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. 2024 Feb;35(2):183-189.
doi: 10.1016/j.annonc.2023.11.008. Epub 2023 Nov 21.

Circulating tumor DNA and radiological tumor volume identify patients at risk for relapse with resected, early-stage non-small-cell lung cancer

H T Tran  1 , S Heeke  1 , S Sujit  2 , N Vokes  1 , J Zhang  1 , M Aminu  2 , V K Lam  3 , A Vaporciyan  4 , S G Swisher  4 , M C B Godoy  5 , T Cascone  1 , B Sepesi  1 , D L Gibbons  1 , J Wu  6 , J V Heymach  7
Affiliations

Circulating tumor DNA and radiological tumor volume identify patients at risk for relapse with resected, early-stage non-small-cell lung cancer

H T Tran et al. Ann Oncol. 2024 Feb.

Abstract

Background: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome.

Patients and methods: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation.

Results: Our results showed that patients with detectable ctDNA at baseline or after treatment and patients who did not clear ctDNA after treatment had a significantly worse clinical outcome. Integrating radiological analysis allowed the stratification in risk groups prognostic of clinical outcome as confirmed in an independent cohort of 32 patients.

Conclusions: Our findings suggest ctDNA and radiological monitoring could be valuable tools for guiding follow-up care and treatment decisions for early-stage NSCLC patients.

Keywords: MRD; ctDNA; early-stage NSCLC; liquid biopsy; tumor volume.

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Figures

Figure 1.
Figure 1.. Detection of ctDNA before surgery and/or after completion of standard of care (SOC) therapies are associated with worsen clinical outcomes. (A) RFS and (B) OS based on ctDNA detection before surgery. (C) RFS and (D) OS based on ctDNA detection after SOC.
RFS was calculated from time of surgery to relapse, death or censoring and OS was calculated from time of surgery to death or censoring. Log-rank tests were used to compute P values, and Cox proportional HRs were calculated in comparison to patients with detectable ctDNA. ctDNA, circulating tumor DNA; HR, hazard ratio; OS, overall survival; RFS, relapse-free survival; SOC, standard-of-care.
Figure 2.
Figure 2.. Failure to clear ctDNA after completion of SOC therapies are associated with greater risks for disease recurrence and shortened overall survival. (A) RFS and (B) OS in patients without detectable ctDNA throughout the study (Never Detected), patients who cleared ctDNA during treatment (Cleared), and patients with persistent ctDNA detectable (Persistent).
Log-rank tests were used to compute P values. ctDNA, circulating tumor DNA; OS, overall survival; RFS, relapse-free survival.
Figure 3.
Figure 3.. Validation of a risk model with combination of ctDNA and radiologic tumor volume. (A) RFS in patients with detectable ctDNA and radiological tumor volume above the computed threshold (high risk), patients with undetectable ctDNA and radiological tumor volume below the computed threshold (low risk), patients with detectable ctDNA but tumor volume below the calculated threshold, or patients with undetectable ctDNA but tumor volume above the calculated threshold (medium risk) as well as in (B) an independent cohort (cohort 2) of 32 patients. (C) OS for cohort 1 as well as (D) in the independent cohort (cohort 2).
Log-rank tests were used to compute P values. ctDNA, circulating tumor DNA; OS, overall survival; RFS, relapse-free survival.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33. - PubMed
    1. Pantel K, Alix-Panabières C. Liquid biopsy and minimal residual disease — latest advances and implications for cure. Nat Rev Clin Oncol. 2019;16(7):409–424. - PubMed
    1. Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer. Ann Oncol. 2019;30(11): 1804–1812. - PubMed
    1. Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. - PMC - PubMed
    1. Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 2017;7(12):1394–1403. - PMC - PubMed

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