Next-Generation Sequencing in Lung Cancer

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Molecular pathology has become an integral part of thoracic oncology, as the number of molecular markers and clinical targets continues to expand. In December 2013, the FDA granted marketing authorization to the first in vitro diagnostic next-generation sequencing (NGS) system, MiSeqDx. These systems are very cost effective, Mark G. Kris, MD, states, with an analyzer generally costing under $50,000.

With the growing focus on molecular pathology and the rapidly decreasing cost of multiplex testing it has become increasingly easy to incorporate reflex testing, Kris suggests. Technology has advanced dramatically in recent years, allowing for the human genome to be sequenced rapidly at the cost of less than $5,000. In general, Kris notes, NGS is now cheaper than ordering separate tests for 3 oncogenes, such as ALK, EGFR, and KRAS. As a result of this cost advantage and the practical information gained, Kris recommends NGS for all lung cancer histologies.

At this point, some practices are not utilizing molecular testing for patients with pure squamous histology, since driver mutations are uncommon in this subset, Benjamin P. Levy, MD, notes. For patients with non-squamous histology, reflexive testing is generally ordered for EGFR, ALK, KRAS, and ROS. This approach speeds up the testing process, potentially delivering results in time for the patient's first appointment following tissue collection.

Different gene panels can be utilized reflexively, depending on the histology, Mark A. Socinski, MD, notes. In some institutions, molecular testing may be reserved for patients with stage III and IV disease, in the interest of cost savings. However, particularly at institutions that run clinical trials in the adjuvant setting, molecular sequencing may still be ordered for early stage patients, notes Heather A. Wakelee, MD.

A standard solid tumor NGS panel may include 40 mutations, including many of the common aberrations seen in lung cancer, notes Corey J. Langer, MD. This panel also provides information on BRAF status, which has emerged as a potential target in clinical trials, specifically with the BRAF inhibitor dabrafenib.

Utilizing NGS facilitates the accumulation of large databases of potential driver mutations that could be utilized for future research. In France a collaboration of industry, academia, and government has led to the molecular testing of all patients with lung cancer, Kris notes. This effort has culminated in the addition of clinical data for 20,000 new patients each year, which can be examined for potential new targets for therapy. Moreover, the French experience has demonstrated the ease of widespread NGS utilizaton.

The success seen so far with molecular profiling would not have been possible without the dedication of pathologists, Kris points out. Continued success in this area will require close collaboration between pathologists and oncologists. Moving forward, Kris adds that further effort will be placed on finding new targets and treatments for patients with recalcitrant cancers, such as small cell lung cancer.