Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable XXXX .

@entity1 @entity32 @entity3123 @entity788 @entity137 @entity5
BACKGROUND: The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of @entity5 specific effector T cells in the @entity5 . Accumulating evidence exists on the ability of ionizing radiation to modify the @entity5 microenvironment and generate @entity32 . The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in @entity1 with @entity788 . METHODS/DESIGN: This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. @entity1 who are candidates for resection of @entity788 will be randomized into 4 arms. A total of 40 @entity1 will be enrolled. The @entity1 receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their @entity3123 . Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to @entity5 infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include @entity5 control and recurrence patterns, survival, radiogenic treatment @entity137 and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of @entity5 reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrollment of 20 @entity1 for safety reasons. The evaluation of the primary endpoint will start four weeks after the last @entity1 's enrollment. DISCUSSION: This trial will answer the question whether a low dose radiotherapy localized to the @entity788 only can increase the number of @entity5 infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome.
