Circulating Tumor DNA as a Biomarker of Radiographic Tumor Burden in SCLC

Jarrod T. Smith, Aneri Balar, Dhairya A. Lakhani, Christien Kluwe, Zhiguo Zhao, Prasad Kopparapu, Karinna Almodovar, Anel Muterspaugh, Yingjun Yan, Sally York, Leora Horn, Sanja Antic, Caterina Bertucci, Tristan Shaffer, Lauren Hodsdon, Kavita Garg, Seyed Ali Hosseini, Lee Lim, Evan Osmundson, Pierre P. MassionChristine M. Lovly, Wade Iams

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number100110
JournalJTO Clinical and Research Reports
Volume2
Issue number3
DOIs
StatePublished - Mar 2021
Externally publishedYes

Keywords

  • Circulating tumor DNA (ctDNA)
  • Small cell lung cancer (SCLC)
  • Total-body tumor volume (TV)
  • Variant allele frequency (VAF)

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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