Lead-time trajectory of CA19-9 as an anchor marker for pancreatic cancer early detection.
Fahrmann JF, Schmidt CM, Mao X, Irajizad E, Loftus M, Zhang J, Patel N, Vykoukal J, Dennison JB, Long JP, Do KA, Zhang J, Chabot JA, Kluger MD, Kastrinos F, Brais L, Babic A, Jajoo K, Lee LS, Clancy TE, Ng K, Bullock A, Genkinger J, Yip-Schneider MT, Maitra A, Wolpin BM, Hanash S
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 prior to diagnosis of pancreatic cancer and from 875 matched controls from the 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 non-cancerous pancreatic cysts). The complementary value of two additional protein markers, TIMP1 and LRG1, was determined.
RESULTS: In the PLCO cohort, levels of CA19-9 increased exponentially starting at two years prior to diagnosis with sensitivities reaching 60% at 99% specificity within 0-6 months prior to 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 non-cancerous cysts 30% sensitivity at 99% specificity. For pre-diagnostic cases below cut-off value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (p=0.031) 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.
- 2016-0018: Validation of serum autoantibody for pancreatic cancer early detection (Johannes Fahrmann - 2016)