Abstract：
We investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies.
Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients\' baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher\'s exact test and log-rank test were used to determine the statistical differences in this study.
A total of 1134 clinical samples were collected from NSCLC patients, and TP53mut was identified in 644 cases and EGFRmut in 622 cases. A low frequency of TP53mut or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53mut in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53mut, whereas EGFR-TKI therapy was favorable for TP53wt patients. Furthermore, TP53mut could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.
Various characteristics of TP53mut affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients\' survival with prognostic TP53mut, which provides an important reference for treatment management of EGFRmut patients.
Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients\' baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher\'s exact test and log-rank test were used to determine the statistical differences in this study.
A total of 1134 clinical samples were collected from NSCLC patients, and TP53mut was identified in 644 cases and EGFRmut in 622 cases. A low frequency of TP53mut or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53mut in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53mut, whereas EGFR-TKI therapy was favorable for TP53wt patients. Furthermore, TP53mut could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.
Various characteristics of TP53mut affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients\' survival with prognostic TP53mut, which provides an important reference for treatment management of EGFRmut patients.
摘要：
背景：我们研究了影响TP53突变的因素对EGFR-酪氨酸激酶抑制剂疗效和潜在治疗策略的影响。
方法：收集肿瘤样本，通过下一代测序筛选基因突变，以及患者的基线特征。基于每个随访时间点的间期计算机断层扫描来评估对TKI治疗的总体反应。Fisher精确检验和对数秩检验用于确定本研究中的统计学差异。
结果：共收集了1134例NSCLC患者的临床样本，在644例中发现了TP53mut，在622例中发现了EGFRmut。TP53mut的低频率或EGFR共突变率超过50%与TKI治疗患者的预后相关。此外,DB域以外区域的TP53mut与TKI抗性的相关性最强，而DB域中的各种类型的突变仅对PFS有影响。一项基于EGFR-TKI治疗的分组研究显示，EGFR-TKIs联合化疗与TP53mut预后患者的生存获益更显著相关，而EGFR-TKI治疗对TP53wt患者有利。此外，TP53mut可以缩短患者术后复发的时间，他们也可能对化疗后的EGFR-TKIs反应良好。
结论：TP53mut的各种特征不同程度地影响TKI治疗患者的预后。EGFR-TKIs联合化疗对预后TP53mut患者的生存有益，为EGFRmut患者的治疗管理提供重要参考。
方法：收集肿瘤样本，通过下一代测序筛选基因突变，以及患者的基线特征。基于每个随访时间点的间期计算机断层扫描来评估对TKI治疗的总体反应。Fisher精确检验和对数秩检验用于确定本研究中的统计学差异。
结果：共收集了1134例NSCLC患者的临床样本，在644例中发现了TP53mut，在622例中发现了EGFRmut。TP53mut的低频率或EGFR共突变率超过50%与TKI治疗患者的预后相关。此外,DB域以外区域的TP53mut与TKI抗性的相关性最强，而DB域中的各种类型的突变仅对PFS有影响。一项基于EGFR-TKI治疗的分组研究显示，EGFR-TKIs联合化疗与TP53mut预后患者的生存获益更显著相关，而EGFR-TKI治疗对TP53wt患者有利。此外，TP53mut可以缩短患者术后复发的时间，他们也可能对化疗后的EGFR-TKIs反应良好。
结论：TP53mut的各种特征不同程度地影响TKI治疗患者的预后。EGFR-TKIs联合化疗对预后TP53mut患者的生存有益，为EGFRmut患者的治疗管理提供重要参考。
