Circulating Tumor Cells Dynamics in Pancreatic Adenocarcinoma Correlate with Disease Status: Data from a Prospective Trial
Georgios Gemenetzis*, Vincent P. Groot*, Jun Yu*, Ding Ding*, Jonathan A. Teinor*, Ammar A. Javed*, Laura D. Wood*, Richard A. Burkhart*, John L. Cameron, Martin A. Makary*, Matthew J. Weiss*, Jin He*, Christopher L. Wolfgang
Johns Hopkins University School of Medicine, Baltimore, MD
Objectives: Previous retrospective studies demonstrate that circulating tumor cell (CTCs) subtypes in patients with pancreatic adenocarcinoma (PDAC) correlate with disease-specific survival. Herein, we report results of a prospective observational trial on CTC dynamics to assess their clinical significance.
Methods: The CLUSTER trial is a prospective longitudinal study on PDAC CTC dynamics (NCT02974764). Multiple peripheral blood samples are collected from 160 consecutively enrolled patients with PDAC diagnosis. CTCs are isolated and characterized by immunofluorescence.
Results: Two major CTC subtypes were identified in all patients: epithelial CTCs (eCTCs) and mesenchymal CTCs (mCTCs). Patients who received neoadjuvant chemotherapy have significantly lower total CTCs (tCTCs) and mCTCs, compared to untreated patients eligible for upfront resection (p<0.001). In multivariable logistic regression analysis, preoperative numbers of tCTCs and mCTCs were the only predictors of early recurrence and disease-associated mortality, within 12 months from surgery (p=0.03, Table 1). Surgical resection of the primary tumor results in significant reduction, but not disappearance, of CTC burden across all cell subtypes (p<0.001). Longitudinal monitoring of CTCs postoperatively shows an increase in CTC numbers within a median time of two months, prior to radiological evidence of disease recurrence.
Conclusions: We report novel findings regarding CTCs from a large prospective trial in patients undergoing PDAC resection. CTC dynamics reflect progression of disease, providing important information on clinical outcomes, not available by current tumor markers and imaging.
| logOR | 95% CI | p value | |
| Age, years | -0.11 | -0.26 - 0.04 | 0.15 |
| Sex, male | 0.93 | -1.68 - 3.55 | 0.46 |
| Smoking Hx, present | -0.25 | -1.49 - 0.97 | 0.66 |
| BMI, kg/m2 | -0.02 | -0.27 - 0.23 | 0.86 |
| Tumor site, R pancreas | -0.07 | -2.28 - 2.13 | 0.94 |
| CA 19-9, >67.8 U/mL | -0.18 | -2.27 - 1.91 | 0.86 |
| Tumor size, >3cm | 1.78 | -1.09 - 4.65 | 0.21 |
| Preoperative tCTCs, >16/mL of blood | 3.08 | 0.42 - 5.74 | 0.03 |
| Preoperative mCTCs, >3/mL of blood | 2.26 | -0.17 - 4.7 | 0.06 |
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