Highlights of these studies include:

• A mini oral presentation on discussing the chronic psychological stress in advanced non-small cell lung cancer (NSCLC) treated with first-line immunotherapy
• Data on Geneseeq’s cfDNA fragmentomics model to predict the risk of colorectal cancer
• Two clinical trial studies evaluate the efficacy and safety of new drug combinations in NSCLC and thymic carcinoma

List of abstracts that will be presented at the ESMO 2023 meeting:

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This study enrolled 87 NSCLC patients who underwent curative surgical resections (23 patients experienced relapses during follow-up). A total of 163 plasma samples were collected at 7 days and 6 months post-surgery and were used for both whole-genome sequencing (WGS). The WGS-based cell-free DNA (cfDNA) fragment profile was used to develop regularized Cox regression models, and the models’ performance was evaluated using leave-one-out cross-validation.

The ultra-sensitive and affordable fragmentomic assay has shown promising results in detecting patients who are at high risk of recurrence. The fragmentomic model was able to detect high-risk patients at 7 days and 6 months post-surgery with an increased risk of 4.6 times and 8.3 times, outperforming the targeted sequencing-based circulating mutations. The overall sensitivity for detecting patients with recurrence reached 78.3% while using both fragmentomics and circulating mutation results from 7 days and 6 months postsurgical, which increased from the 43.5% sensitivity by using only the circulating mutations.

“The non-invasive liquid biopsy assay can effectively detect landmark MRD, which could aid in making informed decisions for post-surgery treatment.”, says Dr. Hua Bao, author and director of Geneseeq Research Institute.

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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.

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