PO.CL09.04 · 临床研究
利用真实世界临床数据转化多种癌症类型中的时序多疾病路径
Translating temporal multi-disease pathways in multiple cancer types using real-world clinical data
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
尽管已描述了若干癌前共病，但作为多疾病路径（MDP）的、医学上可解释的先行诊断在美国人群中的作用仍未得到充分探索。我们分析了来自Ochsner Health（路易斯安那州）2013—2022年跨度的电子健康记录数据，涵盖超过410万例患者。通过分析呈现显著时序相关性的诊断对来识别疾病轨迹。为构建三诊断轨迹，我们合并了重叠的诊断对（例如，D1→D2和D2→C（癌症）合并形成D1→D2→C）。对每位患者，提取所有三步诊断序列，并检验每个三元组内诊断对的方向性显著性。我们将此分析应用于十种高负担癌症——乳腺癌、黑色素瘤、肺癌、前列腺癌、胰腺癌、肝癌、膀胱癌、白血病、卵巢癌和结直肠癌，分别产生了501（11个显著）、507（10个）、194（2个）、349（8个）、49、132（3个）、111、84、39和155个方向性关联。指向癌症的显著方向性轨迹包括：乳腺癌之前的乳房肿块→异常乳腺影像、关节疾病→过度使用/软组织疾病、关节疾病→肩部病变、急性鼻窦炎→急性上呼吸道感染、骨质疏松→其他骨疾病、膝骨关节炎→关节疾病、重度抑郁→焦虑障碍、急性咽炎→急性上呼吸道感染、咳嗽→呼吸异常、关节疾病→其他软组织疾病，以及手指/足趾畸形→骨密度/结构疾病；肝癌之前的急性病毒性肝炎→肝纤维化/肝硬化、慢性病毒性肝炎→肝硬化（未特指）、肝纤维化/肝硬化→其他肝病；前列腺癌之前的尿频→性功能障碍、关节疾病→肩部病变、良性前列腺增生→异常肿瘤标志物、膝骨关节炎→关节疾病、勃起功能障碍→异常肿瘤标志物、关节疾病→其他软组织疾病、梗阻性/反流性尿路病→良性前列腺增生，以及骨关节炎→关节疾病；肺癌之前的膝骨关节炎→关节疾病→软组织疾病；以及黑色素瘤之前的光化性角化病→脂溢性角化病、骨关节炎→关节疾病、过敏性/血管运动性鼻炎→慢性鼻窦炎，以及关节疾病→软组织疾病。此方法的一个重要考量是，虽然这些MDP具有统计学显著性，但它们可能并不代表因果关联。例如，勃起功能障碍等状况可能导致在高癌症风险人群中进行与年龄相适应的筛查。同样，乳房肿块的诊断可能在正式诊断之前直接暗示癌症。所有显著MDP的生物学合理性应逐一进行研究。
查看英文原文 English abstract
Although several pre-cancer comorbidities have been described, the role of medically interpretable preceding diagnoses as multi-disease pathways (MDPs) remains underexplored in the U.S. population. We analyzed electronic health record data from Ochsner Health (Louisiana) spanning 2013-2022, encompassing more than 4.1 million patients. Disease trajectories were identified by analyzing pairs of diagnoses that exhibited significant temporal correlations. To construct three-diagnosis trajectories, we merged overlapping pairs (e.g.,D1→D2 and D2→C (cancer) were combined to form D1→D2→C). For each patient, all three-step diagnostic sequences were extracted, and the pairs within each triplet were tested for directiona lsignificance. We applied this analysis to ten high-burden cancers, breast, melanoma, lung, prostate, pancreatic, liver, bladder, leukemia, ovarian, and colorectal, which yielded 501 (11 significant), 507 (10),194 (2), 349 (8), 49, 132 (3), 111, 84, 39, and 155 directional associations, respectively. Significant directional trajectories to cancer included breast lump → abnormal breast imaging, joint disorder → overuse/soft-tissue disorder, joint disorder → shoulder lesion, acute sinusitis → acute upperrespiratory infection, osteoporosis → other bone disorder, knee osteoarthritis → joint disorder, majordepression → anxiety disorder, acute pharyngitis → acute upper respiratory infection, cough → breathingab normality, joint disorder → other soft-tissue disorder, and finger/toe deformity → bonedensity/structure disorder preceding breast cancer; acute viral hepatitis → liver fibrosis/cirrhosis, chronicviral hepatitis → liver cirrhosis (unspecified), and liver fibrosis/cirrhosis → other liver disease precedingliver cancer; urinary frequency → sexual dysfunction, joint disorder → shoulder lesion, benign prostatichyperplasia → abnormal tumor markers, knee osteoarthritis → joint disorder, erectile dysfunction →abnormal tumor markers, joint disorder → other soft-tissue disorder, obstructive/reflux uropathy →benign prostatic hyperplasia, and osteoarthritis → joint disorder preceding prostate cancer; osteoarthritis of knee → joint disorder → soft-tissue disorder preceding lung cancer; and actinic keratosis → seborrheickeratosis, osteoarthritis → joint disorder, allergic/vasomotor rhinitis → chronic sinusitis, and joint disorder→ soft-tissue disorder preceding melanoma cancer. An important consideration in this approach is that while these MDPs are statistically significant, they may not represent causative associations. For example, conditions such as erectile dysfunction may lead to age-appropriate screening in a high cancer risk population. Likewise, a diagnosis of breast lump may directly imply cancer prior to formal diagnosis. Biologically plausibility of all significant MDPs should be investigated individually.
利益披露 Disclosure
M. Alam, None.