基于真实世界数据的腹膜假黏液瘤诊治现状分析

张颖; 李鑫宝; 林育林; 马茹; 徐大钊; 赵鑫; 闫风彩; 李雁

doi:10.12354/j.issn.1000-8179.2022.20211037

基于真实世界数据的腹膜假黏液瘤诊治现状分析

doi: 10.12354/j.issn.1000-8179.2022.20211037

张颖^{1, 2,},
李鑫宝¹,
林育林¹,
马茹¹,
徐大钊¹,
赵鑫¹,
闫风彩³,
李雁^{1, 3, ,}

1.
首都医科大学附属北京世纪坛医院腹膜肿瘤外科（北京市100038）
2.
首都医科大学大兴教学医院肿瘤科
3.
首都医科大学附属北京世纪坛医院病理科

基金项目: 本文课题受北京市医院管理局“登峰”人才培养计划（编号：DFL20180701）和北京市优秀人才培养资助集体项目（编号：2017400003235J007）资助

详细信息

作者简介:
张颖：专业方向为恶性肿瘤的化疗、靶向治疗、免疫治疗、姑息治疗

通讯作者:
李雁 liyansd2@mail.ccmu.edu.cn

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出版历程
- 收稿日期: 2021-09-15
- 录用日期: 2022-02-21

Analysis of diagnosis and treatment status of pseudomyxoma peritonei based on real-world data

Ying Zhang^{1, 2
,},
Xinbao Li¹,
Yulin Lin¹,
Ru Ma¹,
Dazhao Xu¹,
Xin Zhao¹,
Fengcai Yan³,
Yan Li^{1, 3
, ,}

1.
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
2.
Department of Oncology, Daxing Teaching Hospital of Capital University of Medical Sciences, Beijing 102600, China
3.
Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China

Funds: This work was supported by Beijing Municipal Administration of Hospitals' Ascent Plan (No. DFL20180701) and Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology (No. 2017400003235J007)

More Information

Corresponding author: Yan Li; E-mail: liyansd2@mail.ccmu.edu.cn

摘要

摘要: 目的基于真实世界数据分析腹膜假黏液瘤患者的诊治现状、自然病程及预后因素。方法回顾性分析2009年2月至2020年7月在首都医科大学附属北京世纪坛医院就诊的具有完整自然病程的腹膜假黏液瘤患者的相关资料，包括临床病理特征、非规范化治疗情况（误诊时间、误治时间、既往抗肿瘤治疗情况）、肿瘤细胞减灭术+腹腔热灌注化疗（cytoreductive surgery+hyperthermic intraperitoneal chemotherapy，CRS+HIPEC）治疗情况[手术时间、术中输血情况、腹膜癌指数（peritoneal cancer index，PCI）评分、细胞减灭程度（completeness of cytoreduction，CC）评分、脏器切除数量、腹膜切除区域数量、严重不良事件（serious adverse event，SAE）等]、随访生存时间，随访终点为患者死亡。采用Kaplan -Meier法绘制生存曲线，组间比较采用Log-rank检验。影响5年生存的预后因素采用Cox比例风险回归模型进行单因素和多因素分析。结果共纳入94例患者，其中男性57例（60.6%），女性37例（39.4%），中位年龄54（24～76）岁，既往抗肿瘤治疗者59例（62.8%），中位误诊时间0.8（0～62.5）个月，中位误治时间15.3（0～214.8）个月。所有患者均行CRS+HIPEC治疗，中位手术时间10.1（4.8～16.5）h，中位脏器切除数2（0～8）个，中位腹膜切除区域数5（0～9）个，中位PCI评分32（3～39）分，CC评分2～3分者达80.9%（76/94），SAE发生率35.1%（33/94）。94例患者中位总生存期30.8（2.4～218.4）个月，1、2、3、5年生存率分别为96.8%、63.8%、44.7%和23.4%。分层分析显示，既往腹腔化疗（46.5 个月vs. 26.3个月）、PSS 1～3分（39.0个月 vs. 21.9个月）、低/高级别病理类型（41.5/40.9 个月vs. 20.1个月）、KPS≥80分（41.5 个月vs. 23.9个月）、无淋巴结转移（35.5 个月vs. 17.1个月）、Ki-67<50%（46.4 个月vs. 20.8个月）的患者中位生存时间延长（P<0.05）。5年生存预后分析中，单因素分析显示以下5个因素与5年生存率有关：PSS评分（P=0.021）、既往腹腔化疗（P=0.008）、病理类型（P=0.004）、淋巴结转移（P=0.008）和Ki-67表达程度（P=0.003）。多因素分析显示出以下3个影响5年生存的独立预后因素：既往腹腔化疗（HR=0.458，95%CI：0.253～0.827，P=0.010）、淋巴结转移（HR=2.879，95%CI：1.345～6.163，P=0.006）、Ki-67≥50%（HR=2.502，95%CI：1.418～4.417，P=0.002）。结论 PMP非规范化治疗现象较普遍，误治时间长，淋巴结转移及Ki-67高表达是独立不良预后因素，CRS+HIPEC术前腹腔灌注化疗可能为PMP的治疗提供新的方向。
- 肿瘤细胞减灭术 /
- 腹腔热灌注化疗 /
- 腹膜假黏液瘤 /
- 真实世界研究 /
- 自然病程
Abstract: Objective To analyze diagnosis and treatment status, natural history, and prognostic factors of patients with pseudomyxoma peritonei (PMP) based on real-world data. Methods Real-world data of patients with PMP with a complete natural history, including clinicopathological characteristics, non-standardized treatment (time of misdiagnosis, time of mistreatment, previous anti-tumor treatment), cytoreductive surgery + hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) treatment [operation time, intraoperative blood transfusion, peritoneal cancer index (PCI) score, completeness of cytoreduction (CC) score, number of organs removed, number of peritoneal resection areas, serious adverse events (SAEs)], and follow-up until patient death, were retrospectively analyzed at Beijing Shijitan Hospital, Capital Medical University, from February 2009 to July 2020. The Kaplan-Meier method was used to draw survival curves, and the Log-rank test was used to compare between groups. Prognostic factors affecting survival were analyzed using univariate and multivariate analyses with a Cox proportional hazards regression model. Results : Overall, 94 patients were included, among whom 57 (60.6%) were male and 37(39.4%) were female; the median age of the patients was 54 (24–76) years. Fifty-nine (62.8%) patients previously received antitumor therapy. The median misdiagnosis time was 0.8 (0–62.5) months, and the median time of mistreatment was 15.3 (0–214.8) months. All patients received CRS+HIPEC treatment. The median operation time was 10.1 (4.8–16.5) hours, the mean number of organ resection was 2 (0–8), and the number of median peritonectomy was 5 (0–9). The PCI score was 32 (3–39) points, the CC score was 2–3 in 80.9% (76/94) of patients, and the SAE incidence rate was 35.1% (33/94). The median overall survival of 94 patients was 30.8 (2.4–218.4) months, and the 1-, 2-, 3-, and 5-year survival rates were 96.8%, 63.8%, 44.7%, and 23.4%, respectively. Stratified analysis showed that the median survival time of patients with previous intraperitoneal chemotherapy (46.5 months vs. 26.3 months), PSS 1–3 points (39.0 months vs. 21.9 months), low-/high-grade pathology (41.5/40.9 months vs. 20.1 months), KPS ≥80 (41.5 months vs. 23.9 months), no lymph node metastasis (35.5 months vs. 17.1 months), or Ki-67<50% (46.4 months vs. 20.8 months) was prolonged (P<0.05). Univariate analysis showed that the following five factors were related to 5-year survival rates: PSS score (P=0.021), previous intraperitoneal chemotherapy (P=0.008), pathological type (P=0.004), lymph node metastasis (P=0.008), and Ki-67 expression (P=0.003). Multivariate analysis revealed that the following three independent prognostic factors affected 5-year survival rates: previous intraperitoneal chemotherapy (HR=0.458, 95%CI: 0.253–0.827, P=0.010), lymph node metastasis (HR=2.879, 95%CI: 1.345–6.163, P=0.006), and Ki-67≥50% (HR=2.502, 95%CI: 1.418–4.417, P=0.002). Conclusions : Non-standardized treatment of PMP is common and long-standing in the real world. However, preoperative intraperitoneal infusion chemotherapy may provide a new treatment direction for PMP.
- cytoreductive surgery (CRS) /
- hyperthermic intraperitoneal chemotherapy (HIPEC) /
- pseudomyxoma peritonei (PMP) /
- real-world data study /
- natural history

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图 1 生存期分析

A：94例患者总生存曲线；B：既往腹腔化疗对患者生存的影响；C：不同PSS评分对患者生存的影响；D：不同病理类型对患者生存的影响

下载: 全尺寸图片幻灯片

表 1 患者的主要临床病理特征

临床病理特征	例数（%）
性别
男	57（60.6）
女	37（39.4）
首发症状
腹胀	80（85.1）
腹痛	10（10.6）
食欲减退	1（1.1）
腹泻	1（1.1）
排便困难	2（2.1）
PSS评分（分）
0	29（30.8）
1	31（33.0）
2	31（33.0）
3	3（3.2）
既往静脉化疗
无	39（41.5）
有	55（58.5）
既往腹腔化疗
无	58（61.7）
有	36（38.3）
既往放疗
无	91（96.8）
有	3（3.2）
既往靶向治疗
无	77（81.9）
有	17（18.1）
病理分类
低级别	40（42.5）
高级别	31（33.0）
高级别伴印戒细胞	23（24.5）
术后辅助治疗
无	56（59.6）
有	38（40.4）

下载: 导出CSV

表 2 患者CRS+HIPEC治疗情况

临床指标	例数（%）
CC（分）
0～1	18（19.1）
2～3	76（80.9）
HIPEC药物
紫杉醇+铂类	63（67.0）
丝裂霉素+铂类	31（33.0）
SAE
无	61（64.9）
有	33（35.1）

下载: 导出CSV

表 3 94例患者总生存时间分层分析

指标	中位生存时间（月）	95%CI	Log-rank	P
性别			1.611	0.204
男	29.2	18.209～40.191
女	39.6	25.507～59.633
年龄（岁）			0.072	0.788
≥60	34.8	12.449～57.211
<60	30.8	22.110～34.590
BMI			1.918	0.166
≥21	26.3	19.387～33.213
<21	35.9	24.612～47.328
KPS（分）			5.525	0.019
≥80	41.5	34.130～48.870
<80	23.9	15.745～31.995
既往静脉化疗			0.130	0.718
无	29.8	17.809～41.791
有	34.3	25.311～43.229
既往靶向治疗			1.144	0.285
无	34.8	26.585～43.075
有	26.1	13.800～38.460
PCI（分）			0.041	0.840
<32	27.8	14.963～40.637
≥32	30.8	23.100～38.500
CC（分）			0.783	0.376
0～1	26.1	21.764～30.496
2～3	34.8	27.109～42.551
SAE			1.322	0.250
无	30.8	22.382～39.218
有	34.3	19.144～49.396
HIPEC药物			0.309	0.578
紫杉醇+铂类	29.6	20.153～39.107
丝裂霉素+铂类	36.4	22.905～49.955
淋巴结转移			10.908	0.001
无	35.5	25.503～45.497
有	17.1	13.194～21.066
脉管癌栓			2.361	0.124
无	35.4	25.502～45.238
有	27.7	23.170～32.170
Ki-67（%）			5.504	0.019
<50	46.4	34.127～58.613
≥50	20.8	17.794～23.866
术后辅助治疗			0.031	0.860
无	29.2	22.382～39.218
有	39.6	19.144～49.396

下载: 导出CSV

表 4 94例患者5年生存影响因素分析

预后因素	单因素分析			多因素分析
预后因素	HR	95%CI	P	HR	95%CI	P
既往腹腔化疗（无 vs. 有）	0.509	0.308～0.840	0.008	0.458	0.253～0.827	0.010
淋巴结转移（无 vs. 有）	3.247	1.554～6.784	0.002	2.879	1.345～6.163	0.006
Ki-67（<50% vs. ≥50%）	2.325	1.330～4.065	0.003	2.502	1.418～4.417	0.002

下载: 导出CSV

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