DescriptionOne in two cancer patients are routinely treated with radiotherapy, using a linear accelerator to deliver the radiation dose. Conventionally, a treatment meets guidelines when the tumour is uniformly irradiated, but the surrounding normal tissue is avoided [1]. However, our recent study upsets this radiation therapy "dogma" [2]. We have shown that a radiation field with many high dose gradients may have an advantage over a uniform field [2], because it is more lethal to cancer cells than to normal cells. We attribute this effect predominantly to the production, diffusion and response to radiation induced bystander signals, which is consistent with previous reports of up to 60% of cell death following irradiation being attributed to bystander effects [3,4].The use of a radiation field that delivers a non-uniform dose with high dose gradients is not new. Spatially fractionated radiotherapy or grid therapy, delivers radiation through a collimating grid block or by using the multileaf collimator of a linear accelerator. This approach creates an alternating peak and valley dose across the body surface with a spatial period of a few centimeters. At depth, the dose gradients will smear out and be reduced. Such fields have been known to allow a higher dose to the tumour at depth, while sparing normal tissue at shallower depths. Even though only a limited number of grid therapy cases are carried out in the clinic today, the responses have been encouraging with the achievement of a higher therapeutic ratio [5].Another technique, which by design incorporates high dose gradients within the treatment field, is microbeam radiation therapy (MRT), where the field is created as a composite of micro-scale beams using an x-ray synchrotron. The medical beam line of a synchrotron creates non-divergent photon beams with far higher dose rates than a linear accelerator, therefore delivering a high dose quickly, while maintaining dose modulation [6,7]. To date, only in-vitro [8] and in-vivo animal studies have been performed using MRT, achieving exceptional therapeutic outcomes with preferential tumour toxicity and high normal tissue tolerance [9]. The peak dose in the micro-sized beam is over a hundred times greater than conventional radiotherapy and the outcomes are difficult to explain using the conventional dogma of radiation therapy.The success of MRT has been attributed to the differential response between tumour and normal tissue, particularly in their vasculature [10], but this factor does not explain the invitro therapeutic advantages.Synchrotron facilities are currently not suitable for human cancer treatment, but it is feasible that the therapeutic advantages of MRT may in part be translated to the clinic using new generation linear accelerators. We questioned whether a radiation field created with linear accelerators, to give the finest possible collimated beams and therefore high dose gradients, could achieve a better therapeutic outcome than the conventional uniform field. By using the high definition micro-mult...