Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) can be effective for select basal cell carcinoma (BCC) lesions. However, the histological depth and subtype of tumors that respond to PDT remain uncertain. Here, we report a clinical trial of high-dose oral Vitamin D (VD), used as a PDT neoadjuvant for BCC. In this multi-institutional, intra-patient, randomized trial, 35 patients (9 with Gorlin Syndrome) received three PDT sessions (20% ALA
417 nm blue light) preceded by oral VD, placebo, or no pretreatment. Tumors (122 BC) were monitored using 3D photography and computer-assisted volumetric analysis. Values for absolute volume (3DAbsVol) and average height (3DAvHt) were calculated and used to quantify tumor response kinetics. From histological sections, 3DAvHt was found to correlate with actual tumor depth, although 3DAvHt is only ~10-20% of the latter. Importantly, 3DAvHt measurements revealed a distinct depth threshold that predicts PDT responsiveness. Of 122 tumors analyzed, 70% cleared after PDT
remaining tumors were micronodular or other aggressive histologic subtypes. To evaluate VD's effects upon treatment response kinetics after PDT, only 40% of original lesions were available for analysis. By stratifying remaining tumors by 3DAvHt, we found 65% of thin tumors to be VD-responsive, whereas only 28% of thick tumors responded to VD. Overall, PDT was effective for the majority of BCC lesions in our study. Tumors most likely to respond can be predicted histologically and by noninvasive 3D morphometry. For PDT-appropriate BCC lesions, neoadjuvant oral Vitamin D represents a safe and beneficial way to accelerate tumor resolution.