Dr Pellini on the Development of Increasingly Sensitive ctDNA Assays in NSCLC

Bruna Pellini, MD, assistant member, Department of Thoracic Oncology, Moffitt Cancer Center; assistant professor, Morsani College of Medicine, University of South Florida, discusses how blood-based lung cancer assays have evolved over time and the importance of developing circulating tumor DNA assays with increased sensitivity to accurately determine optimal treatments for patients with non–small cell lung cancer.

Many oncologists are now opting for neoadjuvant chemoimmunotherapy following a paradigm shift in the management of early-stage NSCLC, Pellini begins. Neoadjuvant approaches have substantially increased patient response rates; however, their success has made obtaining surgical specimens for analysis more challenging, she states. Approximately 30% to 40% of these patients will achieve a major pathological response (MPR) or complete pathological response (pCR) with neoadjuvant therapy, leaving limited tissue available for further testing, Pellini expands.

Traditional tissue-based assays developed in the past require a substantial amount of cancer cells and are tumor-informed, meaning they rely on specific tumor characteristics for analysis, Pellini explains. Although these assays demonstrate good sensitivity in detecting disease recurrence, the absence of sufficient surgical specimens from patients with NSCLC poses a significant challenge in their application, she says.

Development of tumor-agnostic, tumor-uninformed assays that are entirely blood-based may help address this challenge, Pellini states. However, current blood-based assay technologies face limitations in sensitivity, Pellini notes. This leads to concerns about accurately detecting minimal residual disease (MRD) and disease recurrence solely from blood samples, Pellini adds.

Effective assays must address the limitations of current technologies to provide reliable prognostic information and guide treatment decisions in early-stage NSCLC, Pellini says, emphasizing that liquid biopsy assays need to be developed with increased sensitivity to detect disease recurrence in the form of MRD. In doing so, oncologists can more accurately identify patients with MRD-negative disease and tailor treatment strategies accordingly, she concludes.