Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation in Colorectal Liver Metastases

Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation in Colorectal Liver Metastases

Randomised Controlled Phase I/II Trail to Evaluate the Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation Therapy in Resectable Colorectal Liver Metastases Patients

The efficiency of T cell based immunotherapies is affected by the insufficient migration and activity of tumor specific effector T cells in the tumor. Aim of this phase I/II clinical trial is to evaluate whether a neoadjuvant, low dose radiotherapy can improve T cell connected anti tumor immune response in colorectal liver metastases. The primary endpoint is the number of tumor infiltrating T cells. Furthermore the T cell activity in situ, the number of regulatory T cells and the frequency of tumor reactive T cells in the blood and bone marrow will be examined.

Radiation: one time Radiation with an intensity of 0.5 Gy Group A Beginning on a weekday 48 hours before surgery

Radiation: one time Radiation with an intensity of 2.0 Gy Group B Beginning on a weekday 48 hours before surgery

Radiation: one time Radiation with an intensity of 5 Gy Group C Beginning on a weekday 48 hours before surgery

Radiation: one time Radiation with an intensity of 0.5 Gy Group A 2.0 Gy Group B 5 Gy Group C Beginning on a weekday 48 hours before surgery

Purpose of the study is the determination of an active local external beam radiotherapy dose leading to a maximal number of tumor infiltrating T-cells. The total T-cell activity serves as primary surrogate parameters for anti- tumor activity

To determine the progression-free survival in patients treated with low dose photon beam radiation therapy

• To determine the surgical morbidity in patients undergoing liver resection who received this protocol treatment

• To determine 30-day post-operative mortality after liver resection in patients who received this protocol treatment

To determine the number of patients with adverse events as a measure of safety and tolerability according to CTCAE, Version 4.0 criteria

Inclusion Criteria: Ability of subject to understand character and individual consequences of the clinical trial Written informed consent (must be available before enrolment in the trial) Age ≥ 50 years Radiological urgently suspected colorectal liver metastasis Exclusion Criteria: second malignancy Pregnancy and lactation no prior liver radiation liver metastasis must be resectable

Reissfelder C, Timke C, Schmitz-Winnenthal H, Rahbari NN, Koch M, Klug F, Roeder F, Edler L, Debus J, Buchler MW, Beckhove P, Huber PE, Weitz J. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer. BMC Cancer. 2011 Sep 30;11:419. doi: 10.1186/1471-2407-11-419.