Clinicopathological and genomic comparisons between different histologic components in combined small cell lung cancer and non-small cell lung cancer

Lin, Min; Su, Kang‐Yi; Su, Te‐Jen; Chang, Chia-Ching; Lin, Jingwei; Lee, Yi‐Hsuan; Yu, Sung-Liang; Chen, Jin‐Shing; Hsieh, Min‐Shu

doi:10.1016/j.lungcan.2018.10.006

Cited by 51 publications

(47 citation statements)

References 36 publications

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“…reported a high consistency in EGFR/TP53/RB1 mutations and expression patterns of p53 and Rb in these two different histologic components of SCLC, indicating that inactivation of TP53/RB1 function might be an early event in the histogenesis of synchronous and metachronous SCLC/NSCLC [62]. In EGFR-mutant lung cancers, RB1 alterations almost always occur concurrently with TP53/EGFR-mutant lung cancers with transformation mimic classical SCLC with RB1 and TP53 biallelic loss [63].…”

Section: Discussionmentioning

confidence: 93%

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Qin

Hou

et al. 2020

Preprint

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Background The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study. Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

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Section: Discussionmentioning

confidence: 93%

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Qin

Hou

et al. 2020

Preprint

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“…Patients with EGFR/RB1/TP53-mutant lung cancers represented approximately 5% of EGFR-mutant lung cancers and were at much higher risk for SCLC transformation than those without baseline TP53 and RB1 alterations [60]. By investigating the genetic backgrounds of patients with de novo combined SCLC/ NSCLC as well as those who experienced SCLC transformation from lung adenocarcinoma after TKI treatment, Lin et al reported a high consistency in EGFR/ TP53/RB1 mutations and expression patterns of p53 and Rb in these two different histologic components of SCLC, indicating that inactivation of TP53/RB1 function might be an early event in the histogenesis of synchronous and metachronous SCLC/NSCLC [61]. In EGFRmutant lung cancers, RB1 alterations almost always occur concurrently with TP53/EGFR-mutant lung cancers with transformation mimic classical SCLC with RB1 and TP53 biallelic loss [62].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

et al. 2020

View full text Add to dashboard Cite

Background: The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)-or anaplastic lymphoma kinase (ALK)-mutated advanced non-small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods: Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR = 1.88, 95%CI: 1.59-2.23, p < 0.001, I 2 = 0.0%, P = 0.792) and overall survival (OS) (HR = 1.92, 95%CI: 1.55-2.38, p < 0.001, I 2 = 0.0%, P = 0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P < 0.001, I 2 = 0.0%, P = 0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P < 0.001, I 2 = 0.0%, P = 0.484). Begg's funnel plots and Egger's tests indicated no significant publication bias in this study. Conclusions: This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

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“…However, it has not been fully elucidated whether RB1 and TP53 loss were early events within EGFR-mutant lung cancers or were acquired late in the process of histologic shift. RB1 and TP53 loss seem necessary instead of sufficient to induce lineage plasticity [61,63]. It is worthwhile to carry out more studies regarding this topic to further elucidate this question in the future.…”

Section: Discussionmentioning

confidence: 96%

“…Cooccurring mutations of the tumor-suppressor genes TP53 and RB1 (RB transcriptional corepressor 1) could be observed in over 75% of patients with SCLC [59,60]. Patients with EGFR/RB1/TP53-mutant lung cancers represented approximately 5% of EGFR-mutant lung cancers and were at much higher risk for SCLC transformation than those without baseline TP53 and RB1 alterations [61]. By investigating the genetic backgrounds of patients with de novo combined SCLC/NSCLC as well as those who experienced SCLC transformation from lung adenocarcinoma after TKI treatment, Lin et al…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Qin

Hou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)-or anaplastic lymphoma kinase (ALK)-mutated advanced non-smallcell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments.Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline,The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients.This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. ResultsIn total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI:1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS:1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg's funnel plots and Egger's tests indicated no significant publication bias in this study.Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced

show abstract

Clinicopathological and genomic comparisons between different histologic components in combined small cell lung cancer and non-small cell lung cancer

Cited by 51 publications

References 36 publications

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

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