Treatment stores

Post-treatment ctDNA predicts poor outcome in early-stage NSCLC

medwireNews: The Presence of Circulating Tumor (ct) DNA After Curatively Intended Treatment for Early-Stage Non-Small Cell Lung Cancer (NSCLC) Is Associated with an Increased Risk of Relapse or Death, According to Data from the LUCID study.

These results suggest that “ctDNA detection after initial treatment […] the use of sensitive patient-specific tests has the potential to identify patients who might benefit from additional therapeutic intervention,” write Nitzan Rosenfeld (Cancer Research UK Cambridge Institute) and co-authors of the Annals of Oncology.

The patient-specific tests described by the authors were created by first sequencing tumor samples from 88 patients with early-stage NSCLC (62.5% adenocarcinomas) who were treated with surgery (n = 61), surgery with adjuvant chemotherapy or radiotherapy (n = 8), or chemoradiotherapy alone (n = 19).

The sequencing results were then used to design patient-specific RaDaR™ next-generation sequencing liquid biopsy assays that target 48 tumor-specific variants unique to each patient.

More than half (56%) of patients were positive for ctDNA in samples taken before or after treatment, and ctDNA was detected in 26% of 363 longitudinal samples tested.

Of the 78 patients for whom pre-treatment samples were available, ctDNA was detected in 51%, including pre-treatment cDNA positivity rates of 24% in 41 individuals with stage I disease, 77% in 22 patients with stage II disease and 87% in the 15 participants with disease. stage III disease.

A total of 28 patients showed clinical recurrence of their primary tumor and 18 (64.3%) of them had ctDNA during follow-up. Twelve of these patients had ctDNA detected in the samples, a median of 212.5 days before recurrence was diagnosed.

When the researchers focused on the landmark, the first sample taken between 2 weeks and 4 months after the end of treatment, they found that 17% of 59 patients had ctDNA, and that all of those 10 patients subsequently experienced a recurrence.

Additionally, these patients had significantly shorter recurrence-free survival (RFS) and overall survival (OS) times than individuals for whom ctDNA was not detected at baseline, at hazard ratios ( HR) of 14.8 and 5.5, respectively.

Pre-treatment ctDNA positivity was also associated with significantly worse RFS and OS, but with smaller HRs of 3.14 and 2.97, respectively.

But only two of the 16 patients in whom cDNA was detected before but not after treatment experienced a recurrence, which the researchers say suggests “the potential for de-escalation of adjuvant therapy.”

However, they caution: “Larger studies and prospective clinical trials are needed to determine the benefit/harm balance in the subsequent treatment of patients after initial therapy with curative intent, when ctDNA is not detected. even using very sensitive tests.”

Rosenfeld et al conclude that their data “adds to the accumulating evidence of the potential utility of cDNA testing for patient risk stratification to identify which patients may benefit most from adjuvant therapy or present high risk of disease recurrence.

medwireNews is an independent medical information service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Anne Oncol 2022; doi:10.1016/j.announce.2022.02.007