EP-1412: Experience using a commercial software for patient in-vivo and pre-treatment quality assurance

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Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain

Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general

Multi-centre real-world validation of automated treatment planning for breast radiotherapy

Purpose: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices. Methods: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan (‘manplan’). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units. Results: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart Dmean, 16.7 % for ipsilateral lung Dmean, and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D0.03cc, D5% and Dmean, respectively (all p &lt; 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0–10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability. Conclusion: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians’ satisfaction with the generated autoplans.</p