Oncotarget

Research Papers:

Early responses of EGFR circulating tumor DNA to EGFR tyrosine kinase inhibitors in lung cancer treatment

Fumio Imamura _, Junji Uchida, Yoji Kukita, Toru Kumagai, Kazumi Nishino, Takako Inoue, Madoka Kimura and Kikuya Kato

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Oncotarget. 2016; 7:71782-71789. https://doi.org/10.18632/oncotarget.12373

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Abstract

Fumio Imamura1, Junji Uchida1, Yoji Kukita2, Toru Kumagai1, Kazumi Nishino1, Takako Inoue1, Madoka Kimura1, Kikuya Kato2

1Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

2Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

Correspondence to:

Fumio Imamura, email: imamura-fu@mc.pref.osaka.jp

Keywords: lung cancer, EGFR, EGFR-TKI, mutation, response evaluation

Received: March 23, 2016     Accepted: September 19, 2016     Published: September 30, 2016

ABSTRACT

Objectives: Early evaluation of the effect of treatment is helpful in the management of cancer patients. Circulating biomarkers are an ideal tool for this if they are highly specific to tumors and respond rapidly to tumor volume changes. Circulating tumor DNA (ctDNA) is one such candidate. We conducted a prospective study to test the utility of EGFR ctDNA in early evaluation of EGFR-TKI effects.

Results: Twenty-one patients with EGFR-mutant lung cancer who were naïve to EGFR-TKI were enrolled. PM scores of EGFR ctDNA with activating mutations decreased rapidly in response to EGFR-TKI. Of the 14 patients with positive pretreatment PM scores, complete disappearance of major EGFR ctDNA was observed in 14.3%, 42.9%, and 57.1% on days 2 – 4, 8, and 15, respectively. These responses of EGFR ctDNA were most prominent among the measures used to evaluate responses, and correlated with early radiologic responses evaluated by chest X-rays.

Materials and methods: EGFR ctDNA in serial plasma samples was amplified and 105 copies were sequenced with a next-generation sequencer. Plasma mutation (PM) score was defined as the number of reads containing deletions/substitutions in 105 EGFR cell free DNA (cfDNA). When EGFR mutation in ctDNA was the same as that detected in cancer tissue, the ctDNA was defined as major EGFR ctDNA.

Conclusions: The results indicate the usefulness of ctDNA as a highly specific biomarker for prediction of early response to treatment and that it can be applied to various types of cancer.


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