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晚期子宫内膜癌序贯放化疗的初步研究

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Objective To evaluate the clinical outcomes and feasibility of multi-modality adjuvant chemotherapy and radiation, which was conducted as postoperative chemotherapy, radiation, and consolidation chemotherapy (CRC) mode for the treatment of advanced endometrial cancer. Methods A retrospective analysis of 124 patients with International Federation of Gynecology and Obstetrics (FIGO) stages Ⅲ and Ⅳ endometrial cancer from Jan. 2004 to Oct. 2012 was conducted in Peking University People′s Hospital and Beijing Obstetrics and Gynecology Hospital. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, and (or) selective pelvic aortic lymphadenectomy, and treatment with adjuvant chemotherapy and (or) radiation. The average age of these patients was (55.9 ± 8.4) years old (range from 23 to 79 years old). According to different postoperative adjuvant treatment modes, the patients were divided into CRC group, chemotherapy-radiotherapy (CR) group and single chemotherapy (C) group. The survival and side effects of the three groups were compared. Results (1) One hundred and twenty-four patients with advanced stage endometrial cancer were identified and received postoperative adjuvant therapies.Sixty-one (49.2%, 61/124) cases of them received postoperative CRC fashion, 19 (15.3%, 19/124) received postoperative CR and 44 (35.5%, 44/124) cases received C. The age, stage, grade and type of surgery of the three groups were not significantly different (all P>0.05);while, the pathology, chemotherapy cycles and chemotherapy regimens differed significantly (all P<0.05). (2) The progression-free survivals (PFS) of the patients with CRC, CR, and C group were (121±7), (68± 15), and (100±11) months, respectively. The 3-year PFS rates were 87.9%, 43.7%, and 61.4%, respectively. The 5-year PFS rates were 82.2%, 36.4%, and 61.4%, respectively. The above indicators were significantly higher in the CRC group than in the CR group (all P<0.01), and there was no difference between the CRC group and the C group (P=0.037). The overall survival (OS) of patients with CRC, CR, and C group were (128 ± 6), (80 ± 12), and (99 ± 10) months, respectively. The 3-year OS rates were 87.8%, 72.4%, and 67.1%, the 5-year OS rate were 84.2%, 54.3%, and 64.1%, respectively. The above indicators were significantly higher in the CRC group than those in the CR group and C group (all P<0.01). (3) There was no difference in the frequency of adverse effects either chemotherapy, such as severe bone suppression or radiotherapy;hepatotoxicity,blood transfusion, dose modifications;or cycle delays between the CRC, CR and C group (all P>0.05). (4) In the univariate analysis shown that, stage, the fashion of postoperative adjuvant therapy and type of surgery were risk factors for tumor progression in patients with advanced endometrial cancer (P<0.05). After adjusted for FIGO stage and type of surgery, the tumor progression hazard ratio (HR) was 3.931 (95%CI:1.734-8.914, P=0.001) for the CR group and 2.188 (95%CI:1.010-4.741, P=0.047) for the C group, compared to the CRC group. Conclusion Sequential CRC delivered in a"sandwich"fashion for the treatment in advanced endometrial cancer could significantly improve the 3-year and 5-year OS rates and have a similar adverse effect profile compared with other sequencing modalities.%目的 评估晚期(Ⅲ~Ⅳ期)子宫内膜癌术后行化疗-放疗-巩固化疗(CRC)的序贯放化疗模式的疗效及可行性.方法 收集2004年1月—2012年12月在北京大学人民医院及首都医科大学附属北京妇产医院实施全面分期手术,并行术后辅助化疗和(或)放疗的Ⅲ~Ⅳ期子宫内膜癌患者共124例,其年龄为(55.9±8.4)岁(23~79岁).根据术后辅助治疗模式的不同,分为CRC组、化疗-放疗(CR)组、单纯化疗?组,比较3组患者的疗效及副反应发生率.结果 (1)124例晚期子宫内膜癌患者中,CRC组61例(49.2%,61/124)、CR组19例(15.3%,19/124)、C组44例(35.5%,44/124).3组患者的年龄、手术病理分期、病理分级及手术满意度分别比较,差异均无统计学意义(P均>0.05);而病理类型、化疗疗程数及化疗方案分别比较,差异均有统计学意义(P均<0.05).(2)CRC组、CR组、C组患者的无进展生存时间(PFS)分别为(121±7)、(68±15)、(100±11)个月,3年无进展生存率分别为87.9%、43.7%、61.4%,5年无进展生存率分别为82.2%、36.4%、61.4%,上述指标CRC组均明显高于CR组(P均<0.01),而CRC组与C组间比较(采用Bonferroni法校正检验水准,P<0.0125为差异有统计学意义),差异无统计学意义(P=0.037).CRC组、CR组、C组患者的总生存时间(OS)分别为(128±6)、(80±12)、(99±10)个月,3年总生存率分别为87.8%、72.4%、67.1%,5年总生存率分别为84.2%、54.3%、64.1%,上述指标CRC组均明显高于CR组和C组(P均<0.01).(3)CRC组、CR组、C组患者的严重骨髓抑制、放疗副反应、输血、肝脏毒性、化疗剂量调整及化疗疗程延迟的发生率分别比较,差异均无统计学意义(P均>0.05).(4)单因素分析显示,手术病理分期、术后辅助治疗模式及手术满意度为影响晚期子宫内膜癌患者肿瘤进展的危险因素(P<0.05);在对患者手术病理分期及手术满意度进行调整后,CR组患者肿瘤进展的风险比(HR)值是CRC组的3.931倍(95%CI为1.734~8.914,P=0.001),C组患者肿瘤进展的HR值是CRC组的2.188倍(95%CI为1.010~4.741,P=0.047).结论 与CR、C的术后辅助治疗模式相比,CRC的序贯放化疗模式应用于晚期子宫内膜癌可明显改善患者的3年及5年生存率,且并未明显增加严重副反应的发生率,患者具有良好的耐受性.

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