Timing of Rectal Cancer Response to Chemoradiation

直肠癌对放化疗的反应时机

• 批准号: 7276761
• 负责人: JULIO GARCIA-AGUILAR
• 金额: $ 64.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-16 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276761
• 关键词: Timing; Rectal; Cancer; Response; Chemoradiation

DESCRIPTION (provided by applicant): The treatment of locally advanced rectal cancer combines chemoradiation followed by radical surgery. A number of rectal cancer patients treated with preoperative chemoradiation have no detectable cancer cells in the surgical specimens. Our long-term objective is to determine whether or not patients with a complete pathologic tumor response to chemoradiation can achieve local control without radical surgery. The benefit to such patients in terms of reduced morbidity and improvement of quality of life, as well as the marked reduction in health care costs will be significant. The potential use of chemoradiation as the only form of therapy in rectal cancer patients is appealing, yet the information on rectal cancer response to radiation is very limited. The reported rate of pathologic complete pathologic response varies between series due to differences in the chemoradiation protocol. Whether pathologic complete response represents transient tumor regression or permanent eradication remains unknown. The diagnostic methods used to image rectal cancer cannot accurately differentiate preoperatively between radiation-induced fibrosis and residual tumor; pathologic assessment of the surgical specimen is the only way to diagnose pathologic complete response. In this study we will first determine the rate of pathologic complete response to chemoradiation of ultrasound-stage II and III rectal cancers treated according to a standardized chemoradiation and surgery protocol, and evaluated by a systematic pathologic exam of the surgical specimen. We will then study whether complete pathologic response is equivalent to permanent tumor eradication. Patients with ultrasound-stage II and III rectal cancer treated with preoperative chemoradiation will be entered in a series of sequential Phase II trials in which the only variable will be the chemoradiation-to-surgery interval. A stable or increasing rate of pathologic complete response with longer chemoradiation-to-surgery intervals will indicate that pathologic complete response represents permanent tumor eradication rather than transient regression. In addition, we will explore the feasibility of using a panel of cancer-specific genetic alterations to detect cancer cells in the rectal cancer specimens of patients treated with preoperative chemoradiation and radical surgery. DNA extracted from cancer cells microdissected from pre-chemoradiation biopsy specimens will be tested for mutations in the p53, k-ras and APC genes, BAT26 deletions, and p16 promoter methylation. We will then investigate whether the specific mutation identified in the pre-chemoradiation cancer cells can be detected in a paired DNA sample obtained from the tumor bed and regional lymph nodes of the post-chemoradiation surgical specimen. This information will help develop molecular assays to diagnose pathologic complete response in transrectal biopsies of the tumor bed before removing the rectum.

描述（由申请人提供）：局部晚期直肠癌的治疗结合了化学放疗，然后进行了根治性手术。许多接受术前化学放疗治疗的直肠癌患者在手术标本中没有可检测的癌细胞。我们的长期目标是确定对化疗的完全病理肿瘤反应的患者是否可以在没有根本手术的情况下实现局部控制。在降低发病率和改善生活质量以及医疗保健费用的明显下降方面，对此类患者的好处将是显着的。在直肠癌患者中，化学放疗作为唯一的治疗形式是吸引人的，但是有关直肠癌对辐射反应的信息非常有限。由于化学放疗方案的差异，报道的病理完全病理反应率在串联之间有所不同。病理完全反应代表瞬态肿瘤回归还是永久性消除仍然未知。用于成像直肠癌的诊断方法无法在辐射诱导的纤维化和残留肿瘤之间准确区分。手术标本的病理评估是诊断病理完全反应的唯一方法。在这项研究中，我们将首先确定对根据标准化的化学放疗和手术方案治疗的超声II和III直肠癌的化学放疗的病理完全反应率，并通过对手术标本的系统病理检查进行了评估。然后，我们将研究完全的病理反应是否等同于消除永久性肿瘤。术前化学放疗治疗的超声II和III直肠癌的患者将在一系列顺序II期试验中输入，其中唯一的变量将是化学放疗间隔间隔。稳定或增加的病理完全反应速率在较长的化学放疗间隔内将表明病理完全反应代表了永久性的消除肿瘤，而不是短暂的回归。此外，我们将探讨使用一组癌症特异性遗传改变来检测接受术前化学辐射和根治性手术的患者的癌细胞的可行性。从从化学前活检标本中微分辨率的癌细胞中提取的DNA将在p53，K-RAS和APC基因，BAT26缺失和p16启动子甲基化中测试突变。然后，我们将研究是否可以在从肿瘤床和化学后手术样本的肿瘤床和区域淋巴结中获得的化学前癌细胞中鉴定出的特异性突变。该信息将有助于开发分子测定，以诊断肿瘤床的转直肠活检中的病理完全反应，然后再去除直肠。