Circulating tumor cells in advanced cervical cancer: NRG oncology—gynecologic oncology group study 240 (NCT 00803062)

Krishnansu S. Tewari, Michael W. Sill, Bradley J. Monk, Richard T. Penson, David H. Moore, Heather A. Lankes, Lois M. Ramondetta, Lisa M. Landrum, Leslie M. Randall, Ana Oaknin, Mario M. Leitao, Eric L. Eisenhauer, Paul DiSilvestro, Linda van Le, Michael L. Pearl, James J. Burke, Ritu Salani, Debra L. Richardson, Helen E. Michael, David W. KindelbergerMichael J. Birrer

Research output: Contribution to journalArticlepeer-review

Abstract

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratinþ/anti-CD45- cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0–18) and, at 36 days posttreatment, was 4 (range, 0–17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79–0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32–1.03) and PFS (HR, 0.59; 95% CI, 0.36–0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.

Original languageEnglish (US)
Pages (from-to)2363-2370
Number of pages8
JournalMolecular Cancer Therapeutics
Volume19
Issue number11
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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