UPDATED LUNG CANCER MOLECULAR TESTING

An update to the 2013 guideline for the molecular analysis of lung cancers provides new recommendations that include testing for additional genes and the use of ultrasensitive assays and other new technologies, according to an expert panel report.

"Additional emphasis was placed on applying advances in technology that enable concurrent testing of multiple mutations from a single sample; ultrasensitive detection of mutations that, in some circumstances, enables diagnosis without needing a surgical procedure to obtain tissue; and advances in medical knowledge that have revealed the clinical necessity to test for mutations in additional genes," expert panel member Dr. Neal Lindeman of Brigham and Women's Hospital, in Boston, told Reuters Health by email.

The panel was convened by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Panel members systematically reviewed the 2013 guideline to affirm its validity; assess the evidence of new genetic discoveries, technologies and therapies; and issue an evidence-based update.

Eighteen new recommendations were drafted, and the panel updated three recommendations from the 2013 guideline, according to the January 23 online report in Archives of Pathology & Laboratory Medicine.

Dr. Lindeman highlighted by email some of the panel's "significant" recommendations:

- Next-generation sequencing (NGS) panels are preferable to single-gene tests. "This enables testing of smaller samples," he said, "which means less invasive procedures for lung cancer patients, and (generating) results more rapidly, which enables directing patients to the most appropriate therapy sooner."

- All non-small-cell lung cancer patients should be tested for the ROS1 gene, and patients with the activating rearrangements in this gene can benefit from treatment with a targeted inhibitor.

- NGS panels should also be used to test for mutations in BRAF, ERBB2, MET and RET, as well as EGFR and ALK, and resulting assessments can help direct patients to appropriate clinical trials.

- Circulating cell-free DNA (or "liquid biopsy") is an approved method for assessing secondary mutations in patients with EGFR mutations who have relapsed after initial anti-EGFR therapy. "This method can detect very low levels of resistance mutations, such as the T790M mutation, which can be targeted with a third-generation EGFR inhibitor," Dr. Lindeman noted. "Patients with a negative result from a cell-free DNA test should undergo biopsy for definitive assessment from a tissue sample."

- For single-gene assessments, immunohistochemistry (IHC) is now as valid as FISH for detecting ALK fusion genes, and can also be used to screen for ROS1 fusions. "IHC generally is more widely available than FISH, and the greater availability will enable patients to get results more quickly," he said.

Dr. Leena Gandhi, a medical oncologist at Perlmutter Cancer Center, NYU Langone Health in New York City, told Reuters Health, "These guidelines reflect what should already be routine clinical practice, but is not the case in many places."

"Hopefully, these guidelines will emphasize the importance of routine clinical testing for not only EGFR mutations, ALK rearrangements (by IHC or FISH) but also for ROS rearrangements," she said by email. "ROS is more difficult to test because IHC for ROS does not have the same sensitivity as ALK IHC, but is clinically just as important to test as ALK."

"The guidelines also emphasize that additional molecular testing is warranted if initial testing is negative," she noted. "Hopefully these guidelines will lead to more uniform testing in a clinically reliable way in laboratories everywhere."

Dr. Raja Flores, Director of the Thoracic Surgical Oncology Program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York City, told Reuters Health by email, "While many clinicians in the United States have already incorporated many of these recommendations into their practice, this evidence-based, updated guideline - collaboratively developed by an international, multidisciplinary panel of expert authors . . . will continue to advance the quality of diagnostic medicine to improve lung cancer patient outcomes."

Resources to help facilitate guideline implementation are available on the website of the College of American Pathologists (http://capatholo.gy/2DS7xNx).

SOURCE: http://bit.ly/2GjlFxu