Lung cancer remains the leading cause of cancer-related deaths worldwide in women and men. In incidence, lung cancer ranks second, surpassed by breast cancer in women and prostate cancer in men. However, the historical differences in mortality and incidence rate between both sexes have changed in the last years. In the last decades, we have also witnessed an increased number of lung cancer in female never-smokers. These disparities have grown our interest in studying the impact of the gender and sex in the presentation of lung cancer. The aetiology is yet to be fully elucidated, but the data are clear so far: there is a growing divide between lung cancer presentation in women and men that will change our management and study of lung cancer. This article aims to review the sex and gender differences in lung cancer.
Introduction: For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue.Methods: NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry.Results: A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptorneutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokinedirected therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission.Conclusions: Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population.
BackgroundMetastatic non-small-cell lung cancer (NSCLC) has a dismal prognosis. EGFR is overexpressed or mutated in a large proportion of cases. Downstream components of the EGFR pathway and crosstalk with the NF-κB pathway have not been examined at the clinical level. We explored the prognostic significance of the mRNA expression of nine genes in the EGFR and NF-κB pathways and of BRCA1 and RAP80 in patients in whom EGFR and K-ras gene status had previously been determined. In addition, NFKBIA and DUSP22 gene status was also determined.MethodsmRNA expression of the eleven genes was determined by QPCR in 60 metastatic NSCLC patients and in nine lung cancer cell lines. Exon 3 of NFKBIA and exon 6 of DUSP22 were analyzed by direct sequencing. Results were correlated with outcome to platinum-based chemotherapy in patients with wild-type EGFR and to erlotinib in those with EGFR mutations.ResultsBRCA1 mRNA expression was correlated with EZH2, AEG-1, Musashi-2, CYLD and TRAF6 expression. In patients with low levels of both BRCA1 and AEG-1, PFS was 13.02 months, compared to 5.4 months in those with high levels of both genes and 7.7 months for those with other combinations (P = 0.025). The multivariate analysis for PFS confirmed the prognostic role of high BRCA1/AEG-1 expression (HR, 3.1; P = 0.01). Neither NFKBIA nor DUSP22 mutations were found in any of the tumour samples or cell lines.ConclusionsThe present study provides a better understanding of the behaviour of metastatic NSCLC and identifies the combination of BRCA1 and AEG-1 expression as a potential prognostic model.
A recent meta-analysis of 11,107 patients with non-small cell lung cancer who had undergone surgical resection showed that the 5-year survival benefit of adjuvant chemotherapy was 4%, and that of adjuvant chemoradiotherapy was 5%. Two trials have shown a trend toward improved survival with adjuvant paclitaxel plus carboplatin. However, the benefit of adjuvant treatment remains suboptimal. We must distinguish between patients who will not relapse-and who can thus be spared adjuvant treatment-and those who will-for whom adjuvant treatment must be personalized. Several gene expression signatures, generally containing nonoverlapping genes, provide similar predictive information on clinical outcome, and a model combining several signatures did not perform better than did each of the signatures separately. The invasiveness gene signature, containing 186 genes, includes genes involved in the nuclear factor κB pathway, the RAS-mitogen-activated protein kinase pathway, and epigenetic control of gene expression. A 15-gene signature has identified JBR.10 patients who are more sensitive to adjuvant chemotherapy.
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