Background: Pancreatic cancer (PC) is a difficult malignancy to diagnosis and properly stage, with extremely poor outcomes even for patients (pts) with resectable disease. Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell common to the blood of cancer pts, whose presence and size (≥50µm) is a prognostic indicator of poor progression free survival (PFS) and overall survival (OS). However, the clinical value of CAMLs in PC has not been evaluated. We recruited treatment naïve PC pts referred for surgical resection before therapy induction to study CAML association to PFS/OS. We investigate whether a simple blood test can better identify pts with metastatic disease and act as a predictor for PFS and OS.

Methods: 68 whole peripheral blood samples were drawn from untreated newly diagnosed PC pts referred for surgical resection prior to induction of therapy. Pts were recruited for a 2 year single blind prospective pilot study testing >5 CAMLs, CAML size (≥50µm), CA19-9, & CEA to clinical stage (CS), pathological stage (PS), and resectability. Pts were referred based on CS with resectable (R) (n=23), borderline resectable (BR) (n=27), or locally advanced (LA)/metastatic (M) (n=16); Stage I (n=50), Stage II (n=12), Stage III (n=0), Stage IV (n=3), and unknown stage (n=2). Blood samples (7.5mL) were taken prior to any neoadjuvant therapy. Blood was filtered by CellSieveTM filtration and CAMLs quantified. Analysis of CAMLs, protein markers, and resectability were used to evaluate PFS and OS significance by log-rank testing.

Results: CAMLs were found in 92% (n=61/66) of pt samples and averaged 7.5 CAMLs/7.5 mL blood. In pts that received surgery, 22 pts were upstaged with PS; stage I (n=20), Stage II (n=16), Stage III (n=5), Stage IV (n=18), & 7 pts withdrawing prior to surgery. All early stage pts with ≥12 CAMLs (n=6) were upstaged to metastatic disease after surgical resection. CEA and CA19-9 serum were not significant for PFS (CEA HR 0.9, p=0.639 and CA19-9 HR 0.6, p=0.288). Further, R vs BR was not significant for PFS (HR 0.4 p=0.10) nor was BR vs LA (PFS HR=0.2 p=0.075), though in both comparisons resectability did trend non-significantly toward better PFS. >5 CAMLs was not a significant indicator of PFS or OS (PFS HR 0.6 p=0.175 and OS HR 1.0 p=0.902). However, ≥50µm CAMLs was a highly significant indicator of both PFS and OS (PFS HR 4.0 CI95% 2.0-7.8, p>0.001 and OS HR 2.3 CI95% 1.1-4.7, p=0.035).

Conclusions: In PC, accurate staging/resectability is difficult, with 60% of pts being upstaged post-surgery and ~80% recurring in 2 years. There is a need for a better method to stratify surgical candidates that won't benefit from surgical resection. These data suggest that high CAML numbers at diagnosis identifies pts with metastatic disease which are less likely to benefit from surgical resection, and enlarged CAML size correlates to poorer PFS and OS.

Citation Format: Kirby P. Gardner, Daniel L. Adams, Mohammed Aldakkak, Cha-Mei Tang, Susan Tsai. Circulating stromal cells in resectable pancreatic cancer is associated with high pathological stage and poor clinical outcomes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6478.