Cui Yuning, Dong Weixuan, Li Yifu, Janitz Amanda E, Pokala Hanumantha R, Zhu Rui
School of Industrial and Systems Engineering, The University of Oklahoma, Norman, OK, 73019, USA.
Department of Biostatistics and Epidemiology, The University of Oklahoma Health Sciences, Oklahoma City, OK, 73104, USA.
Comput Biol Med. 2025 Jun;191:110118. doi: 10.1016/j.compbiomed.2025.110118. Epub 2025 Apr 7.
Acute lymphoblastic leukemia (ALL) is the most common type of leukemia among children and adolescents and can be life-threatening. The incidence of new cases has been increasing in recent years. Developing a predictive model to forecast the risk of death can help improve survival rates by enabling clinicians to provide timely and effective treatments. Traditional statistical survival models are limited by predefined assumptions, while current deep survival models, despite their flexibility, struggle with capturing complex and dynamic feature dependencies. Transformers provide a promising solution by using self-attention and multi-head attention mechanisms to overcome these challenges. Moreover, building on recent work in interpretable medical AI, the combination of Transformers and explainable methods can quantify the contributions of each feature to the survival probability prediction.
This paper proposes an explainable Transformer-based deep survival model to predict patient-specific survival probabilities for ALL. The model combines feedforward networks with Transformer architecture and is trained to minimize a loss function that measures the difference between predicted and actual survival outcomes. In addition, we use Shapley Additive Explanations (SHAP) to interpret the contributions of clinical attributes to the predictions, providing insights from both global and local perspectives.
The proposed model demonstrates robustness by consistently providing higher average survival probabilities for censored patients compared to deceased patients. It achieves an average concordance index (C-index) of 0.945, demonstrating strong predictive accuracy. Through SHAP analysis, we identify three key factors affecting survival outcomes, namely prognosis status, diagnosis year, and histology. Experiment results reveal that our model outperforms state-of-the-art deep survival models in terms of C-index when these important variables are included.
The proposed explainable Transformer-based deep survival model shows strong potential for providing accurate patient-specific survival predictions for ALL. Moreover, the insights gained from SHAP improve the model's interpretability for clinicians, helping them make better-informed decisions regarding prognosis and treatment.
急性淋巴细胞白血病(ALL)是儿童和青少年中最常见的白血病类型,可能危及生命。近年来新发病例的发病率一直在上升。开发一个预测死亡风险的模型可以帮助临床医生提供及时有效的治疗,从而提高生存率。传统的统计生存模型受到预定义假设的限制,而当前的深度生存模型尽管具有灵活性,但在捕捉复杂和动态的特征依赖关系方面仍存在困难。Transformer通过使用自注意力和多头注意力机制提供了一个有前景的解决方案来克服这些挑战。此外,基于可解释医学人工智能的最新研究成果,Transformer与可解释方法的结合可以量化每个特征对生存概率预测的贡献。
本文提出了一种基于Transformer的可解释深度生存模型,用于预测ALL患者的个体生存概率。该模型将前馈网络与Transformer架构相结合,并通过最小化一个衡量预测生存结果与实际生存结果之间差异的损失函数进行训练。此外,我们使用Shapley值加法解释(SHAP)来解释临床属性对预测的贡献,从全局和局部两个角度提供见解。
所提出的模型表现出稳健性,与死亡患者相比,对截尾患者始终提供更高的平均生存概率。它实现了0.945的平均一致性指数(C指数),显示出很强的预测准确性。通过SHAP分析,我们确定了影响生存结果的三个关键因素,即预后状态、诊断年份和组织学类型。实验结果表明,当纳入这些重要变量时,我们的模型在C指数方面优于当前最先进的深度生存模型。
所提出的基于Transformer的可解释深度生存模型在为ALL患者提供准确的个体生存预测方面显示出强大的潜力。此外,从SHAP获得的见解提高了模型对临床医生的可解释性,帮助他们在预后和治疗方面做出更明智的决策。