Photodynamic Therapy for Benign Cutaneous Neurofibromas Using Aminolevulinic Acid Topical Application and 633 nm Red Light Illumination

Neurofibromatosis type 1 (NF1) has no current effective treatments beyond surgery. Topical photodynamic therapy (PDT) has the potential to provide a less invasive treatment modality.

In the first reported clinical trial of PDT for NF1, PDT targeted neurofibromas specifically, and may offer a normal tissue-sparing treatment modality in the future. This study is registered at Clintrials.gov (NCT01682811).

Based on murine data, we hypothesized PDT could be used for the treatment of cutaneous neurofibromas (cNF).

We conducted a phase I trial to examine absorption and conversion of topical aminolevulinic acid (ALA) in cNF and determine safety in a dose escalation study. ALA or control vehicle was applied to neurofibromas through microneedle-assisted delivery (n = 4) and excised specimens were examined 24 h later for protoporphyrin IX fluorescence. Fluorescence was detected in the tumors at 304 ± 94 U/μm2, while adjacent paralesional normal skin and vehicle-treated tumors showed no fluorescence (p < 0.0001). Subsequently, neurofibromas (n = 27) were treated with ALA and irradiated with 633 nm red light 18 h later, at escalating dosages of 50 and 100 mJ/cm2. Maximum tolerable dose was established at 100 mJ/cm2. Light microscopy study of tumors biopsied 48 h after PDT (ALA n = 14 and vehicle n = 4) showed mixed inflammatory infiltrate in the ALA, but not in the vehicle-treated tumors or perilesional normal skin. TUNEL evaluation showed 42.5 ± 19.9 apoptotic cells per visual field for ALA-treated and 1.1 ± 1.4 for vehicle-treated tumors (p = 0.002). Conclusions: In the first reported clinical trial of PDT for NF1, PDT targeted neurofibromas specifically, and may offer a normal tissue-sparing treatment modality in the future. This study is registered at Clintrials.gov (NCT01682811).