Abstract
BackgroundLiquid biopsy has evolved from being a promising line to becoming a validated approach for biomarker testing. However, its utility for individualization of therapy has been scarcely reported. In this study, we show how monitoring levels of EGFR mutation in plasma can be useful for the individualization of treatment.ResultsLongitudinal EGFR mutation levels in plasma always correlated with tumor response ascertained by RECIST criteria. Moreover, decreasing EGFR mutation levels were detected in all patients benefiting from locoregional radiotherapy, whereas the opposite occurred when a patient progressed soon after radiotherapy treatment. Similarly, increasing EGFR mutation levels anticipated disease progression after TKI dose reduction, discontinuation of treatment, or reduced bioavailability due to drug interactions. In addition, EGFR mutation levels were useful to monitor treatment outcome of new therapies and constituted a decisive factor when the clinical situation of the patient did not correlate with responses ascertained by radiologist. Finally, our results indicate that cancer associated body fluids (pleural, pericardial or cerebrospinal fluid) are certainly a suitable source for biomarker testing that can extend EGFR mutation detection to biofluids other than blood.Materials and MethodsA total of 180 serial plasma samples from 18 non-small-cell lung cancer patients who carried an activating EGFR mutation were investigated by digital PCR.ConclusionsMonitoring levels of EGFR mutation in plasma allows resolving doubts that frequently arise in daily clinical practice and constitutes a major step towards achieving personalized medicine.
Highlights
Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have substantially improved the quality of life and survival of advanced non-small-cell lung cancer (NSCLC) patients [1,2,3,4,5]
Monitoring levels of EGFR mutation in plasma allows resolving doubts that frequently arise in daily clinical practice and constitutes a major step towards achieving personalized medicine
This study reports daily clinical practice data obtained from 18 NSCLC patients
Summary
Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have substantially improved the quality of life and survival of advanced non-small-cell lung cancer (NSCLC) patients [1,2,3,4,5]. Several studies have indicated that RECIST assessment may have some limitations when measuring tumor response to TKIs [6,7,8]. Oncologists usually continue to treat NSCLC patients harbouring sensitizing EGFR mutation with TKIs for extended periods after RECIST progression [9,10,11] this may be continuing ineffective treatments. It has been reported that the p.T790M resistance mutation can be effectively detected in plasma of advanced lung cancer patients several months prior to clinical progression [12, 13]. We show how monitoring levels of EGFR mutation in plasma can be useful for the individualization of treatment
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