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宫颈癌是妇科常见的恶性肿瘤,其临床分期与预后呈显著正相关[1-2]。根治性手术联合术后放化疗是ⅡA1期宫颈癌患者的标准治疗方法之一。大多数宫颈癌患者因存在术后高危因素,需进一步行术后放化疗,进而易导致急性放射性损伤发生率高、治疗耐受性差和获益比低等问题,严重影响了患者的生活质量,给患者及其家庭带来沉重的经济负担和精神负担[3]。新辅助放化疗具有减轻肿瘤负荷、提高手术完整切除率、减少术后高危因素等特点,已经被广泛应用于局部晚期宫颈癌患者的治疗中[4]。宫颈癌患者行新辅助放化疗可取得较好的近期疗效,尤其是在临床分期的降期及减少术后过度治疗等方面 [5]。本研究通过回顾性分析ⅡA1期宫颈癌患者的临床资料,对比新辅助放化疗联合根治性手术和单纯行根治性手术2种治疗模式的临床疗效,旨在优化ⅡA1期宫颈癌患者的治疗方案。
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由表1可知,2组患者在年龄、病理学类型、美国东部肿瘤协作组(ECOG)评分、分化程度和是否绝经等一般资料间的比较,差异均无统计学意义(均P>0.05)。
项目 研究组(n=60) 对照组(n=60) χ2值 P值 年龄 0.139 0.709 >50岁 23(38.3) 25(41.7) ≤50岁 37(61.7) 35(58.3) 病理学类型 0.121 0.941 鳞癌 51(85.0) 50(83.3) 腺癌 4(6.7) 5(8.3) 腺鳞癌 5(8.3) 5(8.3) ECOG评分 0.240 0.624 0分 49(81.7) 51(85.0) 1分 11(18.3) 9(15.0) 分化程度 0.387 0.824 低分化 5(8.3) 6(10.0) 中分化 47(78.3) 48(80.0) 高分化 8(13.3) 6(10.0) 是否绝经 0.086 0.769 是 53(88.3) 54(90.0) 否 7(11.7) 6(10.0) 注:ECOG为美国东部肿瘤协作组 表 1 2组ⅡA1期宫颈癌患者一般资料的比较[例(%)]
Table 1. Comparison of general data of two groups of patients with stage ⅡA1 cervical cancer (case (%) )
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研究组60例患者接受新辅助放化疗后,临床分期如下:ⅠA1期的患者占50.0%(30/60)、ⅠB1期的患者占31.7%(19/60)、ⅠB2期的患者占13.3%(8/60)、ⅡA1期的患者占5.0%(3/60),患者临床分期的降期率为95.0%(57/60),稳定率为5.0%(3/60)。研究组患者术后病理完全缓解的占15.0%(9/60),46例患者术后未接受后续治疗,14例患者接受后续放疗(仅2例患者接受同步放化疗)。在对照组60例患者中,35例患者术后未接受后续治疗,25例患者接受后续放疗(9例患者接受同步放化疗)。2组患者术后的再次治疗率分别为23.3%(14/60)、41.7%(25/60),差异有统计学意义(χ2=4.596,P=0.032)。
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所有患者均顺利完成宫颈癌根治性切除术+盆腔淋巴结清扫术,手术成功率为100%。由表2可知,研究组和对照组患者在围手术期出血量、围手术期并发症和术后恢复时间之间的差异均无统计学意义(均P>0.05)。
指标 研究组(n=60) 对照组(n=60) χ2值 P值 围手术期出血量 0.430 0.512 <500 ml 45(75.0) 48(80.0) ≥500 ml 15(25.0) 12(20.0) 围手术期并发症 0.137 0.711 术后切口感染 1(1.7) 1(1.7) 泌尿系统损伤 0(0) 0(0) 肠粘连 1(1.7) 0(0) 下肢静脉血栓 4(6.7) 5(8.3) 下肢水肿 18(30.0) 20(33.3) 术后恢复时间 0.100 0.752 <2周 55(91.7) 54(90.0) ≥2周 5(8.3) 6(10.0) 术后高危因素 5.335 0.020 淋巴结(+) 2(3.3) 5(8.3) 残端(+) 1(1.7) 2(3.3) 宫旁浸润 0(0) 4(6.7) 间质浸润情况 15.875 0.001 病理完全缓解 9(15.0) 0(0) 浅1/3 19(31.7) 12(20.0) 中1/3 25(41.7) 30(50.0) 深1/3 7(11.7) 18(30.0) 脉管癌栓(+) 16(26.7) 34(56.7) 11.109 0.001 表 2 2组ⅡA1期宫颈癌患者手术状况、围手术期并发症、术后高危因素、间质浸润情况及脉管癌栓的比较[例(%)]
Table 2. Comparison of surgery status, perioperative complications, postoperative high-risk factors, interstitial invasion and vascular tumor thrombus of two groups of patients with stage ⅡA1 cervical cancer (case (%) )
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由表2可知,研究组患者术后高危因素的发生率均低于对照组,且差异有统计学意义(χ2=5.335,P<0.05)。研究组发生术后间质浸润的患者中,病理完全缓解率、间质浸润浅1/3的百分比高于对照组;间质浸润中1/3、深1/3的百分比低于对照组,且差异有统计学意义(χ2=15.875,P<0.01)。研究组患者术后脉管癌栓的发生率低于对照组,且差异有统计学意义(χ2=11.109,P<0.01)。
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在随访过程中,所有患者均未见3~4级急慢性放射性肠炎和放射性膀胱炎。研究组和对照组患者3~4级急性血液学毒性反应的发生率分别为1.7%(1/60)、6.7%(4/60),差异无统计学意义(χ2=1.878,P=0.171),所有发生3~4级急性血液学毒性反应的患者经对症治疗后均恢复正常。在发生1~2级急慢性放射性损伤的患者中,研究组患者急慢性放射性肠炎、急慢性放射性膀胱炎、急性血液学毒性反应的发生率均低于对照组,且差异均有统计学意义(均P<0.05,表3)。
组别 急性放射性肠炎 急性放射性膀胱炎 急性血液学毒性反应 慢性放射性肠炎 慢性放射性膀胱炎 慢性血液学毒性反应 研究组(n=60) 6(10.0) 4(6.7) 5(8.3) 5(8.3) 2(3.3) 1(1.7) 对照组(n=60) 17(28.3) 13(21.7) 12(20.0) 13(21.7) 8(13.3) 3(5.0) χ2值 6.508 5.551 4.615 4.183 3.927 1.034 P值 0.011 0.018 0.032 0.041 0.048 0.309 表 3 2组ⅡA1期宫颈癌患者发生1~2级急慢性放射性损伤的比较[例(%)]
Table 3. Comparison of grade 1−2 acute or chronic radiation injuries of two groups of patients with stage ⅡA1 cervical cancer (case (%))
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截至2020年6月1日,本研究对患者的随访时间为48~74个月,中位随访时间为57.2个月。由图1可见,研究组患者的5年PFS率和OS率分别为66.7%、80.0%,高于对照组的65.0%、78.3%,但差异均无统计学意义(χ2=1.27、1.96,均P>0.05)。
新辅助放化疗联合根治性手术在ⅡA1期宫颈癌患者中的应用价值
Application value of neoadjuvant chemoradiotherapy combined with radical resection in patients with stage ⅡA1 cervical cancer
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摘要:
目的 评价ⅡA1期宫颈癌患者接受新辅助放化疗联合根治性手术的临床疗效及预后。 方法 回顾性分析2012年6月至2014年12月于中国人民解放军联勤保障部队第九〇〇医院确诊的120例ⅡA1期宫颈癌患者的临床资料,年龄41~63(49.2±4.6)岁。按照治疗方式的不同,将患者分为研究组和对照组(各60例),研究组患者行新辅助放化疗联合根治性手术,对照组患者行根治性手术。观察研究组患者接受新辅助放化疗后临床分期的变化;比较2组患者围手术期并发症、术后高危因素、间质浸润情况以及脉管癌栓的差异;采用后期放射性损伤评分标准评估比较2组患者急慢性放射性损伤的差异;通过随访比较2组患者5年无进展生存(PFS)率和总生存(OS)率的差异。计数资料的组间比较采用χ2检验,采用Kaplan-Meier法进行生存分析并进行Log-rank检验。 结果 研究组患者接受新辅助放化疗后,临床分期的降期率为95.0%(57/60),术后病理完全缓解的患者占15.0%(9/60)。2组患者围手术期出血情况、围手术期并发症的发生率、术后恢复时间的比较,差异均无统计学意义(χ2=0.430、0.137、0.100,均P>0.05)。在术后高危因素的比较中,研究组患者淋巴结(+)、残端(+)、宫旁浸润的发生率分别为3.3%(2/60)、1.7%(1/60)、0(0/60),低于对照组患者的8.3%(5/60)、3.3%(2/60)、6.7%(4/60),且差异有统计学意义(χ2=5.335,P<0.05);研究组发生术后间质浸润的患者中,病理完全缓解率、间质浸润浅1/3的百分比分别为15.0%(9/60)、31.7%(19/60),高于对照组的0(0/60)、20.0%(12/60),间质浸润中1/3和深1/3的百分比分别为41.7%(25/60)、11.7%(7/60),低于对照组的50.0%(30/60)、30.0%(18/60),且差异有统计学意义(χ2=15.875,P<0.01);研究组患者术后脉管癌栓的发生率为26.7%(16/60),显著低于对照组的56.7%(34/60),且差异有统计学意义(χ2=11.109,P<0.01)。研究组患者1~2级急慢性放射性肠炎、急慢性放射性膀胱炎和急性血液学毒性反应的发生率均低于对照组,且差异均有统计学意义(χ2=3.927~6.508,均P<0.05)。研究组患者的5年PFS率、OS率分别为66.7%、80.0%,高于对照组的65.0%、78.3%,但差异均无统计学意义(χ2=1.27、1.96,均P>0.05)。 结论 ⅡA1期宫颈癌患者接受新辅助放化疗联合根治性手术可有效减少术后高危因素和放射性损伤,但不影响术后并发症的发生率及预后。 Abstract:Objective To evaluate the clinical efficacy and prognosis of neoadjuvant chemoradiotherapy combined with radical resection in patients with stage ⅡA1 cervical cancer. Methods The clinical data of 120 patients aged 41–63 (49.2±4.6) years old with stage ⅡA1 cervical cancer and who were diagnosed at the 900th Hospital of Joint Logistics Support Force of PLA from June 2012 to December 2014 were analyzed retrospectively. The patients were divided into the study group and the control group (60 cases in each group) in accordance with different treatment methods. The patients in the study group underwent neoadjuvant chemoradiotherapy combined with radical resection and those in the control group underwent radical resection. The changes in the clinical stages of the patients in the study group after undergoing neoadjuvant chemoradiotherapy were observed. The differences in perioperative complications, postoperative high-risk factors, interstitial invasion, and vascular tumor thrombus between the two groups were compared. The acute and chronic radiation injuries of the two groups were evaluated and compared by using the later radiation injury scoring standard. The differences in the 5-year progression-free survival (PFS) rate and overall survival (OS) rate between the two groups were compared. χ2 test was used to compare the count data of the groups, and the Kaplan-Meier method and Log-rank test were used for survival analysis. Results In the study group, the decline rate of the clinical stage was 95.0% (57/60) and the pathological complete remission rate was 15.0% (9/60) after neoadjuvant chemoradiotherapy. No significant differences in perioperative bleeding, incidences of perioperative complications, and postoperative recovery time were observed between the two groups (χ2=0.430, 0.137, 0.100; all P>0.05). The comparison of postoperative high-risk factors revealed that the incidences of lymph node (+), stump (+), and parauterine infiltration in the study group were 3.3% (2/60), 1.7% (1/60), and 0 (0/60), respectively, and were lower than those (8.3% (5/60), 3.3% (2/60), and 6.7% (4/60)) in the control group (χ2=5.335, P<0.05). Among the patients with postoperative interstitial infiltration in the study group, the pathological complete remission rate and the proportion of shallow interstitial infiltration in 1/3 were 15.0% (9/60) and 31.7% (19/60), respectively, and were higher than those (0 (0/60) and 20.0% (12/60)) in the control group. The proportions of the middle 1/3 and deep 1/3 in the study group were 41.7% (25/60) and 11.7% (7/60), respectively, and were lower than those (50.0% (30/60) and 30.0% (18/60)) in the control group (χ2=15.875, P<0.01). The incidence of postoperative vascular tumor thrombus in the study group was 26.7% (16/60) and was significantly lower than that (56.7% (34/60)) in the control group (χ2=11.109, P<0.01). The incidences of grade 1–2 acute and chronic radiation enteritis, acute and chronic radiation cystitis, and acute hematological toxicity in the study group were lower than those in the control group (χ2=3.927–6.508, all P<0.05). The 5-year PFS rate and OS rate in the study group were 66.7% and 80.0% respectively, and were higher than those (65.0% and 78.3%) in the control group. However, no significant difference was observed between groups (χ2=1.27, 1.96; both P>0.05). Conclusion In patients with stage Ⅱ A1 cervical cancer, neoadjuvant chemoradiotherapy combined with radical resection can effectively reduce postoperative high-risk factors and radiation injuries but did not affect the incidence of perioperative complications and prognosis. -
表 1 2组ⅡA1期宫颈癌患者一般资料的比较[例(%)]
Table 1. Comparison of general data of two groups of patients with stage ⅡA1 cervical cancer (case (%) )
项目 研究组(n=60) 对照组(n=60) χ2值 P值 年龄 0.139 0.709 >50岁 23(38.3) 25(41.7) ≤50岁 37(61.7) 35(58.3) 病理学类型 0.121 0.941 鳞癌 51(85.0) 50(83.3) 腺癌 4(6.7) 5(8.3) 腺鳞癌 5(8.3) 5(8.3) ECOG评分 0.240 0.624 0分 49(81.7) 51(85.0) 1分 11(18.3) 9(15.0) 分化程度 0.387 0.824 低分化 5(8.3) 6(10.0) 中分化 47(78.3) 48(80.0) 高分化 8(13.3) 6(10.0) 是否绝经 0.086 0.769 是 53(88.3) 54(90.0) 否 7(11.7) 6(10.0) 注:ECOG为美国东部肿瘤协作组 表 2 2组ⅡA1期宫颈癌患者手术状况、围手术期并发症、术后高危因素、间质浸润情况及脉管癌栓的比较[例(%)]
Table 2. Comparison of surgery status, perioperative complications, postoperative high-risk factors, interstitial invasion and vascular tumor thrombus of two groups of patients with stage ⅡA1 cervical cancer (case (%) )
指标 研究组(n=60) 对照组(n=60) χ2值 P值 围手术期出血量 0.430 0.512 <500 ml 45(75.0) 48(80.0) ≥500 ml 15(25.0) 12(20.0) 围手术期并发症 0.137 0.711 术后切口感染 1(1.7) 1(1.7) 泌尿系统损伤 0(0) 0(0) 肠粘连 1(1.7) 0(0) 下肢静脉血栓 4(6.7) 5(8.3) 下肢水肿 18(30.0) 20(33.3) 术后恢复时间 0.100 0.752 <2周 55(91.7) 54(90.0) ≥2周 5(8.3) 6(10.0) 术后高危因素 5.335 0.020 淋巴结(+) 2(3.3) 5(8.3) 残端(+) 1(1.7) 2(3.3) 宫旁浸润 0(0) 4(6.7) 间质浸润情况 15.875 0.001 病理完全缓解 9(15.0) 0(0) 浅1/3 19(31.7) 12(20.0) 中1/3 25(41.7) 30(50.0) 深1/3 7(11.7) 18(30.0) 脉管癌栓(+) 16(26.7) 34(56.7) 11.109 0.001 表 3 2组ⅡA1期宫颈癌患者发生1~2级急慢性放射性损伤的比较[例(%)]
Table 3. Comparison of grade 1−2 acute or chronic radiation injuries of two groups of patients with stage ⅡA1 cervical cancer (case (%))
组别 急性放射性肠炎 急性放射性膀胱炎 急性血液学毒性反应 慢性放射性肠炎 慢性放射性膀胱炎 慢性血液学毒性反应 研究组(n=60) 6(10.0) 4(6.7) 5(8.3) 5(8.3) 2(3.3) 1(1.7) 对照组(n=60) 17(28.3) 13(21.7) 12(20.0) 13(21.7) 8(13.3) 3(5.0) χ2值 6.508 5.551 4.615 4.183 3.927 1.034 P值 0.011 0.018 0.032 0.041 0.048 0.309 -
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