Transformation or Progression from Adenocarcinoma to Small Cell Lung Cancer Detected by Serially Tracking Mutations in the Blood

Arutha Kulasinghe,Ken O’Byrne,Rahul Ladwa,Mark Nalder,Connor O’Leary,James Monkman

doi:10.3390/reports3040033

Abstract

Background: Circulating tumour DNA (ctDNA) has emerged as a promising biomarker for monitoring non-small-cell lung cancer (NSCLC). This has enabled the monitoring of clinically actionable mutations over the course of therapy. Case presentation: We present the case of a 74-year-old female who was treated with EGFR inhibitors for NSCLC which later transformed to SCLC. The kinetics of ctDNA was monitored by measuring the EGFR Exon 19 mutant L747–A750 > P and PIK3CA E545K over the course of therapy. Stabilisation of the PIK3CA mutation was found in response to therapy, however there appeared to be increasing levels of the EGFR mutant, potentially reflective of untreated EGFR-driven disease. Conclusion: The key finding described here, revealed by mutational tracking of mutations from the blood, is that clinically actionable mutations are assessable and may demonstrate clinical utility in measuring disease burden, multiple clones and progression non-invasively for lung cancer.

Highlights

There have been studies in non-small-cell lung cancer (NSCLC) with mutated EGFR which returns as SCLC when there is resistance to tyrosine kinase inhibitors and reports about the co-existence of NSCLC and SCLC [1]
We assessed the changes in circulating tumour DNA in EGFR-mutated NSCLC over the course of treatment using the Lung UltraSeek mutation Panel (Agena Biosciences, San Diego, CA, USA) [2]
No further immunohistochemistry was performed. She was commenced on epidermal growth factor inhibitor Erlotinib (Figure 1; T0–T1) which continued for six months when she developed an enlarging right hilar lymph node

Summary

Introduction

There have been studies in non-small-cell lung cancer (NSCLC) with mutated EGFR which returns as SCLC when there is resistance to tyrosine kinase inhibitors and reports about the co-existence of NSCLC and SCLC [1]. Whilst repeat tissue biopsy can potentially identify these changes, it remains a limited and invasive procedure to perform, which does not reflect dynamic tumoural changes in real time. We assessed the changes in circulating tumour DNA (ctDNA) in EGFR-mutated NSCLC over the course of treatment using the Lung UltraSeek mutation Panel (Agena Biosciences, San Diego, CA, USA) [2]

Case Report

Ethics Approvals