Polyploid circulating stromal cells in blood to identify invasive solid tumors and to prognosticate for highly aggressive cancer subtypes.

person Daniel L Adams Creatv MicroTech, Inc., Monmouth Junction, NJ info_outline Daniel L Adams, Steven H. Lin, Harvey I. Pass, Martin Joseph Edelman, Toshiaki Iwase, Naoto Tada Ueno, Raymond C. Bergan, Susan Tsai, Mohammed Aldakkak, Rebecca Aft, Mark Watson, Amy K. Kim, Kazuaki Chikamatsu, Masanori Hayashi, David Loeb, Navin Pinto, Thai Huu Ho, Sandra M. Gaston, Sanoj Punnen, Jeffrey R Marks

Authors person Daniel L Adams Creatv MicroTech, Inc., Monmouth Junction, NJ info_outline Daniel L Adams, Steven H. Lin, Harvey I. Pass, Martin Joseph Edelman, Toshiaki Iwase, Naoto Tada Ueno, Raymond C. Bergan, Susan Tsai, Mohammed Aldakkak, Rebecca Aft, Mark Watson, Amy K. Kim, Kazuaki Chikamatsu, Masanori Hayashi, David Loeb, Navin Pinto, Thai Huu Ho, Sandra M. Gaston, Sanoj Punnen, Jeffrey R Marks Organizations Creatv MicroTech, Inc., Monmouth Junction, NJ, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, NYU Langone Health, New York, NY, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, University of Hawaii Cancer Center, Honolulu, HI, Fred & Pamela Buffett Cancer Center, Omaha, NE, The Ohio State University Wexner Medical Center, Columbus, OH, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, Washington University, St. Louis, MO, Washington University School of Medicine, Alliance for Clinical Trials in Oncology, St Louis, MO, Johns Hopkins School of Medicine, Baltimore, MD, Gunma University, Maebashi, Japan, University of Colorado at Denver - Anschutz Medical Campus, Aurora, CO, Albert Einstein College of Medicine, Bronx, NY, Seattle Children's Hospital, Seattle, WA, Mayo Clinic Arizona, Scottsdale, AZ, University of Miami Miller School of Medicine, Miami, FL, Desai Sethi Urology Institute at the University of Miami and Sylvester Comprehensive Cancer Center, Miami, FL, Duke University, Durham, NC Abstract Disclosures Research Funding DARPA DOD U.S. National Institutes of Health Background: Recently, early studies have identified circulating stromal cells (CStCs), i.e. Cancer Associated Macrophage-Like cells (CAMLs), in patients (pts) with newly diagnosed invasive cancers, which are phagocytic myeloid immune cells emanating from primary tumors. However, no study has evaluated CAMLs as a pan solid tumor screening tool nor their clinical impact on pt outcomes. We analyzed the blood of untreated newly diagnosed cancer pts (n=441), or in non-malignant conditions (i.e. pancreatic cysts, n=77), or healthy controls (n=100). We found that CAMLs are prevalent (82%) in cancer pt blood, absent in healthy controls (0%) and less common in non-malignant conditions (36%), with correlations to worse clinical outcomes. Methods: Anonymized peripheral blood was taken from n=441 pts before or after confirmation of invasive malignancy [stage I (n=105), stage II (n=125), stage III (n=114), stage IV (n=97) with pathologically confirmed lung (n=84), pancreas (n=61), breast (n=73), prostate (n=65), esophageal (n=34), Renal Cell (n=29), Sarcoma (n=27), or Other (n=68). In addition, anonymized blood was taken from pts with untreated non-malignant conditions including benign breast masses (n=19), Lupus (n=11), liver Cirrhosis (n=6), rising PSA (n=24), or other benign mass (n=17); and from healthy control volunteers (n=100). CAMLs were isolated by CellSieve microfiltration, defined as enlarged polyploid cells with cytokeratin+ and/or CD45/CD14+. Pts were monitored for 0-8 years (median=2.6) for progression free survival (PFS) and overall survival (OS). Results: CAMLs were found in 82% of all cancer pts averaging 5.4 CAMLs, specifically, in 66% of Stage I, 85% Stage II, 84% Stage III, and 92% Stage IV. No CAMLs were found in any healthy controls, but were in 36% of non-malignant pts. CAML sensitivity in cancer vs healthy was 82% (CI95% 78-85%), specificity=100% (CI95% 96-100%), PPV=100% (CI95% 99-100%), NPV=55% (CI95% 50-60%). CAML sensitivity in cancer vs benign was 82% (CI95% 78-85%), specificity=64% (CI95% 32-44%), PPV=93% (CI95% 90-95%), NPV=38% (CI95% 32-44%). CAML presence was significantly associated with worse PFS (HR=2.0, 95%CI 1.4-2.9, p<0.0001) & OS (HR=2.2, 95%CI 1.4-3.3, p=0.0004), with engorged phagocytic CAMLs (>50um), highly significant for worse PFS (HR=3.3, 95%CI 2.5-4.5, p<0.0001) & OS (HR=3.0, 95%CI 2.1-4.3, p<0.0001). Further, in benign pts positive for CAMLs, 2 pts were in situ, 16 had histologies with increased cancer risk (i.e. IPMN, atypical hyperplasia), and 5 pts died within 3 years. Conclusions: CAMLs appear to be a highly sensitive blood based biomarker that can identify invasive carcinoma in all stages of cancer regardless of subtype, but are not found in healthy controls & rare in non-malignant conditions. Further, enlarged phagocytic CAMLs appeared to correlate with shorter PFS and OS prior to treatment induction.