Interpretable multimodal artificial intelligence model for predicting advanced neoplasia in pancreatic cystic lesions

Table 1 Baseline clinical, imaging, and cyst fluid characteristics stratified by outcome (n = 187)

Characteristic	Total (n = 187)	Advanced neoplasia (n = 58)	Non-advanced (n = 129)	P value
Age, median (IQR), year	66 (60-73)	69 (63-76)	63 (57-70)	0.002
Female sex	98 (52.4)	28 (48.3)	70 (54.3)	0.52
Unintentional weight loss	31 (16.6)	18 (31.0)	13 (10.1)	< 0.001
New-onset diabetes	26 (13.9)	13 (22.4)	13 (10.1)	0.04
Enhancing mural nodule on EUS	48 (25.7)	33 (56.9)	15 (11.6)	< 0.001
MPD ≥ 5 mm	52 (27.8)	31 (53.4)	21 (16.3)	< 0.001
Cyst size > 30 mm	81 (43.3)	39 (67.2)	42 (32.6)	< 0.001
Serum CA 19-9 > 37 U/mL	42 (22.5)	27 (46.6)	15 (11.6)	< 0.001
Cyst fluid CEA > 192 ng/mL	58 (31.0)	35 (60.3)	23 (17.8)	< 0.001
Cyst fluid glucose < 50 mg/dL	51 (27.3)	31 (53.4)	20 (15.5)	< 0.001
Hard elastography pattern (score ≥ 3)	41 (21.9)	24 (41.4)	17 (13.2)	< 0.001
Cyst type				< 0.001
BD-IPMN	127 (67.9)	29 (50.0)	98 (76.0)
MD/mixed IPMN	34 (18.2)	20 (34.5)	14 (10.9)
MCN	21 (11.2)	6 (10.3)	15 (11.6)
Other	5 (2.7)	3 (5.2)	2 (1.5)

Data are presented as n (%) or median (interquartile range). Categorical variables were compared using χ² or Fisher’s exact test, as appropriate; continuous variables were compared using the Mann-Whitney U test. MPD: Main pancreatic duct; BD-IPMN: Branch-duct intraductal papillary mucinous neoplasm; MD: Main-duct; MCN: Mucinous cystic neoplasm; IQR: Interquartile range; CEA: Carcinoembryonic antigen; CA 19-9: Carbohydrate antigen 19-9; IPMN: Intraductal papillary mucinous neoplasms.

Table 2 Diagnostic performance of prediction models in the validation cohort and area under the curve values of guideline-based criteria

Model/criteria	AUC (95%CI)	Sensitivity	Specificity	PPV	NPV
Core clinical-EUS model	0.87 (0.76-0.95)	76.5% (13/17)	79.5% (31/39)	61.9% (13/21)	88.6% (31/35)
Integrated multimodal model	0.91 (0.82-0.97)	82.4% (14/17)	89.7% (35/39)	77.8% (14/18)	92.1% (35/38)
Kyoto 2024 criteria1	0.79	-	-	-	-
Fukuoka 2017 criteria	0.77	-	-	-	-
European 2018 criteria	0.76	-	-	-	-
AGA 2015 criteria	0.70	-	-	-	-

¹Kyoto 2024 was evaluated in the intraductal papillary mucinous neoplasms subset (n = 161), consistent with its intended scope.

Validation distribution (model evaluation): 17 advanced neoplasia, 39 non-advanced (n = 56). DeLong tests comparing the integrated model with each guideline-based strategy were significant (all P < 0.01). AUC: Area under the receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value; EUS: Endoscopic ultrasound; AGA: American Gastroenterological Association.

Table 3 Counterfactual decision table at representative risk thresholds (validation cohort, n = 56)

Risk threshold	Surgical candidates (n)	Advanced neoplasia correctly classified	Patients without advanced neoplasia potentially spared surgery	Advanced neoplasia missed (n)
20%	20	14/17	33/39	3
30%	16	13/17	36/39	4
40%	13	12/17	37/39	5

Validation distribution: 17 advanced neoplasia, 39 non-advanced. All patients in the cohort underwent resection; therefore, the number of surgeries potentially avoided represents counterfactual estimates based on model classification rather than observed clinical avoidance of surgery.