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学科主题: 肿瘤学
题名:
舒尼替尼治疗不同外显子11突变类型胃肠间质瘤临床获益分析
作者: 董智
答辩日期: 2016-05-19
导师: 李健
专业: 肿瘤学
授予单位: 北京大学
授予地点: 北京大学临床肿瘤学院
学位: 硕士
关键词: 胃肠间质瘤 ; 伊马替尼加量 ; 舒尼替尼 ; exon11突变
其他题名: Clinical Benefit Analysis of Sunitinib in Gastrointestinal Stromal Tumors Patients with Different Exon 11 Mutations
分类号: R735.2
摘要:

研究背景:伊马替尼(Imatinib,IM)是晚期胃肠间质瘤(Gastrointestinal Stromal Tumors,GIST)标准一线治疗方案,但大多患者在随访2年后出现耐药或者无法耐受治疗。对于exon11突变人群后续是选择伊马替尼加量还是直接换用二线舒尼替尼仍然没有定论,且不同exon11突变类型是否影响方案选择,目前尚缺乏研究。

研究目的:不同exon11突变类型GIST接受二线SU治疗临床获益情况比较;IM加量后进展序贯至SU与直接换用SU两种治疗模式的比较。

研究方法:从2003年至2013年在北京大学肿瘤医院接受治疗的963例GIST患者数据库中筛选出75名IM加量进展后换用SU或者直接换用SU的GIST患者,收集并回顾性分析上述患者临床病理资料,运用Kaplan-Meier法绘制生存曲线,运用Log-rank进行单因素分析。

研究结果:一线IM中位PFS为32个月。当一线IM治疗进展后,有38名患者选择IM加量后序贯至SU治疗,37名患者直接换用SU治疗。两者疾病控制率分别为44.7%和78.4%(P=0.002),但从IM加量到序贯至SU的总PFS与OS无统计学差异(13 VS 14个月,P=0.187;20 VS 21个月,P=0.230)。在exon11缺失突变患者中,SU组中位PFS优于IM加量组,无论是IM加量后的中位PFS 3个月(16 VS 3个月,P<0.001)还是IM加量后换用SU的中位PFS(16 VS 8个月,P=0.024)。在SU组,exon11缺失突变患者中位PFS长于非缺失突变患者,尽管结果无统计学意义(16 VS 9 个月,P=0.291)。

结论:在一线标准伊马替尼治疗失败后,选择伊马替尼增加剂量再序贯至舒尼替尼的治疗模式和直接换用舒尼替尼的治疗模式生存获益是相当的,均是可以选择的。根据本研究结果,对于exon11缺失突变患者可能从舒尼替尼治疗中获得更多生存益处。

 

英文摘要:

Background:Imatinib,as the standard first-line treatment in the metastatic gastrointestinal stromal tumors(GISTs) patients, may eventually develop to resistance or intolerance after 2 years follow-up. There is no consensus whether to Imtinib escalation or Sunitinib in the condition of patients with exon 11 mutation .More comparisons of these strategies on different exon 11 mutation types are required.

Objectives:Compare the clinical benefit of Sunitinib therapy with different exon 11 mutation types; Explore and optimize sequential therapy of IM escalation failure to sunitinib and direct shift to Sunitinib as the second-line treatment.

Methods:We screened and retrospectively analysed 75 patients who received sunitinib therapy after IM failure from the database of 963 GIST patients who were hospitalized in Beijing University Cancer Hospital from 2003 to 2013. The survival rate was calculated using the Kaplan-Meier method and survival analysis was operated with the one-way analysis of variance.

Results:The median Progression Free Survival(PFS) of first-line Imatinib is 32 months. 38 of 75 patients were ed to IM Escalation Group,who transferred to sunitinib treatment after progression again, 37 left to Sunitinib Group.The disease control rate was 44.7% and 78.4%, respectively(P=0.002).However,there was no significantly difference in total PFS including the subsequent sunitinib treatment  and Overall Survival(13 VS 14 months,P=0.187; 21 VS 20 months,P=0.230). In exon 11 deletion mutation subgroup, the median PFS of Sunitinib Group was longer than IM Escalation Group regardless of IM escalation(16 VS 3 months,P<0.001) or progression to sunitinib(16 VS 8 months,P=0.024).In Sunitinib Group,exon 11 deletion group had a preferable PFS, even though no difference was found(16 VS 9 months,P=0.291).

Conclusions:Either of sequential therapy or shift to sunitinib directly after the failure of fisrt-line treatment was operable with similar survival benefit.Accordiong to our study, choosing to sunitinib therpy was more rational in exon 11 deletion mutation,as not obvious in IM escalation group.

 

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/125697
Appears in Collections:北京大学临床肿瘤学院_学位论文

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作者单位: 北京大学临床肿瘤学院

Recommended Citation:
董智. 舒尼替尼治疗不同外显子11突变类型胃肠间质瘤临床获益分析[D]. 北京大学临床肿瘤学院. 北京大学. 2016.
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