Lung cancer is the most common cancer in China [1] and the most deadly. Unlike in many Western countries, the number of lung cancer diagnoses is also continuing to rise. By harnessing ctDNA technology, we have an opportunity to significantly improve patient care and outcomes.

Traditionally to confirm a cancer diagnosis, a suspected cancerous tumour is biopsied and the tissue sent for diagnosis by the laboratory medicine team. But defining a cancer with just one small sample can be misleading, and repeat tissue biopsies are not always possible, especially in lung cancer. Once a patient has been treated for lung cancer, obtaining repeat tissue biopsies can be challenging and carries the risks inherent to any invasive procedure.

Laboratories with the right expertise can offer physicians an attractive alternative in such situations. Liquid biopsies, which measure the circulating tumour DNA (ctDNA) levels, are less invasive and avoid biopsy-related complications. Using the genetic and epigenetic data obtained from ctDNA, the lab team can provide the oncologist with high-quality precision data on the cancer’s genotype and real-time behaviour to better manage a patient’s disease.

Unlocking the wealth in a vial of blood

Given ctDNA’s short half-life of an hour or less, it can be an accurate indicator of the real-time tumour burden in response to therapy [2]. Access to this real-time information can enable the care team to detect any residual disease at an early time. In fact, it has been shown that in 72% of patients with localised lung cancer, residual disease can be identified using ctDNA 5.2 months earlier than using radiological imaging [3] alone.

In patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer, for example, emerging resistance to tyrosine kinase inhibitor treatment presents another opportunity to use ctDNA in real-time to monitor the disease’s genetic evolution. Half the patients treated with tyrosine kinase inhibitors acquire the EGFR T790M mutation [4]. Wakelee et al demonstrated in their ASCO 2016 presentation [5] that plasma and urine EGFR analysis can accurately detect these mutations and may pinpoint them when the biopsy does not due to the heterogeneity of the tumour. ctDNA also enables such patients to be identified a median of 2.2 months before clinical disease progression [4], Zheng et al demonstrated.

Forging closer ties between clinic and lab

As with all nascent technologies, knowing when to apply ctDNA testing and how to analyse and interpret results are key. Having access to a lab team that is up-to-date with the latest research and trained to deliver high-quality precision analytics can help oncologists better manage their patients’ disease. ctDNA analysis identifies cancer mutations that can be used as biomarkers for an FDA-approved drug in 49% of patient cases [6]. Experts in laboratory medicine need to work hand-in-hand with oncologists to determine when liquid biopsies may be the most appropriate diagnostic tool.

We are on the cusp of providing treatment that is personalised not only to the patient at the point of diagnosis, but throughout the entire illness. ctDNA provides information on the genetic makeup of cancer and its inherent heterogeneity. It can also provide clues to the prognosis, including risk of relapse and overall survival rates.

With robust and accurate information from the laboratory, oncologists will soon be able to answer some of the most difficult questions their patients ask with greater confidence and certainty.

[1] Zhou, C., 2014. Lung cancer molecular epidemiology in China: recent trends. Translational Lung Cancer Research, 3(5), pp.270-279.

[2] Corcoran, B.R., Chabner A.B., 2018. Application of Cell-free DNA Analysis to Cancer Treatment. New England Journal of Medicine, 379, pp.1754-1765

[3] Chaudhuri, A.A, et al., 2018. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. American Association for Cancer Research, 7(12), pp.1394-1403.

[4] Zheng, X.Y, et al., 2016. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance. Scientific Reports, 6, 20913.

[5] Wakelee, A.H., et al., 2016. Epidermal growth factor receptor (EGFR) genotyping of matched urine, plasma and tumor tissue from non-small cell lung cancer (NSCLC) patients (pts) treated with rociletinib. Journal of Clinical Oncology, 34(15) supplementary, pp.9001-9001.

[6] Zill, A.O., et al., 2016. Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA. Journal of Clinical Oncology, 34(18), supplementary, LBA11501

This article is based on a presentation “Conquering Cancer: ctDNA’s application in NSCLC” at the Belt and Road Diagnostic Summit Forum 2018 in Suzhou, China.