Introduction Proton therapy is very sensitive to treatment uncertainties. These uncertainties can induce proton range variations and may lead to severe dose distortions. However, most commercial tools only offer a limited integration of these uncertainties during treatment planning. In order to verify the robustness of a treatment plan, this study aims at developing a comprehensive Monte Carlo simulation of the treatment delivery, including the simulation of setup and range errors, variation of the breathing motion, and interplay effect. Method Most clinically relevant uncertainties have been modeled and implemented in the fast Monte Carlo dose engine MCsquare. Especially, variation of the breathing motion is taken into account by deforming the initial Four‐dimensional computed tomography (4DCT) series and generating multiple new 4DCT series with scaled motion. Systematic and random errors are randomly sampled, following a Monte Carlo approach, to generate individual erroneous treatment scenarios. The robustness of treatment plans is analyzed and reported with dose‐volume histogram (DVH) bands. The statistical uncertainty coming from the Monte Carlo scenario sampling is studied. Results A validation demonstrated the ability of the motion model to generate new 4DCT series with scaled motion amplitude and improved image quality in comparison to the initial 4DCT. The robustness analysis is applied to a lung tumor treatment. Considering the proposed uncertainty model, the simulation of 300 treatment scenarios was necessary to reach an acceptable level of statistical uncertainty on the DVH band. Conclusion A comprehensive and statistically sound method of treatment plan robustness verification is proposed. The uncertainty model presented in this paper is not specific to protons and can also be applied to photon treatments. Moreover, the generated 4DCT series, with scaled motion, can be imported in commercial TPSs.

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In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.

Background: Tumor hypoxia increases resistance to radiotherapy and systemic therapy. Our aim was to develop and validate a disease-agnostic and disease-specific CT (+FDG-PET) based radiomics hypoxia classification signature. Material and methods: A total of 808 patients with imaging data were included: N = 100 training/N = 183 external validation cases for a disease-agnostic CT hypoxia classification signature, N = 76 training/N = 39 validation cases for the H&N CT signature and N = 62 training/N = 36 validation cases for the Lung CT signature. The primary gross tumor volumes (GTV) were manually defined by experts on CT. In order to dichotomize between hypoxic/well-oxygenated tumors a threshold of 20% was used for the [ 18 F]-HX4derived hypoxic fractions (HF). A random forest (RF)-based machine-learning classifier/regressor was trained to classify patients as hypoxia-positive/ negative based on radiomic features. Results: A 11 feature ''disease-agnostic CT model" reached AUC's of respectively 0.78 (95% confidence interval [CI], 0.62-0.94), 0.82 (95% CI, 0.67-0.96) and 0.78 (95% CI, 0.67-0.89) in three external validation datasets. A ''disease-agnostic FDG-PET model" reached an AUC of 0.73 (0.95% CI, 0.49-0.97) in validation by combining 5 features. The highest ''lung-specific CT model" reached an AUC of 0.80 (0.95% CI, 0.65-0.95) in validation with 4 CT features, while the ''H&N-specific CT model" reached an AUC of 0.84 (0.95% CI, 0.64-1.00) in validation with 15 CT features. A tumor volume-alone model was unable to significantly classify patients as hypoxia-positive/ negative. A significant survival split (P = 0.037) was found between CT-classified hypoxia strata in an external H&N cohort (n = 517), while 117 significant hypoxia gene-CT signature feature associations were found in an external lung cohort (n = 80). Conclusion:The disease-specific radiomics signatures perform better than the disease agnostic ones. By identifying hypoxic patients our signatures have the potential to enrich interventional hypoxiatargeting trials.