A55
DNA ploidy as a prognostic biomarker after ALA photodynamic therapy for high grade dysplasia in Barretts oesophagus
Jason Dunn, Dahmane Oukrif, Marco Novelli, Laurence Lovat
University College London, UK
Background
Photodynamic therapy (PDT) is an approved minimally invasive treatment for high grade dysplasia (HGD) in Barretts oesophagus (BE). Complete reversal of HGD at 1 year post therapy occurs in up to 90% of patients, but late relapse has been documented in 20%. DNA ploidy (aneuploidy/tetraploidy), as analysed by flow cytometry, is a strong predictor of future cancer risk in untreated Barretts oesophagus, independent of histology grade. Image cytometry is a simpler method that allows accurate evaluation of nuclear morphology on parrafin embedded samples.
Aim
To determine whether residual aneuploidy after successful treatment with ALA-PDT predicts late relapse to HGD or cancer.
Method
28 patients (82% male, mean age 66 years (range 45-86)) successfully treated with ALA PDT for HGD in BE between 1998-2006 were included in analysis. All patients had HGD confirmed by two specialist GI pathologists prior to treatment. Four quadrant biopsies were taken every 2cm from the treated segment at 2, 4, 12, 18 and 24 months after PDT, then annually. DNA ploidy was analysed by image cytometry of monolayer preparations stained with Feulgen. 405 samples were analysed; 148 prior to PDT; 131 at 4 months post PDT; 104 at 1 year post PDT.
Results
24 patients had aneuploidy prior to treatment. 11 of those remained aneuploid at 1 year post PDT and 9/11 have subsequently relapsed; 5 to invasive cancer and 4 HGD. The median time to relapse was 30 months (range 14-64).
13 patients reverted to diploid at 4 month follow up and remained diploid at 1 year. None have relapsed after median 45 month follow up (range 32-60 months) (Fishers exact p<0.001).
Conclusion
Following successful PDT for HGD in BE, patients that remain aneuploid are significantly more likely to develop HGD or cancer than those who become diploid. This may allow change in surveillance patterns to be tailored to the patient, with persistent aneuploidy one year post PDT necessitating closer follow up. Moreover, patients that have reverted to diploid may return to 2 yearly follow up and be reassured of a very low 3 year cancer risk. These data demonstrate the utility of DNA ploidy as a prognostic biomarker following ablative therapy.
24 patients had aneuploidy prior to treatment.
11 of those remained aneuploid at 1 year post PDT and 9/11 have subsequently relapsed; 5 to invasive cancer and 4 HGD. The median time to relapse was 30 months (range 14-64).
13 patients reverted to diploid at 4 month follow up and remained diploid at 1 year. None have relapsed after median 45 month follow up (range 32-60 months) (Fishers exact p<0.001).
4 patients were diploid prior to treatment and 2/4 patients have relapsed, one to cancer (diploid throughout) and one to HGD (aneuploidy at 1 year). There was no significant difference in rates of aneuploidy within this small subset of patients.
