新辅助化疗治疗Ⅰb2～Ⅱb期子宫颈癌的疗效评价
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摘要
目的：通过对比新辅助化疗+手术治疗和单独手术治疗的疗效,探讨新辅助化疗在Ⅰb2-Ⅱb期宫颈癌治疗中的临床作用。
方法：以我院2002年2月1日-2008年9月1日期间收治的49例Ⅰb2-Ⅱb期宫颈癌作为实验组,中位年龄43岁(29岁-62岁),肿瘤直径：4.9cm±0.9cm,按FIGO临床分期,Ⅰb2期2例,Ⅱa期19例,Ⅱb期28例,组织学分类：鳞癌44例,腺癌2例,腺鳞癌3例,病理学分级：Ⅰ级2例,Ⅱ级37例,Ⅲ级8例,不详2例。先给予1-2疗程的以铂类为基础的新辅助化疗,2周后行根治性手术；以同期49例直接行根治性手术的患者作为对照组。中位年龄46岁(32岁-67岁),肿瘤直径：5.0cm±0.7cm,FIGO分期工b期11例,Ⅱa期15例,Ⅱb期23例,组织学分类：鳞癌45例,腺癌3例,腺鳞癌1例,病理学分级：Ⅰ级3例,Ⅱ级39例,Ⅲ级3例,不详4例。两组在年龄(P=0.194)、肿瘤大小(P=0.681)、FIGO分期(P=0.095)、组织学分类(P=1.000)、病理分级(P=0.086)等方面均无明显差异。所有病人在住院前均未做过其他的治疗,均经过宫颈活组织检查或者阴道镜下活检确诊为宫颈癌。所有病人的宫颈局部的病灶直径均>4cm,白细胞≥4.0×109/L,血红蛋白≥90g/L,肝肾功能均无明显异常,均没有化疗及手术的禁忌症。化疗结束后的2周内,通过妇科检查、B超检查等来观察肿瘤的大小变化、化疗后的毒副反应等来判定化疗的临床疗效。通过对比两组的手术切除率、术中出血量、手术时间、术中分离组织难易程度、术后病理检查盆腔淋巴的结转移率、术后并发症等,比较两组的疗效。
结果：实验组患者的化疗有效率为83.7%,其中4例完全缓解,PR 18例(36.7%),MR 19例(38.8%),SD 8例(16.3%)。患者对化疗的疗效与临床分期无关(P=0.789)；鳞癌的化疗疗效优于非鳞癌(腺癌、腺鳞癌),但差别无统计学意义(P=0.182)；不同病理分级的肿瘤对化疗的疗效无明显差异(P=0.260)。不同化疗方案的化疗效果无统计学意义(P=0.943)。化疗后的毒副反应较轻,一般的患者均可耐受。实验组手术切除率达100%,对照组仅为89.8%。手术时间实验组184.6min±37.6min,对照组196.3min±62.9min,两组比较无显著性差异(P=0.267)。术中出血量实验组321.0ml±378.4ml,对照组280.6ml±118.5ml,两组比较无显著性差异(P=0.479)。新辅助化疗没有增加术中出血量,没有增加手术时间。两组术后并发症比较无统计学意义(P>0.05)。实验组术后病检肿瘤直径明显比对照组小(P=0.000)；实验组盆腔淋巴结转移明显较对照组少(P=0.027)。实验组复发率明显低于对照组,两组比较有统计学意义(P=0.002)。实验组的无瘤生存时间平均为63个月,对照组为53个月,两组比较无统计学意义(P=0.06)。实验组的总的生存时间平均为63个月,对照组为56个月,两组比较无统计学意义(P=0.1221)。对化疗有效的生存时间平均为65个月,对化疗无效的生存时间平均39个月,两组比较有统计学意义(P=0.0406)
结论：新辅助化疗对局部巨块型宫颈癌是安全有效的,化疗副反应轻,近期疗效肯定,能够提患者的手术切除率,减少复发率,对患者的生存有一定的益处,有较大的临床应用价值。
Objective:To investigate the action of neoadjuvant chemotherapy on cervical cancer in stageⅠb2～Ⅱb through compare the clinical effect about neoadjuvant chemotherapy followed with radical surgery and surgery alone.
Methods:Forty nine patients with locally advanced stageⅠb2～Ⅱb cervical cancer were chosen for the experimental group which received 1～2 course of treatment based with cisplatin or carboplatin.In the experimental group,medianage is 29～62 age, tumor size is 4.9cm±0.9cm, FIGO stage in 2 patients is stageⅠb2, in 19 patients is stageⅡa, in 28 patients is stageⅡb, histologic classification in 44 patients is squamous, in 2 patients is adenocarcinoma, in 3 patients is adenosquamouscarcinoma, pathologic grades in 1 patients is gradeⅠ, in 37 is gradeⅡ, in 8 patients is gradeⅢ, in 2 patients is not clear, Two weeks after when the chemotherapy regimen was completed, radical surgery was performed while the control group composed by 49 cases with the same diagnoses only received radical surgery. In control group, medianage is 32～67 age, tumor size is 5.0cm±0.7cm, FIGO stage in 11 patients is stageⅠb2, in 15 patients is stageⅡa, in 23 patients is stageⅡb, histologic classification in 45 patients is squamous, in 3 patients is adenocarcinoma, in 1 patients is adenosquamouscarcinoma, pathologic grades in 3 patients is gradeⅠ, in 39 patients is gradeⅡ, in 3 patiens is gradeⅢ, in 4 patients is not clear.There have not significantly difference about medianage (P=0.194), tumor size (P=0.681), FIGO stage (P=0.095), histologic classification (P=1.000),pathologic grades (P=0.086) in experimental group and control group.All patiens never give treatment before been in hospital.And all patients have been make a definite diagnosis as cervical cancer by made a cervical biopsy or made a cervical biopsy under uterine electron microscope.The locally tumor size of all patients are>4cm. leucocyte≥4.0×109/L,hemoglobin≥90g/L,liver/kidney function are all nomal, have not contraindication in chemotherapy and operation. Evaluate the effect of neoadjuvant chemotherapy by gynaecological examination,B ultrasound,the observing contents was tumorous size and toxic and side reaction.Compare the difference in this two groups by observe the operative resection rate, amount of blood loss during operation,operating time,the difficult degree of separate organs in operation,the matastasis rate of pelvic lymph node,by compare the operative resection rate, complications after operative etc.
Results:The effective rate of chemotherapy for patients in the experimental group was 83.7 % with complete responses in four patients. PR in 18 patients (36.7%), MR in 19 patients (38.8 %), SD in 8 patients (16.3%).The chemotherapy effect in patients with squamous cancer is prior than nonsquamous cancer,but its have not statistics significance(P=0.182). There have not significant difference in histologic classification(P=0.260).There have not statistics significance in chemotherapy regimens (P=0.943). Operation time in experimental group is 184.6min±37.6min, in contral group is 196.3min±62.9min, there have significantly difference in experimental group and control group (P=0.267).Bleeding in operation is 321.0ml±378.4ml, in control group is 280.6ml±118.5ml, there have significantly difference in experimental group and contral group (P=0.479).Neoadjuvant chemotherapy without increasing bleeding and operation time.The operative resection rate was 100% in experimental group but 89.8% in control group. The tumor size in experimental group was significantly smaller than that in control group after operation(P=0.000). The metastasis rate of pelvic lymph nodes in experimental group was significantly decreased compared with control group (P=0.027). The complication after surgury in two groups have not statistic significance (P>0.05).The recurrence rate in experimental group is significantly decrease than control group,there have statistic significance in experimental group and control group (P=0.002).The average period with no-tumor occurrence in experimental group are 63 months, in control group are 53 months, there have not statistic significance in experimental group and control group (P=0.06).The overll survival time in experimental group are 63 months, in control group are 56 months, there have not statistic significance in experimental group and control group (P=0.1221).The average survival time in patients whose have responder are 65months, the patients have nonresponder are 39 months, there have statistic significance in two groups (P=0.0406).
Conclusion:It is suggested that neoadjuvant chemotherapy would be a safe and effective approach for the patients with bulky cervical cancer. its side reactions were slight,and that its short-term effect would benefit Neoadjuvant chemotherapy can increase the respectability, decrease reccurrence rate, it would be useful to patients' survival. It shows promising prospect in clinical application.
方法：以我院2002年2月1日-2008年9月1日期间收治的49例Ⅰb2-Ⅱb期宫颈癌作为实验组,中位年龄43岁(29岁-62岁),肿瘤直径：4.9cm±0.9cm,按FIGO临床分期,Ⅰb2期2例,Ⅱa期19例,Ⅱb期28例,组织学分类：鳞癌44例,腺癌2例,腺鳞癌3例,病理学分级：Ⅰ级2例,Ⅱ级37例,Ⅲ级8例,不详2例。先给予1-2疗程的以铂类为基础的新辅助化疗,2周后行根治性手术；以同期49例直接行根治性手术的患者作为对照组。中位年龄46岁(32岁-67岁),肿瘤直径：5.0cm±0.7cm,FIGO分期工b期11例,Ⅱa期15例,Ⅱb期23例,组织学分类：鳞癌45例,腺癌3例,腺鳞癌1例,病理学分级：Ⅰ级3例,Ⅱ级39例,Ⅲ级3例,不详4例。两组在年龄(P=0.194)、肿瘤大小(P=0.681)、FIGO分期(P=0.095)、组织学分类(P=1.000)、病理分级(P=0.086)等方面均无明显差异。所有病人在住院前均未做过其他的治疗,均经过宫颈活组织检查或者阴道镜下活检确诊为宫颈癌。所有病人的宫颈局部的病灶直径均>4cm,白细胞≥4.0×109/L,血红蛋白≥90g/L,肝肾功能均无明显异常,均没有化疗及手术的禁忌症。化疗结束后的2周内,通过妇科检查、B超检查等来观察肿瘤的大小变化、化疗后的毒副反应等来判定化疗的临床疗效。通过对比两组的手术切除率、术中出血量、手术时间、术中分离组织难易程度、术后病理检查盆腔淋巴的结转移率、术后并发症等,比较两组的疗效。
结果：实验组患者的化疗有效率为83.7%,其中4例完全缓解,PR 18例(36.7%),MR 19例(38.8%),SD 8例(16.3%)。患者对化疗的疗效与临床分期无关(P=0.789)；鳞癌的化疗疗效优于非鳞癌(腺癌、腺鳞癌),但差别无统计学意义(P=0.182)；不同病理分级的肿瘤对化疗的疗效无明显差异(P=0.260)。不同化疗方案的化疗效果无统计学意义(P=0.943)。化疗后的毒副反应较轻,一般的患者均可耐受。实验组手术切除率达100%,对照组仅为89.8%。手术时间实验组184.6min±37.6min,对照组196.3min±62.9min,两组比较无显著性差异(P=0.267)。术中出血量实验组321.0ml±378.4ml,对照组280.6ml±118.5ml,两组比较无显著性差异(P=0.479)。新辅助化疗没有增加术中出血量,没有增加手术时间。两组术后并发症比较无统计学意义(P>0.05)。实验组术后病检肿瘤直径明显比对照组小(P=0.000)；实验组盆腔淋巴结转移明显较对照组少(P=0.027)。实验组复发率明显低于对照组,两组比较有统计学意义(P=0.002)。实验组的无瘤生存时间平均为63个月,对照组为53个月,两组比较无统计学意义(P=0.06)。实验组的总的生存时间平均为63个月,对照组为56个月,两组比较无统计学意义(P=0.1221)。对化疗有效的生存时间平均为65个月,对化疗无效的生存时间平均39个月,两组比较有统计学意义(P=0.0406)
结论：新辅助化疗对局部巨块型宫颈癌是安全有效的,化疗副反应轻,近期疗效肯定,能够提患者的手术切除率,减少复发率,对患者的生存有一定的益处,有较大的临床应用价值。
Objective:To investigate the action of neoadjuvant chemotherapy on cervical cancer in stageⅠb2～Ⅱb through compare the clinical effect about neoadjuvant chemotherapy followed with radical surgery and surgery alone.
Methods:Forty nine patients with locally advanced stageⅠb2～Ⅱb cervical cancer were chosen for the experimental group which received 1～2 course of treatment based with cisplatin or carboplatin.In the experimental group,medianage is 29～62 age, tumor size is 4.9cm±0.9cm, FIGO stage in 2 patients is stageⅠb2, in 19 patients is stageⅡa, in 28 patients is stageⅡb, histologic classification in 44 patients is squamous, in 2 patients is adenocarcinoma, in 3 patients is adenosquamouscarcinoma, pathologic grades in 1 patients is gradeⅠ, in 37 is gradeⅡ, in 8 patients is gradeⅢ, in 2 patients is not clear, Two weeks after when the chemotherapy regimen was completed, radical surgery was performed while the control group composed by 49 cases with the same diagnoses only received radical surgery. In control group, medianage is 32～67 age, tumor size is 5.0cm±0.7cm, FIGO stage in 11 patients is stageⅠb2, in 15 patients is stageⅡa, in 23 patients is stageⅡb, histologic classification in 45 patients is squamous, in 3 patients is adenocarcinoma, in 1 patients is adenosquamouscarcinoma, pathologic grades in 3 patients is gradeⅠ, in 39 patients is gradeⅡ, in 3 patiens is gradeⅢ, in 4 patients is not clear.There have not significantly difference about medianage (P=0.194), tumor size (P=0.681), FIGO stage (P=0.095), histologic classification (P=1.000),pathologic grades (P=0.086) in experimental group and control group.All patiens never give treatment before been in hospital.And all patients have been make a definite diagnosis as cervical cancer by made a cervical biopsy or made a cervical biopsy under uterine electron microscope.The locally tumor size of all patients are>4cm. leucocyte≥4.0×109/L,hemoglobin≥90g/L,liver/kidney function are all nomal, have not contraindication in chemotherapy and operation. Evaluate the effect of neoadjuvant chemotherapy by gynaecological examination,B ultrasound,the observing contents was tumorous size and toxic and side reaction.Compare the difference in this two groups by observe the operative resection rate, amount of blood loss during operation,operating time,the difficult degree of separate organs in operation,the matastasis rate of pelvic lymph node,by compare the operative resection rate, complications after operative etc.
Results:The effective rate of chemotherapy for patients in the experimental group was 83.7 % with complete responses in four patients. PR in 18 patients (36.7%), MR in 19 patients (38.8 %), SD in 8 patients (16.3%).The chemotherapy effect in patients with squamous cancer is prior than nonsquamous cancer,but its have not statistics significance(P=0.182). There have not significant difference in histologic classification(P=0.260).There have not statistics significance in chemotherapy regimens (P=0.943). Operation time in experimental group is 184.6min±37.6min, in contral group is 196.3min±62.9min, there have significantly difference in experimental group and control group (P=0.267).Bleeding in operation is 321.0ml±378.4ml, in control group is 280.6ml±118.5ml, there have significantly difference in experimental group and contral group (P=0.479).Neoadjuvant chemotherapy without increasing bleeding and operation time.The operative resection rate was 100% in experimental group but 89.8% in control group. The tumor size in experimental group was significantly smaller than that in control group after operation(P=0.000). The metastasis rate of pelvic lymph nodes in experimental group was significantly decreased compared with control group (P=0.027). The complication after surgury in two groups have not statistic significance (P>0.05).The recurrence rate in experimental group is significantly decrease than control group,there have statistic significance in experimental group and control group (P=0.002).The average period with no-tumor occurrence in experimental group are 63 months, in control group are 53 months, there have not statistic significance in experimental group and control group (P=0.06).The overll survival time in experimental group are 63 months, in control group are 56 months, there have not statistic significance in experimental group and control group (P=0.1221).The average survival time in patients whose have responder are 65months, the patients have nonresponder are 39 months, there have statistic significance in two groups (P=0.0406).
Conclusion:It is suggested that neoadjuvant chemotherapy would be a safe and effective approach for the patients with bulky cervical cancer. its side reactions were slight,and that its short-term effect would benefit Neoadjuvant chemotherapy can increase the respectability, decrease reccurrence rate, it would be useful to patients' survival. It shows promising prospect in clinical application.
引文
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42. Duenas-Gonzalez A, Cetina-Perez L, Onate-Ocana LF, et al. Multimodal treatment of locally advanced cervical cancer. Arch Med Res 2005;36(2):129-135.
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44. Choi YS, Sin JI, Kim JH, Ye GW, Shin IH, Lee TS. Survival benefits of neoadjuvant chemotherapy followed by radical surgery versus radiotherapy in locally advanced chemoresistant cervical cancer. J Korean Med Sci 2006;21(4):683-689.
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48. Kornovski Y, Gorchev G. Histopathological findings in postoperative specimens in cervical cancer patients with stages IB2-IVA after neoadjuvant chemotherapy and preoperative plus postoperative radiotherapy. J Buon 2007;12(1):57-63.
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54. Chen H, Liang C, Zhang L, Huang S, Wu X. Clinical efficacy of modified preoperative neoadjuvant chemotherapy in the treatment of locally advanced (stage ⅠB2 to ⅡB) cervical cancer: randomized study. Gynecol Oncol 2008;110(3):308-315.
55.陈慧君,吴绪峰,梁川,李晓兰。新辅助化疗在局部晚期宫颈癌中的疗效观察。中国肿瘤临床2007；34(4)：226-229。
56.游艳琴,宋磊。Pvm新辅助化疗方案用于局部晚期宫颈癌治疗。中国临床医学2007；14(5)：708-710。
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75.赵淑萍,王泽华。紫杉醇联合顺铂用于局部晚期宫颈癌新辅助化疗近期疗效观察。华中医学杂志2006；30(1)：43-44。
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52. Sardi JE, Boixadera MA, Sardi JJ. Neoadjuvant chemotherapy in cervical cancer:a new trend. Curr Opin Obstet Gynecol 2005;17(1):43-47.
53. Nagata Y, Araki N, Kimura H, et al. Neoadjuvant chemotherapy by transcatheter arterial infusion method for uterine cervical cancer. J Vasc Interv Radiol 2000; 11(3):313-319.
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57. Cai HB, Chen HZ, Yin HH. Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer. J Obstet Gynaecol Res 2006;32(3):315-323.
58.刘继红,熊樱。对宫颈癌新辅助化疗临床价值的评价。Chin J Clin Obstet Gynecol 2008;9(3):22-27。
59. Ivanov S, Zervoudis S, Ivanov S. Metastatic cancer in transposed ovaries after radical Wertheim-Meigs hysterectomy for a stage Ⅰ B and Ⅱ A cervical cancer. Akush Ginekol (Sofiia) 2003;42(5):22-24.
60.于月成,汪海丹,辛晓燕,李贵容,赵海波,王滨。术前介入化疗治疗巨块型宫颈癌52例疗效分析。第四军医大学学报2004；25(6)：557-559。
61. Bae JH, Lee SJ, Lee A, et al. Neoadjuvant cisplatin and etoposide followed by radical hysterectomy for stage 1B-2B cervical cancer. Gynecol Oncol 2008; 111(3):444-448.
62. Namkoong SE, Park JS, Kim JW, et al. Comparative study of the patients with locally advanced stages Ⅰ and Ⅱ cervical cancer treated by radical surgery with and without preoperative adjuvant chemotherapy. Gynecol Oncol 1995;59(1):136-142.
63. Benedetti-Panici PL, Zullo MA, Muzii L, et al. The role of neoadjuvant chemotherapy followed by radical surgery in the treatment of locally advanced cervical cancer. Eur J Gynaecol Oncol 2003;24(6):467-470.
64. Sardi JE, Giaroli A, Sananes C, et al. Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ⅰb squamous carcinoma of the cervix:the final results. Gynecol Oncol 1997;67(1):61-69.
65.王晓燕,邵淑丽。Ⅰb-Ⅱb期巨块型宫颈鳞癌术前新辅助化疗疗效观察。山西医药杂志2008；37(11)：963-964。
66. Kobierski J, Mielcarek P, Brzoska B, Krolikowska B, Emerich J. Neoadjuvant chemotherapy in the treatment of advanced cervical cancer. Ginekol Pol 2002;73(9):807-810.
67. deSouza NM, Soutter WP, Rustin G, et al. Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer:monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome. Br J Cancer 2004;90(12):2326-2331.
68. Heredia F, Bravo M, Pierotic M, Majlis A, Carmona L. Neoadjuvant combined chemotherapy followed by external whole pelvic irradiation in two cases of primary extranodal non-Hodgkin's lymphoma of the uterine cervix. Gynecol Oncol 2005;97(1):285-287.
69.吕卫国,金卓杏。宫颈癌新辅助化疗的临床病理观察。浙江大学学报：医学版2000；29(3)：111-113。
70. Chen CA, Cheng WF, Wei LH, Su YN, Hsieh CY. Radical hysterectomy alone or combined with neoadjuvant chemotherapy in the treatment of early stage bulky cervical carcinoma. J Formos Med Assoc 2002;101(3):195-202.
71. Yamakawa Y, Fujimura M, Hidaka T, Hori S, Saito S. Neoadjuvant intraarterial infusion chemotherapy in patients with stage ⅠB2-ⅢB cervical cancer. Gynecol Oncol 2000;77(2):264-270.
72. Modarress M, Maghami FQ, Golnavaz M, Behtash N, Mousavi A, Khalili GR. Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IB-IIB bulky cervical cancer and with tumor diameter greater than 4 cm. Int J Gynecol Cancer 2005;15(3):483-488.
73. Abe A, Furumoto H, Nakayama A, Nishimura M, Irahara M, Ikushima H. [Neoadjuvant chemotherapy followed by radical surgery compared to concurrent chemotherapy in stage Ⅰ b2-Ⅲ b cervical cancer]. Gan To Kagaku Ryoho 2008;35(9):1535-1539.
74.李金枝,杨兴升,赵俊红。宫颈癌新辅助化疗的Meta分析。国际妇产科学杂志2008；35(5)：379-383。
75.赵淑萍,王泽华。紫杉醇联合顺铂用于局部晚期宫颈癌新辅助化疗近期疗效观察。华中医学杂志2006；30(1)：43-44。
76. Fujiwaki R, Takahashi K, Kitao M. Decrease in tumor volume and histologic response to intraarterial neoadjuvant chemotherapy in patients with cervical and endometrial adenocarcinoma. Gynecol Oncol 1997;65(2):258-264.
77.陈春林。妇产科血管性介入治疗的应用现状和展望。中华妇产科杂志2003；38(8)：506-509。
78. Aoki Y, Tomita M, Sato T, et al. Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix. Gynecol Oncol 2001;83(2):263-267.
79.安云婷,李隆玉,邓克华。紫杉醇联合顺铂/卡铂在宫颈癌新辅助化疗中的作用。实用癌症杂志2006；21(5)：499-501。
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81.刘志鹏,吕娟。宫颈癌新辅助化疗。华夏医药2005；9(6)：518-521。