Should tumors be clamped in radiobiological fractionation experiments?

In radiobiological fractionation experiments tumors are often clamped during irradiation. This is done not only to facilitate the interpretation of the data by eliminating the influence of reoxygenation but also to avoid uncontrolled changes in the hypoxic fraction that are caused by anesthesia or stress from physical restraint. In this study it is shown that clamping of tumors during irradiation also affects repair, repopulation, and redistribution. From these results it is concluded that clamping of tumors during fractionated irradiation treatment does not appear to be an adequate measure to elucidate the mechanisms that determine tumor response to radiotherapy. Even some of the fundamental concepts of tumor radiobiology might contain some uncertainties, since they are often based on data resulting from clamped tumors.