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

Photodiagnosis Photodyn Ther. 2015 Dec;12(4):561-6. doi: 10.1016/j.pdpdt.2015.10.006. Epub 2015 Oct 22.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / adverse effects
  • Aminolevulinic Acid / therapeutic use*
  • Biomarkers
  • Dose-Response Relationship, Drug
  • Erythema / chemically induced
  • Female
  • Humans
  • Keratosis, Actinic / drug therapy*
  • Male
  • Pain / chemically induced
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / adverse effects
  • Photosensitizing Agents / therapeutic use*
  • Protoporphyrins / biosynthesis*
  • Spectrometry, Fluorescence

Substances

  • Biomarkers
  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX