Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study)
Menée à partir d'échantillons plasmatiques prélevés sur 233 patients atteints d'un cancer du poumon non à petites cellules (durée médiane de suivi : 51,4 mois), cette étude multicentrique met en évidence l'intérêt de suivre l'évolution de l'ADN tumoral circulant pour guider la prise en charge thérapeutique après un traitement chirurgical
Background : Circulating tumor DNA (ctDNA) is valuable for detecting minimal residual disease (MRD). However, studies involving long-term blood sampling are required to comprehensively interpret the clinical use of ctDNA analyses.
Methods : We conducted a prospective multicenter cohort study (LUNGCA) for dynamic ctDNA monitoring in lung cancer patients receiving curative-intent surgery. ctDNA analysis was conducted on preoperative plasma samples, at postoperative three days and one month, and then every three–six months for up to three years.
Results : 233 non-small cell lung cancer (NSCLC) patients and 2336 longitudinal plasma samples were included; the median follow-up was 51.4 months. Post-comprehensive treatment (after radical surgery + necessary adjuvant therapy) MRD status was better at predicting relapse than postoperative MRD status (positive predictive value: 100% vs 90.0%; negative predictive value: 90.3% vs 90.1%). Patients with positive pre-adjuvant ctDNA and targetable mutations in tumor tissues had improved recurrence-free survival (RFS) with corresponding adjuvant TKI treatment [hazard ratio (HR) = 0.01, P = .005], but adjuvant chemotherapy failed to improve RFS (HR = 0.6, P = .491). Of patients receiving adjuvant therapies, patients with a negative- or positive-negative ctDNA change pattern had favourable and similar RFS (P = .419), whereas patients with a positive- or negative-positive pattern had worse RFS (P < .001). TKI therapy was more effective than chemotherapy in clearing ctDNA. Post-relapse ctDNA negativity was associated with favorable OS (HR = 0.4; P = .029).
Conclusions : Comprehensive interpretation of dynamic ctDNA monitoring data can inform precise whole-course postsurgical management of NSCLC patients.
Journal of the National Cancer Institute , article en libre accès, 2025