子宫内膜癌（EC）的分子分类及其与无复发生存期（RFS）和总生存期（OS）结果的关联：GOG-0258的辅助分析

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-02-01 DOI:10.1016/j.ygyno.2025.01.006

Aine Clements , Danielle Enserro , Kyle C. Strickland , Rebecca Previs , Daniela Matei , David Mutch , Matthew Powell , Ann Klopp , David Scott Miller , William Small Jr. , Paul DiSilvestro , Nick Spirtos , Casey Cosgrove , Greg Sfakianos , J. Rebecca Liu , Roberto Vargas , Mark Shahin , Bradley Corr , Kimberly Dessources , Frederick Ueland , Angeles Alvarez Secord

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Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype.</div></div><div><h3>Results</h3><div>ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (<em>p</em> < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). 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引用次数: 0

摘要

目的：确定错配修复（MMR）和p53蛋白表达的分子分类是否能预测化疗和放疗（CRT）与化疗（CT）治疗的子宫内膜癌（EC）患者的无复发生存（RFS）和总生存（OS）。方法：GOG-0258，一项III期随机试验（NCT00942357），比较CRT和CT。免疫组织化学评估MMR和p53状态。Kaplan-Meier曲线和校正Cox模型按分子亚型分析生存结果。结果：ECs分为MMR缺陷型（dMMR）（27%）、p53异常型（p53abn）（24%）和p53野生型（p53wt）（49%）。p53abn更常见于年龄较大、黑人和浆液组织学的患者(p结论：分子分类似乎具有预测性和预后性，p53abn肿瘤患者的生存率较差。在一项探索性分析中，p53wt似乎可以预测改善的RFS，比CT更有利于CRT。不同分子亚型对OS的治疗效果无差异。

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Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

Purpose

Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods

GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype.

Results

ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34–4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16–6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85–1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99–2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32–0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups.

Conclusion

Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy