Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival
Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival
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DOI：
10.3390/cancers11010124
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发表时间：
2019-01-01
期刊：
影响因子：
5.2
通讯作者：
Stenzinger, Albrecht
中科院分区：
文献类型：
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作者：
Christopoulos, Petros;Dietz, Steffen;Stenzinger, Albrecht
间变性淋巴瘤激酶(ALK)测序可以确定ALK(+)非小细胞肺癌(NSCLC)的耐药机制和指导下一线治疗，但其他再活检结果的临床意义尚不清楚。我们分析了在我们机构接受治疗的所有具有纵向可评估的TP53状态的IV期ALK(+)非小细胞肺癌患者(n=62)。TP53基因突变在基线水平的患者(TP53mut(Bas)，n=23)的总存活率(OS)比最初野生型肿瘤患者(tp53wt(Bas)，n=39，44比62个月，中位数，p=0.018)更差。在总体有利的TP53wt(Bas)组中，检测到进展期的TP53突变定义了一个具有较差OS的“转换”亚组(TP53mut(Conv)，n=9)，类似于TP53mut(Bas)，并且比保留TP53野生型的患者(TP53wt(Pror)，45个月比94个月，p=0.043)更短。酪氨酸激酶抑制剂治疗的TP53mut(Conv)患者的无进展生存期(PFS)与TP53mut(Bas)相当，也短于TP53wt(Pror)患者(5和8个月对13个月，p=0.0039)。TP53wt(预见组)较TP53mut(bas组)或TP53mut(conv组)在诊断时出现转移的病例少(67%vs.91%或100%，p<；0.05)。因此，在ALK(+)非小细胞肺癌中，进展期获得的TP53突变与更具侵袭性的疾病、更短的TKI反应和较差的OS有关，与原发的TP53突变病例相当。
Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK(+) non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK(+) NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mut(bas), n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wt(bas), n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wt(bas) group, detection of TP53 mutations at progression defined a "converted" subgroup (TP53mut(conv), n = 9) with inferior OS, similar to that of TP53mut(bas) and shorter than that of patients remaining TP53 wild-type (TP53wt(progr), 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mut(conv) was comparable to that of TP53mut(bas) and also shorter than that of TP53wt(progr) cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wt(progr) than TP53mut(bas) or TP53mut(conv) cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK(+) NSCLC, comparable to primary TP53 mutated cases.