Early detection of pancreatic cancer with a multi-omic liquid biopsy

Background: Early diagnosis is the central challenge in pancreatic ductal adenocarcinoma (PDAC) and the successful development of an early detection biomarker test would revolutionize the field. PDAC is the 3rd leading cause of cancer-related deaths in the United States with 66,400 new diagnoses in 2024. The five-year survival is only 12.8% because 80% of patients are diagnosed in advanced stages limiting the potential for curative surgical resection. There is an urgent need to facilitate the triage of high-risk groups into the diagnostic pathway, particularly those with pancreatic cysts, chronic pancreatitis and new-onset diabetes over the age of 50. However, the incidence of PDAC in these at-risk populations is ~1% over the next 3 years. Imaging modalities, such as CT/MRI and endoscopic ultrasound with fine-needle aspiration, are too expensive and invasive to serve as primary screening tools. Methods: Here the ability of a spectroscopic blood test as an alternative strategy for PDAC detection is assessed. The technology utilizes infrared (IR) spectroscopy, and interrogates a blood sample with IR light to produce a distinctive signature that is sensitive to the hallmarks of cancer. When combined with machine learning, the test detects PDAC by monitoring of all biomolecular components of the sample. In this proof-of-concept study, 166 PDAC patients were classified against 459 symptomatic patients with a non-cancer diagnosis. Results: The receiver operating characteristic (ROC) curve reported an area under the curve (AUC) value of 0.84. The diagnostic algorithm reported 92% sensitivity with 52% specificity. Importantly, the model did not seem to be affected by cancer stage. The detection rates with the sensitivity-tuned model were 88% stage I, 94% stage II, 99% stage III and 95% stage IV. Conclusions: The detection of PDAC in early stages would improve prognosis and survival rates of affected patients. Advancements in genetic sequencing have opened opportunities for tumor-derived biomarkers, using genomics, epigenomics, and transcriptomics to isolate circulating tumor DNA, exosomes, and/or microRNA. However, these biomarkers are limited in PDAC at early stages due low release and near-undetectable signals. A spectroscopy-based multi-omic blood test represents an alternative strategy, particularly for high-risk populations, that may address the gap in PDAC diagnostics.