Endoscopic Therapy of Early Cancer in Barretts Esophagus

描述（申请人提供）：食管癌是西方国家白人男性中增长最快的癌症。它与巴雷特食管有关，这是一种恶性前病变，目前的指南建议进行内窥镜筛查和监测。这导致越来越多的早期腺癌被诊断出有可能通过内窥镜治疗。虽然手术切除和放化疗是有效的消除癌症，从这些治疗的发病率是可观的。早期癌症的内镜治疗包括内镜粘膜切除和光动力治疗。内镜下粘膜切除术可以切除含癌组织，并可以准确地确定肿瘤的深度和范围。然而，粘膜切除术通常不能切除所有的癌前粘膜，残留的非癌Barrett粘膜的癌症复发率很高。我们的假设是内镜治疗可以治疗早期食管腺癌。该研究的主要目的是确定在内镜下粘膜切除术之外是否需要光动力疗法来增加早期腺癌患者的无癌生存率。该研究将涉及100例早期食管腺癌患者，这些患者可以通过粘膜切除术完全切除。切除肿瘤后，这些患者将随机接受光动力治疗或仔细观察。本研究的第二个目的是确定预测癌症进展的生物标志物，包括使用新的细胞学技术检测的非整倍体、p53或p16的杂合性缺失是否与组织流式细胞术相关。本研究的第三个目的是确定这些已知的生物标志物是否可以用于识别进展性肿瘤患者并从额外治疗中获益。除了这些已知的生物标志物外，还将储存这些患者的组织，以确定是否有其他生物标志物可用于确定适当的治疗组。本研究的第四个目的是确定这些治疗后患者的生活质量，因为这是选择内镜治疗的重要原因。将按季度进行一般和特定疾病健康相关的生活质量评估，以确定患者在治疗前、治疗期间和治疗后的健康状况。这些特定目标的实现有助于设计未来的试验，以确定治疗早期食管腺癌的最佳策略。本研究开发的诊断和治疗技术可应用于其他胃肠道肿瘤。

DESCRIPTION (provided by applicant): Esophageal adenocarcinoma is the most rapidly increasing cancer among Caucasian males in Western countries. It is associated with Barrett's esophagus, a pre-malignant condition, for which current guidelines recommend both endoscopic screening and surveillance. This has resulted in increasing numbers of early adenocarcinomas being diagnosed that are potentially endoscopically curable. Although surgical resection and chemoradiation are effective in eliminating cancer, the morbidity from these treatments is substantial. The endoscopic treatment of early cancer includes endoscopic mucosal resection and photodynamic therapy. Endoscopic mucosal resection can remove the cancer containing tissue and permits accurate histological determination of tumor depth and extent. However, mucosal resection usually does not removal all of the premalignant mucosa and there has been a high incidence of cancer recurrence in the residual non-cancerous Barrett's mucosa. Our hypothesis is that endoscopic therapy can treat early esophageal adenocarcinoma. The primary aim of the study will be to determine if photodynamic therapy will be needed in addition to endoscopic mucosal resection to increase cancer free survival in patients with early adenocarcinoma. The study will involve one hundred patients with early esophageal adenocarcinoma that can be completely removed by mucosal resection. After removal of the cancer, these patients will be randomized to receive either photodynamic therapy or careful observation. A secondary aim of this study will be to determine if biomarkers that predict cancer progression including aneuploidy, loss of heterozygosity for p53 or p16 performed using novel cytological techniques can be correlated with flow cytometry performed on tissue. The third aim of this study will be to determine if these known biomarkers can be used to identify the patients that have progressive neoplasia and benefit from additional therapy. In addition to these known biomarkers, tissue will be stored from these patients to determine if other biomarkers might be useful in defining appropriate treatment groups. A fourth aim of this study will be to determine the patient's quality of life after these treatments since this is an important reason for choosing endoscopic therapy. General and disease specific health related quality of life assessments would be performed on a quarterly basis to determine their health status before, during and after treatment. The achievement of these specific aims is needed to help design future trials to determine the best strategy for treatment of early esophageal adenocarcinoma. Diagnostic and therapeutic techniques developed in this study can be applied to other gastrointestinal tumors.