PET/CT images of lung cancer patients were obtained from public databases and used to establish two datasets, respectively to classify histological subtypes (156 adenocarcinomas and 32 squamous cell carcinomas) and EGFR mutation status (38 mutant and 100 wild-type samples).
Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less ≥1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients.
Conventional CT-features, including emphysema, degree of primary tumor lobulation, and lymph node size and status, help to predict the presence or absence of EGFR mutations in advanced pulmonary adenocarcinoma.
The favor ADC group tended to have a higher percentage of EGFR positivity and ALK positivity than the favor SQC group (25% vs. 11% and 7% vs. 0%, respectively).
Validation cohorts including our biobank confirmed that the AXL expression significantly correlated with expression of genes encoding programmed death-ligand1 (PD-L1) and CXC chemokine receptor 6 (CXCR6) in lung adenocarcinoma, especially in epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma.
The results highlight the importance of distinguishing synchronous primary tumors from intrapulmonary metastases, and of assessing the relative abundance of EGFR mutation and ALK rearrangement in patients with multifocal adenocarcinomas with EGFR/ALK co-alterations.
p65BTK was significantly over-expressed in EGFR-wild type (wt) adenocarcinomas (AdC) from non-smoker patients and its expression was also preserved at the metastatic site. p65BTK was also over-expressed in cell lines mutated for KRAS or for a component of the RAS/MAPK pathway and in tumors from Kras/Trp53 null mice.
PD-L1 expression was adversely associated with epidermal growth factor receptor mutation status (P < .001) and was significantly associated with invasive adenocarcinomas rather than preinvasive lesions and minimally invasive adenocarcinomas (P < .001).
However, not all adenocarcinomas harboring EGFR mutations respond to therapy, so predictive biomarkers of therapeutic outcomes, as well as novel therapies sensitizing these tumors to EGFR inhibition, are needed.
Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Combination of IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma cell lines and decreased tumor volume in mice models.
This analysis showed two significant differentially methylated changes (cg12169243 [<i>DPH6</i>] and cg25429010 [<i>IMP3</i>]) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [<i>USP7</i>], cg06366994 [<i>CPE</i>], cg24992236 [<i>MEG9</i>], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [<i>RSL24D1</i>], cg04989085 [<i>FAM113B</i>], cg20905681 [<i>CKAP4</i>], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC.
Eight different heterozygous EGFR germline mutations from 14 adenocarcinoma patients (0.12%) were identified within or adjacent to the kinase domain, including K757R (n = 5), R831H (n = 2), D1014N (n = 2), G724S, V786M, T790M, L792F, and L844V.
In the subgroup of wild-type EGFRadenocarcinoma patients, TTF-1 positivity was also a good prognostic indicator for OS and progression-free survival (PFS) after first-line cytotoxic chemotherapy.
EGFR mutations were closely associated with lepidic predominant (65%, P = 0.56) but less commonly associated with solid predominant with mucin production adenocarcinoma (24%, P = 0.02).
Paired genomic analysis from our sample provides early clinical evidence of the ADC to SCC lineage transition that might be provoked by an alteration in the PI3K/AKT/mTOR pathway during EGFR TKI treatment.
The aim of the study is to develop and validate a novel nomogram, incorporating epidermal growth factor receptor mutation status and treatments, for predicting 1-year and 2-year survival probability of patients with advanced adenocarcinoma.