TORONTO, 12 Oct 2022 – Approximately 30% of non-small cell lung cancer (NSCLC) are non-metastatic and eligible for surgical resection with curative intent. Yet up to half of these patients developed recurrence and eventually lead to death despite curative resection. Recurrence is suspected to arise due to minimal residual disease (MRD), which are cancer cells remaining post-surgery that cannot be detected using conventional imaging methods. However, circulating tumor DNA (ctDNA) is shed by tumor cells into the patient’s bloodstream, with a matching mutational profile of the primary tumor cells. A recent prospective study published in the Journal of Hematology & Oncology, led by Jiangsu Oncology Hospital and Geneseeq demonstrated the clinical utility of longitudinal ctDNA monitoring in MRD detection and prognosis prediction in patients with resectable NSCLC.
This study included 128 stage I-III NSCLC patients who received curative surgical resection at the Jiangsu Oncology Hospital. Primary tumor and lymph node metastasis (LNM) samples were collected from surgeries as the standard of care. Plasma samples were collected pre-surgically, 7 days post-surgically, and every three months thereafter. Both tissue and plasma samples were sequenced using the 425-gene Geneseeqprime panel. A total of 645 tissue samples and 628 plasma samples were included in the analyses. The clonal phylogeny of each patient was reconstructed from multi-region tissue sequencing to aid the ctDNA detection.
Interestingly, patients with lung squamous-cell carcinoma displayed more frequent positive ctDNA results than those with lung adenocarcinoma. The detection rates positively correlated with TNM stages and LNM statuses. Smokers were more frequently ctDNA-positive than non-smokers pre-surgically, but not postsurgically. Notably, postsurgical ctDNA monitoring at as early as seven days after surgeries could indicate a high risk of recurrence (HR = 3.90, 95%CI: 1.85-8.20, P = 0.00011), independently of clinicopathological characteristics (multivariate-Cox: HR = 5.49, 95%CI: 1.86-16.20, P = 0.002). ctDNA detection at 3 months and 6 months could also serve as prognostic markers (3 months – HR = 4.32, 95%CI: 2.06-9.08, P < 0.0001; 6 months – HR = 6.19, 95%CI: 2.44-15.69, P < 0.0001). They remained statistically significant after adjusted for clinicopathological characteristics (multivariate-Cox: 3 months – HR = 4.17, 95%CI: 1.80-9.70, P < 0.001; 6 months – HR = 4.59, 95%CI: 1.68-12.50, P < 0.003). Longitudinal ctDNA detection accurately identified patients at high risk of recurrence (univariate-Cox: HR = 7.59, 95%CI: 3.53-16.32, P < 0.0001; multivariate-Cox: HR = 8.33, 95%CI: 3.59 -19.30, P < 0.001) and covered the majority of recurrence cases (73.5%, 25/34). In these cases, ctDNA MRD detection preceded radiographic relapse by a median of 145 days. The time intervals were similar in LUAD (144 days) and LUSC (150 days)
“ctDNA could serve as a promising biomarker for risk of recurrence in NSCLC patients who receive curative surgeries. Longitudinal ctDNA surveillance could reliably predict recurrence, opening a window of ~145 days for timely and optimal disease management”, says Dr. Hua Bao, author and director of Geneseeq Research Institute.