Yujie Dong1, Zhen Zhou2, Jianguo Wang3, Li Ma4, Zichen Liu1, Yuxuan Wang1, Jing Song1, Shucai Zhang5, Nanying Che6. 1. Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. 2. Department of Radiology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. 3. School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China; Department of Medical Engineering, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China. 4. Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. 5. Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. Electronic address: sczhang6304@163.com. 6. Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China; Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China. Electronic address: cheny0448@163.com.
Abstract
OBJECTIVE: Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis. PATIENTS AND METHODS: Matched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay. RESULTS: Of the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P = 0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P < 0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p = 0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p = 0.031, HR 0.310, 95% CI: 0.107-0.900). CONCLUSION: The ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment.
OBJECTIVE: Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis. PATIENTS AND METHODS: Matched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay. RESULTS: Of the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P = 0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P < 0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p = 0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p = 0.031, HR 0.310, 95% CI: 0.107-0.900). CONCLUSION: The ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment.
Authors: Weiting Li; Klaas Kok; Geok Wee Tan; Pei Meng; Mirjam Mastik; Naomi Rifaela; Frank Scherpen; T Jeroen N Hiltermann; Harry J M Groen; Anthonie J van der Wekken; Anke van den Berg Journal: Cancers (Basel) Date: 2022-07-19 Impact factor: 6.575