PO.BCS02.04 · 生物信息与计算
利用PR-等距引导的深度学习解码基于CT的肿瘤异质性并改善NSCLC预后评估
Leveraging PR-isometric guided deep learning to decode CT-based tumor heterogeneity and enhanced NSCLC prognosis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景:非小细胞肺癌(NSCLC)造成大多数肺癌相关死亡,其在CT影像上表现出具有预后意义的瘤内异质性,而定性评估常常忽视这一点。为推进精准肿瘤学中的定量风险分层,我们开发了一个深度学习框架,以提取EGFR突变NSCLC中基于CT的放射组学表型,并评估其与总生存的关联。
方法:分析了来自斯坦福放射基因组学数据集的130例NSCLC患者队列,均带有专家标注的肿瘤掩膜。为提高放射组学的稳定性并降低采样方差,使用受控增强协议生成了1,300个增强的2D肿瘤层面。对于每位患者,选择性地筛选肿瘤负荷最大的层面,以在后续建模中强调瘤内异质性。通过预训练的ResNet50提取高层形态描述符,并将所得嵌入通过Parzen-Rosenblatt等距映射(PR-Isomap)投影到低维流形,保留与异质性生长动态相关的非线性几何关系。间隙统计量(Gap statistics)确定了最优潜在维度。随后使用这些低维向量生物标志物对生存结局进行分类。
结果:PR-Isomap衍生的嵌入对患者生存队列展现出显著的分层,凸显了该方法编码肿瘤表型内临床相关异质性的能力。ResNet50主干网络使用基于自适应矩估计(Adam)的优化器经过200多个训练轮次进行优化,学习率初始化为10^-4并自适应衰减以确保稳定收敛。模型训练采用交叉熵损失函数以增强跨生存类别的判别能力。所得分类器达到97%的层面级准确率,在所有增强方案中表现出稳健的泛化能力。值得注意的是,得益于分割引导的层面筛选系统性地排除了非肿瘤混杂因素,模型对生存终点的判别归因于具有生物学意义的肿瘤固有结构模式,而非无关的解剖噪声。
结论:将基于深度学习的CT衍生异质性特征与PR-Isomap嵌入相整合,可增强NSCLC的生存分层。这些由影像驱动的低维Deepomics特征提供了具有临床可操作性的预后生物标志物,能够更早识别高风险患者并为精准治疗计划提供依据。
查看英文原文 English abstract
Background: Non-small cell lung cancer (NSCLC), responsible for the majority of lung cancer-related deaths, displays prognostically meaningful intratumoral heterogeneity on CT imaging that is frequently overlooked by qualitative assessment. To advance quantitative risk stratification in precision oncology, we develop a deep learning framework to derive CT-based radiomic phenotypes in EGFR-mutated NSCLC and evaluate their association with overall survival.
Method: A cohort of 130 NSCLC patients with expert-annotated tumor masks from the Stanford Radiogenomics Dataset was analyzed. To improve radiomic stability and reduce sampling variance, 1,300 augmented 2D tumor slices were generated using controlled augmentation protocols. For each patient, slices with maximal tumor burden were selectively curated to emphasize intratumoral heterogeneity in subsequent modeling. High-level morphological descriptors were extracted through a pre-trained ResNet50, and the resulting embeddings were projected into a lower-dimensional manifold via Parzen-Rosenblatt Isometric Mapping (PR-Isomap), preserving nonlinear geometric relationships linked to heterogeneous growth dynamics. Gap statistics determined the optimal latent dimensionality. These low-dimensional vector biomarkers were then used to classify survival outcomes.
Results: PR-Isomap-derived embeddings demonstrated pronounced stratification of patient survival cohorts, underscoring the method's capacity to encode clinically salient heterogeneity within tumor phenotypes. A ResNet50 backbone was optimized over 200+ training epochs using an Adaptive Moment Estimation-based optimizer with a learning rate initialized at 10 -4 and adaptively decayed to ensure stable convergence. Model training employed a cross-entropy loss function to enhance discriminative capability across survival categories. The resulting classifier attained a 97% slice-level accuracy, exhibiting robust generalization across all augmentation regimes. Notably, model discrimination of survival endpoints was attributable to biologically meaningful tumor-intrinsic structural patterns, rather than extraneous anatomical noise, owing to segmentation-informed slice curation that systematically excluded non-tumoral confounders.
Conclusion: Integrating deep learning-based CT-derived heterogeneity signatures with PR-Isomap embeddings enhances survival stratification in NSCLC. These imaging-driven, low-dimensional Deepomics features provide clinically actionable prognostic biomarkers, enabling earlier identification of high-risk patients and informing precision treatment planning.
利益披露 Disclosure
H. Siezen, None..
L. Ma, None..
J. Azarnoosh, None..
B. Rodd, None.