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Summary: Introduction: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are frequently detected in lung adenocarcinomas with bronchioloalveolar (BAC) differentiation and have been associated with increased response to small molecule EGFR inhibitors in some clinical studies. However, further molecular characterization of tumor cells carrying EGFR mutations (EGFR-mut) is warranted. Methods: By DNA sequencing, 120 patients with lung adenocarcinomas (70 tumors with BAC components) were screened for EGFR mutations within exons 18–21. Performing comparative genomic hybridization (CGH) and immunohistochemistry, chromosomal imbalances and protein expression levels of EGFR, ErbB3 and VEGF (vascular endothelial growth factor) were analyzed, respectively. Results: EGFR mutations were detected in 20/120 tumors. Tumors with BAC components carried more frequently EGFR mutations compared to adenocarcinomas without BAC histology (17/70=24% vs 3/50=6.0%; p =0.012). In a subsequent matched-pair analysis, CGH-analysis demonstrated similar mean numbers of chromosomal imbalances for EGFR mutated and wild-type tumors (8.6 vs 7.8 gains; 2.4 vs 2.7 losses), respectively. Furthermore, tumors with mutated EGFR demonstrated gains in chromosomes 7p, 16p and 20q and losses in chromosome 8p. Interestingly, EGFR mutated tumors showed higher VEGF expression (p =0.03) while differences in EGFR expression were not statistically significant. Conclusion: EGFR gene mutations are frequently seen in lung adenocarcinomas with BAC differentiation and can be linked to chromosomal imbalances and increased VEGF expression. [Copyright &y& Elsevier]

Purpose: The aim of this prospective study was to assess the prognostic impact of serum tumor markers (Cyfra21-1, carcinoembryonic antigen, neuron-specific enolase, squamous cell carcinoma-antigen and TPAcyk) in patients with non-small cell lung cancer (NSCLC) receiving complete resection. Methods: Sixty-seven patients with histologically proven NSCLC and complete resection of stage I–IIIA disease were included. The serum levels of all markers were measured using commercially available immunoassays. Results: With a median follow-up of 86 months for surviving patients, those with initial Cyfra21-1 serum levels higher than 3.57 ng/ml had a significantly worse prognosis (P=0.014). The remaining serum tumor markers showed no prognostic impact. In a Cox regression model, Cyfra21-1 proved to be an independent prognostic factor for both overall survival and disease-free interval. In addition, Cyfra21-1 sustained as an independent prognostic factor in completely resected stage I/II disease. Conclusions: With a cut-off value of 3.57 ng/ml, Cyfra 21-1 was an independent prognostic factor for survival in NSCLC-patients with complete resection. Further evaluation is needed, particularly in stage I/II disease. When the prognostic impact is confirmed with larger patient numbers this may contribute to the identification of stratification variables for future treatment approaches of NSCLC. [Copyright &y& Elsevier]

Summary: Cytotoxic therapy for lung-cancer patients has only moderately improved during the last decades. Simultaneously, efforts of intensive research to increase our understanding of the molecular basis of lung cancer have been undertaken. The cancer cell has been characterised by several genetic changes that lead to altered cellular functions. In addition, multiple factors of the cancer-cell environment further affect the tumour cell via various receptors and subsequent signaling pathways. The increased knowledge of cellular signaling offers the opportunity to develop novel substances that target specific pathway molecules. In the current review, some of the most essential receptors and signaling pathways involved in lung cancer will be described. In conjunction, examples of novel target-specific agents that have already found their way into clinical trials will be discussed. [Copyright &y& Elsevier]

• In CASPIAN, first-line durvalumab + EP improved OS vs EP in patients with ES-SCLC. • Patient-reported outcomes (PROs) were prespecified secondary endpoints. • Symptom burden was reduced in both arms over 12 months or until progression. • Durvalumab + EP delayed worsening of symptoms, functioning, and QoL vs EP. • Addition of durvalumab to EP had no additional detrimental impact on PROs. In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs). Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed. In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, −4.5; 99% CI: −9.04, −0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL. Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP. [ABSTRACT FROM AUTHOR]