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23-03-2022 | Non-small-cell lung cancer | News

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

Author: Laura Cowen

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medwireNews: The presence of circulating tumor (ct)DNA following treatment with curative intent for early-stage non-small-cell lung cancer (NSCLC) is associated with an increased risk for relapse or death, LUCID study data show.

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

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

The results of sequencing 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 either before or after treatment, and ctDNA was detected in 26% of all 363 longitudinal samples tested.

Of the 78 patients with pretreatment samples available, ctDNA was detected in 51%, including pretreatment ctDNA positivity rates of 24% among 41 individuals with stage I disease, 77% in 22 patients with stage II disease, and 87% in the 15 participants with stage III disease.

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

When the researchers focused on the landmark timepoint, namely the first sample collected between 2 weeks and 4 months from the end of treatment, they found that 17% of 59 patients had ctDNA, and all 10 of these patients subsequently experienced recurrence.

Furthermore, these patients had significantly shorter recurrence-free survival (RFS) and overall survival (OS) durations than individuals for whom ctDNA was not detected at the landmark timepoint, at hazard ratios (HRs) of 14.8 and 5.5, respectively.

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

But just two of 16 patients who had ctDNA detected before but not after treatment experienced recurrence, which the researchers say suggests “the potential for de-escalation of adjuvant treatment.”

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

Rosenfeld et al conclude that their data “adds to accumulating evidence for the potential utility of ctDNA testing to risk-stratify patients to identify which patients may benefit most from adjuvant therapy or be at high risk of disease recurrence.”

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

Ann Oncol 2022; doi:10.1016/j.annonc.2022.02.007

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