scholarly journals Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma

Theranostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 257-267
Author(s):  
Tao Jiang ◽  
Liyan Jiang ◽  
Xiaorong Dong ◽  
Kangsheng Gu ◽  
Yueyin Pan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Dna Profiling ◽  
First Line ◽  
Cell Free Dna ◽  
Free Dna ◽  
Line Chemotherapy ◽  
Circulating Cell Free Dna

scholarly journals Detection of somatic mutations in circulating cell-free DNA from patients with esophageal squamous cell carcinoma

2020 ◽  
Author(s):  
Zuyang Yuan ◽  
Xinfeng Wang ◽  
Xiao Geng ◽  
Yin Li ◽  
Juwei Mu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Solid Tumor ◽  
Somatic Mutations ◽  
White Blood Cells ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna

Abstract Background: The aim of this study was to assess whether both ubiquitous and heterogeneous somatic mutations could be detected in circulating cell-free DNA (cfDNA) from patients with esophageal squamous cell carcinoma (ESCC). Methods: Paired multi-regional tumor tissues, cfDNA and white blood cells (WBCs) collected from five ESCC patients before treatment from a prospective study (NCT02395705). Of them, samples from Cohort 1 (E102 and E110) were sequenced by whole-exome sequencing (WES) and those from Cohort 2 (E104, E111 and E121) were sequenced by targeted captured sequencing with a panel of 560 cancer-related genes respectively. To call somatic single nucleotide variations (SNVs) by comparing the solid tumor or cfDNA with matched WBCs, the minimal variant allele frequency (VAFmin) as 0.1% and P value <0.05 were allowed. Results: Genomic DNA (gDNA) and plasma-derived cfDNA from 26 samples were successfully sequenced. In Cohort 1, 596 (596/712, 83%) and 562 (562/796, 71%) were heterogeneous SNVs in E102 and E110 respectively. There was a statistically significant linear relationship between the VAFs for tumor and cfDNA (R2 = 0.78, P <0.0001). In Cohort 2, 296 (296/323, 92%), 384 (384/423, 91%) and 331 (331/357, 93%) were heterogeneous SNVs in E104, E111 and E121respectively. cfDNA could recover an average of 60.7% (31/51; range, 35.7%-76.2%) of somatic mutations present in matched solid tumors. The correlation of VAFs between cfDNA and matched solid tumor was significantly positive (r2 =0.92, P <0.0001).Conclusions: Both sequencing approaches revealed the highly intratumoral heterogeneity in ESCC and enabled the detection of both ubiquitous and heterogeneous mutations in cfDNA. Further validation in cfDNA is required to define its potential utility for ESCC in clinical practice. Trial registrationAll patients selected in this study were from the registered clinical trial from ClinicalTrials.gov (NCT02395705). Date of registration: March 24, 2015.

Comparative effectiveness of regimens of first-line platinum-based chemotherapy for advanced lung squamous cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18034-e18034
Author(s):  
Kuo-Hsing Chen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Multivariate Analyses ◽  
Lung Squamous Cell Carcinoma ◽  
Platinum Compound ◽  
First Line ◽  
Hazard Ratios ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

e18034 Background: Platinum-based cytotoxic chemotherapy remains the standard first-line therapy for patients with lung squamous cell carcinoma. This study aims to compare the effectiveness of first-line platinum-based chemotherapy regimens for advanced lung squamous cell carcinoma in the general population in Taiwan. Methods: We searched the Taiwan Cancer Registry database and the claim database of National Health Insurance, Taiwan for patients with newly diagnosed advanced lung squamous cell carcinoma from 2004 to 2007. Patients who received first-line combination chemotherapy with a platinum compound (cisplatin or carboplatin) plus either gemcitabine (G), docetaxel (D), paclitaxel (T), or vinorelbine (V) were included in the study. Overall survival (OS) was defined as the duration from the start of chemotherapy to death. Kaplan-Meier method was used to estimate the survival, which was univariately compared by the log-rank test. The Cox’s proportional hazard model was used to estimate the adjusted hazard ratios in multivariate analyses. Results: A total of 935 patients with advanced lung squamous cell carcinoma received first-line chemotherapy with a platinum compound (P) plus either G (57.6%), D (14.9%), T (11.3%), or V (16.0%). The proportion of elderly patients (age ≥ 70) who received P+D is lower than that of P+G, P+T, or P+V (35.71% vs 47.68%, 53.77%, 48.00% respectively, p = 0.0264). Patients who received P+G, P+D, P+T, or P+V had similar OS (median, 8.6 vs. 7.9 vs. 8.8 vs. 8.1 months, respectively; p = 0.969). Subgroup analyses based on age (≥ 70 or < 70), gender, stage (IIIB or IV by AJCC 6th edition), and the use of cisplatin revealed no differences in OS, either. In multivariate analyses adjusting for age, gender, and stage, the first-line chemotherapy regimen was still not a predictor of OS. With P+G as the reference group, the adjusted hazard ratios of P+D, P+T, and P+V were 1.02, 0.96, 1.03, respectively (p = 0.945). Conclusions: In patients with advanced lung squamous cell carcinoma, different treatment regimens did not have significant impact on the survival outcomes

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