Terrance T Healey is the director of Thoracic Radiology at Rhode Island Hospital (RI, USA) and an Assistant Professor of Diagnostic Imaging at the Alpert Medical School of Brown University (RI, USA). Healey received his medical degree from the combined Dartmouth Medical School–Brown Medical School Program in 2003, completed his residency in radiology at Brown University in 2008 and a thoracic radiology fellowship at the Massachusetts General Hospital (MA, USA) in 2009. He joined the faculty staff at Rhode Island Hospital and Brown University in 2009. Robert C Ward is one of the chief residents within the Department of Diagnostic Imaging at Rhode Island Hospital (RI, USA) and the Alpert Medical School of Brown University (RI, USA). Ward received his medical degree from the George Washington University (Washington, DC, USA) in 2010. Damian E Dupuy is the director of Tumor Ablation at Rhode Island Hospital (RI, USA) and a Professor of Diagnostic Imaging at The Warren Alpert Medical School of Brown University (RI, USA). Dupuy received his medical degree from the University of Massachusetts Medical School (MA, USA) in 1988 and completed his residency in radiology at The New England Deaconess Hospital (MA, USA) and Harvard Medical School (MA, USA) in 1993. After residency, Dupuy joined the staff at Massachusetts General Hospital (MA, USA) where he worked in the Abdominal Imaging and Bone and Joint Divisions. In 1997, Dupuy joined the Department of Diagnostic Imaging at Rhode Island Hospital and Brown University. Dupuy, a pioneer in the use of image-guided ablation, helped broaden clinical applications to successfully combat cancer involving the kidney, liver, lung, head and neck, adrenal gland and skeleton. Other newer technologies, such as percutaneous microwave ablation, cryoablation and combination therapies using radiofrequency ablation with external radiation or brachytherapy, have been pioneered by Dupuy who has been the principal investigator of two National Cancer Institute-funded multicenter trials. Dupuy has received national awards for research and teaching from the American College of Radiology Imaging Network and the Radiological Society of North America where he is currently the Chair of the Interventional Oncology Symposium featured at the Annual Meeting of the Radiological Society of North America and a Fellow of the American College of Radiology. Dupuy is a member of the Radiological Society of North America, The New England Roentgen Ray Society, The American College of Radiology, Rhode Island Radiological Society and the Society of Interventional Radiology. Dupuy has published over 150 publications and given over 120 invited lectures in the field of radiology and image-guided ablation, both nationally and internationally.

SUMMARY Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy, has emerged as an effective treatment for inoperable early-stage non-small-cell lung cancer. SABR differs from conventional radiotherapy by virtue of its tight spatial tolerances and use of oligofractionated radiation. The modern technique is characterized by management of tumor motion, image guidance before each fraction and specialized radiation delivery techniques. The result is a highly conformal target dose with a sharp gradient that spares normal tissues with great accuracy. This enables delivery of very potent (ablative) doses, causing more rapid and durable responses than traditional radiation therapy treatment regimens can achieve. The established techniques, new developments and ongoing questions related to SABR for early-stage non-small-cell lung cancer are reviewed herein.

SUMMARY Staging of the mediastinum has long been a part of essential best practice in lung cancer management. This review aims to provide an overview of important key issues, such as anatomical considerations from the 2009 International Association for the Study of Lung Cancer lymph node map, as well as noninvasive and invasive staging techniques for the mediastinum. A suggested sequence of staging the mediastinum is provided, which is by no means prescriptive, but will evolve over time as more evidence is gathered regarding this important step in the clinical work-up of lung cancer patients.

9 ISSN 1758-1966 10.2217/LMT.12.59 © 2013 Future Medicine Ltd Lung Cancer Manage. (2013) 2(1), 9–12 Cancer is caused by structural and functional gene abnormalities affecting cell proliferation and survival. DNA sequence changes (mutations) are not the sole source of gene abnormalities [1]. Gene availability and expression are subject to DNA sequence-independent levels of control (epigenetics), which encompass a variety of activities, from pretranscriptional to post-translational events [2]. The most wellstudied of these involve the control of transcription and translation, including histone modification, noncoding RNAs and DNA methylation. Enzymatic addition of methyl groups to DNA is a frequent and normal mechanism of control of gene expression, generally silencing transcription though interaction with DNA-associated proteins. Although DNA methylation has been studied for over 20 years, the phenotypes and predictions associated with DNA methylation are complex and difficult to define. One reason for this difficulty is that methylation of DNA occurs globally throughout the genome in noncoding regions and at genespecific sites [3]. Global methylation is thought to maintain chromosome stability by silencing DNA elements that move from one location to another in the genome through transcriptional intermediates. Methylation at gene-specific sites occurs mainly on the cytosine residues of clusters of cytosine–guanine dinucleotides (CpG) in CpG islands. In these capacities, both hyperand hypo-methylation of DNA can contribute to tumorigenesis and malignancy [3]. Hypermethylation at gene-specific sites would be the most easily defined biomarker, compared with global hypomethylation. Normally, methylation at gene-specific sites epigenetically regulates transcription to provide gene products at the appropriate time in cell development and metabolism [4]. DNA methylation is permanent for genes in cell types where particular gene products are not required. Some genes, such as SHP1 (coding for a protein tyrosine phosphatase with potential tumor suppressor activity), have multiple promoters (start sites of transcription) with different methylation patterns [5]. These promoters may be methylated in some cell types and unmethylated in others.

Major advances in pathology, molecular biology, patient diagnosis and care, as well as the advent of personalized therapy, have resulted in a greatly increased role for the pathologist, who has emerged as a key member of the lung cancer management team. A new multidisciplinary, clinically relevant classification of pulmonary adenocarcinoma has resulted in a paradigm shift in how we view and practice lung cancer pathology. In the future, the role of the pathologist will continue to grow and become fully integrated with clinical care.

Lung squamous cell carcinoma (SqCC) is the second most common subtype of non-small-cell lung cancer and leads to 40,000-50,000 deaths per year in the USA. Management of non-small-cell lung cancer has dramatically changed over the past decade with the introduction of targeted therapeutic agents for genotypically selected individuals with lung adenocarcinoma. These agents lead to improved outcomes, and it has now become the standard of care to perform routine molecular genotyping of lung adenocarcinomas. By contrast, progress in lung SqCC has been modest, and there has yet to be a successful demonstration of targeted therapy in this disease. Here, we review exciting work from ongoing genomic characterization and biomarker validation efforts that have nominated several likely therapeutic targets in lung SqCCs. These studies suggest that targeted therapies are likely to be successful in the treatment of lung SqCCs and should be further explored in both preclinical models and in clinical trials.

87 ISSN 1758-1966 10.2217/LMT.12.16 © 2012 Future Medicine Ltd Lung Cancer Manage. (2012) 1(2), 87–90 Patients with metastatic bone disease may suffer from skeletal-related events (SREs) such as fractures, pain requiring radiation or bone surgery, spinal cord compression or hypercalcemia, severely affecting their quality of life as well as generating significant hospital and financial costs. Notably, approximately 30–50% of patients suffering from lung cancer develop bone metastases at some point or have bone involvement at the time of diagnosis. These patients are known to present with a high frequency of SREs comparable to other solid tumors often metastasizing to bone, such as breast and prostate cancers [1,2]. The occurrence of non-small-cell lung cancer (NSCLC) SREs was shown to predict an unexpectedly short life expectancy for these patients [3]. Zoledronic acid acts on bone metabolism by disrupting the HMG-CoA reductase pathway and blocking osteoclastogenesis, as well as osteoclast cytoskeletal arrangement. It is frequently administered as part of the overall management of patients with bone metastases and was demonstrated to be effective compared with placebo in prolonging time to first SRE in patients with bone metastases [1,2,4]. Recently, targeting the OPG/RANKL/ RANK pathway was revealed to be an interesting strategy in patients suffering from virtually all bone metastatic advanced solid tumors [5–7]. The RANK pathway plays a major role in osteoclast function and therefore contributes to the subtle regulation of bone turnover. RANK is a member of the TNFR superfamily. RANK and OPG are both receptors for RANKL. However, whereas RANK signaling is stimulated upon RANKL binding, OPG is a secreted decoy receptor that acts as a natural inhibitor of the pathway [8]. Biologically, RANKL is a potent osteoclastogenic factor expressed on osteoblasts and osteocytes, promoting survival, proliferation, differentiation and activation of mature osteoclasts. While the RANK pathway is specifically involved in bone homeostasis, its deregulation was shown to be one of the initiators of SREs in cancer [9]. Apart from bone matrix cells, the transmembrane RANK protein is strongly expressed on lymphocytes, dendritic cells,