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Comment & Response
August 2016

Early Intervention in Lung Cancers With Rapid Plasma Genotyping for EGFR and KRAS Mutations

Author Affiliations
  • 1National Oncology Center, Royal Hospital, Muscat, Sultanate of Oman
JAMA Oncol. 2016;2(8):1096. doi:10.1001/jamaoncol.2016.2161

To the Editor Sacher and colleagues1 are to be congratulated on demonstrating the specificity (high) and sensitivity (not so great) of the droplet digital polymerase chain reaction technology. Of the 2 cohorts of epidermal growth factor receptor (EGFR)-mutant patients tested, the second cohort had already developed resistance (presumably diagnosed on radiological progression) and is by definition enriched for higher levels of (new) mutations. How would this test perform if patients were routinely monitored after starting first-line EGFR tyrosine kinase inhibitor treatment, before the development of resistance? Patients with chronic myeloid leukemia are tested for evidence of resistance at the molecular level at time points in their natural history, without waiting for features of overt resistance (such as alterations in peripheral blood cell counts, organomegaly, or symptoms) to appear.2 Early detection and intervention is arguably one of the reasons for the high survival rates achieved in this cancer. BCR-ABL translocation in chronic myeloid leukemia and EGFR mutation in a subset of lung cancers are similar in their driver functions. Regular monitoring and early intervention (without waiting for radiographic progression, by which time multiple other mutations would have developed) should be feasible in mutant lung cancers if the test is sensitive enough. Looking forward, a paradigm shift toward routine monitoring in patients with lung (and other solid) tumors carrying identifiable sensitizing mutants should encourage development of more sensitive tests and newer drugs and, with hope, to improved survival.

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