Circulating Tumor DNA as a Biomarker of Radiographic Tumor Burden in SCLC
| Autor: | Dhairya A. Lakhani, Wade T. Iams, Karinna Almodovar, Christien Kluwe, Aneri B. Balar, Evan C. Osmundson, Leora Horn, S. Antic, Prasad R. Kopparapu, Anel Muterspaugh, Jarrod T. Smith, Zhiguo Zhao, Seyed Ali Hosseini, Lauren Hodsdon, Lee Lim, Christine M. Lovly, Caterina Bertucci, Pierre P. Massion, Kavita Garg, Yingjun Yan, Sally York, Tristan Shaffer |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology Univariate analysis medicine.medical_specialty medicine.diagnostic_test business.industry Radiography Brief Report Tumor burden Small cell lung cancer (SCLC) lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 respiratory tract diseases Total-body tumor volume (TV) Circulating tumor DNA Positron emission tomography Internal medicine Cohort medicine Biomarker (medicine) business Circulating tumor DNA (ctDNA) Variant allele frequency (VAF) Blood drawing |
| Zdroj: | JTO Clinical and Research Reports JTO Clinical and Research Reports, Vol 2, Iss 3, Pp 100110-(2021) |
| ISSN: | 2666-3643 |
| Popis: | Introduction: Blood-based next-generation sequencing assays of circulating tumor DNA (ctDNA) have the ability to detect tumor-associated mutations in patients with SCLC. We sought to characterize the relationship between ctDNA mean variant allele frequency (VAF) and radiographic total-body tumor volume (TV) in patients with SCLC. Methods: We identified matched blood draws and computed tomography (CT) or positron emission tomography (PET) scans within a prospective SCLC blood banking cohort. We sequenced plasma using our previously developed 14-gene SCLC-specific ctDNA assay. Three-dimensional TV was determined from PET and CT scans using MIM software and reviewed by radiation oncologists. Univariate association and multivariate regression analyses were performed to evaluate the association between mean VAF and total-body TV. Results: We analyzed 75 matched blood draws and CT or PET scans from 25 unique patients with SCLC. Univariate analysis revealed a positive association between mean VAF and total-body TV (Spearman’s ρ = 0.292, p < 0.01), and when considering only treatment-naive and pretreatment patients (n = 11), there was an increase in the magnitude of association (ρ = 0.618, p = 0.048). The relationship remained significant when adjusting for treatment status and bone metastases (p = 0.046). In the subgroup of patients with TP53 variants, univariate analysis revealed a significant association (ρ = 0.762, p = 0.037) only when considering treatment-naive and pretreatment patients (n = 8). Conclusions: We observed a positive association between mean VAF and total-body TV in patients with SCLC, suggesting mean VAF may represent a dynamic biomarker of tumor burden that could be followed to monitor disease status. |
| Databáze: | OpenAIRE |
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