Liquid Biopsy May Be a Noninvasive Measure for Treatment Response in NSCLC

Liquid Biopsy
Liquid Biopsy
Patients with PD-L1-positive malignancies have shown higher response rates to immune checkpoint inhibition and consequently prolonged progression-free/overall survival compared with others.

PD-L1 status in circulating tumor cells (CTCs) and white blood cells (WBCs) correlates with PD-L1 status in non–small cell lung cancer (NSCLC) tissues, according to recently published research.1

Among 71 evaluable samples with matched tissue and CTCs, researchers detected 1 or more PD-L1 positive CTCs in 8% of patients, and 1%+ PD-L1-positive cells in the tumor tissue of 15% of patients. There was a 93% concordance between tissue and CTCs, with a sensitivity of 55% and a specificity of 100%.

“We showed that PD-L1 status in the ISET-captured ‘liquid microenvironment’ correlates with PD-L1 status in tumor tissue from advanced-stage NSCLC patients,” said lead author Marius Ilié, MD, PhD, and senior author Paul Hofman, PhD, in a joint statement to Cancer Therapy Advisor. “Our study demonstrates the potential use of ISET-enriched CTCs and circulating WBCs as a sensitive and specific diagnostic testing of PD-L1 for immunotherapy stratification or monitoring of treatment response in patients with advanced NSCLC.”

Blood cells are filtered, but the CTCs, which are larger, are retained at the filter surface, leading to cell identification using classical morphological assessment of malignant cells. Researchers can stain enriched CTCs on the filter for cytomorphological examination and then characterize them by immunocytochemistry or fluorescent in situ hybridization (FISH).

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“It was important for us to evaluate if CTCs, as a liquid biopsy, represent an accessible, non-invasive sample that might allow an overall snapshot of PD-L1 status in NSCLC patients, in particular in vulnerable NSCLC patients for whom tissue biopsies are inaccessible or extremely difficult to perform and to repeat longitudinally,” said Drs Ilié and Hofman.

Drs Ilié and Hofman also noted that liquid biopsy can be useful in cases where small bronchial biopsies contain a low number of tumor cells, and the repeatability of liquid biopsies can offer new approaches for monitoring patients treated with immunotherapy.

The authors indicated that a larger cohort would assess whether patients with negative a PD-L1 biopsy tissue may have PD-L1-positive CTCs — possibly making them eligible for immune checkpoint inhibition.

“PD-L1 expression on tumor cells and/or tumor-infiltrating immune cells from pre-treatment tumor samples has been correlated with increased efficacy of PD-1/PD-L1 inhibitors in patients with previously treated and untreated advanced NSCLC,” said Drs Ilié and Hofman. “The expression of PD-L1 in clinical studies has, however, mostly been assessed on archived or fresh biopsy specimens that may not reflect the PD-L1 status of the whole primary tumor.”

Numerous studies show that patients with PD-L1-positive malignancies have higher response rates to immune checkpoint inhibition and consequently prolonged progression-free/overall survival compared with others.2-4

Dr Ilié is an assistant professor of pathology at Nice Sophia Antipolis University in Nice, France. Dr Hofman is a professor of pathology, head of the Laboratory of Clinical and Experimental Pathology, and director of the “FHU” OncoAge at Nice Sophia Antipolis University.


  1. Ilié M, Szafer-Glusman E, Hofman V, et al. Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small cell lung cancer [published online October 9, 2017]. Ann Oncol. doi:10.1093/annonc/mdx636
  2. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non–small cell lung cancer. N Engl J Med. 2015; 372:2018-2028.
  3. Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837-1846.
  4. Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016;17(11):1590-1598.

This article originally appeared on Cancer Therapy Advisor