背景:HER2和HR的免疫组织化学测试(IHC)可以为浸润性乳腺癌患者提供预后信息和治疗指导。我们旨在开发HER2和HR的非侵入性图像特征ISHER2和ISHR,分别。我们独立评估它们的可重复性,再现性,与新辅助化疗的病理完全缓解(pCR)相关。
方法:治疗前DWI,IHC受体状态HER2/HR,回顾性收集多机构ACRIN6698试验的222例患者的新辅助化疗的pCR.他们是为了发展而预先分开的,独立验证,和重新测试。在手动肿瘤分割内从DWI导出的ADC图提取1316个图像特征。ISHER2和ISHR通过RIDGE逻辑回归使用与IHC受体状态相关的非冗余和测试重测可重复特征来开发。我们使用二值化后的受试者工作曲线下面积(AUC)和比值比(OR)评估了它们与pCR的关联。使用具有类内相关系数(ICC)的测试-重测集进一步评估了它们的可重复性。
结果:开发了针对HER2的5特征ISHER2(AUC=0.70,95%CI0.59至0.82),并进行了验证(AUC=0.72,95%CI0.58至0.86),具有高扰动重复性(ICC=0.92)和重测重复性(ICC=0.83)。ISHR是使用5个特征开发的,这些特征与开发过程中的HR(AUC=0.75,95%CI0.66至0.84)和验证(AUC=0.74,95%CI0.61至0.86)以及相似的可重复性(ICC=0.91)和可重复性(ICC=0.82)具有较高的相关性。在验证队列中,两种图像特征均显示与pCR的显著关联,ISHER2的AUC为0.65(95%CI0.50至0.80),ISHER2的AUC为0.64(95%CI0.50至0.78)。具有高ISHER2的患者更有可能达到新辅助化疗的pCR,验证OR为4.73(95%CI1.64至13.65,P值=0.006)。低ISHR患者的pCR较高,OR=0.29(95%CI0.10至0.81,P值=0.021)。从图像签名得到的分子亚型显示出与基于IHC的分子亚型相当的pCR预测值(P值>0.05)。
结论:针对IHC受体HER2和HR的非侵入性评估,开发并验证了基于ADC的稳健图像特征。我们还证实了它们在预测新辅助化疗治疗反应方面的价值。有必要在治疗指导中进行进一步评估,以充分验证其作为IHC替代的潜力。
The immunohistochemical test (IHC) of HER2 and
HR can provide prognostic information and treatment guidance for invasive breast cancer patients. We aimed to develop noninvasive image signatures ISHER2 and ISHR of HER2 and
HR, respectively. We independently evaluate their repeatability, reproducibility, and association with pathological complete response (pCR) to neoadjuvant chemotherapy.
Pre-treatment DWI, IHC receptor status HER2/
HR, and pCR to neoadjuvant chemotherapy of 222 patients from the multi-institutional ACRIN 6698 trial were retrospectively collected. They were pre-separated for development, independent validation, and test-retest. 1316 image features were extracted from DWI-derived ADC maps within manual tumor segmentations. ISHER2 and ISHR were developed by RIDGE logistic regression using non-redundant and test-retest reproducible features relevant to IHC receptor status. We evaluated their association with pCR using area under receiver operating curve (AUC) and odds ratio (OR) after binarization. Their reproducibility was further evaluated using the test-retest set with intra-class coefficient of correlation (ICC).
A 5-feature ISHER2 targeting HER2 was developed (AUC = 0.70, 95% CI 0.59 to 0.82) and validated (AUC = 0.72, 95% CI 0.58 to 0.86) with high perturbation repeatability (ICC = 0.92) and test-retest reproducibility (ICC = 0.83). ISHR was developed using 5 features with higher association with
HR during development (AUC = 0.75, 95% CI 0.66 to 0.84) and validation (AUC = 0.74, 95% CI 0.61 to 0.86) and similar repeatability (ICC = 0.91) and reproducibility (ICC = 0.82). Both image signatures showed significant associations with pCR with AUC of 0.65 (95% CI 0.50 to 0.80) for ISHER2 and 0.64 (95% CI 0.50 to 0.78) for ISHER2 in the validation cohort. Patients with high ISHER2 were more likely to achieve pCR to neoadjuvant chemotherapy with validation OR of 4.73 (95% CI 1.64 to 13.65, P value = 0.006). Low ISHR patients had higher pCR with OR = 0.29 (95% CI 0.10 to 0.81, P value = 0.021). Molecular subtypes derived from the image signatures showed comparable pCR prediction values to IHC-based molecular subtypes (P value > 0.05).
Robust ADC-based image signatures were developed and validated for noninvasive evaluation of IHC receptors HER2 and
HR. We also confirmed their value in predicting treatment response to neoadjuvant chemotherapy. Further evaluations in treatment guidance are warranted to fully validate their potential as IHC surrogates.