發(fā)布時間：2018-04-23 14:24

  本文選題：卵巢上皮性癌 + 新輔助化療�。� 參考：《廣西醫(yī)科大學》2017年碩士論文

【摘要】：背景:卵巢上皮性癌(Epithelial ovarian carcinoma,EOC)的治療包含基于鉑類的新輔助化療后中間性腫瘤細胞減滅術(Neoadjuvant chemotherapy with interval debulking surgery,NACT-IDS)及初始腫瘤細胞減滅術(Primary debulking surgery,PDS)兩種方式。大量研究發(fā)現(xiàn)NACT-IDS的無進展生存期(Progression free survival,PFS)比PDS的明顯縮短,且NACT-IDS后6個月內(nèi)復發(fā)概率高于PDS。其機制可能與NACT誘導TP53促調(diào)亡功能的四聚化結(jié)構(gòu)域(tetramerization domain,TD)突變介導的獲得性鉑類耐藥有關。目的:研究EOC患者中PDS組與NACT組是否存在TP53 TD突變及其與臨床預后關系,尤其是在NACT組中。方法:采用組織DNA提取技術、巢式PCR、DNA測序技術檢查108例EOC患者(其中NACT組51例,PDS組57例)是否存在TP53 TD突變。并通過查閱病例、電話隨訪的方式獲取臨床資料,對患者TP53 TD突變與鉑類耐受進行相關性分析。結(jié)果:1、在51例新輔助化療的EOC患者中,檢測出4例EOC患者存在TP53 K351N突變(7.8%,4/51),且出現(xiàn)于18例接受4~6周期基于鉑類的NACT中,突變率為22.2%(4/18)。2、在PDS組和NACT前標本中未檢測出TP53 TD K351N突變。3、NACT組與PDS組患者總生存期(Overall survival,OS)及PFS差別有統(tǒng)計學意義(POS=0.013,PPFS=0.005)。PDS組病人的生存狀況明顯優(yōu)于NACT組病人。NACT組中術后6個月內(nèi)復發(fā)的概率為58.2%(30/51),明顯高于PDS組6個月內(nèi)復發(fā)的概率(35.1%,20/57);兩組6月內(nèi)復發(fā)率差別有統(tǒng)計學意義(P=0.014)。4、在NACT組內(nèi),術前化療3周期的患者的中位PFS較術前化療≤3周期的患者的中位PFS短,兩者差別有統(tǒng)計學意義(P=0.044)。單因素及多因素COX回歸分析結(jié)果顯示,TP53 K351N突變是NACT組中6個月內(nèi)復發(fā)患者較短PFS的獨立因素(Hazard ratio,HR=9.309,P=0.043)。結(jié)論:1)治療周期3個周期的,以鉑類為基礎的NACT可能是導致卵巢癌患者TP53 K351N突變和耐藥復發(fā)的風險因素之一;2)不超過3個周期的以鉑類為基礎的NACT可能對降低TP53 K351N突變介導的鉑類耐藥發(fā)生有一定的作用;3)以鉑類為基礎的NACT-IDS后,檢測TP53 K351N突變有利于規(guī)避化療耐藥,以及對制定后續(xù)化療方案的選擇具有重要的臨床意義。
[Abstract]:Background: the treatment of epithelial ovarian carcinoma of ovary (EOC) includes two methods: Neoadjuvant chemotherapy with interval debulking surgeryn NACT-IDSs and primary debulking SurgeryPDSs based on platinum-based neoadjuvant chemotherapy with interval debulking query. A large number of studies showed that the progressive free survival of NACT-IDS was significantly shorter than that of PDS, and the probability of recurrence within 6 months after NACT-IDS was higher than that of PDS. The mechanism may be related to acquired platinum resistance mediated by tetramerization domain tetramerization domain (tetramerization domain) mutation of TP53 induced by NACT. Objective: to study the relationship between TP53 TD mutation and clinical prognosis in PDS and NACT in EOC patients, especially in NACT group. Methods: tissue DNA extraction technique and nested PCR DNA sequencing technique were used to detect the presence of TP53 TD mutation in 108 patients with EOC (including 51 patients with NACT and 57 patients with NACT). The correlation between TP53 TD mutation and platinum tolerance was analyzed. Results in 51 EOC patients with neoadjuvant chemotherapy, 4 patients with EOC had TP53 K351N mutation 7.8 / 51N, and 18 patients with 4G / 6 cycles of platinum-based NACT. The mutation rate was 22. 2 / 18. 2. There was no TP53 TD K351N mutation. 3NACT group and PDS group had significant difference in total survival time and PFS. The survival status of patients in the PDS group was significantly better than that in the NACT group. NACT group was significantly better than the NACT group in the 6 patients after operation. The survival rate of the patients in the PDS group was significantly higher than that in the NACT group. There was no significant difference in the total survival time of the patients in the PDS group and the total survival time of the patients in the PDS group. There was a significant difference in the survival status of the patients in the PDS group and in the PDS group. The probability of recurrence within months was 58.2 / 51%, which was significantly higher than that in PDS group (35.1a / 57) in 6 months. The difference of recurrence rate within six months between the two groups was statistically significant (P 0.014). 4, in NACT group, there was a significant difference between the two groups in the recurrence rate within 6 months. The median PFS of patients with 3 cycles of preoperative chemotherapy was shorter than that of patients with less than 3 cycles of preoperative chemotherapy. The difference between the two groups was statistically significant. Univariate and multivariate COX regression analysis showed that TP53 K351N mutation was an independent factor for short PFS in patients with recurrence within 6 months in NACT group. ConclusionsThe treatment cycle is 3 cycles. Platinum-based NACT may be one of the risk factors for TP53 K351N mutation and drug resistance recurrence in ovarian cancer patients.) Platinum-based NACT with no more than 3 cycles may play a role in reducing platinum resistance mediated by TP53 K351N mutation. After platinum-based NACT-IDS, Detection of TP53 K351N mutation is helpful to avoid chemotherapeutic resistance and has important clinical significance in the selection of subsequent chemotherapy regimen.
【學位授予單位】：廣西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R737.31
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本文編號：1792337