Clinical Use of Circulating Tumor DNA in Patients with ALK Translocated Non-small-cell Lung Cancer

PhD project

Maiken Parm Ulhøi, MD

Publications (link to AU profile)

I am a medical doctor and PhD student at Aarhus University Hospital (AUH). I am running a Danish multi-centre PhD project on the clinical use of circulating tumour DNA (ctDNA) in patients with incurable ALK translocated Non Small-cell Lung Cancer.

We aim to include 60 patients with incurable ALK-translocated NSCLC. All patients receive standard 1st line ALK-targeted treatment according to Danish guidelines. Unlike most patients with metastatic lung cancer, this patient group live longer, usually for years. However, treatment resistance is inevitable, and little is known of the mechanisms behind.

The standard procedure to detect ALK is by tissue biopsy. This is an invasive procedure that can be difficult to perform, and it is sometimes not representative when it comes to the tumour genetic profile. Tumours have a high cell turnover and hence shed ctDNA to the bloodstream. This ctDNA holds information of the genetic code of the tumour from all tumour sites.

In this project we investigate the use of ctDNA from blood (liquid biopsies) to evaluate treatment outcome and potential oncogene resistance mechanisms.

We collect blood samples from the patients during routine clinical visits. The ctDNA is extracted from the plasma and targeted NGS-sequencing is performed. When the NGS analysis is complete, we have an individual tumour genetic profile of each patient. The NGS analysis is performed before treatment start, approx. 14 days after treatment start and at progressive disease or death, whichever comes first.

The perspectives of this explorative project are that:

  • We have an easy-accessible monitoring of treatment response
  • We can discover potential resistance mechanisms (known and new resistance mechanisms)
  • Liquid biopsies hold potential to guide treatment decisions

We hope that this project can help optimizing the future treatment of metastatic ALK-driven NSCLC.