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Background: TP53 mutation heterogeneity should be considered when using TP53 as a predictive biomarker for anti–programmed death (ligand) 1 (PD‐(L)1) monotherapy in lung adenocarcinoma (LUAD). However, whether TP53 variant allele frequency (VAF) should also be considered remains unknown. Methods: Patients with LUAD from both published research and the local cohort were included to discover and validate the relationship between TP53 VAF and the efficacy of PD‐(L)1 inhibitors. The Cancer Genome Atlas (TCGA) LUAD data were included for genomic, transcriptomic, and tumor microenvironment analysis. Results: Among 159 patients in the discovery cohort, low TP53 VAF patients (VAF ≤ 25%) experienced significantly longer progression‐free survival (PFS) than both high TP53 VAF (5.4 vs. 3.3 months; p =.021) and TP53‐wild‐type patients (5.4 vs. 2.5 months; p =.011). Multivariate Cox regression revealed low TP53 VAF as an independent biomarker of better efficacy. Among 50 patients in the combined validation cohort, median PFS of low TP53 VAF patients was also significantly longer than that of high TP53 VAF patients (12.0 vs. 2.1 months; p =.037). Analyzed with 469 TCGA LUAD samples, low TP53 VAF is associated with significantly higher PD‐L1 expression, enrichment of gene sets related to T‐cell activation, T cell–mediated immunity, and interferon‐γ signaling pathways, and independently associated with more tumor‐infiltrating CD8+ T cells compared with both high TP53 VAF and TP53‐wild type. Conclusions: TP53 VAF should also be considered when using TP53 as a predictive biomarker. Only low TP53 VAF is independently associated with better efficacy of anti–PD‐(L)1 monotherapy, which may result from higher PD‐L1 expression and more tumor‐infiltrating CD8+ T cells. Low TP53 variant allele frequency (VAF), instead of high TP53 VAF, is a new independent biomarker for anti–programmed death (ligand) 1 (PD‐(L)1) monotherapy among patients with lung adenocarcinoma. Low TP53 VAF is associated with higher PD‐L1 expression and independently associated with higher tumor‐infiltrating CD8+ T cells, compared with high TP53 VAF and TP53‐wild type. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors conducted a retrospective study to evaluate the effects of thoracic radiation therapy (TRT) for patients with extensive-stage small cell lung cancer (ED-SCLC). METHODS: Between January 2003 and December 2006, the records of 119 patients who were diagnosed with ED-SCLC (all with distant metastasis [M1]) were included in the study. Sixty patients received chemotherapy (ChT) and TRT (ChT/TRT), and 59 patients received ChT alone. The ChT regimens consisted of either carboplatin and etoposide (CE) or cisplatin and etoposide (PE). The total dose of TRT ranged from 40 to 60 grays (Gy) at 1.8 to 2.0 Gy per fraction. RESULTS: For the entire group, the median survival was 13 months, and the 2-year and 5-year overall survival (OS) rates were 26.1% and 6.5%, respectively. The median survival and the 2-year and 5-year OS rates were 17 months, 35%, and 7.1%, respectively, in the ChT/TRT group and 9.3 months, 17%, and 5.1%, respectively, in the ChT group ( P = .014). However, this improvement was achieved at the expense of low toxicity. Multivariate analysis revealed that receiving ≥4 cycles of ChT ( P = .032) and TRT ( P = .005) were favorable prognostic factors for OS. Of all toxicities, only high-grade leucopenia (grade >3) was more frequent in the ChT/TRT group. CONCLUSIONS: The addition of TRT to ChT improved the OS of patients with ED-SCLC. Furthermore, receiving ≥4 cycles of ChT and TRT were independent, favorable prognostic factors for OS. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]