###### Abstract  
FLASH irradiations use dose-rates orders of magnitude higher than commonly used in patient treatments. Such irradiations have shown interesting normal tissue sparing in cell and animal experiments, and, as such, their potential application to clinical practice is being investigated. Clinical accelerators used in proton therapy facilities can potentially provide FLASH beams; therefore, the topic is of high interest in this field. However, a clear FLASH effect has so far been observed in presence of high dose rates (>40 Gy/s), high delivered dose (tens of Gy), and very short irradiation times (<300 ms). Fulfilling these requirements poses a serious challenge to the beam diagnostics system of clinical facilities. We will review the status and proposed solutions, from the point of view of the beam definitions for FLASH and their implications for beam diagnostics. We will devote particular attention to the topics of beam monitoring and control, as well as absolute dose measurements, since finding viable solutions in these two aspects will be of utmost importance to guarantee that the technique can be adopted quickly and safely in clinical practice. FLASH; proton therapy; pencil beam scanning +
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context: that ultra-high dose rates might substantially improve tissue sparing while keeping tumor control levels at least to the level of standard dose rates. Dose rates of more than 40 Gy/s have been applied to different animal models, in-vitro and in-vivo [2], and lung, smooth muscle, and epithelial cell sparing has been reported [4]. In addition, dose rates above 100 Gy/s have shown memory sparing effects on live mice undergoing whole-brain irradiation [5]. These results pose many questions about the differential response of tumor and healthy tissues at high dose rates, which require biological understanding at the cellular and systemic level [6]. Several groups tested modifications of clinical machines to enable small animal irradiation studies at high dose rates [7; 8; 9]. Since the biological mechanism has not yet been understood, it is hard to precisely define the beam conditions to trigger the FLASH effect. Average dose rates thresholds of 40 Gy/s have been identified in older studies of animal models, while more recent results seem to show larger importance of instantaneous dose rate and total irradiation time. Experiments with electron and photon beams have shown FLASH effects for instantaneous dose rates between \(10^{4}\) and \(10^{9}\) Gy/s, and total irradiation time below 200 ms [10]. Clinical proton accelerators already are able to deliver dose rates in the low end of this range and, therefore, are excellent candidates for a first clinical translation of FLASH irradiations [11]. There is also likely a minimum amount of dose to be delivered to trigger the effect, as reported in older studies on radio-resistance [3]. In addition, for this reason, the main scenario considered for the application of FLASH with patients is hypofractionation or even single-fraction treatments [2; 10]. This means that a direct clinical translation of the technique in standard radiotherapy practice will still require substantial work, from the point of view of not only the understanding of the biological aspects, but also from a technological point of view. Only a handful of human patient have been so far treated with this technique [12; 13]. In this paper, we will review some of the challenges faced by proton therapy facilities who want to upgrade to a FLASH irradiation modality. A simplistic sketch of a proton therapy facility is shown in Figure 1. Standard proton therapy is delivered at a dose rate of a few Gy/minute (1-2 Gy/min for standard fractionation schemes and PBS, 10 Gy/min for hypoffractionated eye melanoma treatments with scattering). Switching to a FLASH regime means increasing the dose rate by a couple of orders of magnitude.