甲磺酸伊马替尼治疗后转移性胃肠道间质瘤（GIST）患者的手术治疗。

Surgical management in metastatic gastrointestinal stromal tumor (GIST) patients after imatinib mesylate treatment.

机构信息

GIST team, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

出版信息

J Surg Oncol. 2010 Nov 1;102(6):599-603. doi: 10.1002/jso.21630.

DOI:10.1002/jso.21630

PMID:20976730

Abstract

PURPOSE

Imatinib mesylate (IM) demonstrates substantial efficacy in most patients with metastatic gastrointestinal stromal tumors (GISTs). However, progression of GIST eventually develops and emerges as a challenge. To assess the role of surgery in the multidisciplinary management of GISTs, we studied the surgical outcomes in GIST patients receiving IM.

MATERIALS AND METHODS

Between 2001 and May 2009, 161 metastatic GIST patients received IM. Among them, 35 patients undergoing 38 surgeries were investigated. Patients were categorized based on extent of disease before surgery (responsive or stable disease (PR, SD), local progression (LP), and generalized progression (GP)). Each tumor was investigated for genetic alteration before and after surgery.

RESULTS

Disease status before surgery was significantly associated with surgical result. Gross tumor clearance was achieved in 42.9% of patients with responsive disease, but only 4.8% of those with focal resistance and 0% of those with disease progression (P = 0.022). GIST patients with PR, SD, and LP had significant better 2-year progression-free survival and overall survival than those with GP. Secondary mutations tended to be found more frequently in GIST patients with LP after surgery than those with response (10/21 (47.6%) vs. 2/14 (14.3%); P = 0.07), indicating that surgery may prevent potential development of secondary mutation in GIST patients with response. Secondary kit mutations were also found more frequently with primary exon 11 mutation than those with exon 9 mutation (38.7% vs. 16.7%; P = 0.394).

CONCLUSIONS

Surgery may benefit selected GIST patients with PR, SD, and LP, especially for patients with LP because patients with LP had comparable survival to that of patients with responsive lesion. Surgery may prevent potential development of secondary mutations in selected patients with response after IM treatment. Secondary kit mutation was found more frequently in GIST patients with a primary kit exon 11 mutation than those with a primary kit exon 9 mutation.

摘要

目的

甲磺酸伊马替尼（IM）在大多数转移性胃肠道间质瘤（GIST）患者中显示出显著的疗效。然而，GIST 最终会进展并成为一个挑战。为了评估手术在 GIST 多学科管理中的作用，我们研究了接受 IM 治疗的 GIST 患者的手术结果。

材料和方法

2001 年至 2009 年 5 月期间，161 例转移性 GIST 患者接受了 IM 治疗。其中，35 例患者接受了 38 次手术。根据手术前疾病的严重程度（反应或稳定疾病（PR、SD）、局部进展（LP）和全身进展（GP））对患者进行分类。在手术前后对每个肿瘤进行了遗传改变的调查。

结果

手术前的疾病状态与手术结果显著相关。在反应性疾病患者中，42.9%的患者实现了肿瘤的完全清除，但在局部耐药患者中只有 4.8%，在疾病进展患者中则没有（P=0.022）。PR、SD 和 LP 的 GIST 患者的 2 年无进展生存率和总生存率明显优于 GP 患者。术后 LP 的 GIST 患者比有反应的患者更容易发现继发突变（10/21（47.6%）比 2/14（14.3%）；P=0.07），表明手术可能预防反应性 GIST 患者潜在的继发突变。继发的 kit 突变也比 exon 9 突变更常见于原发 exon 11 突变（38.7%比 16.7%；P=0.394）。

结论

手术可能对 PR、SD 和 LP 的 GIST 患者有益，特别是对 LP 患者，因为 LP 患者的生存与有反应性病变的患者相当。手术可能预防 IM 治疗后反应性患者潜在的继发突变。在原发 kit exon 11 突变的 GIST 患者中，发现继发的 kit 突变比原发 kit exon 9 突变更常见。