围绝经期卵巢型子宫内膜异位症恶变风险预测模型的建立及评估

Establishment and evaluation of a malignant transformation risk prediction model for perimenopausal ovarian endometriosis

摘要

目的 构建围绝经期卵巢型子宫内膜异位症(OE)恶变风险的预测模型。方法 回顾性分析2013年1月至2021年12月就诊于郑州大学第三附属医院、河南省人民医院、河南省肿瘤医院,处于围绝经期并经病理确诊的236例OE患者及41例子宫内膜异位症相关性卵巢癌(EAOC)患者的临床资料.采用多因素Logistic回归分析确定围绝经期OE患者发生恶变的危险因素,运用R软件绘制列线图模型并进行模型的评估。结果 建模集OE组与建模集EAOC组的绝经状态、既往巧囊剥除史、合并自身癌症、直系亲属癌症、痛经时间5年及以上、进行性痛经、月经紊乱、术前疾病管理3年以上、不孕、包块压痛触痛、OE分型、重型内异症、超声下病变侧别、超声下包块呈现血流信号、磁共振成像下乳头状结构、磁共振成像下结合带完整的分布,以及初次性生活年龄、孕次、初次妊娠年龄、初次分娩年龄,经比较差异均有统计学意义(χ²值分别为17.527、16.255、1.634、7.609、20.822、15.313、5.140、4.751、13.303、5.264、8.448、8.920、5.248、8.385、7.029、4.223,t值分别为2.228、2.052、3.863、3.046,P<0.1).验证集OE组与验证集EAOC组的绝经状态、既往巧囊剥除史、月经量多、伴发痛经、痛经时间5年及以上、进行性痛经、术前疾病管理3年以上、不孕、包块固定不动、OE分型、重型内异症、超声下包块呈现血流信号、磁共振成像下囊壁增厚、磁共振成像下乳头状结构的分布比较差异均有统计学意义(χ²值分别为3.558、20.707、5.004、5.920、10.616、2.325、6.727、4.964、4.234、5.384、1.251、2.325、7.892、6.950,P<0.1).多因素Logistic回归分析结果显示:绝经状态(OR=5.007,95%CI:1.363~18.394)、进行性痛经(OR=3.583,95%CI:0.909~14.122)、不孕(OR=22.489,95%CI:3.552~42.382)、重型内异症(OR=3.800,95%CI:0.894~16.147)、超声下包块呈现血流信号(OR=3.431,95%CI:1.044~11.280)均是围绝经期OE恶变发生的独立危险因素(P<0.1).ROC曲线分析结果显示,建模集曲线下面积(AUC)为0.848(95%CI:0.769~0.928),验证集AUC为0.880(95%CI:0.725~0.941).建模集和验证集的校正曲线与理想曲线均拟合良好,Hosmer-Lemeshow拟合优度检验结果分别为χ²=3.691,P=0.884;χ²=4.166,P=0.842。结论 绝经状态、进行性痛经、不孕、重型内异症、超声下包块呈现血流信号均是围绝经期OE恶变发生的独立危险因素,基于上述指标建立的列线图模型具有良好的区分度,预测值与实际值之间具有较好的准确性和一致性,对高危人群有较高地筛选能力.

Abstract

Objective To construct a predictive model for the malignant risk of perimenopausal ovarian endometriosis (OE). Methods Clinical data of 236 patients with OE and 41 patients with endometriosis-associated ovarian cancer (EAOC) who were in perimenopause and diagnosed pathologically from January 2013 to December 2021 attending the Third Affiliated Hospital of Zhengzhou University, Henan Provincial People's Hospital and Henan Provincial Cancer Hospital were retrospectively analysed. Multivariate logistic regression was used to determine the risk factors for malignant transformation in perimenopausal OE patients. R software was used to draw and evaluate nomogram models. Results The modeling OE set and modeling EAOC set exhibited statistically significant differences in menopausal status, previous cyst removal history, self-merging cancer, direct family history of cancer, dysmenorrhea duration of 5 years or more, progressive dysmenorrhea, menstrual disorders, preoperative disease management of 3 years or more, infertility, mass tenderness, OE type, severe internal endometriosis, lesion side under ultrasound, blood flow signals in ultrasound-detected masses, nipple-like structures under magnetic resonance imaging, and distribution of combined bands under magnetic resonance imaging, as well as age at first sex, parity, age at first pregnancy and age at first delivery (χ ²=17.527, 16.255, 1.634, 7.609, 20.822, 15.313, 5.140, 4.751, 13.303, 5.264, 8.448, 8.920, 5.248, 8.385, 7.029 and 4.223; t=2.228, 2.052, 3.863 and 3.046, P<0.1). The validation OE set and validation EAOC set also exhibited statistically significant differences in menopausal status, previous cyst removal history, increased menstrual volume, concomitant dysmenorrhea, dysmenorrhea duration of 5 years or more, progressive dysmenorrhea, preoperative disease management of 3 years or more, infertility, immobile masses, OE typy, severe internal endometriosis, blood flow signals in ultrasound-detected masses, thickening of cyst walls under magnetic resonance imaging, and distribution of nipple-like structures under magnetic resonance imaging (χ²=3.558, 20.707, 5.004, 5.920, 10.616, 2.325, 6.727, 4.964, 4.234, 5.384, 1.251, 2.325, 7.892 and 6.950, P<0.1). Multivariate logistic regression analysis showed that menopausal status (OR=5.007, 95%CI: 1.363-18.394), progressive dysmenorrhea (OR=3.583, 95%CI: 0.909-14.122), infertility (OR=22.489, 95%CI: 3.552-42.382), severe endometriosis (OR=3.800, 95%CI: 0.894-16.147), and blood flow signal in ultrasound-detected masses (OR=3.431, 95%CI: 1.044-11.280) were independent risk factors for malignant transformation of ovarian endometriosis during perimenopause (P<0.1). The area under the curve (AUC) of the modeling set was 0.848 (95%CI: 0.769-0.928), and the AUC of the validation set was 0.880 (95%CI: 0.725-0.941). The calibration curves of the modeling set and the validation set fitted well with the ideal curve. The Hosmer-Lemeshow goodness-of-fit test results were χ²=3.691, P=0.884 and χ²=4.166, P=0.842, respectively. Conclusions Menopausal status, progressive dysmenorrhea, infertility, severe endometriosis and blood flow signal in ultrasound-detected masses are independent risk factors for malignant transformation in perimenopausal patients with ovarian endometriosis. The nomogram model established based on these indicators has a good discriminatory degree, with high accuracy and consistency between predicted and actual values. It has good screening ability for high-risk groups of malignant transformation.

关键词

卵巢型子宫内膜异位症 / 恶变 / 围绝经期 / 列线图

Key words

ovarian endometriosis / malignant transformation / perimenopausal period / nomogram

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基金资助

河南省高等学校重点科研项目计划(20B320055)