Johannes F Fahrmann1, C Max Schmidt2, Xiangying Mao1, Ehsan Irajizad1, Maureen Loftus3, Jinming Zhang3, Nikul Patel1, Jody Vykoukal1, Jennifer B Dennison1, James P Long4, Kim-Anh Do4, Jianjun Zhang2, John A Chabot5, Michael D Kluger5, Fay Kastrinos6, Lauren Brais3, Ana Babic3, Kunal Jajoo7, Linda S Lee7, Thomas E Clancy8, Kimmie Ng3, Andrea Bullock9, Jeanine Genkinger5, Michele T Yip-Schneider2, Anirban Maitra10, Brian M Wolpin3, Samir Hanash11. 1. Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. 2. Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. 3. Dana-Farber Brigham and Women's Cancer Center, Division of Gastrointestinal Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 4. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. 5. Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, Department of Epidemiology, Columbia Mailman School of Public Health, New York, New York. 6. Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, New York, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, Department of Surgery, New York, New York. 7. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 8. Dana-Farber Brigham and Women's Cancer Center, Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 9. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 10. Division of Digestive and Liver Diseases, Columbia University Irving Medical Cancer and the Vagelos College of Physicians and Surgeons, New York, New York, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. 11. Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Electronic address: shanash@mdanderson.org.
Abstract
BACKGROUND & AIMS: There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. METHODS: CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined. RESULTS: In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection. CONCLUSION: CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
BACKGROUND & AIMS: There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. METHODS: CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined. RESULTS: In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection. CONCLUSION: CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
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