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David S. Ettinger, MD, FACP, FCCP

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AACR 2022: Circulating Tumor DNA–Based Monitoring After Surgery for NSCLC

By: Gavin Calabretta, BS
Posted: Friday, April 15, 2022

Gene panels based on whole-exome sequencing of tumor samples are increasingly more prevalent in circulating tumor DNA (ctDNA)-based detection of molecular residual disease (MRD). Moreover, patient-specific flexible gene panels may have an advantage over fixed panels in that they can incorporate more unique genomic regions than fixed panels, but there has been little research done to compare the ability of these two approaches to monitor disease after surgery. However, in a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5916), Kezhong Chen, MD, of Peking University People’s Hospital, Beijing, and colleagues directly compared the prognosis performance of a novel patient-specific tumor-informed panel with other fixed tumor-informed and tumor-naive panels; they found patient-specific monitoring to be better than fixed-panel monitoring in enabling risk stratification early in the posteropative setting.

The study enrolled 53 patients with stage I to III resected non–small cell lung cancer from the MEDAL study, which had previously analyzed the prognostic value of ctDNA methylation in surveillance monitoring. The researchers’ assay was given the acronym PROPHET, for patient-specific prognostic and potential therapeutic marker tracking tumor-informed ctDNA assay. PROPHET, which works by identifying somatic mutations to customize a patient-specific panel composed of 50 single nucleotide variants, was compared with fixed-panel processing of blood samples with 168 other gene panels.

The PROPHET assay accurately predicted MRD-positive cases among relapsed patients at 1 month after surgery and correctly determined that all disease-free patients achieved MRD negativity. Additionally, the 3-year prognostication with PROPHET yielded a higher sensitivity, negative predictive value, and hazard ratio than tumor-informed and tumor-naive fixed panel assays. Lastly, according to the investigators, PROPHET accurately predicted MRD risk in 70% of relapsed patients, compared with fixed tumor-informed (43%) and tumor-naive (37%) panels.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.


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