Circulating tumor DNA as markers of dynamic recurrence risk and adjuvant chemotherapy benefit in resected non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3028-3028
Author(s):  
Wei Guo ◽  
Fan Zhang ◽  
Fang Lv ◽  
Ying Ji ◽  
Yue Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Joint Modeling ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Nsclc Patients ◽  
Tumor Dna

3028 Background: A significant proportion of non-small cell lung cancer (NSCLC) patients relapse after surgical resection with or without adjuvant therapy. The detection of molecular residual disease (MRD) has great potentials to stratify postoperative risk and facilitate early recurrence diagnosis. Here, we aim to evaluate the clinical utility of serial plasma circulating tumor DNA (ctDNA) in MRD detection, adjuvant therapy guidance, and recurrence risk prediction in resected NSCLC patients. Methods: This prospective cohort study recruited 116 patients with NSCLC following surgery and/or adjuvant therapy. Thirteen patients discontinued, leaving 103 patients for analysis. Tumor samples were obtained at surgery. Plasma samples were collected at baseline, after surgery, after adjuvant therapy and every 3 months thereafter and were analyzed by ultradeep (30000×) next-generation sequencing with molecular barcode and in-silico error correction. Results: Pretreatment ctDNA was detected in 69.8% of patients. ctDNA positivity after surgery and after completion of adjuvant chemotherapy (ACT) were significantly associated with worse recurrence-free survival (RFS) (HR: 4.0; 95% CI: 2.0-8.0; P<.001 and HR:3.2; 95% CI: 1.3-8.2; P <.05, respectively). In stage II-III patients who were positive for ctDNA after surgery, ACT-treated patients had a better RFS than those without ACT ( P<.05), whereas ACT did not confer significant clinical benefits in patients with negative postsurgical ctDNA. During surveillance after definitive therapy, ctDNA positivity was associated with worse RFS (HR: 8.5, 95% CI: 3.7-20, P <.001) and preceded radiological recurrence by a median of 88 days. Using joint modeling of serial ctDNA and time-to-recurrence, we accurately predicted patients’ 12-month and 15-month recurrence status, with areas under receiver-operating characteristics curves (AUROC) of 0.88 and 0.84, respectively. Conclusions: These results indicate that ultradeep ctDNA sequencing could sensitively detect MRD, thus identifying patients with high recurrence risk and guiding the adjuvant therapy decision in resected NSCLC. We also demonstrate that joint modeling of serial ctDNA levels and time to recurrent can provide an accurate dynamic risk prediction for NSCLC patients during surveillance. Clinical trial information: ChiCTR1900024656.

Fusion detection and longitudinal circulating tumor DNA (ctDNA) profiling in ALK+ non-small cell lung cancer (NSCLC) patients.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21031-e21031 ◽  
Author(s):  
Aurélie Swalduz ◽  
Sandra Ortiz-Cuaran ◽  
Virginie Avrillon ◽  
Solène Marteau ◽  
Séverine Martinez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Fusion Detection

NGS to reveal heterogeneity between cerebrospinal fluid and plasma ctDNA among non-small cell lung cancer patients with leptomeningeal carcinomatosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9022-9022 ◽  
Author(s):  
Ben-Yuan Jiang ◽  
Yangsi LI ◽  
Shaokun Chuai ◽  
Zhou Zhang ◽  
Jin-Ji Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Leptomeningeal Carcinomatosis ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

9022 Background: In current clinical setting, NSCLC patients harboring specific driver mutation were usually treated guiding by prior profiling of the primary tumor when developed to brain metastasis. Some studies have shown that circulating tumor DNA (ctDNA) derived from cerebrospinal fluid (CSF) can reveal unique genomic alterations present in brain malignancies. We assessed CSF as a liquid biopsy media and compared to matched plasma. Methods: We performed capture-based ultra deep sequencing on ctDNA derived from matched CSF, plasma of 40 non-small cell lung cancer (NSCLC) patients with suspected leptomeningeal carcinomatosis (LC) using a panel consisting of 168 genes. Results: Among the 40 suspected LC cases, 35 were confirmed to have LC, ctDNA in CSF from the 5 non-LC cases are all undetectable. Circulating tumor DNA was detected in 93.8% of CSF and 66.7% of plasma. We compared mutation profiles and identified 86 and 46 SNVs from CSF and plasma, respectively, with 42 SNVs overlapping. Furthermore, ctDNA from CSF revealed many copy number variations (CNVs) that were not detected from plasma (189 CNVs vs. 3 CNVs). The average maximum allelic fraction (AF) of CSF ctDNA is significantly higher than in plasma (56.7% vs. 4.4% p < 10^-6). Twenty-eight patients were pre-treated with EGFR-TKIs and developed subsequent resistance. EGFR T790M and MET amplification were detected in 21% and 39% in CSF, respectively, showing a unique resistance profile among leptomeningeal metastases patients compared to the general population. Interestingly, 60% of CSF samples harbor TP53 loss of heterozygosity, only 11% of which were detected in the matched plasma samples. Such heterogeneity may reflect unique biological themes for brain metastatic tumor sub-clones. Furthermore, 26 patients received molecular targeted therapy based on the results from CSF, and 23 reported alleviation of symptoms at subsequent evaluations. Conclusions: Collectively, our data reveal that ctDNA derived from CSF provides a unique and more comprehensive characterization of genomic alterations of leptomeningeal carcinomatosis than plasma, supporting the importance of CSF as a liquid biopsy media.

scholarly journals The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Haowei Wang ◽  
Fei Zhou ◽  
Meng Qiao ◽  
Xuefei Li ◽  
Chao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

BackgroundThe use of circulating tumor DNA (ctDNA) to reflect clinical benefits of advanced non-small cell lung cancer (NSCLC) patients during immune checkpoint inhibitor (ICI) therapy remains controversial. This study aimed to determine the association of pre-treatment and early dynamic changes of ctDNA with clinical outcomes in advanced NSCLC patients treated with ICIs.MethodsElectronic databases (PubMed, Embase, Web of Science, and Cochrane) were systematically searched to include relevant studies published in English up to November 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS) and the secondary outcome was objective response rate (ORR) with RECIST criteria.ResultsA total of 1017 patients from 10 studies were identified. The baseline ctDNA levels (detected versus not detected) showed no significant association with clinical outcomes regarding OS (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.93-1.51), PFS (HR, 0.98; 95% CI, 0.80-1.21), and ORR (odds ratio [OR], 0.89; 95% CI, 0.54-1.46). Interestingly, when taken early longitudinal assessment of ctDNA into consideration, the early reduction of the concentration of ctDNA was associated with significant improvements of OS (HR, 0.19; 95% CI, 0.10-0.35), PFS (HR, 0.30; 95% CI, 0.22-0.41) and ORR (OR, 0.07; 95% CI, 0.03-0.18). Further subgroup analyses revealed that the reduction magnitude did not significantly impact the association between ctDNA and clinical outcomes, suggesting that both patients with decreased ctDNA or a ≥50% reduction of ctDNA was associated with improved OS, PFS and ORR.ConclusionEarly reduction of ctDNA was associated with improved OS, PFS and ORR in advanced NSCLC patients treated with ICIs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, CRD42021226255.

Genomic profiling of circulating tumor DNA in small cell lung cancer: comparison of relapsed disease to initial tumor biopsies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20017-e20017
Author(s):  
Priyanka Bhateja ◽  
Gary Wildey ◽  
Mary Beth Lipka ◽  
Neelesh Sharma ◽  
Afshin Dowlati
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pre Treatment ◽  
Nsclc Patients ◽  
Tumor Dna

e20017 Background: Genomic studies in small cell lung cancer (SCLC) are hampered by the small amounts of biopsy tissue typically available. The emergence of ‘liquid biopsy’ to identify tumor DNA mutations in plasma (circulating tumor DNA or ctDNA) has the potential to overcome this restriction and also facilitates multiple sampling during disease treatment. Here we use ctDNA to compare mutation profiles in SCLC and non-small cell lung cancer (NSCLC)patients and to identify changes that occur post-relapse in SCLC. Methods: Targeted exome sequencing of 73 genes in plasma from 13 SCLC and 17 NSCLC patients was obtained along with matched patient targeted exome sequencingof 315 genes for 6 SCLC and 8 NSCLC tumor biopsies. Only the 70 genes analyzed by both assays were studied. Results: 3 SCLC and 8 NSCLC ctDNA specimens were collected pre-treatment, with the remainder post-relapse. In SCLC, 46 total gene mutations were detected in ctDNA with a mean allelic fraction (mAF) of 16.0%. TP53 (mAF 30.8%, N= 15) and ARID1A (mAF 16.0%, N= 6) were the most frequently mutated SCLC genes. In NSCLC, 53 gene mutations were detected with a mAF of 2.5%. TP53 (mAF 5.9%, N= 13), EGFR (mAF 2.3%, N= 10) and KRAS (mAF 4.4%, N= 5) were frequently mutated NSCLC genes. 44 and 10 gene amplifications were detected in SCLC and NSCLC ctDNA, respectively. 5 SCLC patients with tumor DNA profiles obtained pre-treatment had matching ctDNA profiles obtained post-relapse. TP53 mutation status agreed in 4 of the matched specimens. 6 new gene mutations occurred post-relapse in ctDNA, notably a TSC1 mutation (AF 8.4%) in one patient. 7 tumor gene mutations were lost post-relapse, notably ARID1A and NTRK1 mutations were lost in two patients each. Remarkably, 23 new gene amplifications were detected post-relapse in ctDNA, including PIK3CA ( N= 5) and CCNE1 ( N= 5), whereas only 1 was detected in pre-treatment tumors. Conclusions: SCLC exhibits much greater ctDNA mAF values than NSCLC, although their overall mutation profiles agree with published tumor DNA mutation profiles. Interestingly, the predominant change observed in SCLC ctDNA profiles in relapsed specimens is increased gene amplification.

Comprehensive analysis of genomic alterations detected by next-generation sequencing-based tissue and circulating tumor DNA assays in Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20534-e20534
Author(s):  
Hua Yang ◽  
Junjie Zhang ◽  
Lemeng Zhang ◽  
Xiaoping Wen ◽  
Yongzhong Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Chinese Patients ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Generation Sequencing

e20534 Background: While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. The aim of the study was to evaluate whether the frequency of multiple genomic alterations observed following ctDNA sequencing was similar to that observed following tissue sequencing in NSCLC. Methods: A total of 99 NSCLC patients were enrolled in this study, including 40 tissue and 59 plasma samples. All kinds of variants of oncogenic drivers in NSCLC were identified by next-generation sequencing (NGS) with Acornmed panel. Results: The frequencies of genetic alterations detected in ctDNA were significantly correlated to those detected via tissue profiling (Spearman’s r = 0.812, P = 0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor ( EGFR) and tumor protein 53 ( TP53; P = 0.020) and between those in EGFR and Kirsten rat sarcoma viral oncogene homolog ( KRAS; P = 0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 ( ERBB2; P = 0.059). Furthermore, the EGFR mutant allele frequency (MAF) was strongly correlated with the TP53 MAF in individual tumors (Spearman’s r = 0.773, P = 0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P = 0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher than those in patients without ctDNA-detectable mutations. Conclusions: This study provides a better understanding of the spectra of genomic alterations detected by tissue and plasma ctDNA assays in Chinese patients with NSCLC. The present data also highlights the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of NSCLC patients.

scholarly journals Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jialiang Yang ◽  
Yan Hui ◽  
Yanxiang Zhang ◽  
Minghui Zhang ◽  
Binbin Ji ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Clinical Applications ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

BackgroundNon-small cell lung cancer (NSCLC) is one of the most prevalent causes of cancer-related death worldwide. Recently, there are many important medical advancements on NSCLC, such as therapies based on tyrosine kinase inhibitors and immune checkpoint inhibitors. Most of these therapies require tumor molecular testing for selecting patients who would benefit most from them. As invasive biopsy is highly risky, NSCLC molecular testing based on liquid biopsy has received more and more attention recently.ObjectiveWe aimed to introduce liquid biopsy and its potential clinical applications in NSCLC patients, including cancer diagnosis, treatment plan prioritization, minimal residual disease detection, and dynamic monitoring on the response to cancer treatment.MethodWe reviewed recent studies on circulating tumor DNA (ctDNA) testing, which is a minimally invasive approach to identify the presence of tumor-related mutations. In addition, we evaluated potential clinical applications of ctDNA as blood biomarkers for advanced NSCLC patients.ResultsMost studies have indicated that ctDNA testing is critical in diagnosing NSCLC, predicting clinical outcomes, monitoring response to targeted therapies and immunotherapies, and detecting cancer recurrence. Moreover, the changes of ctDNA levels are associated with tumor mutation burden and cancer progression.ConclusionThe ctDNA testing is promising in guiding the therapies on NSCLC patients.

scholarly journals Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongliang Zhang ◽  
Yu Yao ◽  
Yaping Xu ◽  
Lifeng Li ◽  
Yan Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Chinese Patients ◽  
Plasma Samples ◽  
Small Cell Lung ◽  
Pan Cancer ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) provides a noninvasive approach to elucidate a patient’s genomic landscape and actionable information. Here, we design a ctDNA-based study of over 10,000 pan-cancer Chinese patients. Using parallel sequencing between plasma and white blood cells, 14% of plasma cell-free DNA samples contain clonal hematopoiesis (CH) variants, for which detectability increases with age. After eliminating CH variants, ctDNA is detected in 73.5% of plasma samples, with small cell lung cancer (91.1%) and prostate cancer (87.9%) showing the highest detectability. The landscape of putative driver genes revealed by ctDNA profiling is similar to that in a tissue-based database (R2 = 0.87, p < 0.001) but also shows some discrepancies, such as higher EGFR (44.8% versus 25.2%) and lower KRAS (6.8% versus 27.2%) frequencies in non-small cell lung cancer, and a higher TP53 frequency in hepatocellular carcinoma (53.1% versus 28.6%). Up to 41.2% of plasma samples harbor drug-sensitive alterations. These findings may be helpful for identifying therapeutic targets and combined treatment strategies.

Sign in / Sign up

Export Citation Format

Share Document