Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2020
ReviewMolecular Diagnostics in Non-Small Cell Lung Carcinoma.
Current clinical practice guidelines recognize EGFR, BRAF, ALK, and ROS1 as essential molecular biomarkers, and a host of other genetic alterations as emerging biomarkers for non-small cell lung carcinoma patients. The available approaches to detecting relevant alterations in these genes are diverse and often complementary. Laboratories have increasingly migrated away from a "single-gene test" approach, embracing assays that incorporate panels of genes capable of detecting a diverse set of alterations. ⋯ Choice of molecular diagnostics assay, be it single-gene or NGS-based panel, will be driven by cost, urgency, clinical and laboratory focus, and professional considerations. Preanalytic factors including operator expertise, sample type and choice of fixative, and postanalytic factors including informatics pipeline and approaches to variant reporting have a significant impact on the quality of molecular diagnostics results. There is no real "one-size-fits-all" test for genomic profiling for lung cancer; clinicians and laboratorians must be prepared to offer a diverse set of assays in order to address turnaround time requirements and optimize detection of critical but difficult-to-detect tumor alterations such as gene fusions.
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Lung cancer is a heterogeneous disease, and the availability of comprehensive genomic profiling has allowed for the characterization of its molecular subtypes. This has increased the ability to deliver "personalized medicines" by tailoring therapies to target driver mutations in a patient's cancer. The development of targeted therapies for non-small cell lung cancer (NSCLC) has helped define the era of precision medicine throughout oncology. ⋯ The first section discusses mutations in the epidermal growth factor receptor (EGFR) gene, and the second section examines rearrangements in the anaplastic lymphoma kinase (ALK) and ROS1 fusions. Finally, we explore the rarer molecular alterations in BRAF, RET, MET, HER2, and KRAS. Given the many available therapies, it is important to understand the molecular alterations in NSCLC, and how to target them.
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Semin Respir Crit Care Med · Jun 2020
ReviewLocal Ablative Therapies in Oligometastatic NSCLC: New Data and New Directions.
The oligometastatic and oligoprogressive disease states have been recently recognized as common clinical scenarios in the management of non-small cell lung cancer (NSCLC). As a result, there has been increasing interest in treating these patients with locally ablative therapies including surgery, conventionally fractionated radiotherapy, stereotactic ablative radiotherapy, and radiofrequency ablation. ⋯ Phase II randomized controlled trials and retrospective series suggest that ablative treatment of oligometastases may substantially improve progression-free survival and overall survival, and additional large randomized studies testing this hypothesis in a definitive context are ongoing. However, several challenges remain, including quantifying the possible benefits of ablative therapies for oligoprogressive disease and developing prognostic and predictive models to assist in clinical decision making.
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Semin Respir Crit Care Med · Jun 2020
Review Comparative StudyVATS and Minimally Invasive Resection in Early-Stage NSCLC.
Lung carcinoma widely affects men and women in the sixth and seventh decades of life. Thorough workup with radiographic imaging, pathologic diagnosis, and cardiopulmonary functional assessment is key to successful treatment. Accurate staging is essential for both assessing prognosis and directing therapy. ⋯ Compared with standard thoracotomy, VATS lobectomy offers improved postoperative outcomes as well as potential survival benefit. Thoracoscopic lobectomy is also cost-effective. This article focuses on the technique, outcomes, adaptation, and evolution of thoracoscopic lobectomy and other minimally invasive techniques in the treatment of lung cancer.
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Enhanced recovery programs (ERPs) aim to reduce psychological and physiological stress related to surgery, and minimize opioid use. This article describes the tenets of enhanced recovery, the guidelines for ERP in lung surgery, and the University of Virginia experience with developing and implementing a program. The impact of these strategies on short-term patient outcomes and potential long-term benefits including influence on lung cancer-specific outcomes are reviewed. The opioid crisis is of utmost importance; this article will explore how ERPs may be a mitigating factor.