EP1.18-17 Pre-Radical Radiotherapy Plasma EGFR DNA Levels in Lung Cancer Patients May Predict for Early Disease Progression

Circulating cell-free tumour DNA is an alternative method to detect for and monitor sensitising EGFR mutations in metastatic lung adenocarcinoma. The clinical utility of plasma EGFR (pEGFR) DNA is increasing but there is limited data for its use in early stage patients. We performed a pilot prospective study to test for and monitor pEGFR DNA in lung cancer patients planned for radical lung radiotherapy (RT). Patients with biopsy proven lung adenocarcinoma harbouring sensitising EGFR mutations that were referred for radical lung RT were recruited in our centre. Patients who tested positive on baseline plasma (Pre-RT) sample would be monitored at 1 month post-RT. Detection of pEGFR p.E746_A750del, p.L858R and p.T790M was performed by mutation-specific quantitative PCR. The protocol was later updated to allow the use of next-generation sequencing, LiquidMARKTM Lung assay. Patients baseline characteristics, tumour and treatment details were recorded. Follow-up data was collected prospectively. From April 2017 to August 2018 a total of 9 patients (3 Stage IA/B, 1 IIB, 3 IIIA and 2 IIIC) were enrolled. All were PET staged. 8 underwent radical lung radiotherapy (3 SBRT, 5 chemo-radiotherapy). 3 patients had detectable baseline pEGFR. These patients had stage IIIA/C disease at diagnosis. None of the 4 Stage I/II patients had a detectable pEGFR DNA. Gross tumour volume did not correlate with pEGFR detection rate (GTV range 9.1cc - 124.9cc). Median follow-up was 300 days (range 196-404 days). Of the 3 patients with positive pEGFR DNA mutations, 1 defaulted treatment, 1 had a positive post-RT blood test and 1 refused 2nd blood test. These patients had distal metastatic relapse shortly after RT while patients with an undetectable baseline pEGFR DNA remained disease free on last follow-up. On analysis, a positive baseline pEGFR DNA predicted for early disease progression (Median time to progression 99.5 days vs NR, p=0.004). Our study was terminated due to poor recruitment. In early stage I/II lung cancers, pEGFR DNA was not detectable suggesting limited utility of this test in these patients. Detection rate was higher in stage III patients. Detection of baseline pEGFR DNA in patients with treatable lung cancers appears to have a negative prognostic value and could suggest evidence of micro-metastatic disease. This test may be a useful biomarker to guide treatment and follow-up in locally advanced patients and should be explored in larger studies.