New research has concluded that while plasma-based comprehensive molecular profiling can be a reliable tool in the primary diagnostic setting of advanced non small-cell lung cancer (NSCLC), it cannot fully replace standard-of-care, protocol-based tissue-based molecular profiling.

Instead, the authors suggested that complementary profiling – which that combines both modalities – may help to increase the proportion of patients who are eligible for targeted treatment.

Reporting in a recent issue of JCO Precision Oncology, a team of Dutch investigators explained that while comprehensive molecular profiling plays a vital clinical decision-making role in patients with metastatic NSCLC, such efforts are often hampered by tumor tissue that is unsuitable for molecular analysis or a lack of available tumor tissue. By comparison, analysis of circulating tumor DNA in a patient's blood – which has been shown have high sensitivity and high concordance with standard-of-care tissue-based molecular profiling – offers a minimally invasive option for molecular tumor profiling.

“In this study,” the authors wrote, “we aim to explore the additional value of centralized circulating tumor DNA profiling next to current standard-of-care protocolled tissue-based molecular profiling in the primary diagnostic setting of metastatic NSCLC in the Netherlands.”

With this goal in mind, the researchers analyzed pre-treatment plasma samples from 224 patients with confirmed metastatic NSCLC who were taking part in the Lung cancer Early Molecular Assessment trial (NCT02894853) at nine institutions across the Netherlands. 

Tissue analyses was performed according to the local institution’s standard of care during routine clinical diagnostic workup, and comprised next-generation sequencing and single gene analyses for rearrangements.

Plasma-based comprehensive molecular profiling was performed with the AVENIO ctDNA Targeted Kit (Roche Diagnostics), a panel designed to detect single-nucleotide variants, copy-number variations, insertions or deletions, and tyrosine kinase fusion in 17 genes. These results were then compared with paired pre-treatment tissue-based molecular profiling samples from patient records. 

According to lead author Robert D. Schouten, MD, of the Netherlands Cancer Institute in Amsterdam, the final study analysis comprised 209 patient records. Among these, the median time between the collection of tissue for standard diagnostic purposes and the collection of blood for plasma- comprehensive molecular profiling was 14 days; 84.3% of paired samples were taken within 30 days.

In total, 363 oncogenic variants were detected in 209 patients. It was found that potentially targetable drivers were detected with standard of care tissue molecular profiling alone in 34.4% of patients (72/209). Adding plasma-based comprehensive molecular profiling increased this number to 39.7% of patients (83/209; P<0.001). When the researchers considered level 1-4 drivers, the number of patients identified also increased significantly with the addition of plasma-based comprehensive molecular profiling, from 121 (57.9%) to 135 (64.6%) patients (P<0.001).

Interestingly, the concordance between standard of care tissue molecular profiling and plasma-comprehensive molecular profiling was 86.6% for potentially targetable drivers; the clinical sensitivity of plasma-comprehensive molecular profiling was 75.2% for any oncogenic driver. Finally, the investigators found that the specificity and positive predictive value exceeded 90% for all oncogenic drivers.

Given these findings, the investigators concluded that in-house plasma-comprehensive molecular profiling improves the detection of clinically relevant oncodriver mutations in metastatic NSCLC patients. 

“With an expanding palette of treatable mutations, rapid advances in molecular diagnostics, and increasing affordability and performance of plasma-comprehensive molecular profiling,” the authors wrote, “this relatively new technique is establishing its role in the diagnostic workup of metastatic NSCLC. However, analysis of the cost effectiveness is warranted to determine the optimal implementation in routine clinical care.”


Photo Credit: Getty Images