A Prospective Study of Pain Control by a 2-Step Irradiance Schedule During Topical Photodynamic Therapy of Nonmelanoma Skin Cancer

Abstract

Background Topical photodynamic therapy (PDT) for selected non-melanoma skin cancer, employing 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has yielded high long-term complete response rates with very good cosmesis. Pain during light activation of the photosensitizer can be a serious adverse event. A two-step irradiance protocol has previously been shown to minimize ALA-PDT pain. Objectives To determine the irradiance-dependent pain threshold for MAL-PDT, to adapt the two-step protocol to an LED light source, and assess clinical response. Methods In this prospective study, 25 superficial basal cell carcinoma (sBCC) received an initial irradiance by laser at 40 or 50 mW/cm2, or LED at 35 mW/cm2 followed by an irradiance at 70 mW/cm2 for a total of 75 J/cm2. Pain levels were recorded for both irradiance steps. Efficacy was assessed at 6, 12 or 24 months. Results Pain was mild in the 40/70 mW/cm2 laser cohort. Three instances of irradiance-limiting pain occurred at 50/70 mW/cm2. Pain was minimal in the 35/70 mW/cm2 LED cohort. Clinical response rates were 80% in the 50/70 mW/cm2 laser cohort and 90% in the 35/70 mW/cm2 LED cohort. Conclusions Topical PDT can be effectively delivered to sBCC with minimal treatment related pain by a two-step irradiance protocol.

Conventional and combination topical photodynamic therapy for basal cell carcinoma: systematic review and meta-analysis

“…Calculation of cumulative pain showed that there was no difference between imiquimod and MAL‐PDT, whereas fluorouracil was less painful than PDT . Recent PDT studies utilizing low irradiance protocols (≤ 35 mW cm −2 vs. 50–200 mW cm −2 in this review) show reduced pain with apparent preservation of efficacy …”

Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions

“…No difference in pain was observed in patients treated for nBCC with or without debulking the tumors [ 176 ]. A reduction in pain during illumination of sBCC’s could be accomplished by delivering the light according to a two-step irradiance schedule for both ALA and MAL [ 181 , 182 ]. Illumination is started with a low fluence rate until 90% of the fluorescence is photobleached after which the fluence rate is increased until the total fluence is delivered.…”

Photodynamic Therapy-Induced Microvascular Changes in a Nonmelanoma Skin Cancer Model Assessed by Photoacoustic Microscopy and Diffuse Correlation Spectroscopy

“…Among these treatment alternatives we have been investigating PDT at preclinical and clinical settings as a viable option for the management of NMSCs [4][5][6]. PDT is a light-based therapy for tumor destruction that requires a combination of light, photosensitizer (PS) and oxygen [7,8].…”