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Inherited lung cancer risk, particularly in nonsmokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden, and specific driver mutations in EGFR, KRAS , and STK11 . A local Native American ancestry risk score was more strongly correlated with EGFR mutation frequency compared with global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities. SIGNIFICANCE: The frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity, but we do not understand why. Our study suggests that the variation in EGFR and KRAS mutation frequency is associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association. See related commentary by Gomez et al., p. 534 . This article is highlighted in the In This Issue feature, p. 521 ., (©2020 American Association for Cancer Research.)

Lung carcinoma is the leading cause of death by cancer worldwide. When possible, surgery is the best treatment strategy for patients with non-small-cell lung cancer. However, even with curative-intent therapy, most patients will develop local or systemic recurrence and, ultimately, succumb to their disease. In recent years, evidence on the role of the antitumor activity of the immune system and the understanding of tumor immunosurveillance have resulted in the emergence of immunotherapy as a promising therapeutic approach in lung cancer. The main approaches are immune checkpoint inhibition, such as blockade of the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 receptors and the programmed cell death-1 ligand, and vaccine therapy, which elicits specific antitumor immunity against relevant tumor-associated antigens. We have reviewed recently reported results from clinical trials and the possible future role of vaccine therapy and immune checkpoint inhibition in the treatment of small cell lung cancer and non-small-cell lung cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in diverse tumors. To determine the clinical utility of detecting BIM deletion polymorphisms (par4226 bp/ par363 bp) in EGFR positive non-small-cell lung cancer (NSCLC) we examined the outcomes of patients with and without BIM alterations., Results: BIM deletion was present in 14 patients (15.7%). There were no significant differences between patients with and without BIM-del in clinical characteristics or EGFR mutation type; however, those with BIM-del had a worse overall response rate (ORR) to erlotinib (42.9% vs. 73.3% in patients without BIM-del; p=0.024) as well as a significantly shorter progression-free survival (PFS) (10.8 BIM-del+ vs. 21.7 months for patients without BIM-del; p=0.029) and overall survival (OS) (15.5 BIM-del+ vs. 34.0 months for patients without BIM-del; p=0.035). Multivariate Cox regression analysis showed that BIM-del+ was an independent indicator of shorter PFS (HR 3.0; 95%CI 1.2-7.6; p=0.01) and OS (HR 3.4; 95%CI 1.4-8.3; p=0.006)., Methods: We studied 89 NSCLC Hispanic patients with EGFR mutation who were treated with erlotinib between January 2009 and November 2014. BIM deletion polymorphisms (BIM-del) was analyzed by PCR in formalin-fixed paraffin-embedded (FFPE) tissues of tumor biopsies. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM-del., Conclusions: The incidence of BIM-del found in Hispanic patients is similar to that previously described in Asia. This alteration is associated with a poor clinical response to erlotinib and represents an independent prognostic factor for patients who had NSCLC with an EGFR mutation.

Introduction: The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort., Methods: A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information., Results: Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p=0.014) and 0.99 (0.27-3.48; p=0.99)., Conclusions: KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings., (© 2013.)

Lung cancer has become a leading cause of cancer-related death in the world. Patient survival has improved with the introduction of new chemotherapy regimens and targeted drugs, but still, because of tumour progression or deterioration in performance status, a high percentage of patients do not receive more than one line of treatment. Given this situation, studies of maintenance therapies have begun, with results that have led to the clinical use of various drugs in a maintenance scenario. Additionally, results obtained in various clinical trials have raised the question of personalized approaches based on the clinical, pathologic, and molecular features of the cancer-not only in the initial approach, but also in the context of maintenance. Overall, the survival benefit seen with maintenance treatment has introduced a new therapy option that should be considered and discussed with patients, and (given the controversies that currently remain) chosen based on the preferences of patients and physicians.

The association of cancer and thrombotic events was first described by Trousseau in 1865. The spectrum of these episodes vary in severity, and these can present during or even prior to the diagnosis of cancer. Multiple factors in patients with lung cancer are associated with a higher risk of thrombosis. Patient-related, cancer-related and treatment-related factors contribute to the development of a thrombotic event. The incidence of thrombotic events in patients with lung cancer is one of the highest among all cancers. Certain particular conditions in lung cancer may be responsible to elevate this risk. Tissue factor (TF) over-expression is considered to be the most important element in cancer-related thrombosis. Several oncogenes and tumor suppressor genes have been implicated with this over-expression. The development of thrombosis in a cancer patient adversely influences prognosis. The use of prophylactic anticoagulation in lung cancer patients has been investigated but no consensus has been obtained regarding which patients are more likely to benefit. Models exist that can help predict this risk, but validation is required. Treatment guidelines of anticoagulation in patients who develop a thrombotic event are also discussed, but lung cancer patients have distinct characteristics that have to be taken in consideration. It is of great importance to identify the elements that will predict the risk of developing cancer-associated thrombosis because it will consequently influence the management and prognosis of the patient., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Immunotherapy as a possible therapeutic option for cancer has been of great importance due to the innovative development of vaccines. Various molecules have been tested and emepepimut-S (Biomira Liposomal Peptide 25 (BLP 25)) has emerged as an option, particularly in lung cancer., Areas Covered: A PubMed literature and ClinicalTrials.gov search was conducted using the terms: emepepimut, BLP25, NSCLC, cancer immunotherapy, cancer vaccine and MUC1. This review covers how emepepimut-S acts against the mucin 1 (MUC1) tumor-associated antigen producing a cellular immune response against the cells that express MUC1 and the most important clinical data available that led to the ongoing Phase III trial., Expert Opinion: The results obtained in the Phase I/II trials are promising, showing a favorable toxicity with a benefit in survival in NSCLC patients. As future trials develop, demonstration of the long-term survival benefit, understanding of the various mechanisms of immune response initiated by the drug and the selection of patients that will highly benefit from the immunotherapy will be elucidated. The safety and extension in survival makes emepepimut-S a very interesting drug and could, therefore, offer a possibility of treatment and maintenance, particularly for good performance status patients with locally advanced NSCLC.