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• W2891726384 abstract "9060 Background: Genomic profiling of tumor DNA has revealed the diversity in NSCLC. The retinoblastoma gene ( RB1) encodes for RB pocket protein that plays an important role in cell cycle progression by interacting with various transcriptional factors. Here we determine the frequency and prognostic significance of RB1mutation in NSCLC and compare it to that in small cell lung cancer (SCLC). Methods: This IRB-approved retrospective review on NSCLC patients included Stage III and IV patients with genomic and clinical data. Primary outcome was median overall survival (OS) and secondary outcome was progression-free survival (PFS). OS and PFS were calculated by the Kaplan-Meier method and compared between mutant and wild-type (wt) RB1using the Log-Rank test. The effect of RB1mutation status on OS and PFS was further evaluated using the multivariable Cox model, controlling the effects of age, sex, stage, smoking history and chemotherapy. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Results: We identified RB1 mutation in 8.2% of NSCLC patients (16 of 195 patients). With a median follow-up of 15.1 months, the median OS for wt RB1was 28.3 months and for mutant RB1 was 8.3 months (HR = 2.59, p-value = 0.002). The median PFS for wt RB1 was 21.8 months vs 6.4 months for mutant RB1 (HR = 2.85, p-value = 0.0002). RB1 mutation was associated with worse OS ( p= 0.017, HR = 2.17) and PFS ( p= 0.005, HR = 2.37) in multivariate analyses after adjusting for traditional risk factors like, age, sex, stage, smoking history and chemotherapy. Interestingly, a previously described benign deletion (A16-A18) in RB1 protein was identified in 5 of the 16 RB1 mutant patients and was associated with far worse outcomes compared to other RB1 mutations. In contrast to NSCLC, RB1 mutation was identified in 75% of 64 SCLC patients. Furthermore, wt RB1 was associated with significantly shorter OS ( p= 0.002), PFS ( p= 0.004) and chemotherapy refractoriness ( p= 0.033) in SCLC. Conclusions: RB1 mutation is present in a minority of patients with advanced NSCLC and is associated with poor prognosis. In contrast, RB1 mutation is present in the majority of SCLC patients and is associated with a favorable prognosis." @default.
• W2891726384 created "2018-09-27" @default.
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• W2891726384 date "2017-05-20" @default.
• W2891726384 modified "2023-09-28" @default.
• W2891726384 title "Retinoblastoma mutation to predict poor outcomes in non-small cell lung cancer (NSCLC)." @default.
• W2891726384 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.9060" @default.
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