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基于列线图的预后模型(LASSO-COX回归)的建立,用于预测接受辅助中药治疗的原发性非小细胞肺癌患者的无进展生存期:一项病例系列回顾性研究。

Establishment of a Nomogram-Based Prognostic Model (LASSO-COX Regression) for Predicting Progression-Free Survival of Primary Non-Small Cell Lung Cancer Patients Treated with Adjuvant Chinese Herbal Medicines Therapy: A Retrospective Study of Case Series.

作者信息

Luo Bin, Yang Ming, Han Zixin, Que Zujun, Luo Tianle, Tian Jianhui

机构信息

Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Front Oncol. 2022 Jul 8;12:882278. doi: 10.3389/fonc.2022.882278. eCollection 2022.

Abstract

Nowadays, Jin-Fu-Kang oral liquid (JFK), one of Chinese herbal medicines (CHMs) preparations, has been widely used as an adjuvant therapy for primary non-small cell lung cancer (PNSCLC) patients with the syndrome of deficiency of both Qi and Yin (Qi-Yin deficiency pattern) based on Traditional Chinese Medicine (TCM) theory. However, we found insufficient evidence of how long-term CHM treatment influence PNSCLC patients' progression-free survival (PFS). Thus, using electronic medical records, we established a nomograph-based prognostic model for predicting PNSCLC patients' PFS involved with JFK supplementary formulas (JFK-SFs) over 6 months, in order to preliminarily investigate potential predictors highly related to adjuvant CHMs therapies in theoretical epidemiology. In our retrospective study, a series of 197 PNSCLC cases from Long Hua Hospital were enrolled by non-probability sampling and divided into 2 datasets at the ratio of 5:4 by Kennard-Stone algorithm, as a result of 109 in training dataset and 88 in validation dataset. Besides, TNM stage, operation history, sIL-2R, and CA724 were considered as 4 highly correlated predictors for modeling based on LASSO-Cox regression. Additionally, we respectively used training dataset and validation dataset for establishment including internal validation and external validation, and the prediction performance of model was measured by concordance index (C-index), integrated discrimination improvement, and net reclassification indices (NRI). Moreover, we found that the model containing clinical characteristics and bio-features presented the best performance by pairwise comparison. Next, the result of sensitivity analysis proved its stability. Then, for preliminarily examination of its discriminative power, all eligible cases were divided into high-risk or low-risk progression by the cut-off value of 57, in the light of predicted nomogram scores. Ultimately, a completed TRIPOD checklist was used for self-assessment of normativity and integrity in modeling. In conclusion, our model might offer crude probability of uncertainly individualized PFS with long-term CHMs therapy in the real-world setting, which could discern the individuals implicated with worse prognosis from the better ones. Nevertheless, our findings were prone to unmeasured bias caused by confounding factors, owing to retrospective cases series.

摘要

如今,中药制剂金复康口服液(JFK)已根据中医理论,被广泛用作气阴两虚证原发性非小细胞肺癌(PNSCLC)患者的辅助治疗药物。然而,我们发现关于长期中药治疗如何影响PNSCLC患者无进展生存期(PFS)的证据不足。因此,我们利用电子病历,建立了一个基于列线图的预后模型,用于预测接受JFK辅助配方(JFK-SFs)治疗超过6个月的PNSCLC患者的PFS,以便在理论流行病学中初步研究与辅助中药治疗高度相关的潜在预测因素。在我们的回顾性研究中,通过非概率抽样纳入了来自龙华医院的197例PNSCLC病例,并根据Kennard-Stone算法以5:4的比例分为2个数据集,结果训练数据集有109例,验证数据集有88例。此外,TNM分期、手术史、sIL-2R和CA724被视为基于LASSO-Cox回归建模的4个高度相关预测因素。此外,我们分别使用训练数据集和验证数据集进行包括内部验证和外部验证的模型建立,并通过一致性指数(C-index)、综合判别改善和净重新分类指数(NRI)来衡量模型的预测性能。此外,通过成对比较,我们发现包含临床特征和生物特征的模型表现最佳。接下来,敏感性分析结果证明了其稳定性。然后,为了初步检验其判别能力,根据预测的列线图分数,将所有符合条件的病例按照57的临界值分为高风险或低风险进展组。最后,使用完整的TRIPOD清单对建模的规范性和完整性进行自我评估。总之,我们的模型可能会在现实环境中提供长期中药治疗不确定个体PFS的粗略概率,这可以区分预后较差的个体和预后较好的个体。然而,由于是回顾性病例系列,我们的研究结果容易受到混杂因素导致的未测量偏差的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ac0/9304868/7f079956c05b/fonc-12-882278-g001.jpg

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