Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy

Abstract

Background: Although aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT.

Methods: A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48-76 h after treatment (n=13).

Results: PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p<0.022) (n=70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n=13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r=0.17, p<0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r=0.55, p<0.051) and erythema (r=0.58, p<0.039) in the 48-72 h following treatment.

Conclusions: These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes.

Keywords: Actinic keratosis; Optical dosimetry; Photodynamic therapy.

Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1

PpIX yield optically quantitated in AK and non-AK sites for all patients (n=70). Marks above bars denote patients on which data only available on AK.

Figure 2

(a) Shows PpIX yield is higher in AK than non-AK sites, and (b) shows PpIX is higher in measurements on the face than on other areas of the body (e.g. arms, legs, torso).

Figure 3

Shows the change PpIX concentration during therapeutic light dose vs. the PpIX concentration measured prior to light dose. A linear fit to the data yields a slope equivalent to the average photobleaching percentage of 72 %.

Figure 4

(a) Shows PpIX yield vs. pain reported on the day of treatment for all patients, and (b) shows that PpIX is higher for patients reporting high amounts of pain (i.e. VAS>=5).