Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer (2017 Frontiers of Medicine free full text)

Over the past decade, major advances have been made in the management of advanced non-small cell lung cancer (NSCLC). There has been a particular focus on the identification and targeting of putative driver aberrations, which has propelled NSCLC to the forefront of precision medicine. Several novel molecularly targeted agents have now achieved regulatory approval, while many others are currently in late-phase clinical trial testing. 

These antitumor therapies have significantly impacted the clinical outcomes of advanced NSCLC and provided patients with much hope for the future. Despite this, multiple deficiencies still exist in our knowledge of this complex disease, and further research is urgently required to overcome these critical issues. This review traces the path undertaken by the different therapeutics assessed in NSCLC and the impact of precision medicine in this disease. We also discuss the areas of “imprecision” that still exist in NSCLC and the modern hypothesis-testing studies being conducted to address these key challenges.

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Tracking the Evolution of Non–Small-Cell Lung Cancer (Free full text NEJM 2017)

Lung cancer is the leading cause of cancer-related death worldwide, with non–small-cell lung cancer (NSCLC) being the most common type. Large-scale sequencing studies have revealed the complex genomic landscape of NSCLC and genomic differences between lung adenocarcinomas and lung squamous-cell carcinomas. However, in-depth exploration of NSCLC intratumor heterogeneity (which provides the fuel for tumor evolution and drug resistance) and cancer genome evolution has been limited to small retrospective cohorts. Therefore, the clinical significance of intratumor heterogeneity and the potential for clonality of driver events to guide therapeutic strategies have not yet been defined.

Tracking Non–Small-Cell Lung Cancer Evolution through Therapy (TRACERx) is a multicenter, prospective cohort study, which began recruitment in April 2014 with funding from Cancer Research UK. The target enrollment is 842 patients from whom samples will be obtained for high-depth, multiregion whole-exome sequencing of surgically resected NSCLC tumors in stages IA through IIIA. One primary objective of TRACERx is to investigate the hypothesis that intratumor heterogeneity — in terms of mutations (single or dinucleotide base substitutions or small insertions and deletions) or somatic copy-number alterations (reflecting gains or losses of chromosome segments) - is associated with clinical outcome. Here, we report on the first 100 patients who were prospectively recruited in the study.
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http://www.nejm.org/doi/full/10.1056/NEJMoa1616288#t=articleTop

2017 Lung Cancer Guidelines: The Eighth Edition Lung Cancer Stage Classification

Stage classification provides a nomenclature about the anatomic extent of a cancer; a consistent language provides the ability to communicate about a specific patient and about cohorts of patients in clinical studies. This paper summarizes the eighth edition of lung cancer stage classification, which is the worldwide standard as of January 1, 2017. 

This revision is based on a large global database, a sophisticated analysis, extensive internal validation as well as multiple assessments confirming generalizability. 

Practicing clinicians must be familiar with the stage classification system when managing contemporary patients with lung cancer.

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http://journal.publications.chestnet.org/article.aspx?articleID=2578191