A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer

BMC Cancer

Christoph Reissfelder²  Carmen Timke¹  Hubertus Schmitz-Winnenthal²  Nuh N Rahbari²  Moritz Koch²  Felix Klug³  Falk Roeder¹  Lutz Edler¹  Jürgen Debus¹  Markus W Büchler²  Philipp Beckhove³  Peter E Huber¹  Jürgen Weitz² 

[1] Department of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, Germany

[2] Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Germany

[3] Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany

关键词: tumor specific T cells;    low dose radiation;    colorectal liver metastasis;   

Others  :  1080716
DOI  :  10.1186/1471-2407-11-419

 received in 2011-02-08, accepted in 2011-09-30,  发布年份 2011

【 摘 要 】

Background

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.

Discussion

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.

Trial registration

ClinicalTrials.gov: NCT01191632

【 授权许可】

   
2011 Reissfelder et al; licensee BioMed Central Ltd.

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