Environmental inhaled noxious particles have been known to play a role in several lung diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer, the deadliest malignancy in the world in both sexes. Of the known noxious agents, tobacco smoking is the leading preventable cause of death worldwide and is a recognized risk for the development of both diseases.

The association between COPD and lung cancer has been demonstrated in population-based studies, lung cancer screening programs, epidemiological surveys, and case control and biological mechanistic studies. There is evidence that cumulative smoking history is associated with the risk of developing lung cancer and COPD; however, the majority of smokers do not develop clinical COPD or lung cancer. This suggests the presence of one or several factors that modulate the responses to the offending agents and define the final risk for disease development.

The 54th Aspen Lung Conference was convened to provide a forum for a systematic dissection of the potential mechanisms by which persons exposed to the causative agents are able to handle and control the process or, in the case of dysfunctional response, the mechanisms that take off in different directions and result in injury and disease.

This summary reviews the themes presented and attempts to integrate them for those clinicians and researchers interested in these topics. The challenges and future directions emanating from the discussions may help frame future conferences and hopefully inspire the interest of young researchers.

Recent advances in non-small cell lung cancer biology and clinical management.

Discov Med. 2012 Apr;13(71):287-97

Authors: Saintigny P, Burger JA

Abstract
Despite advances in surgery, chemotherapy, and radiotherapy over the last decades, the death rate from lung cancer has remained largely unchanged, which is mainly due to metastatic disease. Because of the overall poor prognosis, new treatment strategies for lung cancer patients are urgently needed. In this review, we summarize recent advances in non-small cell lung cancer (NSCLC) screening and diagnostic workup. We discuss current clinical management, highlighting stage-specific therapy approaches, chemotherapy options for advanced-stage patients, along with new agents such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) monoclonal antibodies, and the EGFR-targeting tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase (ALK) inhibitor crizotinib. Finally, we give an outlook into NSCLC disease biology, focusing on the importance of EGFR activating mutations and the role of the tumor-microenvironment. CXCR4 chemokine receptors expressed on NSCLC cells are a central pathway of NSCLC cross talk with the tumor microenvironment, as they induce activation, migration, and tumor cell adhesion to stromal cells, which in turn provides growth- and drug resistance-signals. Because of the growing evidence that the microenvironment in NSCLC promotes disease progression, we expect that selected molecular pathways of cross talk between NSCLC cells and their microenvironment will become alternative therapeutic targets in the near future.

PMID: 22541616 [PubMed - in process]

Tumor Recurrence After Complete Resection for Non-Small Cell Lung Cancer.

Ann Thorac Surg. 2012 Apr 25;

Authors: Taylor MD, Nagji AS, Bhamidipati CM, Theodosakis N, Kozower BD, Lau CL, Jones DR

Abstract
BACKGROUND: Long-term survival after R0 resection for non-small-cell lung cancer (NSCLC) is less than 50%. The majority of mortality after resection is related to tumor recurrence. The purpose of this study was to identify independent perioperative and pathologic variables that are associated with NSCLC recurrence after complete surgical resection. METHODS: A retrospective examination was performed of a prospectively maintained database of patients who underwent resection for NSCLC from July 1999 to August 2008 at a single institution. Clinicopathologic variables were evaluated for their influence on time to recurrence. Cox's proportional regression hazard model examined the association of recurrence in NSCLC. RESULTS: A total of 1,143 patients met inclusion criteria and had complete follow-up information. Of these patients, 378 (33.1%) had recurrence of the primary cancer. Median follow-up was 24 months (range, 3-134 months). Preoperative tumor maximum standardized uptake value (SUV(max)) greater than 5 was associated with increased risk of recurrence (hazard ratio [HR], 1.81; p = 0.01). Preoperative radiation was independently associated with recurrence (HR, 1.98; p = 0.05) as well as the presence of pathologic stage II and stage III disease (stage II: HR, 2.53; p = 0.05; stage III: HR, 6.49; p = 0.006). Subgroup analysis found that sublobar resection was also associated with locoregional recurrence after resection (HR, 4.17; p = 0.02) and lymphovascular invasion of distant recurrence (HR, 4.21; p = 0.002). CONCLUSIONS: In the largest series reported to date on postresectional recurrence of NSCLC, SUV(max) greater than 5, increasing pathologic stage, and the administration of preoperative radiation were independently associated with NSCLC recurrence after resection. Sublobar resection was independently associated with locoregional recurrence, and lymphovascular invasion was associated with distant recurrence.

PMID: 22542070 [PubMed - as supplied by publisher]

[COPD and lung cancer: Epidemiological and biological links].

Rev Mal Respir. 2012 Apr;29(4):545-56

Authors: Prevot G, Plat G, Mazieres J

Abstract
Lung cancer and chronic obstructive lung disease (COPD) are two common fatal diseases. Apart from their common link to tobacco, these two diseases are usually considered to be the result of separate distinct mechanisms. In the past 15years, numerous studies have produced arguments in favour of a relationship between these two pathologies that goes beyond a simple addition of risk factors. At the epidemiological level, there are data that demonstrate an increased incidence of bronchial carcinoma in patients with COPD. The links between these two pathologies are still unexplained but there are numerous arguments supporting a common physiopathology. Common genetic and epigenetic abnormalities, mechanical factors and signalisation pathways have been quoted. COPD and lung cancer appear to be two diseases possessing a genetic basis that creates a predisposition to environmental or toxic assaults, resulting in a different clinical manifestation in each disease. Consequently, improvements in the management of these two diseases will involve a more intensive investigation of their physiopathology, and require a closer collaboration between research centres and clinical units.

PMID: 22542412 [PubMed - in process]