Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy
Emma Purcell,
Zeqi Niu,
Sarah Owen,
Madeline Grzesik,
Abigail Radomski,
Anna Kaehr,
Nna-Emeka Onukwugha,
Heather Fairbairn Winkler,
Nithya Ramnath,
Theodore Lawrence,
Shruti Jolly,
Sunitha Nagrath
Affiliations
Emma Purcell
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Zeqi Niu
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Sarah Owen
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Madeline Grzesik
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Abigail Radomski
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Anna Kaehr
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Nna-Emeka Onukwugha
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Heather Fairbairn Winkler
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Nithya Ramnath
Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA
Theodore Lawrence
Michigan Medicine, Department of Radiation Oncology, Ann Arbor, MI 48105, USA; Rogel Cancer Center, Ann Arbor, MI 48105, USA
Shruti Jolly
Michigan Medicine, Department of Radiation Oncology, Ann Arbor, MI 48105, USA; Rogel Cancer Center, Ann Arbor, MI 48105, USA; Corresponding author
Sunitha Nagrath
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, Ann Arbor, MI 48105, USA; Corresponding author
Summary: Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lung cancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.
