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1384例腹膜癌病患者接受细胞减灭术加腹腔内热灌注化疗的疗效

[Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

作者信息

Yu Y, Li X B, Lin Y L, Ma R, Ji Z H, Zhang Y B, An S L, Liu G, Yang X J, Li Y

机构信息

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

Department of Gastrointestinal Surgery & Peritoneal Cancer Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Mar 25;24(3):230-239. doi: 10.3760/cma.j.cn.441530-20201110-00603.

Abstract

Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all <0.05). CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

摘要

腹膜癌病是指腹膜表面的一组异质性(原发性或继发性)恶性肿瘤。细胞减灭术(CRS)联合腹腔内热灌注化疗(HIPEC)是针对腹膜癌病的一种综合治疗策略。本研究分析了CRS+HIPEC治疗腹膜癌病患者的疗效和安全性,并探讨了预后因素。在这项描述性病例系列研究中,回顾性收集了2004年1月至2020年1月在武汉大学中南医院(330例)和首都医科大学世纪坛医院(1054例)接受治疗的1384例连续性腹膜癌病患者的临床病理资料。分析了CRS+HIPEC的治疗模式特征(手术时间、切除器官数量、剥离腹膜数量、吻合口数量和HIPEC方案)、安全性[失血量、术后严重不良事件(SAE)和治疗结果]、生存时间以及影响生存的预后因素。SAE根据国际腹膜表面肿瘤学组织教科书定义为III-IV级不良事件。围手术期定义为从CRS+HIPEC当天至术后第30天。总生存期(OS)从CRS+HIPEC当天计算至死亡日期或最后一次随访日期。采用Kaplan-Meier法进行生存分析,采用log-rank检验进行组间比较。采用Cox回归模型确定预后因素。在1384例腹膜癌病患者中,男性529例(38.2%);中位年龄为55岁(10-87岁);中位体重指数(BMI)为22.6kg/m²;164例(11.8%)患者的腹膜癌病源于胃癌,287例(20.7%)源于结直肠癌,356例(25.7%)源于腹膜假黏液瘤,90例(6.5%)源于恶性腹膜间皮瘤,300例(21.7%)源于妇科癌症或原发性腹膜癌,187例(13.5%)源于腹膜后肉瘤、肺癌、乳腺癌和其他罕见肿瘤。CRS+HIPEC的中位持续时间为595分钟(90-1170分钟),中位切除器官数量为2个(0-10个),中位切除腹膜面积为4个(0-9个),中位腹膜癌指数(PCI)为21(1-39)。857例(61.9%)患者的细胞减灭完全性(CC)评分为0-1分。关于HIPEC方案,917例(66.3%)采用顺铂加多西他赛,183例(13.2%)采用顺铂加丝裂霉素,43例(3.1%)采用阿霉素加异环磷酰胺,其他240例(17.3%)采用改良方案。331例(23.9%)腹膜癌病患者围手术期发生SAE,共500例次,其中21例(1.5%)患者围手术期因治疗无效死亡,其他患者经积极治疗后康复。在中位随访时间8.6个月(0.3-82.7个月)期间,有414例死亡(29.9%)。中位OS为38.2个月(95%CI:30.6-45.8),1年、3年、5年生存率分别为73.5%、50.4%和39.3%。胃癌、结直肠癌、腹膜假黏液瘤、恶性腹膜间皮瘤以及女性生殖器癌或原发性腹膜癌病患者的中位OS分别为11.3个月(95%CI:8.9-13.8)、18.1个月(95%CI:13.5-22.6)、59.7个月(95%CI:48.0-71.4)、19.5个月(95%CI:6.0-33.0)和51.7个月(95%CI:14.6-88.8),组间差异有统计学意义(<0.001)。单因素和多因素分析显示,原发性胃癌(HR=4.639,95%CI:1.692-12.724)、原发性结直肠癌(HR=4.292,95%CI:1.957-9.420)、原发性恶性腹膜间皮瘤(HR=2.741,95%CI:1.162-6.466)、卡氏功能状态(KPS)评分为60分(HR=4.606,95%CI:2.144-9.895)、KPS评分为70分(HR=3.434,95%CI:1.977-5.965)、CC评分为1分(HR=2.683,95%CI:1.440~4.999)、CC评分为2-3分(HR=3.661,95%CI:1.956-6.852)以及围手术期SAE(HR=2.588,95%CI:1.846-3.629)是影响生存的独立预后因素,差异有统计学意义(均<0.05)。CRS+HIPEC是治疗腹膜癌病患者的一种有效的综合治疗策略,可在可接受的安全性下延长生存期。术前评估患者的一般状况很有必要,对于术前KPS评分<80分的患者应谨慎考虑实施CRS+HIPEC。在手术过程中,应在确保安全的前提下实现最佳的CRS。此外,有必要预防围手术期SAE以降低腹膜癌病患者的死亡风险。

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