或转移性GIST患者的缓解率达到40% - 55%,并延长了无进展生存期。此外,最近的临床试验表明,在高危病例的根治性切除后给予伊马替尼可在辅助治疗中延长无复发生存期和总生存期。目前正在进行几项伊马替尼新辅助治疗的临床试验;然而,在临床实践中,仍有一些问题需要解决,如最佳药物、给药持续时间和术后管理等。在本综述中,我们讨论了手术方案的应用,以及辅助/新辅助或围手术期伊马替尼治疗及其对原发性、复发性或转移性GIST患者生存的潜在影响。