This study is designed to follow through on unique observations made during our last period of funding which established the importance of p16 in treatment response to photodynamic therapy (PDT). We demonstrated that ablative therapy with PDT was able to eliminate most biomarkers of neoplasia after therapy. In addition, we found that PDT is comparable to surgery in its ability to prevent esophageal adenocarcinoma related mortality. In this proposal, we will be investigating alternative forms of therapy for patients Barrett's esophagus and high-grade dysplasia that have p16 abnormalities. In order to investigate this hypothesis, we have established two specific aims. The first is to assess the effect of radiofrequency (RFA) and sodium porfimer based PDT in patients with HGD that have p16 intact in a randomized study with 20 patients per arm.
The second aim will be to assess the effect of RFA and ALA based PDT in patients with Barrett's esophagus and HGD that have abnormal p16 with 30 patients per arm. RF ablation produces injury through different mechanisms and may not be influenced by p16 loss. ALA PDT relies on a pro-drug that is converted to active form within the mucosa and also is known to initiate a different mechanism of cell death compared with sodium porfimer based PDT. In this revised application, we propose to enroll 100 out of the 110 we initially proposed within a two year time frame by decreasing the period of follow-up and increasing staffing to increase patient recruitment. In the patients who receive either for of PDT, we will be assessing tissue dosimetry using a novel reflectance probe that can assess tissue scattering and absorption coefficients as well as oximetry information. We will also be assessing the quality of life after therapy using general and disease specific measures. Novel elements of this proposal include the assessment of the extent of dysplasia using an imaging technique combining high-resolution narrow band imaging and autofluorescence imaging. We will continue to assess the response to ablation therapy in these patients with our biomarkers to increase our understanding of their value in predicting the course of the disease. These studies will provide an improved understanding regarding the response of Barrett's esophagus to ablation therapy.
Project Relevance Esophageal cancer is the most rapidly increasing cancer in Caucasian males. At the current time, treatment is limited to surgical resection of the esophagus. These studies are designed to provide a much less invasive option for patients with Barrett's esophagus that are at high risk for this cancer allowing for an improved quality of life. In the process, we are learning about important ways in which cancers can develop and methods to stop them.
|Brankley, S M; Halling, K C; Jenkins, S M et al. (2016) Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma. Dis Esophagus 29:513-9|
|Gorospe, Emmanuel C; Wang, Kenneth K (2014) Barrett oesophagus in 2013: risk stratification and surveillance in Barrett oesophagus. Nat Rev Gastroenterol Hepatol 11:82-4|
|Timmer, Margriet R; Brankley, Shannon M; Gorospe, Emmanuel C et al. (2014) Prediction of response to endoscopic therapy of Barrett's dysplasia by using genetic biomarkers. Gastrointest Endosc 80:984-91|
|Okoro, Ngozi I; Tomizawa, Yutaka; Dunagan, Kelly T et al. (2012) Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus. Clin Gastroenterol Hepatol 10:150-4|
|Wang, K K; Tian, J M; Gorospe, E et al. (2012) Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus. Dis Esophagus 25:349-55|
|Owens, V L; Katzka, D A; Lutzke, L S et al. (2012) Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis. Dis Esophagus 25:33-9|
|Wang, Kenneth K (2011) Advanced imaging in GI mucosal disease: do you see what I see? Gastrointest Endosc 73:204-5|
|Namasivayam, Vikneswaran; Wang, Kenneth K; Prasad, Ganapathy A (2010) Endoscopic mucosal resection in the management of esophageal neoplasia: current status and future directions. Clin Gastroenterol Hepatol 8:743-54; quiz e96|
|Badreddine, Rami J; Prasad, Ganapathy A; Wang, Kenneth K et al. (2010) Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus. Gastrointest Endosc 71:697-703|
|Wang, Kenneth K; Prasad, Ganapathy; Tian, Jianmin (2010) Endoscopic mucosal resection and endoscopic submucosal dissection in esophageal and gastric cancers. Curr Opin Gastroenterol 26:453-8|
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