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Among 104 resected ground-glass nodules (GGNs) in 96 patients, epidermal growth factor receptor (EGFR) mutations were noted in 64%, Kirsten rat sarcoma in 4%, anaplastic lymphoma kinase in 3%, and human epidermal growth factor receptor type 2 in 4%. Quadruple-negative tumors were associated with a lack of GGN growth, whereas EGFR mutation-positive tumors displayed a correlation with growth.Background Pulmonary ground-glass nodules (GGNs) include both malignant and benign lesions. Some GGNs become larger, whereas others remain unchanged for years. We have previously reported that smoking history and large diameters are predictors for growth. However, the genetic differences among GGNs remain unclear. Patients and methods GGNs with ground-glass component of ≥50% on a thin-section computed tomography scan that were resected between 2012 and 2014 were evaluated for clinicopathological features and the presence of EGFR/KRAS/ALK/HER2 mutations. ‘Incidence of 2-mm growth’ and ‘Time to 2-mm growth’ were analyzed according to the mutational status. Results Among 104 GGNs in 96 patients, this study included 3 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA), and 55 invasive adenocarcinoma (IA). Among the 71 lesions evaluable for growth, 30 GGNs exhibited growth and 5 lesions remained unchanged for ≥2 years before surgery was carried out. We identified mutations or rearrangements in 75% of GGNs (78/104). EGFR mutations were noted in 64% of samples, KRAS in 4%, ALK in 3%, and HER2 in 4%. The remaining 26 quadruple-negative tumors were significantly associated with AAH/AIS (P < 0.01) and no-growth (P < 0.01) compared with driver mutation-positive tumors, whereas EGFR mutation-positive tumors were correlated with MIA/IA (P < 0.01) and growth (P < 0.01) compared with EGFR-negative tumors. Conclusions Three fourths of resected GGNs were positive for EGFR, KRAS, ALK, or HER2 mutations. Quadruple-negative tumors were associated with a lack of GGN growth, whereas EGFR mutation-positive tumors displayed a correlation with growth. [ABSTRACT FROM PUBLISHER]

Preoperative chemotherapy is a promising strategy in patients with early-stage resectable non-small-cell lung cancer (NSCLC); optimal chemotherapy remains unclear. Clinical (c-) stage IB/II NSCLC patients were randomised to receive either two cycles of docetaxel (D)-cisplatin (P) combination chemotherapy (D 60 mg m(-2) and P 80 mg m(-2) on day 1) every 3-4 weeks or three cycles of D monotherapy (70 mg m(-2)) every 3weeks. Thoracotomy was performed 4-5 weeks (DP) or 3-4 weeks (D) after chemotherapy. The primary end point was 1-year disease-free survival (DFS). From October 2002 to November 2003, 80 patients were randomised. Chemotherapy toxicities were mainly haematologic and well tolerated. There were two early postoperative deaths with DP (one intraoperative bleeding and one empyema). Pathologic complete response was observed in two DP patients. Docetaxel-cisplatin was superior to D in terms of response rate (45 vs 15%) and complete resection rate (95 vs 87%). Both DFS and overall survival were better in DP. Disease-free survival at 1, 2 and 4 years were 78, 65 and 57% with DP, and were 62, 44 and 36% with D, respectively. Preoperative DP was associated with encouraging resection rate and DFS data, and phase III trials for c-stage IB/II NSCLC are warranted. [ABSTRACT FROM AUTHOR]

Subsets of patients with non-small cell lung cancer respond remarkably well to small molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptor (EGFR) such as gefitinib or erlotinib. In 2004, it was found that EGFR mutations occurring in the kinase domain are strongly associated with EGFR-TKI sensitivity. However, subsequent studies revealed that this relationship was not perfect and various predictive markers have been reported. These include EGFR gene copy numbers, status of ligands for EGFR, changes in other HER family genes or molecules downstream to EGFR including KRAS or AKT. In this review, we would like to review current knowledge of predictive factors for EGFR-TKI. As all but one phase III trials failed to show a survival advantage of the treatment arm involving EGFR-TKIs, it is necessary to select patients by these biomarkers in future clinical trials. Through these efforts, it would be possible to individualise EGFR-TKI treatment for patients suffering from lung cancer.British Journal of Cancer (2007) 96, 857–863. doi:10.1038/sj.bjc.6603665 www.bjcancer.com Published online 27 February 2007 [ABSTRACT FROM AUTHOR]

Background: The presence of autoantibodies to p53 protein has been associated with the presence of p53 (also known as TP53) gene mutations in primary tumors and with poor prognosis. This study was undertaken to determine the clinical significance of p53 autoantibodies in patients with non-small-cell lung cancer (NSCLC).Methods: We studied 188 consecutive patients with NSCLC who underwent pulmonary resection and for whom preoperative serum was available. The presence of p53 autoantibodies, detected by use of two amino-terminal and two carboxy-terminal peptides (20-30 mers) as antigens and an enzyme-linked immunosorbent assay, was related to various clinicopathologic parameters and to overexpression of p53 protein in the primary tumor. For 22 patients who had p53 autoantibodies before surgery, we also examined sera taken during postoperative follow-up. Reported P values are two-sided.Results: Autoantibodies to p53 protein were detected in 38 patients. Patients with squamous cell carcinoma, those with more advanced disease (stage III-IV), and those with tumors that overexpressed p53 had a significantly higher incidence of p53 autoantibodies (P = .05,.0079, and .02, respectively). In all but one of the patients with postoperative serum samples, the antibody titer declined after surgery; however, there was no relationship between clinical course and this change in antibody titer. In addition, there was no relationship between the presence of p53 autoantibodies and overall survival in 171 patients who underwent potentially curative resection (P = .28); however, 13 patients with autoantibodies to amino-terminal peptides had a worse overall survival (P = .02).Conclusions: In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC. [ABSTRACT FROM AUTHOR]

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. • A virtual consensus on the management of EGFR-mutant NSCLC was organized by the ESMO, including 34 experts from 18 countries. • The experts compiled recommendations with supporting evidence on controversial topics about the EGFR-mutant lung cancer. • Recommendations were formulated for tissue and biomarkers analyses; early, locally advanced and metastatic disease; miscellaneous. [ABSTRACT FROM AUTHOR]

Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. Patients and methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). Results: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). Conclusions: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. Clinical trial registration: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking is the major cause of lung cancer (LC). Although the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, little information is available on its possible relation to LC. Patients and methods This case–control study includes a total of 1572 incident LC cases and 1572 non-cancer controls visiting for the first time the Aichi Cancer Center Hospital between 2001 and 2005. We estimated the odds ratio (OR) and 95% confidence interval (CI) for TTFC using a logistic regression model after adjustment for several potential confounders. Results TTFC was inversely associated with the risk of LC. This association was consistent across histological subtypes of LC. For all LCs considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC >60 min, the adjusted ORs were 1.08 (95% CI, 0.73–1.61) for TTFC of 31–60 min, 1.40 (0.98–2.01) for 6–30 min and 1.86 (1.28–2.71) for within 5 min (Ptrend, < 0.001). Statistically marginally significant heterogeneity by histological subtype was observed (Pheterogeneity, 0.002). Conclusions Nicotine dependence, as indicated by the TTFC, is associated with increased risk of LC and is therefore an independent marker of exposure to tobacco smoking. [ABSTRACT FROM PUBLISHER]