Postoperative ctDNA Prognostic Marker for Disease Recurrence in Patients with NSCLC

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In non–small-cell lung cancer (NSCLC), circulating tumor DNA (ctDNA) is released from primary tumors, metastatic sites, circulating tumor cells, and minimal residual disease (MRD) into the bloodstream.1 ctDNA is a noninvasive means of helping to detect early disease, predict prognosis, detect mutations, and monitor disease activity.1

ctDNA was studied as a novel means to predict MRD in patients with NSCLC after treatment. Tian and colleagues reported the results of a study on its use in predicting the risk of relapse and monitoring the effect of adjuvant therapy on postoperative patients with NSCLC. The study enrolled 41 patients, 18 patients with stage 1 disease, 2 with stage 2 disease, and 21 with stage 3 disease. Surgery only was performed on 6 patients with 35 patients receiving adjuvant therapy. Tumor tissues were collected at surgery and serial peripheral blood samples were collected at 1 month postoperatively and then at 3 or 6 months.

A total of 41 tumor samples and 137 plasma samples were collected. The tumor samples were tested for 1021 cancer-related genes, and the blood samples were tested for 338 cancer-related genes. Examination of the tissue samples detected 323 somatic variations and a median of 8 gene variations in each patient. The most common mutation was the TP53 mutation, which was found in 63.41%. EGFR was found in 58.53%, LRP1B in 17.07%, and KRAS in 14.63%.

Positive ctDNA was found following surgery in 13 patients: 9 in patients with stage 3 NSCLC, 2 with stage 2 disease, and 2 with stage 1. Recurrence occurred in 5 of the 13 patients, whereas 1 of the 28 patients with undetectable ctDNA experienced a recurrence. When disease-free state was examined, ctDNA was detected after surgery in 17 patients, with 5 experiencing a recurrence. Of the 24 patients without postoperative ctDNA detection, 1 had disease recurrence. Disease recurrence was detected by serial ctDNA ahead of radiologic evidence by a median of 5.25 months. For the 35 patients who received adjuvant therapy, the recurrence ratio was 33.33% for those with detectable ctDNA and 4.34% in those without detectable ctDNA before adjuvant therapy. When ctDNA after adjuvant therapy was analyzed, 33.33% of patients with a positive ctDNA had a recurrence, and no patients with a negative ctDNA had disease recurrence. The 4 patients who had ctDNA cleared by adjuvant therapy were disease free.

Reference

  1. Li RY, Liang ZY. Circulating tumor DNA in lung cancer: real-time monitoring of disease evolution and treatment response. Chin Med J (Engl). 2020;133(20):2476-2485.

Source: Tian X, Wang R, Qian K, et al. Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non–small cell lung cancers. J Clin Oncol. 2022;40(16):suppl, 8533-8533.

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