## 4 Discussion
The reliability of the new beamline for performing radiobiological experiments has been demonstrated by the results obtained for proton-induced cancer cell death when irradiation was performed in the absence of the \({}^{11}\)B. Clinically used proton beams do exhibit a low LET, which is the very reason of the poor biological effectiveness of PT, yielding usually shouldered survival curves in the low-dose region; however, it is known that close to the distal portion of the SOBP, where the LET increases, the RBE also increases [36] and the clonogenic survival curves tend to become steeper and with a predominance of the \(\alpha\) parameter: the dose-response curves obtained here for non-BSH irradiated cancer cells are in line with this observation and in fact appear as a purely decreasing exponential functions of the dose, as the incident LET is actually higher than that for typical high-energy PT facilities. More significantly, the clonogenic dose-response curves obtained at the newly developed proton beamline in the presence of BSH are also described by a pure exponential function of the dose and present a much steeper slope, typical of high-LET radiation, strongly supporting a role for the high-LET \(\alpha\)-particles from the pB reaction. Moreover, they clearly show that the enhancement due to the pB reaction is the greatest thus far reported and as evaluated by the Dose-Modifying Factor at 10% cell survival level or DMF\({}_{10}\). This was 1.85 for DU145 cells and around 1.56 for the more radioresistant PANC-1 cells: the former is actually higher than the maximum value reported for the DU145 in the first experimental study on PBCT at a relatively low-energy clinical proton beamline (INFN-LNS, Catania, Italy), which was of around 1.7 but just on the distal portion of the proton SOBP [16]. The significant pB-mediated radiosensitization observed for PANC-1 cells is novel and particularly relevant in view of making PT amenable for RT resilient cancer given the inherent radioresistance of the tumour histological type from which these cells originate. In conclusion, the availability of the newly developed beamline at the CIRCE tandem accelerator will provide the opportunity to perform a wide range of radiobiology experiments and, in the context of PBCT, to further corroborate the mechanistic basis for this potentially clinically relevant strategy which, together with other physics-based approaches such as those envisaging the use of nanoparticles [10], as well as FLASH [37] or ultra-high dose rate irradiation regimes [38; 39], may render PT even more readily available, safe and effective. **Author Contributions:** Conceptualization, V.R. and L.M. ; methodology, V.R., L.G. and L.M. ; design of the irradiation setup: V.R., R.B. and G.P. ; software, V.R. and K.M. ; formal analysis, V.R., L.M. and P.B. ; investigation, V.R., G.P. and G.C. ([PERSON]), R.B. and L.M. ; resources, S.P. and L.M. ; data curation, V.R. and L.M. ; writing--original draft preparation, V.R. and L.M. ; writing--review and editing, V.R. and L.M. ; funding acquisition, G.C. ([PERSON]), L.G., L.M. and S.P. All authors have read and agreed to the published version of the manuscript. **Funding:** This work was financially supported by INFN grant NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNravEled) and MIUR PRIN Proton-Boron Capture Therapy 2017 XKWWK9. **Data Availability Statement:** Data are not publicly available but can be made available on request by the corresponding author. **Acknowledgments:** The authors would like to thank [PERSON] and [PERSON] from the technical staff of the Universita della Campania \"[PERSON]\" and INFN mechanical workshops for their support in the design and original mechanical components' production phase. **Conflicts of Interest:** The authors declare no conflict of interest.