间歇性肿瘤细胞减灭术+腹腔热灌注化疗在晚期上皮性卵巢癌治疗中的应用

张颖; 杨波; 印天; 赵越; 张新怡; 李莹

doi:10.16766/j.cnki.issn.1674-4152.003499

间歇性肿瘤细胞减灭术+腹腔热灌注化疗在晚期上皮性卵巢癌治疗中的应用

doi: 10.16766/j.cnki.issn.1674-4152.003499

张颖¹,
杨波^1, ,,
印天¹,
赵越¹,
张新怡¹,
李莹²

1.
蚌埠医科大学第一附属医院肿瘤妇科，安徽蚌埠 233004
2.
联勤保障部队第902医院妇儿科，安徽蚌埠 233000

基金项目:

安徽省高等学校自然科学研究项目 KJ2021A0727

详细信息

通讯作者:
杨波，E-mail：yangbo@bbmc.edu.cn

中图分类号: R737.31 R730.53
计量
- 文章访问数: 42
- HTML全文浏览量: 20
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2023-11-14
- 网络出版日期: 2024-07-20

Application of intermittent cytoreductive surgery + hyperthermic intraperitoneal chemotherapy in the treatment of advanced ovarian cancer

1.
Department of Gynaecologic Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的探索在晚期上皮性卵巢癌治疗中采用间歇性肿瘤细胞减灭术+腹腔热灌注化疗(HIPEC)的有效性和安全性。方法选取蚌埠医科大学第一附属医院2020年11月—2021年9月诊断为晚期上皮性卵巢癌的患者90例，根据是否使用HIPEC分为观察组及对照组，每组各45例。比较2组患者近期疗效、术后及化疗后不良反应发生情况。结果观察组客观有效率(ORR)为86.7%，明显高于对照组的68.9%(P=0.043)；观察组2年生存率为86.7%，高于对照组的64.4%(P=0.014)；观察组无进展生存期(PFS)为(29.03±1.07)个月，明显高于对照组[(16.60±1.12)个月，P<0.001]；化疗后不良反应中恶心/呕吐分级2组差异有统计学意义(P<0.05)，肝功能损伤分级2组差异有统计学意义(P<0.05)；术后不良反应中观察组腹胀、低蛋白血症的发生率分别为57.8%、37.8%，对照组分别为2.2%、2.2%，差异均有统计学意义(P<0.05)。结论采用间歇性肿瘤细胞减灭术联合HIPEC有望在控制范围内提高晚期上皮性卵巢癌患者的近期治疗效果，保证治疗的安全性。
- 卵巢癌 /
- 肿瘤细胞减灭术 /
- 腹腔热灌注化疗 /
- 近期疗效 /
- 不良反应
Abstract: Objective To explore the efficacy and safety of intermittent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced ovarian cancer. Methods Patients diagnosed with advanced ovarian cancer in the First Affiliated Hospital of Bengbu Medical University from November 2020 to September 2021 were selected. According to whether to use HIPEC, the patients were divided into an experimental group and a control group, with 45 cases in each group. The short-term outcomes and incidence of adverse effects after surgery and chemotherapy in two groups of patients were compared. Results The objective response rate (ORR) was 86.7% in the experimental group and 68.9% in the control group (P=0.043). The 2-year survival rate was 86.7% in the experimental group and 64.4% in the control group (P=0.014). The average progression-free survival (PFS) of the experimental group was (29.03±1.07) months, which was significantly higher than the control group [(16.60±1.12) months, P<0.001]. The adverse reactions after chemotherapy in the two groups were statistically significant in nausea/vomiting (P<0.05), and liver function injury (P<0.05). The incidences of abdominal distension and hypoproteinemia were 57.8% and 37.8% in the experimental group, and 2.2% and 2.2% in the control group, respectively (P<0.05). Conclusion The use of intermittent cytoreductive surgery combined with HIPEC is expected to improve the short-term treatment effect of patients with advanced ovarian cancer within a controlled range and ensure the safety of treatment.
- Ovarian cancer /
- Cytoreductive surgery /
- Intraperitoneal thermoperfusion chemotherapy /
- Short-term efficacy /
- Adverse reactions

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图 1 2组晚期上皮性卵巢癌患者PFS的Kaplan-Meier生存曲线

Figure 1. Kaplan-Meier survival curve for progression-free survival in advanced epithelial ovarian cancer patients across two groups

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表 1 2组晚期上皮性卵巢癌患者临床疗效比较[例(%)]

Table 1. Comparison of clinical efficacy in two groups of patients with advanced epithelial ovarian cancer

组别	例数	CR	PR	SD	PD	ORR
观察组	45	27(60.0)	12(26.7)	1(2.2)	5(11.1)	39(86.7)
对照组	45	18(40.0)	13(28.9)	11(24.4)	3(6.7)	31(68.9)
注：2组ORR比较，χ²=4.114，P=0.043。

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表 2 2组晚期上皮性卵巢癌患者CA125及HE4水平比较[M(P₂₅, P₇₅)]

Table 2. Comparison of CA125 and HE4 levels in two groups of patients with advanced epithelial ovarian cancer [M(P₂₅, P₇₅)]

组别	例数	CA125(IU/mL)		HE4(pmol/L)
组别	例数	治疗前	治疗后	治疗前	治疗后
观察组	45	1 406.00(592.50, 2 358.00)	19.80(13.35, 35.95)^a	622.60(352.50, 830.55)	64.40(55.50, 85.30)^a
对照组	45	1 514.20(887.00, 2 715.00)	30.10(15.90, 63.30)^b	608.00(430.00, 1 195.00)	85.70(60.25, 98.80)^b
Z值		-0.771	-2.216	-0.722	-2.571
P值		0.441	0.027	0.470	0.010
注：与观察组治疗前比较，^aZ=-5.840, P<0.001；与对照组治疗前比较，^bZ=-5.842，P<0.001。

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表 3 2组晚期上皮性卵巢癌患者化疗后不良反应分级比较[M(P₂₅, P₇₅)]

Table 3. Comparison of adverse reaction grading in two groups of patients with advanced epithelial ovarian cancer post-chemotherapy [M(P₂₅, P₇₅)]

组别	例数	骨髓抑制	肝功能损伤	肾功能损伤	恶心/呕吐	心脏毒性
观察组	45	2.0(2.0, 3.0)	1.0(1.0, 1.5)	1.0(1.0, 2.0)	1.0(1.0, 2.0)	1.0(1.0, 1.0)
对照组	45	2.0(2.0, 2.0)	2.0(1.0, 2.0)	1.0(1.0, 1.5)	2.0(2.0, 2.0)	1.0(1.0, 1.0)
Z值		-1.350	-2.996	-1.144	-3.267	-1.422
P值		0.177	0.003	0.253	0.001	0.155
注：1表示0级，2表示Ⅰ~Ⅱ级，3表示Ⅲ~Ⅳ级。

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表 4 2组晚期上皮性卵巢癌患者术后不良反应发生情况比较[例(%)]

Table 4. Comparison of postoperative adverse reactions in two groups of patients with advanced epithelial ovarian cancer [cases (%)]

组别	例数	发热>38.5 ℃	恶心/呕吐	腹痛	腹胀	肠梗阻	低蛋白血症	伤口愈合不良	血栓形成	电解质紊乱
观察组	45	18(40.0)	19(42.2)	11(24.4)	26(57.8)	4(8.9)	17(37.8)	3(6.7)	2(4.4)	25(55.6)
对照组	45	12(26.7)	12(26.7)	10(22.2)	1(2.2)	2(4.4)	1(2.2)	1(2.2)	6(13.3)	29(64.4)
χ²值		1.800	2.411	0.062	33.069	0.179	17.778	0.262	1.235	0.741
P值		0.180	0.120	0.803	<0.001	0.673	<0.001	0.609	0.266	0.389

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表 5 2组晚期上皮性卵巢癌患者生存情况比较

Table 5. Comparative survival analysis of two groups of patients with advanced epithelial ovarian cancer

组别	例数	1年生存[例(%)]	2年生存[例(%)]	无进展生存时间(x±s, 月)
观察组	45	43(95.6)	39(86.7)	29.03±1.07
对照组	45	41(91.1)	29(64.4)	16.60±1.12
χ²值		1.786	6.016	24.853
P值		0.673	0.014	<0.001
注：表中采用Kaplan-Meier生存分析。

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参考文献(16)

[1]	南云泽, 李萌萌, 王彤, 等. 新辅助化疗联合间歇型肿瘤细胞减灭术治疗34例晚期卵巢癌的疗效及预后分析[J]. 延边大学医学学报, 2021, 44(1): 52-55. https://www.cnki.com.cn/Article/CJFDTOTAL-YBYB202101015.htm NAN Y Z, LI M M, WANG T et al. Efficacy and prognostic analysis of neoadjuvant chemotherapy combined with intermittent cytoreductive surgery in the treatment of 34 cases of advanced ovarian cancer[J]. Medical Journal of Yanbian University, 2021, 44(1): 52-55. https://www.cnki.com.cn/Article/CJFDTOTAL-YBYB202101015.htm
[2]	COLERIDGE S L, BRYANT A, KEHOE S, et al. Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced ovarian epithelial cancer[J]. Cochrane Database Syst Rev, 2021, 7(7): CD005343. DOI: 10.1002/14651858.CD005343.
[3]	LHEUREUX S, BRAUNSTEIN M, OZA A M. Epithelial ovarian cancer: evolution of management in the era of precision medicine[J]. CA Cancer J Clin, 2019, 69(4): 280-304. doi: 10.3322/caac.21559
[4]	CHO J H, KIM S, SONG Y S. Neoadjuvant chemotherapy in advanced ovarian cancer: optimal patient selection and response evaluation[J]. Chin Clin Oncol, 2018, 7(6): 58. DOI: 10.21037/cco.2018.10.11.
[5]	SPRATT J S, ADCOCK R A, MUSKOVIN M, et al. Clinical delivery system for intraperitoneal hyperthermic chemotherapy[J]. Cancer Res, 1980, 40(2): 256-260.
[6]	中国抗癌协会妇科肿瘤专业委员会. 卵巢恶性肿瘤诊断与治疗指南(2021年版)[J]. 中国癌症杂志, 2021, 31(6): 490-500. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGAZ202106007.htm Gynecological Oncology Committee of Chinese anti-Cancer Association. Guidelines for the diagnosis and treatment of ovarian malignant tumors (2021 edition)[J]. Chinese Journal of Cancer, 2021, 31(6): 490-500. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGAZ202106007.htm
[7]	朱秀红, 毛翠玉, 张燕, 等. 卵巢癌新辅助化疗的研究进展[J]. 现代妇产科进展, 2023, 32(11): 865-869. https://www.cnki.com.cn/Article/CJFDTOTAL-XDFC202311016.htm ZHU X H, MAO C Y, ZHANG Y, et al. Research progress of neoadjuvant chemotherapy for ovarian cancer[J]. Progress of Modern Obstetrics and Gynecology, 2023, 32(11): 865-869. https://www.cnki.com.cn/Article/CJFDTOTAL-XDFC202311016.htm
[8]	中国抗癌协会宫颈癌专业委员会, 李晶, 林仲秋. 妇科肿瘤腹腔热灌注治疗临床应用指南(2023年版)[J]. 中国实用妇科与产科杂志, 2023, 39(9): 926-934. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF202309016.htm Cervical Cancer Committee of China Anti-Cancer Association, LI J, LIN Z Q. Group of Chinese Association of Obstetricians and Gynecologists Expert consensus on application of clinical medicines for hyperthermic intraperitoneal chemotherapy in the treatment of gynecological tumors (2024 edition)[J]. Chinese Journal of Applied Gynecology & Obstetrics, 2023, 39(9): 926-934. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF202309016.htm
[9]	LIM P Q, HAN I H, SEOW K M, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC): an overview of the molecular and cellular mechanisms of actions and effects on epithelial ovarian cancers[J]. Int J Mol Sci, 2022, 23(17): 10078. DOI: 10.3390/ijms231710078.
[10]	WHITE M G, BADGWELL B. Oncologic components of HIPEC: key question: in patients with gastric or colorectal adenocarcinoma metastatic to the peritoneum, does cytoreductive surgery (CRS) plus hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC) prolong survival or increase the risk of complications relative to CRS alone?[J]. Ann Surg Oncol, 2022, 29(11): 6561-6564. doi: 10.1245/s10434-021-11253-x
[11]	宋敏. CRS联合顺铂腹腔热灌注化疗治疗卵巢癌的近远期效果观察[J]. 当代医学, 2020, 26(19): 114-116. doi: 10.3969/j.issn.1009-4393.2020.19.046 SONG M. Observation of short-term and long-term effect of CRS combined with cisplatin intraperitoneal hyperthermic perfusion chemotherapy in the treatment of ovarian cancer[J]. Contemporary Medicine, 2020, 26(19): 114-116. doi: 10.3969/j.issn.1009-4393.2020.19.046
[12]	李会俭, 项达军, 赵敏. 高精度持续循环腹腔热灌注化疗联合静脉化疗与常规静脉化疗治疗卵巢癌的疗效对比分析[J]. 贵州医药, 2017, 41(11): 1168-1170. doi: 10.3969/j.issn.1000-744X.2017.11.020 LI H J, XISNG D J, ZHAO M. Comparison of the efficacy of high-precision continuous cyclic hyperthermic intraperitoneal chemotherapy combined with intravenous chemotherapy and conventional intravenous chemotherapy in the treatment of ovarian cancer[J]. Guizhou Medical Journal, 2017, 41(11): 1168-1170. doi: 10.3969/j.issn.1000-744X.2017.11.020
[13]	褚永姣, 任婷婷. 腹腔热灌注化疗联合肿瘤细胞减灭术对卵巢癌患者的治疗效果[J]. 癌症进展, 2023, 21(9): 966-969. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ202309009.htm CHU Y J, REN T T. Effect of hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery on patients with ovarian cancer[J]. Cancer Progression, 2023, 21(9): 966-969. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ202309009.htm
[14]	郭钰, 徐鹏, 王蓓蒂, 等. 血清肿瘤标志物在卵巢癌诊断中的研究进展[J]. 中华全科医学, 2021, 19(8): 1362-1366. doi: 10.16766/j.cnki.issn.1674-4152.002061 GUO Y, XU P, WANG B D, et al. Research progress of serum tumor markers in the diagnosis of ovarian cancer[J]. Chinese Journal of General Practice, 2021, 19(8): 1362-1366. doi: 10.16766/j.cnki.issn.1674-4152.002061
[15]	DRAPKIN R, VON HORSTEN H H, LIN Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas[J]. Cancer Res, 2005, 65(6): 2162-2169. doi: 10.1158/0008-5472.CAN-04-3924
[16]	VAN DRIEL W J, KOOLE S N, SZKORSKA K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer[J]. N Engi J Med, 2018, 378(3): 230-240. doi: 10.1056/NEJMoa1708618