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Background and Purpose: Deep learning techniques excel in MR-based CT synthesis, but missing uncertainty prediction limits its clinical use in proton therapy. We developed an uncertainty-aware framework and evaluated its efficiency in robust proton planning., Materials and Methods: A conditional generative-adversarial network was trained on 64 brain tumour patients with paired MR-CT images to generate synthetic CTs (sCT) from combined T1-T2 MRs of three orthogonal planes. A Bayesian neural network predicts Laplacian distributions for all voxels with parameters (μ, b). A robust proton plan was optimized using three sCTs of μ and μ±b. The dosimetric differences between the plan from sCT (sPlan) and the recalculated plan (rPlan) on planning CT (pCT) were quantified for each patient. The uncertainty-aware robust plan was compared to conventional robust (global ± 3 %) and non-robust plans., Results: In 8-fold cross-validation, sCT-pCT image differences (Mean-Absolute-Error) were 80.84 ± 9.84HU (body), 35.78 ± 6.07HU (soft tissues) and 221.88 ± 31.69HU (bones), with Dice scores of 90.33 ± 2.43 %, 95.13 ± 0.80 %, and 85.53 ± 4.16 %, respectively. The uncertainty distribution positively correlated with absolute prediction error (Correlation Coefficient: 0.62 ± 0.01). The uncertainty-conditioned robust optimisation improved the rPlan-sPlan agreement, e.g., D95 absolute difference (CTV) was 1.10 ± 1.24 % compared to conventional (1.64 ± 2.71 %) and non-robust (2.08 ± 2.96 %) optimisation. This trend was consistent across all target and organs-at-risk indexes., Conclusion: The enhanced framework incorporates 3D uncertainty prediction and generates high-quality sCTs from MR images. The framework also facilitates conditioned robust optimisation, bolstering proton plan robustness against network prediction errors. The innovative feature of uncertainty visualisation and robust analyses contribute to evaluating sCT clinical utility for individual patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments., Material and Methods: Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared., Results: The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %., Conclusion: CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Skull-base chondrosarcoma (ChSa) is a rare bone tumor and the outcome of patients with this malignancy has been documented only in a limited number of series with a restricted number of patients., Objective: This study was conducted to assess the outcome and prognostic factors of a large cohort of ChSa patients treated with radiotherapy in two proton therapy centers., Materials and Methods: From 1996 to 2015, 251 (male, 43.4%) patients (mean age, 42.0 ± 16.2 years) were treated with protons with (n = 135; 53.8%) or without photons (n = 116; 46.2%). Median delivered dose was 70.2 Gy RBE . Failure-free survival (FFS), overall survival (OS) and CTCAE grade ≥3 toxicity free survival (TFS) were calculated using the Kaplan-Meier method., Results: After a median follow-up of 88.0 months for surviving patients, local and distant failures were observed in 12 (4.8%) and 4 (1.6%) patients, respectively. Late failures >6 years were observed in 4 (33.3%) patients. The estimated 7-year FFS was 93.1%. Twenty-five (10%) patients died. The estimated 7-year OS was 93.6%. Tumor volume (p = 0.006) and optic pathway compression (p = 0.027) were significantly associated with the risk of treatment failure on univariate analysis. Treatment failure was significantly associated with a higher risk of death (hazard ratio = 126). The estimated 7-year TFS was 84.2%., Conclusions: The outcome of skull-base ChSa patients treated with high-dose protons with or without photons is excellent, particularly for patients with small tumors with no optic pathway compression. Treatment failure was however associated with a significantly increased risk of death., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe., Material and Methods: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015., Results: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets., Conclusions: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The study aimed to determine whether post-radiation vaginal side effects in cervical cancer patients can be correlated with DVH parameter D(2cc). The result was negative in that no correlation could be demonstrated between D(2cc) and the presence and grade of side effects in this patients' subset treated with high brachytherapy doses., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To assess feasibility, safety and effectiveness of CT-based 3D conformal external beam radiotherapy (EBRT) plus concurrent cisplatin and MRI-based 3D conformal HDR-brachytherapy (HDR-BT) in the treatment of advanced cervical cancer., Patients and Methods: A total of 48 patients with advanced cervical cancer, treated with CT-based EBRT plus simultaneous cisplatin chemotherapy (40mg/m(2) of body surface per week for 5 weeks) and MRI-based HDR-BT, were included for analysis., Results: All patients completed radiotherapy as planned and 90% received at least four cycles chemotherapy. Frequencies of CTC grade 3 anaemia, grade 3-4 leucopenia and grade 3 thrombocytopenia were 4, 23 and 10%, respectively. Two patients developed deep vein thrombosis and one non-fatal pulmonary embolism. Grade 4 genitourinary late side effects (bladder) occurred in 2 patients. No grade 3-4 gastrointestinal side effects were observed. Complete response (CR) was obtained in 45 patients (94%). After a median follow-up of 33 months, 27 patients were disease free. Actuarial overall survival at 3 years was 61%, progression free survival 51% and continuous complete remission for true pelvis 85%., Conclusions: MRI-based 3D HDR-BT and 3D EBRT plus cisplatin appears to be safe and effective, although acute haematological toxicity is increased. Gastrointestinal morbidity is minimal when prospectively applying 3D dose volume constraints and MRI-based 3D dose volume adaptation.