Emerging non-invasive imaging biomarkers of Ki-67 in pancreatic cancer: Toward predictive precision oncology

Figure 3 Integrated imaging biomarker pathway for Ki-67 prediction and treatment allocation in biopsy-contraindicated pancreatic ductal adenocarcinoma. This clinical workflow outlines a decision-making pathway for suspected pancreatic ductal adenocarcinoma, integrating imaging biomarkers to support personalized treatment planning. Following initial contrast-enhanced computed tomography or magnetic resonance imaging for anatomical staging, the feasibility of tissue biopsy is assessed. If biopsy is possible, histopathological Ki-67 grading provides a direct evaluation of tumor proliferative activity. When biopsy is not feasible - such as in patients on anticoagulation therapy or with poor clinical condition - noninvasive contrast-enhanced ultrasound becomes essential. Quantitative contrast-enhanced ultrasound parameters, including elevated rise slope 10%-90% or maximum intensity, are indicative of high Ki-67 expression (≥ 50%), while a low 50% falling slope suggests low Ki-67 expression (< 50%). Optional supplementary imaging, such as magnetic resonance imaging-derived apparent diffusion coefficient or positron emission tomography-derived maximum standardized uptake value, may further enhance risk stratification when needed. These multimodal imaging biomarkers are then integrated via an artificial intelligence-based model to generate a probabilistic Ki-67 score. Based on this prediction, patients are stratified into two therapeutic pathways: Those with high predicted Ki-67 (≥ 50%) are directed toward neoadjuvant therapy due to increased proliferative risk, while those with low predicted Ki-67 (< 50%) are considered suitable for surgical resection planning. PDAC: Pancreatic ductal adenocarcinoma; CT: Computed tomography; MRI: Magnetic resonance imaging; CEUS: Contrast-enhanced ultrasound; Rs1090: Rise slope 10%-90%; IMAX: Maximum intensity; Fs50: Falling slope 50%; ADC: Apparent diffusion coefficient; PET: Positron emission tomography; SUVmax: Maximum standardized uptake value.