Development and Internal Validation of a Patient-Level Diagnostic Model Integrating Folate Receptor-Positive Circulating Tumor Cells and Peripheral CD8 Count for Malignant-Versus-Benign Pathology Discrimination in a Pathology-Enriched Pulmonary Nodule Cohort.
In pathology-enriched referred hospital cohorts, stable radiologic-pathologic linkage is often unavailable, so patient-level malignant pathology may be a more reliable endpoint than lesion-specific malignancy. We aimed to develop and internally validate a blood-based model for patient-level malignant-versus-benign pathology discrimination.
We retrospectively reviewed 283 consecutive eligible source records from 22 February 2023 to 12 May 2025. After excluding unclassifiable pathology, lesions > 30 mm when verifiable, and obvious extrapulmonary primary tumors, we defined a strict primary cohort. A prespecified complete-case logistic regression model including FR + CTC, peripheral CD8 count, age, and sex was developed and internally validated with bootstrap resampling.
The strict primary cohort included 234 patients (166 malignant, 68 benign). In the main model (n = 232), FR + CTC was associated with higher odds of malignant pathology (OR 1.31 per 1 FU/3 mL, 95% CI: 1.14-1.50; p < 0.001), whereas peripheral CD8 count was inversely associated (OR 0.50 per 100 cells/μL, 95% CI: 0.41-0.61; p < 0.001). Apparent and optimism-corrected AUCs were 0.877 and 0.867, respectively. Adding an adjudicated patient-level CT vascular sign yielded limited incremental value.
In this retrospective single-center, pathology-enriched cohort, FR + CTC and peripheral CD8 provided useful internally validated discrimination for patient-level malignant pathology. The model requires external validation and setting-appropriate recalibration before broader clinical use.
We retrospectively reviewed 283 consecutive eligible source records from 22 February 2023 to 12 May 2025. After excluding unclassifiable pathology, lesions > 30 mm when verifiable, and obvious extrapulmonary primary tumors, we defined a strict primary cohort. A prespecified complete-case logistic regression model including FR + CTC, peripheral CD8 count, age, and sex was developed and internally validated with bootstrap resampling.
The strict primary cohort included 234 patients (166 malignant, 68 benign). In the main model (n = 232), FR + CTC was associated with higher odds of malignant pathology (OR 1.31 per 1 FU/3 mL, 95% CI: 1.14-1.50; p < 0.001), whereas peripheral CD8 count was inversely associated (OR 0.50 per 100 cells/μL, 95% CI: 0.41-0.61; p < 0.001). Apparent and optimism-corrected AUCs were 0.877 and 0.867, respectively. Adding an adjudicated patient-level CT vascular sign yielded limited incremental value.
In this retrospective single-center, pathology-enriched cohort, FR + CTC and peripheral CD8 provided useful internally validated discrimination for patient-level malignant pathology. The model requires external validation and setting-appropriate recalibration before broader clinical use.