Exploratory Multimodal Analysis of Vascular Changes in Basal Cell Carcinoma Before and After Topical Imiquimod...

Background/Objectives: Topical imiquimod is an established non-invasive treatment for superficial basal cell carcinoma (sBCC). However, data on treatment-associated changes in tumor microvascularization remain limited. This study investigated vascular changes before and after imiquimod therapy using multimodal non-invasive imaging. Methods: In this single-center, prospective observational study, 31 basal cell carcinomas in 20 patients were examined before and 12-16 weeks after topical imiquimod therapy (5%, five times weekly for six weeks) using dermoscopy, dynamic optical coherence tomography (D-OCT), and line-field confocal optical coherence tomography (LC-OCT). Analyses were performed as paired before-and-after comparisons. While approved for sBCC, a small number of thin nodular and infiltrative BCCs were included exploratorily; subgroup analyses were not powered. Results: Dermoscopy showed a nominally significant shift toward smaller vessel diameter categories after therapy (ATS = 8.183, df = 1, p = 0.004). D-OCT-derived parameters (vessel density, vessel diameter, and depth of the vascular plexus) did not show nominally significant changes. LC-OCT showed nominally lower apparent intratumoral flow scores (ATS = 13.285, df = 1, p < 0.001), reduced occurrence of vessel-wall-associated intraluminal structures showing a rolling-like motion pattern (86.7% before treatment versus 33.3% after treatment; ATS = 13.357; df = 1, p < 0.001), and a reduction in maximum vessel diameter (ATS = 6.110, df = 1, p = 0.013). The primary LC-OCT inferential analyses were performed at the lesion level without adjustment for within-patient clustering and should therefore be interpreted as exploratory. An additional patient-cluster-adjusted paired change-score sensitivity analysis for LC-OCT maximum vessel diameter yielded a directionally consistent estimate (-17.81 µm; 95% CI: -34.40 to -1.23; p = 0.037). The primary exploratory endpoints were LC-OCT-based apparent intratumoral flow and maximum vessel diameter; secondary endpoints included dermoscopic and D-OCT-based vascular parameters. In the exploratory response-stratified analysis, the change in LC-OCT-based maximum vessel diameter did not differ significantly among the assigned response groups (Kruskal-Wallis H = 3.870, df = 2, raw p = 0.144; BH-adjusted p = 0.753). Conclusions: LC-OCT detected several exploratory vascular changes between the pre-treatment examination and follow-up and may provide complementary information for the non-invasive assessment of BCC after imiquimod therapy. Given the exploratory design, limited sample size, and lack of systematic histological confirmation, these findings are hypothesis-generating and require validation in larger prospective studies.