Baseline patient characteristics.

<p>Baseline patient characteristics.</p

Baseline ¹⁸F-FDG PET and CT tumor response measurements with PERCIST and EORTC criteria and progression-free survival per patient with ALK positive NSCLC.

<p>Baseline ¹⁸F-FDG PET and CT tumor response measurements with PERCIST and EORTC criteria and progression-free survival per patient with ALK positive NSCLC.</p

¹⁸F-FDG maximum intensity projection of patient 2 and 8 prior to (A, B) and after 6 weeks of treatment with crizotinib (C, D).

<p>Scale is from 0–15 SUV. These images illustrate the clinically dramatic decrease in ¹⁸F-FDG uptake, with both patients having a PMR according to both PERCIST criteria and the EORTC recommendations.</p

Chronic Obstructive Pulmonary Disease Is Not Associated with <i>KRAS</i> Mutations in Non-Small Cell Lung Cancer

<div><p>Mutations in epithelial growth factor receptor <i>(EGFR)</i>, as well as in the EGFR downstream target <i>KRAS</i> are frequently observed in non-small cell lung cancer (NSCLC). Chronic obstructive pulmonary disease (COPD), an independent risk factor for developing NSCLC, is associated with an increased activation of EGFR. In this study we determined presence of <i>EGFR</i> and <i>KRAS</i> hotspot mutations in 325 consecutive NSCLC patients subjected to <i>EGFR</i> and <i>KRAS</i> mutation analysis in the diagnostic setting and for whom the pulmonary function has been determined at time of NSCLC diagnosis. Information about age at diagnosis, sex, smoking status, forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV₁) was collected. Chronic obstructive pulmonary disease(COPD) was defined according to 2013 GOLD criteria. Chi-Square, student t-test and multivariate logistic regression were used to analyze the data. A total of 325 NSCLC patients were included, 193 with COPD and 132 without COPD. COPD was not associated with presence of <i>KRAS</i> hotspot mutations, while <i>EGFR</i> mutations were significantly higher in non-COPD NSCLC patients. Both female gender (HR 2.61; 95% CI: 1.56–4.39; p<0.001) and smoking (HR 4.10; 95% CI: 1.14–14.79; p = 0.03) were associated with <i>KRAS</i> mutational status. In contrast, only smoking (HR 0.11; 95% CI: 0.04–0.32; p<0.001) was inversely associated with <i>EGFR</i> mutational status. Smoking related G>T and G>C transversions were significantly more frequent in females (86.2%) than in males (61.5%) (p = 0.008). The exon 19del mutation was more frequent in non-smokers (90%) compared to current or past smokers (36.8%). In conclusion, <i>KRAS</i> mutations are more common in females and smokers, but are not associated with COPD-status in NSCLC patients. <i>EGFR</i> mutations are more common in non-smoking NSCLC patients.</p></div

Logistic regression analysis of patient characteristics associated with COPD, <i>KRAS</i> and <i>EGFR</i>.

<p>Logistic regression analysis of patient characteristics associated with COPD, <i>KRAS</i> and <i>EGFR</i>.</p

Distribution of different <i>EGFR</i> mutations in advanced NSCLC patients.

<p>Distribution of different <i>EGFR</i> mutations in advanced NSCLC patients.</p

Distribution of different <i>KRAS</i> amino acid changes in advanced NSCLC patients^*.

<p>Distribution of different <i>KRAS</i> amino acid changes in advanced NSCLC patients^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152317#t004fn001" target="_blank">*</a>}.</p

NSCLC patient characteristics and<i>KRAS/EGFR</i> mutation^*.

<p>NSCLC patient characteristics and<i>KRAS/EGFR</i> mutation^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152317#t003fn001" target="_blank">*</a>}.</p

<i>KRAS</i> mutations and severity of airflow obstruction.

<p>(A) FEV1/FVC, (B) COPD GOLD classification and (C) FEV1 percentage in <i>KRAS</i> mutant and wildtype patients with NSCLC. ^aP-value was calculated by student t-test. ^bP-value was calculated by Chi-square test.</p

Distribution of different <i>KRAS</i> nucleotide changes in advanced NSCLC patients^*.

<p>Distribution of different <i>KRAS</i> nucleotide changes in advanced NSCLC patients^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152317#t005fn001" target="_blank">*</a>}.</p