Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany.
BMC Cancer. 2011 Sep 30;11:419. doi: 10.1186/1471-2407-11-419.
Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases.
METHODS/DESIGN: This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome.
This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response.
ClinicalTrials.gov: NCT01191632.
肿瘤中肿瘤特异性效应 T 细胞的迁移和激活不足是宿主抗肿瘤免疫反应不足的主要原因之一。外照射似乎能诱导炎症并激活免疫反应。这项 I/II 期临床试验旨在评估低剂量单次分割放疗是否能提高结直肠癌肝转移患者的 T 细胞相关抗肿瘤免疫反应。
方法/设计：这是一项由研究者发起的、前瞻性的、随机的、四臂对照的 I/II 期临床试验。由于结直肠癌肝转移而接受择期肝切除术的患者将被纳入研究。患者将接受 0 Gy、0.5 Gy、2 Gy 或 5 Gy 靶向肝转移灶的外照射放疗。放疗将在术前两天使用 6 MV 直线加速器（Linac）和强度调制放疗（IMRT）技术进行外照射放疗。所有被收入海德堡大学普通、内脏和移植外科的因择期肝切除术而入院的患者都将被连续筛选是否符合该试验的入选标准，并在纳入前获得书面知情同意。主要目的是评估主动局部外照射剂量对肿瘤浸润性 T 细胞的影响，将其作为抗肿瘤活性的替代参数。次要目标包括放射性治疗毒性、术后发病率和死亡率、局部肿瘤控制和复发模式、生存和生活质量。此外，还将分析血液和骨髓中全身肿瘤反应性 T 细胞的频率与临床结果的相关性。
这是一项随机对照患者盲法试验，旨在评估低剂量放疗对转移浸润 T 细胞的安全性和有效性，从而潜在增强抗肿瘤免疫反应。
ClinicalTrials.gov：NCT01191632。
