The Role of Circulating Tumor Cells as Potential Predictive and Prognostic Factors in Cervical Cancers

Abstract

<h3>Purpose/Objective(s)</h3> Circulating tumor cells (CTCs) are emerging biomarkers that may serve as both predictive and prognostic factors to improve the evaluation of cancer patients at risk of recurrence and metastatic spread. While the role of CTCs in gynecologic cancers remains incompletely understood, we know that CTCs have been demonstrated as a prognostic marker in other cancer types, with baseline CTC count appearing to be a strong predictor of outcomes. The aim of this study is to evaluate the potential role of CTCs as a non-invasive method to quantify a patient's risk of both recurrence and death following definitive chemoradiation for locally advanced gynecologic cancers. <h3>Materials/Methods</h3> 23 patients with non-metastatic cervical cancer (CC) receiving definitive radiation +/- chemotherapy were enrolled on a prospective single-arm clinical trial at our institution from 2018-2021. On trial, 4 - 5 blood samples were collected at baseline prior to receiving treatment, mid-treatment, end of treatment, and at 1- and 3-month follow-up. Samples were analyzed utilizing a novel liquid biopsy imaging system, the Axon Dx nCyte® System that allows for detection of CTCs and Hybrid Cells (HC) at very low concentrations with high specificity. HCs are defined as those similar in appearance to CTCs but with white cell expression, suggesting immune response at the site of the CTCs. Patient demographics and clinical outcomes including recurrence patterns were also recorded. <h3>Results</h3> Of the 23 CC patients, 17 (73.9%) had squamous cell carcinoma, 5 (21.7%) adenocarcinoma, and 1 (4.3%) small cell carcinoma. There were 2 (8.7%) patients with stage I disease, 9 (39.1%) stage II, 11 (47.8%) stage III, and 1 (4.3%) stage IV. CTCs were positive (+) in 12 (52.1%) patients, of which 6 (50%) had a recurrence, 5 (41.6%) of whom are deceased secondary to CC. The remaining 6 patients are alive without recurrence at this date, with only 1 having at least 12 months of follow up. HCs were present in 21 (91.3%) of the CC patients, including 11/12 of the CTC+ cases (CTC+HC+); however, they were also identified in another 9 patients as CTC-HC+. Of these CTC-HC+ patients, 4 (44%) have had a recurrence, 2 (22%) of whom are deceased secondary to CC. The remaining 5 are alive without recurrence at this date, with only one having less than 12 months of follow up. There have been no recurrences in the CTC-HC- subset of patients. <h3>Conclusion</h3> We have demonstrated that it is feasible to detect CTCs and HCs in a prospective cohort of patients with locally advanced CC utilizing Axon Dx's nCyte® System. In this single institution experience, the presence of CTCs/HCs correlates with worsened survival amongst women with locally advanced CC, perhaps indicating a prognostic biomarker of potential significant value in this patient population. Longer follow up and additional studies are indicated to further explore the significance of CTC/HC values, trends, and timing on patients' outcomes.