发表机构
George Washington University（乔治华盛顿大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
该研究针对新辅助乳腺癌，发现预处理DCE-MRI的熵可解析病理完全缓解等终点中隐藏的反应质量，识别复发富集组，补充现有终点的不足。
AI 中文摘要
病理完全缓解（pCR）是重要的新辅助治疗终点，但仍有5-15%的完全缓解患者会复发，而临床和基因组变量无法可靠识别这些患者。本研究检验预处理动态对比增强MRI的熵——瘤内强化异质性——是否能解析pCR和残余癌负荷（RCB）中隐藏的反应质量。在四个队列（共1200名患者）中，预设的熵阈值定义了有利和不利的结构状态。将结构与病理结合产生了一个四层框架，在I-SPY1中跨度为4.1倍复发风险，在反应极端值处为7.7倍。在I-SPY2中，219名完全缓解患者中的55名（25.1%）预处理时为结构不利。在外部HER2阳性缓解者综合队列（I-SPY1病理确认的pCR加UCSF最佳缓解替代指标；n=33，10个事件）中，不利结构与更高的复发风险相关（HR=2.87，95%CI 1.38-5.96），捕捉了10次复发中的7次，属于风险富集而非决定性因素。在HER2阳性RCB-0亚组中，有利结构者复发率为12.5%，不利结构者为80.0%；Firth Cox回归保留了该关联（HR=8.13，95%CI 1.71-49.21；n=21，6个事件）。在Duke队列（n=908；76个事件）中，有利结构仍与较低的远处复发风险独立相关（校正后HR=0.61，95%CI 0.41-0.91）。RNA分析将有利结构与I-SPY2中非重叠患者中方向可重复的免疫-架构程序关联；上皮间质转化（EMT）通路富集在有利侧，而不利层级包含广泛免疫耗竭的亚状态。然而全队列RNA模型对结构状态的区分度较弱，且无法恢复连续熵。因此，预处理MRI不能替代pCR或RCB；它揭示了这些终点压缩的反应质量差异，并识别出复发富集组以进行前瞻性验证。
英文摘要
Pathologic complete response (pCR) is a strong neoadjuvant endpoint, yet 5-15% of complete responders recur and clinical/genomic variables do not reliably identify them. We tested whether pretreatment dynamic contrast-enhanced MRI entropy - intratumoral enhancement heterogeneity - resolves response quality hidden within pCR and residual cancer burden (RCB). Across four cohorts (1,200 patients), a prespecified entropy threshold defined favorable and adverse structural states. Crossing structure with pathology yielded a four-tier framework spanning 4.1-fold recurrence in I-SPY1 and 7.7-fold at response extremes. In I-SPY2, 55 of 219 complete responders (25.1%) were structurally adverse, pretreatment. In an external HER2-positive responder synthesis (I-SPY1 pathology-confirmed pCR plus UCSF best-response proxy; n = 33, 10 events), adverse structure was associated with higher recurrence risk (HR = 2.87, 95% CI 1.38-5.96) capturing 7 of 10 recurrences, enriching rather than determining risk. In a HER2-positive RCB-0 subset, recurrence was 12.5% with favorable and 80.0% with adverse structure; Firth Cox regression preserved the association (HR = 8.13, 95% CI 1.71-49.21; n = 21, 6 events). In Duke (n = 908; 76 events), favorable structure remained independently associated with lower distant-recurrence risk (adjusted HR = 0.61, 95% CI 0.41-0.91). RNA linked favorable structure to a directionally reproduced immune-architecture program among non-overlapping patients within ISPY2; EMT-pathway enrichment was favorable-side, while the adverse tier contained a broadly immune-depleted substate. Yet full-cohort RNA models weakly discriminated structural state and did not recover continuous entropy. Pretreatment MRI therefore does not replace pCR or RCB; it reveals response-quality differences that these endpoints compress and identifies a recurrence-enriched group for prospective validation.
