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.

The post Geneseeq published new research on the clinical use of circulating-free DNA fragmentomic in monitoring minimal residual disease for patients with non-small-cell lung cancer appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.

The ADJUVANT-CTONG1104 trial, the first phase III exploratory biomarker study on the adjuvant therapy in EGFR-mutated lung cancer population, examined the survival benefit of adjuvant gefitinib against adjuvant chemotherapy (vinorelbine and cisplatin, VP) in patients with stage II-IIIA EGFR-mutant NSCLC. The exploratory cohort enrolled 171 resected NSCLC patients with EGFR 19 deletion or EGFR L858R, including 95 adjuvant gefitinib-treated patients and 76 adjuvant VP-treated patients. The adjuvant gefitinib-treated group showed a superior disease-free survival compared with the VP group (31.7months vs 19.6months)¹. Genome profiling of tumor tissues allowed researchers to identify five predictive biomarkers for adjuvant treatment, including TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC. Given the high tumor heterogeneity of lung cancer, these predictive biomarkers were further integrated as the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, a predictive score based on Z scores of each biomarker, and combination of variables method. The MINERVA score categorized patients into three subgroups with distinct survival outcomes including highly TKI-Preferable group(HTP, significant superiority with adjuvant gefitinib), TKI-Preferable group(TP), and Chemo-Preferable Group(CP). The MINERVA multi-gene score was internally validated using ten-fold cross-validation and leave-one-out cross-validation procedures, and then externally validated in an independent cohort from the EMERGING-CTONG1103 trial.

“Comprehensive evaluation of the patient’s baseline molecular profile is crucial for optimal personalized treatment strategy for cancers at all stages,” said Dr. Hua Bao, author and R&D Director of Geneseeq. In recent years, clinical trials such as ADAURA and EVAN have highlighted the importance of targeted therapy as adjuvant treatment for early NSCLC, therefore early and mid-stage tumor perioperative management is no longer limited to radical treatment. Next-generation sequencing has been employed to reveal the characteristics of baseline genomic landscape and postoperative minimal/molecular residual disease to predict the risk of recurrence and metastasis of patients.

Reference

1. Zhong, W.-Z. et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II–IIIA (N1–N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. The Lancet Oncology 19, 139–148 (2018).

The post Geneseeq collaborates on research identifying predictive biomarkers for guiding personalized adjuvant treatment in resected EGFR-positive non-small cell lung cancer appeared first on Geneseeq Technology Inc. | A Precision Oncology Company.