How Effective Is Cell-Free ctDNA Profiling in Managing Advanced Lung Cancer?

By: Victoria Kuhr, BA
Posted: Tuesday, March 22, 2022

Liquid biopsy appears to be the likely choice to identify genomic alterations in untreated patients with non–small cell lung cancer (NSCLC) as well as to monitor and detect resistance mechanisms. Venceslau Hespanhol, MD, PhD, of Centro Hospitalar Universitário de São João, Porto, Portugal, and colleagues propose that clinical and functional evaluation of a patient’s condition and disease extension—combined with tumor morphologic, immunohistochemical, and molecular characterization—is paramount for clinical decision-making. These study findings were published in Cancer Cell International.

“In the NSCLC setting, liquid biopsy, particularly circulating tumor DNA genomic analysis, has an expanding role in detecting oncogenic driver alterations as well as emerging resistance mechanisms,” said the authors.

For lung cancer genotyping, the cell-free circulating tumor DNA (cfDNA) test performance depends on the technology used, with overall sensitivity at around 70% to 81% and very high specificity, as proven in various studies. Further studies testing multicomplex polymerase chain reaction covering 12 specific genomic regions revealed a sensitivity of 58% and a specificity of 87%, with tumor samples as references. Improvements were made to increase the sensitivity and specificity to a range of more than 75% sensitivity and closer to 100% specificity.

However, adopting liquid biopsy in lung cancer management, specifically cfDNA analysis, has some challenges, noted the study authors. First, there is some discrepancy between cfDNA results and paired tissue samples relating to the reduced sensitivity of cfDNA responsible for false-negative results. Next, cell-free DNA analysis is technically demanding, requiring rigorous standardized protocols for plasma collection preservation, DNA isolation, library preparation, and sequencing, and thus it is susceptible to failures. Additionally, the intrinsic nature of lung cancer may compromise the lung biopsy results. Some tumors release little or no DNA to the circulation. The lung biopsy may show inaccurate results since the amount of ctDNA is related to the disease stage, tumor burden, localization, and size of metastasis.

Disclosure: The study authors reported no conflicts of interest.

Cancer Cell International