Low Incidence of Esophageal Adenocarcinoma Following Optimal Regimen of ALA PDT for High Grade Dysplasia in Barrett's Esophagus

Abstract

Introduction: Photofrin photodynamic therapy (PDT) has recently been licensed to treat high grade dysplasia (HGD) for the prevention of adenocarcimoma in Barrett's Esophagus. Aminolaevulinic acid (ALA) PDT is a potentially attractive alternative because of the short light photosensitivity (24 hours) and lack of esophageal stricture formation. Many different ALA regimens have been suggested in the literature for the eradication of dysplasia in Barrett's Esophagus including varying light dose, drug dose and wavelength of the activating light. The optimal regimen of ALA PDT remains unknown. Aims and Methods: 72 patients were treated for high grade dysplasia with different parameters of ALA PDT to determine the optimal regimen. All patients were hydrated with intravenous fluids prior to the oral administration of ALA to prevent systemic hypotension. Three groups of patients were studied: Group A: High Dose ALA (60 mg/kg) activated by High Dose Red Light (1000 J/cm), Group B: High dose ALA activated by Lower Doses of Red Light (500-750 J/cm), and Group C: Low Dose ALA (30 mg/kg) activated by High Light Dose. Additionally, 24 patients in groups A and C were randomised to either red (1000 J/cm) or green laser light (1000 J/cm) activation. Success was determined by regular endoscopic follow up and quadrantic biopsies every 2 cm through the treated area. The primary outcome was development of adenocarcinoma. Results: One patient was lost to follow up. Kaplan Meier analysis demonstrated that patients treated in group A, with high red light and high drug dose had a very significant decrease in cancer risk at 36 months at 3% compared with 34% in those treated with other regimens (Log rank statistic = 0.002). In patients randomised to either red or green light activation the difference in adenocarcinoma rates were also significantly different in favour of red light at 8% versus 45% (p value <0.05). No patients suffered photosensitivity reactions or developed esophageal strictures. Conclusions: This case series of 72 patients demonstrates a statistically significant difference in the cancer rates between ALA regimens. The adenocarcinoma incidence rate following ALA PDT with the most effective regimen was low at 3% compared to the other regimens at 34%. This data compares favourably to the cancer rates in the randomized trial of PPI versus Photofrin PDT at 28% and 14% respectively at two years follow up. These data would support the use of the optimal regimen of ALA in a randomized controlled trial of ALA versus Photofrin PDT.