Intravoxel incoherent motion diffusion-weighted imaging for early response stratification of neoadjuvant immune checkpoint inhibitor plus tyrosine kinase inhibitor in renal cell carcinoma: an exploratory study.

PURPOSE: To evaluate intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for stratifying early response to neoadjuvant immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) therapy in renal cell carcinoma (RCC) and explore correlations between IVIM‑DWI parameters and tumor immune cell infiltration.

MATERIALS AND

METHODS

This retrospective exploratory analysis utilized prospectively collected data from a single‑center study enrolling patients with advanced, metastatic or unresectable RCC scheduled for neoadjuvant ICI‑TKI therapy. Two radiologists independently segmented primary tumors on baseline IVIM‑DWI to obtain the true diffusion coefficient (D), pseudo‑diffusion coefficient (D*), perfusion fraction (f), and standard apparent diffusion coefficient (ADCstandard). Response was assessed per iRECIST. Baseline parameters were compared between responders and nonresponders; subgroup analysis was conducted for clear cell RCC (ccRCC). Diagnostic performance was evaluated using the area under the curve (AUC). Immune infiltration was analyzed from RNA‑sequencing data, and correlations were assessed with the Spearman's test.

RESULTS

Among 58 patients (44 ccRCC), 33 (56.9%) were responders. Responders showed higher baseline D*, D, f, and ADCstandard values than nonresponders in both the whole cohort and ccRCC subgroup (all P < 0.05). A combined parameter incorporating these variables achieved the highest AUC (whole cohort: 0.903; ccRCC subgroup: 0.979). Nonresponders exhibited higher infiltration of CD8⁺ T cells and follicular helper T cells (all P < 0.05). CD8⁺ T‑cell infiltration correlated negatively with the baseline D (P = 0.015) but not with the ADCstandard (P = 0.062).

CONCLUSION

IVIM‑DWI parameters show promise as a non‑invasive tool for early response stratification of neoadjuvant ICI‑TKI therapy in RCC. The inverse correlation between D values and CD8⁺ T‑cell infiltration suggests that restricted diffusion may reflect a tumor microenvironment associated with treatment resistance.