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We investigate uncertainty guidance mechanisms to support proton therapy (PT) planning visualization. Uncertainties in the PT workflow pose significant challenges for navigating treatment plan data and selecting the most optimal plan among alternatives. Although guidance techniques have not yet been applied to PT planning scenarios, they have successfully supported sense- and decision-making processes in other contexts. We hypothesize that augmenting PT uncertainty visualization with guidance may influence the intended users’ perceived confidence and provide new insights. To this end, we follow an iterative co-design process with domain experts to develop a visualization dashboard enhanced with distinct level-of-detail uncertainty guidance mechanisms. Our approach classifies uncertainty guidance into two dimensions: degree of intrusiveness and detail-orientation. Our dashboard supports the comparison of multiple treatment plans (i.e., nominal plans with their translational variations) while accounting for multiple uncertainty factors. We subsequently evaluate the designed and developed strategies by assessing perceived confidence and effectiveness during a sense- and decision-making process. Our findings indicate that uncertainty guidance in PT planning visualization does not necessarily impact the perceived confidence of the users in the process. Nonetheless, it provides new insights and raises uncertainty awareness during treatment plan selection. This observation was particularly evident for users with longer experience in PT planning.

Background: The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial. Material and methods: A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30. Results: Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p

Radiochromic silicone-based dosimeters are flexible 3D dosimeters, which at appropriate concentration of leucomalachite green (LMG) and curing agent are dose-rate independent for clinical photon beams. However, their dose response is based on chemical processes that can be influenced by temporal and thermal conditions, impacting measurement stability.The aim of this study was to investigate the temporal stability of the dose response of radiochromic dosimeters for different curing times and post-irradiation storage temperatures.Six cylindrical dosimeters (5 cm diameter, 5 cm length) were produced in a single batch and separated into two groups that were irradiated 72 and 118 hours after production. The same photon plan, consisting of two 10 × 1.6 cmStorage temperature influenced the measurement stability, and changes in the optical response with time differed between irradiated and non-irradiated parts of the dosimeters. The relative change between signal and background was greater than 10% for all measurements performed 24 hours or more after irradiation, except for dosimeters stored at 5 ͦC, which changed by 2-5% after 24 hours. The dosimeter temporal stability was not influenced by curing time.For room temperature storage (15 and 20 ͦC), readout should take place as soon as possible after irradiation since the background colour increased rapidly for both curing times (72 and 118 hours), whereas the dosimeters are stored at 5 ͦC, readout can be performed up to 24 hours after. This article is protected by copyright. All rights reserved.

Medical physics has made considerable contributions to recent advances in radiation oncology. Medical physicists are key players in the clinical and scientific radiation oncology context due to their unique skill sets, flexibility, clinical involvement and intrinsic translational character. The continuing development and widespread adoption of "high-tech" radiotherapy has led to an increased need for medical physics involvement. More recently, our field is rapidly changing towards an era of "precision oncology". These changes have opened new challenges for the definition of the professional and scientific roles and responsibilities of medical physicists. In this paper, we have identified four grand challenges of medical physics in radiation oncology: (1) improving target volume definition, (2) adoption of artificial intelligence and automation, (3) development of predictive models of biological effects for precision medicine, and (4) need for leadership. New visions and suggestions to orientate medical physics to successfully face these new challenges are summarized. We foresee that the scientific and professional challenges of our times are pushing medical physicists to accelerate toward multidisciplinarity. Medical physicists are expected to innovatively drive interactions and collaborations with other specialists outside radiation oncology while the radiation physics core will remain central. Medical physicists will retain strong and pivotal roles in quality, safety and in managing ever more complex technologies. The new challenges will require medical physicists to continuously update skills and innovate education, adapt curricula to include new fields, reinforce multi-disciplinary attitude and spirit of innovation. These challenges require visionary and open leadership, which is able to merge established roles with the exciting new fields where medical physics should increasingly contribute. (C) 2020 Elsevier B.V. All rights reserved.

In radiation therapy (RT) for prostate cancer, changes in patient anatomy during treatment might lead to inadequate tumor coverage and higher irradiation of healthy tissues in the nearby pelvic organs. Exploring and analyzing anatomical variability throughout the course of RT can support the design of more robust treatment strategies, while identifying patients that are prone to radiation-induced toxicity. We present VAPOR, a novel application for the exploration of pelvic organ variability in a cohort of patients, across the entire treatment process. Our application addresses: (i) the global exploration and analysis of anatomical variability in an abstracted tabular view, (ii) the local exploration and analysis thereof in anatomical 2D/3D views, where comparative and ensemble visualizations are integrated, and (iii) the correlation of anatomical variability with radiation doses and potential toxicity. The workflow is based on available retrospective cohort data, which include segmentations of the bladder, the prostate, and the rectum through the entire treatment period. VAPOR is applied to four usage scenarios, which were conducted with two medical physicists. Our application provides clinical researchers with promising support in demonstrating the significance of treatment adaptation to anatomical changes.

Intrafractional motion and deformation influence proton therapy delivery for tumours in the thorax, abdomen and pelvis. This study aimed to test the dose–response of a compressively strained three-dimensional silicone-based radiochromic dosimeter during proton beam delivery. The dosimeter was read-out in its relaxed state using optical computed tomography and calibrated for the linear energy transfer, based on Monte Carlo simulations. A three-dimensional gamma analysis showed a 99.3% pass rate for 3%/3 mm and 93.9% for 2%/2 mm, for five superimposed measurements using deformation-including Monte Carlo dose calculations as reference. We conclude that the dosimeter’s dose–response is unaffected by deformations.

Background and purpose Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries. Material and methods CBCT projections of a Catphan and an Alderson phantom were acquired on both a proton and a photon gantry. The scatter corrected CBCTs (corrCBCTs) and the clinical reconstructions (stdCBCTs) were compared against CTs rigidly registered to the CBCTs (rigidCTs). The CBCTs of the Catphan phantom were segmented by materials for CT number analysis. Water equivalent path length (WEPL) maps were calculated through the Alderson phantom while proton plans optimized on the rigidCT and recalculated on all CBCTs were compared in a gamma analysis. Results In medium and high-density materials, the corrCBCT CT numbers were much closer to those of the rigidCT than the stdCBCTs. E.g. in the 50% bone segmentations the differences were reduced from above 300 HU (with stdCBCT) to around 60–70 HU (with corrCBCT). Differences in WEPL from the rigidCT were typically well below 5 mm for the corrCBCTs, compared to well above 10 mm for the stdCBCTs with the largest deviations in the head and thorax regions. Gamma pass rates (2%/2mm) when comparing CBCT-based dose re-calculations to rigidCT calculations were improved from around 80% (with stdCBCT) to mostly above 90% (with corrCBCT). Conclusion Scatter correction leads to substantial artefact reductions, improving accuracy of CBCT-based proton range/dose calculations.

Background and purpose: Proton therapy (PT) is currently being studied to improve normal tissue (NT) sparing beyond what can be achieved with conventional photon-based therapy. Compared to photons, PT dose distributions have a reduced NT low-to-intermediate ‘dose bath’ and a different biological effectiveness, questioning the applicability of photon-based NT complication probability (NTCP) models to PT. The aim of this study was to assess the applicability of photon-based NTCP models to rectum morbidity outcomes following PT. Materials and methods: Treatment planning and morbidity data from 1151 prostate cancer patients treated with passive scattering PT and from 159 patients treated with conventional 3D conformal four-field photon therapy were analysed. Prospectively scored gastrointestinal morbidities (grade >=2) were analysed, with a total of 184 events (protons; medical and procedural) and 12 events (photons; procedural only), respectively. Rectal dose volume histograms were extracted for all patients in both cohorts and used as input to two different NTCP models, with up to six different published photon-based parameter sets. Results: Photon-based rectal NTCP models either over- or underestimated the clinically observed gastrointestinal morbidity when used on the proton cohort, depending on the choice of endpoint (p < 0.05 for all parameter sets, for both morbidity classifications). Four of the six photon-based NTCP models showed a good fit to the photon outcome data (p > 0.05). Conclusion: There were large differences in morbidity predictions between cohorts and modalities, indicating that the validity of NTCP models and parameters across institutions and treatment modalities should be carefully investigated prior to clinical application.

Introduction: Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential of range guidance using water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT. Materials and methods: Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95%Results: The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65-88% for a 2 mm threshold, 83-96% for 3 mm, 90-99% for 4 mm, and 94-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82-100% sensitivity and 75-80% specificity using a 2 mm Hausdorff threshold for the lateral fields. Conclusion: Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.

Radiotherapy (RT) requires meticulous planning prior to treatment, where the RT plan is optimized with organ delineations on a pre-treatment Computed Tomography (CT) scan of the patient. The conventionally fractionated treatment usually lasts several weeks. Random changes (e.g., rectal and bladder filling in prostate cancer patients) and systematic changes (e.g., weight loss) occur while the patient is being treated. Therefore, the delivered dose distribution may deviate from the planned. Modern technology, in particular image guidance, allows to minimize these deviations, but risks for the patient remain. We present PREVIS: a visual analytics tool for (i) the exploration and prediction of changes in patient anatomy during the upcoming treatment, and (ii) the assessment of treatment strategies, with respect to the anticipated changes. Records of during-treatment changes from a retrospective imaging cohort with complete data are employed in PREVIS, to infer expected anatomical changes of new incoming patients with incomplete data, using a generative model. Abstracted representations of the retrospective cohort partitioning provide insight into an underlying automated clustering, showing main modes of variation for past patients. Interactive similarity representations support an informed selection of matching between new incoming patients and past patients. A Principal Component Analysis (PCA)-based generative model describes the predicted spatial probability distributions of the incoming patient’s organs in the upcoming weeks of treatment, based on observations of past patients. The generative model is interactively linked to treatment plan evaluation, supporting the selection of the optimal treatment strategy. We present a usage scenario, demonstrating the applicability of PREVIS in a clinical research setting, and we evaluate our visual analytics tool with eight clinical researchers.

Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Methods: Forty patients (aged 1–17 years) referred from Norwegian institutions to cranial PT abroad during 2014–2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.

Background: Several brain substructures associated with cognition (BSCs) are located close to typical pediatric brain tumors. Pediatric patients therefore have considerable risks of neurocognitive impairment after brain radiotherapy. In this study, we investigated the radiation doses received by BSCs for three common locations of pediatric brain tumor entities. Material and methods: For ten patients in each group [posterior fossa ependymoma (PFE), craniopharyngioma (CP), and hemispheric ependymoma (HE)], the cumulative fraction of BSCs volumes receiving various dose levels were analyzed. We subsequently explored the differences in dose pattern between the three groups and used available dose response models from the literature to estimate treatment-induced intelligence quotient (IQ) decline. Results: Doses to BSCs were found to differ considerably between the groups, depending on their position relative to the tumor. Large inter-patient variations were observed in the ipsilateral structures of the HE groups, and at low doses for all three groups. IQ decline estimates differed depending on the model applied, presenting larger variations in the HE group. Conclusion: While there were notable differences in the dose patterns between the groups, the extent of estimated IQ decline depended more on the model applied. This inter-model variability should be considered in dose–effect assessments on cognitive outcomes of pediatric patients.

Radiation therapy (RT) is one of the major curative approaches for cancer. It is a complex and risky treatment approach, which requires precise planning, prior to the administration of the treatment. Visual Computing (VC) is a fundamental component of RT planning, providing solutions in all parts of the process-from imaging to delivery. Despite the significant technological advancements of RT over the last decades, there are still many challenges to address. This survey provides an overview of the compound planning process of RT, and of the ways that VC has supported RT in all its facets. The RT planning process is described to enable a basic understanding in the involved data, users and workflow steps. A systematic categorization and an extensive analysis of existing literature in the joint VC/RT research is presented, covering the entire planning process. The survey concludes with a discussion on lessons learnt, current status, open challenges, and future directions in VC/RT research.

Background and purpose Proton therapy (PT) of extra-cranial tumour sites is challenged by density changes caused by inter-fractional organ motion. In this study we investigate on-line dose-guided PT (DGPT) to account inter-fractional target motion, exemplified by internal motion in the pelvis. Materials and methods On-line DGPT involved re-calculating dose distributions with the isocenter shifted up to 15 mm from the position corresponding to conventional soft-tissue based image-guided PT (IGPT). The method was applied to patient models with simulated prostate/seminal vesicle target motion of ±3, ±5 and ±10 mm along the three cardinal axes. Treatment plans were created using either two lateral (gantry angles of 90°/270°) or two lateral oblique fields (gantry angles of 35°/325°). Target coverage and normal tissue doses from DGPT were compared to both soft-tissue and bony anatomy based IGPT. Results DGPT improved the dose distributions relative to soft-tissue based IGPT for 39 of 90 simulation scenarios using lateral fields and for 50 of 90 scenarios using lateral oblique fields. The greatest benefits of DGPT were seen for large motion, e.g. a median target coverage improvement of 13% was found for 10 mm anterior motion with lateral fields. DGPT also improved the dose distribution in comparison to bony anatomy IGPT in all cases. The best strategy was often to move the fields back towards the original target position prior to the simulated target motion. Conclusion DGPT has the potential to better account for large inter-fractional organ motion in the pelvis than IGPT.

Background and purpose: Photons and protons have fundamentally different properties, i.e. protons have a reduced dose bath but a higher relative biological effectiveness. Photon-based normal tissue complication probability (NTCP) models may therefore not immediately be applicable to proton therapy (PT). The aim was to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively recorded late morbidity data from PT, focusing on rectal morbidity and prostate cancer. Materials and methods: Prospectively collected data were available for 1151 prostate cancer patients treated with passive scattering PT and prescribed target doses of 78–82 Gy (RBE = 1.1) in 2 Gy fractions. Morbidity data (CTCAE v3.0) consisted of two alternative late grade 2 rectal bleeding endpoints: Medical Grade2A (GR2A) and procedural Grade2B (GR2B), as well as late grade 3 + urinary morbidity. GR2A + 2B were observed in 156/1047 patients (15%), GR2B in 45/1047 patients (4%), and urinary grade 3 + in 51/1151 patients (4%). LKB NTCP model parameters (D50, m, and n) were derived by maximum likelihood estimation. Results: For the rectum/rectal wall the volume parameter n was low (0.07–0.14) for both GR2A + 2B and GR2B, as was the m parameter (range: 0.16–0.20). For the bladder/bladder wall both parameters were high (n-range: 0.20–0.36; m-range: 0.32–0.36). D50 parameters were higher for GR2B of the rectum/rectal wall (95.9–98.0 Gy) and bladder/bladder wall (118.1–119.9 Gy), but lower for GR2A2B (71.7–73.6 Gy). Conclusion: PT specific LKB NTCP model parameters were derived from a population of more than 1000 patients. The D50 parameter differed for all structures and endpoints and deviated from typical photon-based LKB model values.

Background and purpose The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work. Methods A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers. Results The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work). Conclusion COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting.

Survivors of pediatric brain tumors are susceptible to neurovascular disease after radiotherapy, with dose to the chiasm or Circle of Willis (CW) as risk factors. The aims of this study were to develop a delineation atlas of neurovascular structures, to investigate the doses to these structures in relation to tumor location and to investigate potential dose surrogates for the CW dose. An atlas of the CW, the large intracranial arteries and the suprasellar cistern (SC) was developed and validated. Thirty proton plans from previously treated pediatric brain tumor patients were retrieved and grouped according to tumor site: 10 central, 10 lateralized, and 10 posterior fossa tumors. Based on the atlas, neurovascular structures were delineated and dose metrics (mean dose (Dmean) and maximal dose (Dmax)) to these structures and the already delineated chiasm were evaluated. The agreement between dose metrics to the CW vs. chiasm/SC was investigated. The minimal Hausdorff distance (HDmin) between the target and SC was correlated with the SC Dmean. The median Dmean/Dmax to the CW were 53 Gy(RBE)/55 Gy(RBE) in the central tumors, 18 Gy(RBE)/25 Gy(RBE) in the lateralized tumors and 30 Gy(RBE)/49 Gy(RBE) in the posterior fossa tumors. There was a good agreement between the Dmax/Dmean to the CW and the SC for all cases (R2=0.99), while in the posterior fossa group, the CW Dmax was underestimated when using the chiasm as surrogate (R2=0.76). Across all patients, cases with HDmin < 10 mm between the target and the SC received the highest SC Dmean. The pattern of dose to neurovascular structures varied with the tumor location. For all locations, SC doses could be used as a surrogate for CW doses. A minimal distance larger than 10 mm between the target and the SC indicated a potential for neurovascular dose sparing.

Purpose: During radiation therapy for pediatric brain tumors, the brainstem is a critical organ at risk, possibly with different radio-sensitivity across its substructures. In proton therapy, treatment planning is currently performed using a constant relative biological effectiveness (RBE) of 1.1 (RBE1.1), whereas preclinical studies point toward spatial variability of this factor. To shed light on this biological uncertainty, we investigated the spatial agreement between isodose maps produced by different RBE models, with emphasis on (smaller) substructures of the brainstem. Methods and Materials: Proton plans were recalculated using Monte Carlo simulations in 3 anonymized pediatric patients with brain tumors (a craniopharyngioma, a low-grade glioma, and a posterior fossa ependymoma) to obtain dose and linear energy transfer distributions. Doses and volume metrics for the brainstem and its substructures were calculated using a constant RBE1.1, 4 phenomenological RBE models with varying (α/β)x parameters, and with a simpler linear energy transfer-dependent model. The spatial agreement between the dose distributions of constant RBE1.1 versus the variable RBE models was compared using the Dice similarity coefficient. Results: The spatial agreement between the variable RBE dose distributions and RBE1.1 decreased with increasing isodose levels in all patient cases. The patient with ependymoma showed the greatest variation in dose and dose volumes, where V50Gy(RBE) in the brainstem increased from 32% (RBE1.1) to 35% to 49% depending on the applied model, corresponding to a spatial agreement (Dice similarity coefficient) between 0.79 and 0.95. The remaining patients showed similar trends, however, with lower absolute values due to lower brainstem doses. Conclusions: All phenomenological RBE models fully enclosed the isodose volumes of the constant RBE1.1, and the volumes based on variable RBE spatially agreed. The spatial agreement was dependent on the isodose level, where higher isodose levels showed larger expansions and less agreement between the variable RBE models and RBE1.1.

Background: Proton therapy (PT) is sensitive towards anatomical changes that may occur during a treatment course. The aim of this study was to investigate if anatomically robust PT (ARPT) plans incorporating patient-specific target motion improved target coverage while still sparing normal tissues, when applied on locally advanced prostate cancer patients where pelvic irradiation is indicated. Material and methods: A planning computed tomography (CT) scan used for dose calculation and two additional CTs (acquired on different days) were used to make patient-specific targets for the ARPT plans on the eight included patients. The plans were compared to a conventional robust PT plan and a volumetric modulated arc therapy (VMAT) photon plan, which were derived from the planning CT (pCT). Worst-case robust optimisation was used for all proton plans with a setup uncertainty of 5 mm and a range uncertainty of 3.5%. Target coverage (V95% and D95%) and normal tissue doses (V5–75 Gy) were evaluated on 6–8 rCTs per patient. Results: The ARPT plans improved the prostate target coverage for the most challenging patient compared to conventional robust PT plans (20% point increase for V95% and 31 Gy increase for D95%). Across the whole cohort the estimated mean value for V95% was 97% for the ARPT plans and 95% for the conventional robust PT plans. The ARPT plans had a slight, statistically insignificant increase in normal tissue doses compared to the conventional robust proton plans. Compared to VMAT, the ARPT plans significantly reduced the normal tissue doses in the low-to-intermediate dose range. Conclusions: While both proton plans reduced the low-to-intermediate normal tissue doses compared to VMAT, ARPT plans improved the target coverage for the most challenging patient without significantly increasing the normal tissue doses compared to conventional robust PT plans.

Background and purpose Normal tissue complication probability (NTCP) models applied for model-based patient selection to proton therapy (PT) have usually been derived using dose/volume histogram (DVH) parameters from photon-based radiotherapy. This study aimed to derive PT-specific multivariate NTCP models that also accounted for the spatial dose distribution (rectum only) as well as non-dose/volume related factors. Materials and methods The study included rectum and bladder DVHs, 2D rectal dose maps and relevant patient/treatment characteristics from 1151 prostate cancer cases treated with PT. Prospectively scored Grade 2 late rectal bleeding (CTCAE v3.0, also procedural interventions separately) (n = 156 (15%)) and Grade 3+ GU morbidity (n = 51 (4%)) were entered into a multivariate logistic regression analysis. Model evaluation included assessment of the area under the receiver operating characteristic curve (AUC). Results Anticoagulant use was a dominant predictor, chosen in four of the six rectum models and in the bladder model. Age was a dominant predictor in all procedural only rectum models while prostate volume, bladder D5% and V75Gy were predictors in the bladder model. The selection frequency of the dose/volume predictors varied widely, where the percentage of the anterior rectum surface receiving >=75 Gy was the most robust. AUC values ranged from 0.58 to 0.70 across all models, with no clear difference between the DVH- and spatial-based models for the rectum. Conclusion Anticoagulant use and age were the most prominent predictors in the NTCP models. V75Gy of the rectal wall and the bladder was a predictor in the DVH-based models of the rectum and bladder respectively.

Background: Clinically, a constant value of 1.1 is used for the relative biological effectiveness (RBE) of protons, whereas in vitro the RBE has been shown to vary depending on physical dose, tissue type, and linear energy transfer (LET). As the LET increases at the distal end of the proton beam, concerns exist for an elevated RBE in normal tissues. The aim of this study was therefore to investigate the heterogeneity of RBE to brain structures associated with cognition (BSCs) in pediatric suprasellar tumors. Material and methods: Intensity-modulated proton therapy (IMPT) plans for 10 pediatric craniopharyngioma patients were re-calculated using 11 phenomenological and two plan-based variable RBE models. Based on LET, tissue dependence and number of data points used to fit the models, the three RBE models considered the most relevant for the studied endpoint were selected. Thirty BSCs were investigated in terms of RBE and dose/volume parameters. Results: For a representative patient, the median (range) dose-weighted mean RBE (RBEd) across all BSCs from the plan-based models was among the lowest (1.09 (1.02–1.52) vs. the phenomenological models at 1.21 (0.78–2.24)). Omitting tissue dependency resulted in RBEd at 1.21 (1.04–2.24). Across all patients, the narrower RBE model selection gave median RBEd values from 1.22 to 1.30. Conclusion: For all BSCs, there was a systematic model-dependent variation in RBEd, mirroring the uncertainty in biological effects of protons. According to a refined selection of in vitro models, the RBE variation across BSCs was in effect underestimated when using a fixed RBE of 1.1.

The introduction of radiotherapy beam delivery with high spatial modulation, including spot-scanning proton therapy, calls for development of 3D dosimeters for patient-specific treatment verifications. Inherently reusable methods like optically stimulated luminescence (OSL) pose a potential way to introduce a clinically viable 3D-dosimetry solution. Here we present a characterization of the OSL properties of the well-known thermoluminescence material LiF:Mg,Cu,P (MCP). The characterization was performed by monitoring the wavelength-dispersed emission of continuous-wave stimulated MCP pellets. We show that OSL emission is observed under blue (460 nm) and green (532 nm) laser stimulation, while no OSL signal is seen in MCP under red (664 nm) laser stimulation. Long-wavelength fluorescence including accumulating radiophotoluminescence is very intense under blue stimulation and must be suppressed for continuous use of a future 3D-dosimetry system. An evaluation of the number of emitted photons is used to estimate a measurable dose range of 0.1–10 Gy, which prompts further research in the use of MCP for 3D OSL-based dosimetry.

Background and purpose Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries. Material and methods CBCT projections of a Catphan and an Alderson phantom were acquired on both a proton and a photon gantry. The scatter corrected CBCTs (corrCBCTs) and the clinical reconstructions (stdCBCTs) were compared against CTs rigidly registered to the CBCTs (rigidCTs). The CBCTs of the Catphan phantom were segmented by materials for CT number analysis. Water equivalent path length (WEPL) maps were calculated through the Alderson phantom while proton plans optimized on the rigidCT and recalculated on all CBCTs were compared in a gamma analysis. Results In medium and high-density materials, the corrCBCT CT numbers were much closer to those of the rigidCT than the stdCBCTs. E.g. in the 50% bone segmentations the differences were reduced from above 300 HU (with stdCBCT) to around 60–70 HU (with corrCBCT). Differences in WEPL from the rigidCT were typically well below 5 mm for the corrCBCTs, compared to well above 10 mm for the stdCBCTs with the largest deviations in the head and thorax regions. Gamma pass rates (2%/2mm) when comparing CBCT-based dose re-calculations to rigidCT calculations were improved from around 80% (with stdCBCT) to mostly above 90% (with corrCBCT). Conclusion Scatter correction leads to substantial artefact reductions, improving accuracy of CBCT-based proton range/dose calculations.

The use of total body irradiation as part of conditioning regimens for acute leukaemia is progressively declining because of concerns of late toxic effects and the introduction of radiation-free regimens. Total marrow irradiation and total marrow and lymphoid irradiation represent more targeted forms of radiotherapy compared with total body irradiation that have the potential to decrease toxicity and escalate the dose to the bone marrow for high-risk patients. We review the technological basis and the clinical development of total marrow irradiation and total marrow and lymphoid irradiation, highlighting both the possible advantages as well as the current roadblocks for widespread implementation among transplantation units. The exact role of total marrow irradiation or total marrow and lymphoid irradiation in new conditioning regimens seems dependent on its technological implementation, aiming to make the whole procedure less time consuming, more streamlined, and easier to integrate into the clinical workflow. We also foresee a role for computer-assisted planning, as a way to improve planning and delivery and to incorporate total marrow irradiation and total marrow and lymphoid irradiation in multi-centric phase 2–3 trials.

Background and purpose Reducing radiation exposure to the temporal lobes could be beneficial to preserve cognitive function in paediatric brain tumour patients. The distribution of doses to brain substructures associated with cognition (BSCs) both within and outside of the temporal lobe have not been reported. The aim of this study was therefore to investigate temporal lobe sparing photon vs. proton therapy for paediatric suprasellar tumours. Material and methods Data from ten anonymized craniopharyngioma patients were used in this study. Temporal lobe sparing volumetric modulated arc therapy (VMAT) and pencil beam scanning (PBS) proton therapy plans were optimized to maintain consistent target metrics as in the delivered double scattering proton therapy (DSPT) plans. Thirty BSCs were delineated, including temporal lobe substructures (i.e. amygdala, hippocampus, entorhinal cortex). The dose/volume fractions to each BSC were analysed, and intelligence quotient (IQ) as well as memory scores were estimated to compare the different modalities. Results The exposed volumes of the temporal lobes and their substructures were consistently reduced with PBS compared to DSPT and VMAT, e.g. the left hippocampus V10Gy from 100% (VMAT) or 41% (DSPT) to 5% with PBS (p = 0.002). Some of the ventricular substructures were better spared with VMAT compared to both proton modalities. The reduced doses to the temporal lobes achieved with PBS translated into improved predicted memory outcomes, but not for the estimated IQ. Conclusion The irradiated volumes of temporal lobe BSCs were consistently the lowest with PBS, whereas the model-based estimates of cognitive outcomes were less consistent.

The magnetic field in magnetic resonance imaging guided radiotherapy (MRgRT) delivery systems influences charged-particle trajectories and hence the three-dimensional (3D) radiation dose distributions. This study investigated the dose-response as well as dose-rate and fractionation dependencies of silicone-based 3D radiochromic dosimeters for photon irradiation in a magnetic field using a 0.35 T MRgRT system. We found a linear dose response up to 22.6 Gy and no significant dose-rate dependency as a function of depth. A difference in optical response was observed for dosimeters irradiated in a single compared to multiple fractions. The dosimeter showed clinical potential for verification of MRgRT delivery.

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle. The main components from the IBA nozzle were implemented in the FLUKA MC code. We calibrated and verified the following entities to experimental measurements: range of pristine Bragg peaks (PBPs) and spread-out Bragg peaks (SOBPs), energy spread, lateral profiles, compensator range degradation, and absolute dose. We recalculated two patients with different field setups, comparing FLUKA vs. treatment planning system (TPS) dose, also obtaining LET and variable RBE doses. We achieved good agreement between FLUKA and measurements. The range differences between FLUKA and measurements were for the PBPs within ±0.9 mm (83% ⩽ 0.5 mm), and for SOBPs ±1.6 mm (82% ⩽ 0.5 mm). The differences in modulation widths were below 5 mm (79% ⩽ 2 mm). The differences in the distal dose fall off (D80%–D20%) were below 0.5 mm for all PBPs and the lateral penumbras diverged from measurements by less than 1 mm. The mean dose difference (RBE = 1.1) in the target between the TPS and FLUKA were below 0.4% in a three-field plan and below 1.4% in a four-field plan. A dose increase of 9.9% and 7.2% occurred when using variable RBE for the two patients, respectively. We presented a method to recalculate DS proton plans in the FLUKA MC code. The implementation was used to obtain LET and variable RBE dose and can be used for investigating variable RBE for previously treated patients.

PURPOSE: Photon counting detectors (PCDs) are being introduced in advanced x-ray computed tomography (CT) scanners. From a single PCD-CT acquisition, multiple images can be reconstructed, each based on only a part of the original x-ray spectrum. In this study, we investigated whether PCD-CT can be used to estimate stopping power ratios (SPRs) for proton therapy treatment planning, both by comparing to other SPR methods proposed for single energy CT (SECT) and dual energy CT (DECT) as well as to experimental measurements.METHODS: A previously developed DECT-based SPR estimation method was adapted to PCD-CT data, by adjusting the estimation equations to allow for more energy spectra. The method was calibrated directly on noisy data to increase the robustness toward image noise. The new PCD SPR estimation method was tested in theoretical calculations as well as in an experimental setup, using both four and two energy bin PCD-CT images, and through comparison to two other SPR methods proposed for SECT and DECT. These two methods were also evaluated on PCD-CT images, full spectrum (one-bin) or two-bin images, respectively. In a theoretical framework, we evaluated the effect of patient-specific tissue variations (density and elemental composition) and image noise on the SPR accuracy; the latter effect was assessed by applying three different noise levels (low, medium, and high noise). SPR estimates derived using real PCD-CT images were compared to experimentally measured SPRs in nine organic tissue samples, including fat, muscle, and bone tissues.RESULTS: For the theoretical calculations, the root-mean-square error (RMSE) of the SPR estimation was 0.1% for the new PCD method using both two and four energy bins, compared to 0.2% and 0.7% for the DECT- and SECT-based method, respectively. The PCD method was found to be very robust toward CT image noise, with a RMSE of 2.7% when high noise was added to the CT numbers. Introducing tissue variations, the RMSE only increased to 0.5%; even when adding high image noise to the changed tissues, the RMSE stayed within 3.1%. In the experimental measurements, the RMSE over the nine tissue samples was 0.8% when using two energy bins, and 1.0% for the four-bin images.CONCLUSIONS: In all tested cases, the new PCD method produced similar or better results than the SECT- and DECT-based methods, showing an overall improvement of the SPR accuracy. This study thus demonstrated that PCD-CT scans will be a qualified candidate for SPR estimations.

Background and purpose Focal tumour boosting is currently explored in radiotherapy of prostate cancer to increase tumour control. In this study we applied dose response models for both tumour control and normal tissue complications to explore the benefit of proton therapy (PT) combined with focal tumour boosting, also when accounting for inter-fractional motion. Materials and methods CT scans of seven patients fused with MRI-based index volumes were used. Two volumetric modulated arc therapy (VMAT) plans were created for each patient; one with conventional dose (77 Gy) to the entire prostate, and one with an additional integrated boost (total dose of 95 Gy) to the index lesion. Two corresponding intensity modulated PT (IMPT) plans were created using two lateral opposing spot scanning beams. All plans were evaluated using an MRI-based tumour control probability (TCP) model and normal tissue complication probability (NTCP) models for the rectum and bladder. Plan robustness was evaluated using dose re-calculations on repeat cone-beam CTs. Results Across all plans, median TCP increased from 86% (range: 59–98%) without boost to 97% (range: 96–99%) with boost. IMPT plans had lower rectum NTCPs (e.g. 3% vs. 4% for boost plans) but higher bladder NTCPs (20% vs. 18% for boost plans), yet only the bladder NTCPs remained different in the cone beam CT-based re-calculations. Conclusions Focal tumour boosting can be delivered with either VMAT or protons, and increases the predicted TCP. The small benefit of IMPT when assessing the planned dose distributions was lost when accounting for inter-fractional motion.