CHICAGO — Northwestern Medicine scientists have demonstrated that a highly sensitive blood test can detect traces of pancreatic cancer missed by standard testing, potentially helping physicians identify patients whose disease is more likely to return even when scans appear reassuring.
The sensitive blood test focuses on KRAS, a genetic mutation that drives more than 90% of pancreatic cancers. The findings come as a new revolutionary drug targeting KRAS is showing substantial survival benefits and nearing FDA review.
"As we enter the era of KRAS-targeted therapies, having a screening tool that tracks the same mutation becomes increasingly important," said study senior author Dr. Akhil Chawla , clinical associate professor of surgery at Northwestern University Feinberg School of Medicine and complex surgical oncologist at Northwestern Medicine.
"That combination could fundamentally change how we identify high-risk patients, monitor microscopic disease, and potentially intervene earlier before recurrence becomes clinically visible, ultimately getting more patients to cure," he added.
The study will be published June 30 in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Pancreatic cancer is one of the deadliest malignancies, even when diagnosed before it has visibly spread. Many patients undergo months of chemotherapy and surgery, yet their cancer often returns. "In these patients, circulating tumor DNA levels are often extremely low and difficult to detect," Chawla said.
"Many patients and families ask me, 'How do we know if the treatment is working?' This research is part of trying to answer that question more precisely," he added.
How the study was conducted
The study followed 106 Northwestern Medicine patients with localized pancreatic cancer from diagnosis through chemotherapy and surgery. At diagnosis, the study found that the more sensitive blood test, digital droplet PCR (ddPCR), detected signs of cancer in nearly four times as many patients as conventional next-generation sequencing tests (NGS), which are more commonly utilized. Even after chemotherapy and surgery, ddPCR continued detecting cancer in most patients, while NGS and standard testing didn't.
"This suggests physicians may currently be missing residual disease in most patients using currently available testing approaches," Chawla explained.
Better detection meant better prediction of survival outcomes, Chawla's team found. The clearest example of this was the discovery of a previously hidden group of high-risk patients whose cancer was missed by standard NGS but detected by ddPCR. That group survived a median of 27 months after diagnosis, compared with 41 months among patients who tested negative on both tests.
Searching deeper for KRAS
NGS and ddPCR are blood tests (often called liquid biopsies) that search for traces of DNA shed by cancer cells into the bloodstream. Detecting this tumor DNA provides an early sign that cancer is present or may return. Because these tests rely on a simple blood draw, they can be repeated over time without requiring invasive procedures.
While both are increasingly common in oncology, NGS is more commonly utilized because it searches for large numbers of cancer-associated genes simultaneously. By contrast, ddPCR searches for one set of genes at a time. In this study, the Northwestern team used ddPCR to focus specifically on the same KRAS mutations that are targeted by emerging drugs moving closer to FDA approval.
Key findings
The scientists collected blood samples from the study participants (all enrolled in a larger clinical trial) before treatment, after chemotherapy and after surgery between October 2020 and October 2024.
- At diagnosis, ddPCR detected tumor KRAS DNA in 65% of patients, compared with 17% for NGS
- After chemotherapy, ddPCR detected tumor KRAS DNA in 60% of patients, compared with 5% for NGS
- After surgery, ddPCR detected tumor KRAS DNA in 56% of patients, compared with 9% for NGS
- Patients positive on both tests survived for 11 months on average
- Patients negative on both tests survived for 41 months on average
- Patients missed by NGS but detected by ddPCR survived for 27 months on average
Chawla says the findings must be validated in larger multi-center studies before ddPCR can be used routinely in pancreatic cancer care.
The study is titled, "High-Sensitivity ctDNA Analysis Uncovers Relevant Signals Missed by NGS in Pancreatic Cancer." Chawla is supported by the National Institutes of Health (grant 1R50CA293523) and Elsa U. Pardee Foundation.
