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基于连体多任务网络的HER2阳性乳腺癌患者纵向超声图像对新辅助化疗治疗反应的早期预测:一项多中心回顾性队列研究

Early prediction of treatment response to neoadjuvant chemotherapy based on longitudinal ultrasound images of HER2-positive breast cancer patients by Siamese multi-task network: A multicentre, retrospective cohort study.

作者信息

Liu Yu, Wang Ying, Wang Yuxiang, Xie Yu, Cui Yanfen, Feng Senwen, Yao Mengxia, Qiu Bingjiang, Shen Wenqian, Chen Dong, Du Guoqing, Chen Xin, Liu Zaiyi, Li Zhenhui, Yang Xiaotang, Liang Changhong, Wu Lei

机构信息

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhangshan Er Road, Guangzhou 510080, China.

出版信息

EClinicalMedicine. 2022 Jul 30;52:101562. doi: 10.1016/j.eclinm.2022.101562. eCollection 2022 Oct.

Abstract

BACKGROUND

Early prediction of treatment response to neoadjuvant chemotherapy (NACT) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer can facilitate timely adjustment of treatment regimens. We aimed to develop and validate a Siamese multi-task network (SMTN) for predicting pathological complete response (pCR) based on longitudinal ultrasound images at the early stage of NACT.

METHODS

In this multicentre, retrospective cohort study, a total of 393 patients with biopsy-proven HER2-positive breast cancer were retrospectively enrolled from three hospitals in china between December 16, 2013 and March 05, 2021, and allocated into a training cohort and two external validation cohorts. Patients receiving full cycles of NACT and with surgical pathological results available were eligible for inclusion. The key exclusion criteria were missing ultrasound images and/or clinicopathological characteristics. The proposed SMTN consists of two subnetworks that could be joined at multiple layers, which allowed for the integration of multi-scale features and extraction of dynamic information from longitudinal ultrasound images before and after the first /second cycles of NACT. We constructed the clinical model as a baseline using multivariable logistic regression analysis. Then the performance of SMTN was evaluated and compared with the clinical model.

FINDINGS

The training cohort, comprising 215 patients, were selected from Yunnan Cancer Hospital. The two independent external validation cohorts, comprising 95 and 83 patients, were selected from Guangdong Provincial People's Hospital, and Shanxi Cancer Hospital, respectively. The SMTN yielded an area under the receiver operating characteristic curve (AUC) values of 0.986 (95% CI: 0.977-0.995), 0.902 (95%CI: 0.856-0.948), and 0.957 (95%CI: 0.924-0.990) in the training cohort and two external validation cohorts, respectively, which were significantly higher than that those of the clinical model (AUC: 0.524-0.588, < 0.05). The AUCs values of the SMTN within the anti-HER2 therapy subgroups were 0.833-0.972 in the two external validation cohorts. Moreover, 272 of 279 (97.5%) non-pCR patients (159 of 160 (99.4%), 53 of 54 (98.1%), and 60 of 65 (92.3%) in the training and two external validation cohorts, respectively) were successfully identified by the SMTN, suggesting that they could benefit from regime adjustment at the early-stage of NACT.

INTERPRETATION

The SMTN was able to predict pCR in the early-stage of NACT for HER2-positive breast cancer patients, which could guide clinicians in adjusting treatment regimes.

FUNDING

Key-Area Research and Development Program of Guangdong Province (No.2021B0101420006); National Natural Science Foundation of China (No.82071892, 82171920); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No.2022B1212010011); the National Science Foundation for Young Scientists of China (No.82102019, 82001986); Project Funded by China Postdoctoral Science Foundation (No.2020M682643); the Outstanding Youth Science Foundation of Yunnan Basic Research Project (202101AW070001); Scientific research fund project of Department of Education of Yunnan Province(2022J0249). Science and technology Projects in Guangzhou (202201020001;202201010513); High-level Hospital Construction Project (DFJH201805, DFJHBF202105).

摘要

背景

对人表皮生长因子受体2(HER2)阳性乳腺癌患者新辅助化疗(NACT)治疗反应的早期预测有助于及时调整治疗方案。我们旨在开发并验证一种基于NACT早期纵向超声图像预测病理完全缓解(pCR)的连体多任务网络(SMTN)。

方法

在这项多中心回顾性队列研究中,2013年12月16日至2021年3月5日期间,从中国三家医院回顾性纳入了393例经活检证实为HER2阳性乳腺癌患者,并将其分为一个训练队列和两个外部验证队列。接受完整周期NACT且有手术病理结果的患者符合纳入标准。关键排除标准为超声图像和/或临床病理特征缺失。所提出的SMTN由两个可在多个层面连接的子网络组成,这允许整合多尺度特征并从NACT第一/第二周期前后的纵向超声图像中提取动态信息。我们使用多变量逻辑回归分析构建临床模型作为基线。然后评估SMTN的性能并与临床模型进行比较。

结果

训练队列包括215例患者,选自云南省肿瘤医院。两个独立的外部验证队列分别包括95例和83例患者,分别选自广东省人民医院和山西省肿瘤医院。SMTN在训练队列和两个外部验证队列中的受试者操作特征曲线下面积(AUC)值分别为0.986(95%CI:0.977 - 0.995)、0.902(95%CI:0.856 - 0.948)和0.957(95%CI:0.924 - 0.990),显著高于临床模型(AUC:0.524 - 0.588,P < 0.05)。在两个外部验证队列中,抗HER2治疗亚组内SMTN的AUC值为0.833 - 0.972。此外,SMTN成功识别了279例非pCR患者中的272例(97.5%)(训练队列和两个外部验证队列中分别为160例中的159例(99.4%)、54例中的53例(98.1%)和65例中的60例(92.3%)),表明他们可在NACT早期从治疗方案调整中获益。

解读

SMTN能够在NACT早期预测HER2阳性乳腺癌患者的pCR,可指导临床医生调整治疗方案。

资助

广东省重点领域研发计划(编号2021B0101420006);国家自然科学基金(编号82071892、82171920);广东省医学图像分析与应用人工智能重点实验室(编号2022B1212010011);国家自然科学基金青年科学基金(编号82102019、82001986);中国博士后科学基金资助项目(编号:2020M682643);云南省基础研究项目杰出青年科学基金(202101AW070001);云南省教育厅科研基金项目(2022J0249)。广州市科技计划项目(202201020001;202201010513);高水平医院建设项目(DFJH201805,DFJHBF202

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d3b/9343415/b9ba30bddd32/gr1.jpg

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