An analysis of 58 peripheral blood specimens from patients with rectal and esophageal cancers demonstrated that circulating hybrid cells may be a novel, noninvasive biomarker with potential for monitoring treatment response and disease progression to help guide decisions for further therapy, definitive resection, or safe observation. The research was presented by Walker et al at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care (Poster 21).
Real-time monitoring of treatment response with a liquid biomarker may help to inform treatment decisions in patients undergoing neoadjuvant therapies for rectal and esophageal cancers, as well as in patients with metastatic colorectal cancer receiving hepatic arterial infusion therapy.
More About Circulating Hybrid Cells
Circulating hybrid cells are immune-tumor cell fusion hybrids detectable in the peripheral blood of patients with gastrointestinal cancers by their coexpression of the leukocyte marker CD45 and the epithelial protein cytokeratin (CK). The team previously demonstrated that in pancreatic adenocarcinoma, circulating hybrid cells (CD45-positive/CK-positive) are found at higher numbers and better correlate with overall survival than traditional circulating tumor cells (CTCs, CD45-negative/CK-positive). The researchers extended analyses to determine if hybrid cells could be a potential as an indicator of treatment response, which had not been previously explored.
Methodology
The team collected peripheral blood specimens from patients with rectal and esophageal cancers prior to resection or longitudinally during neoadjuvant treatment and hepatic arterial infusion therapy.
For circulating hybrid cells enumeration, peripheral blood mononuclear cells were isolated then immunostained for expression of CD45 and cytokeratin. Treatment response was determined per American Joint Committee on Cancer tumor regression grading.
Fifty-eight samples collected from patients with rectal cancer (n = 23) and esophageal cancer (n = 35) prior to resection and two patients receiving hepatic arterial infusion were evaluated. In the neoadjuvant therapy group, 13 (23%) patients had a pathologic complete response, while 37 (66%) had non–pathologic complete response, and 6 (11%) demonstrated no response.
On receiver operating characteristics analysis, circulating hybrid cells levels successfully discriminated pathologic complete response from non–pathologic complete response in both rectal and esophageal cancers with an area under the curve of 0.82 (95% confidence interval [CI] = 0.71–0.92, P < .001). In patients followed longitudinally during neoadjuvant therapy (n = 2) and hepatic arterial infusion therapy (n = 2), circulating hybrid cell levels decreased by > 90% with initiation of therapy, but increased with dose reductions and prior to clinical evidence of disease progression.
Circulating hybrid cells are a newly discovered biomarker with potential for noninvasively monitoring treatment response and disease progression in patients with gastrointestinal malignancies. Additionally, the level of circulating hybrid cells is predictive of pathologic complete response to neoadjuvant therapy, which could help guide treatment decisions in organ-sparing strategies.
