Background: Methods: Results: Conclusions:

The epidermal growth factor receptor (EGFR) pathway plays a key role in the development and progression of non-small cell lung cancer (NSCLC) and many other malignant epithelial tumors.¹ x 1 Marmor, MD, Skaria, KB, and Yarden, Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 2004; 58: 903–913 Abstract | Full Text | Full Text PDF | PubMed | Scopus (275) | Google Scholar See all References Major achievements in the treatment of lung, colorectal, and head and neck cancer were associated with the development of targeted drugs inhibiting the EGFR pathway.² x 2 Hirsch, FR, Scagliotti, GV, Langer, CJ et al. Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer. 2003; 41: 29–42 Abstract | Full Text | Full Text PDF | PubMed | Scopus (169) | Google Scholar See all References

BACKGROUND.: Increased levels of chromogranin A (CgA), a protein secreted by many neuroendocrine cells, have been detected in sera of patients with neuroendocrine tumors or renal, hepatic, or heart failure. In patients with heart failure, serum CgA correlates with tumor necrosis factor‐α (TNF) and soluble TNF receptors (sTNF‐Rs), with important prognostic implications. The prognostic value of CgA and sTNF‐Rs was investigated in advanced nonsmall cell lung cancer (NSCLC), a histologically heterogeneous group of tumors that may undergo neuroendocrine differentiation.METHODS.: CgA and sTNF‐Rs were analyzed in the sera of 88 patients with NSCLC before chemotherapy by enzyme‐linked immunoadsorbent assay (ELISA) and in tumors by immunohistochemistry.RESULTS.: Thirteen percent of patients had CgA values greater than the highest value observed in normal subjects (distribution range, 9–724 ng/mL and 28–196 ng/mL, respectively). Immunohistochemical studies showed no correlation between CgA expression in tumors and serum levels. Conversely, circulating CgA was associated with worse Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P = .0005), more advanced stage (P = .042), and survival, with CgA being an independent prognostic factor of poor outcome (hazards ratio [HR] 1.31 for 100 ng/mL increase; 95% confidence interval [95% CI], 1.08–1.60 [P = .0071]). sTNF‐R1 and sTNF‐R2 were also associated with ECOG PS (P = .0001 and P = .02, respectively). sTNF‐Rs was weakly correlated with circulating CgA (r = 0.39 for TNF‐R1 and r = 0.40 for TNF‐R2), suggesting a regulatory link between sTNF‐Rs and CgA secretion.CONCLUSIONS.: Increased serum levels of CgA in NSCLC are independent from protein expression in tumors and more likely related to neuroendocrine response associated with worsening of patient condition. In addition to ECOG PS and stage, CgA is an independent indicator of poor prognosis. Cancer 2007. © 2007 American Cancer Society.

Innovative therapeutic agents have significantly improved outcome with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients, who depend on oncogenic molecular alterations for their malignant phenotype. Despite the survival improvement achieved with first line chemotherapy, about 30% of patients do not obtain a tumor response. Moreover, those patients, initially sensitive to treatment, acquire resistance and develop tumor progression after a median of about five months. Approximately 60% of the patients progressing from first line chemotherapy, receive further systemic treatment in the second line setting. Moreover, new options have emerged in the second line armamentarium for the treatment of patients with NSCLC, including immune checkpoint inhibitors and anti-angiogenic agents. The current review provides an overview on the clinical studies that gained the approval of chemotherapy agents (docetaxel and pemetrexed) and EGFR-TKIs as second line treatment options for NSCLC patients, not carrying molecular alterations.

Lung cancer remains the first cause of cancer-related deaths worldwide. Thanks to the improvement in the knowledge of the biology of non-small cell lung cancer (NSCLC), patients’ survival has significantly improved. A growing number of targetable molecular alterations have been identified. Next-generation sequencing (NGS) has become one of the methodologies entered in clinical practice and was recently recommended by the European society for medical oncology (ESMO) to perform a comprehensive molecular characterization in patients with cancer. The current review provides an overview of the clinical trials that have explored the impact of NGS in patients with cancer, its limits, and advantages.

The advent of immune checkpoint inhibitors gave rise to a new era in oncology and general medicine. The increasing use of programmed death-1 (PD-1) inhibitors in non-small cell lung cancer and in other malignancies means clinicians have to face up to new challenges in managing immune-related adverse events (irAEs), which often resemble autoimmune diseases. Neurological irAEs represent an emerging toxicity related to immunotherapy, and it is mandatory to know how to monitor, recognize, and manage them, since they can rapidly lead to patient death if untreated. Guidelines for the diagnosis and treatment of these irAEs have been recently published but sharing some of the most unusual clinical cases is crucial, in our opinion, to improve awareness and to optimize the approach for these patients. A literature review on the diagnosis and treatment of immune-related neurotoxicity’s has been conducted starting from the report of four cases of neurological irAEs regarding cases of polyneuropathy, myasthenia gravis, Bell’s palsy, and encephalopathy, all of which occurred in oncological patients receiving PD-1 inhibitors (pembrolizumab and nivolumab) for the treatment of non-oncogene addicted advanced non-small cell lung cancer. The exclusion of other differential diagnoses and the correlation between the suspension of immunotherapy and improvement of symptoms suggest that immunotherapy could be the cause of the neurological disorders reported.