title: 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.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon NH, USA. Electronic address: stephen.c.kanick@dartmouth.edu.
authors.forename: S C
authors.initials: SC
authors.lastname: Kanick
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon NH, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Davis
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Sheehan
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hasan
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, USA; Biomedical Engineering, Cleveland Clinic, Cleveland, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Maytin
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon NH, USA; Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Chapman
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy*; D008297:Male; D010146:Pain / Q000139:chemically induced; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000096:biosynthesis*; D013050:Spectrometry, Fluorescence
chemical_list: D015415:Biomarkers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: Actinic keratosis; Optical dosimetry; Photodynamic therapy