Search

Purpose: Plan complexity and robustness are two essential aspects of treatment plan quality but there is a great variability in their management in clinical practice. This study reports the results of the 2020 ESTRO survey on plan complexity and robustness to identify needs and guide future discussions and con-sensus.Methods: A survey was distributed online to ESTRO members. Plan complexity was defined as the mod-ulation of machine parameters and increased uncertainty in dose calculation and delivery. Robustness was defined as a dose distribution's sensitivity towards errors stemming from treatment uncertainties, patient setup, or anatomical changes.Results: A total of 126 radiotherapy centres from 33 countries participated, 95 of them (75%) from Europe and Central Asia. The majority controlled and evaluated plan complexity using monitor units (56 centres) and aperture shapes (38 centres). To control robustness, 98 (97% of question responses) photon and 5 (50%) proton centres used PTV margins for plan optimization while 75 (94%) and 5 (50%), respectively, used margins for plan evaluation. Seventeen (21%) photon and 8 (80%) proton centres used robust opti-misation, while 10 (13%) and 8 (80%), respectively, used robust evaluation. Primary uncertainties consid-ered were patient setup (photons and protons) and range calculation uncertainties (protons). Participants expressed the need for improved commercial tools to control and evaluate plan complexity and robust-ness.Conclusion: Clinical implementation of methods to control and evaluate plan complexity and robustness is very heterogeneous. Better tools are needed to manage complexity and robustness in treatment plan-ning systems. International guidelines may promote harmonization.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 173 (2022) 254-261 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Purpose: Mask-immobilized stereotactic radiosurgery (SRS) using a gating window is an emerging technology. However, the amount of intracranial tumor motion that can be tolerated during treatment while satisfying clinical dosimetric goals is unknown. The purpose of this study was to quantify the sensitivity of target dose to tumor motion. Methods and Materials: In clinical SRS plans, where a nose marker was tracked as surrogate for target motion, translational and rotational target movements were simulated using nose-marker displacements of ±0.5 mm, ±1.0 mm, or ±1.5 mm. The effect on minimum dose to 99% of the target (D99) and percent target coverage by prescription dose was quantified using mixed-effect modeling with variables: displacement, target volume, and location. Results: The effect on dose metrics is statistically larger for translational displacements compared with rotational displacements, and the effect of pitch rotations is statistically larger compared with yaw rotations. The mixed-effect model for translations showed that displacement and target volume are statistically significant variables, for rotation the variable target distance to rotation axis is additionally significant. For mean target volume (12.6 cc) and translational nose-marker displacements of 0.5 mm, 1.0 mm, and 1.5 mm, D99 decreased by 2.2%, 7.1%, and 13.0%, and coverage by 0.4%, 1.8%, and 4.4%, respectively. For mean target volume, mean distance midpoint-target to pitch axis (7.6cm), and rotational nose-marker displacement of 0.5 mm, 1.0 mm, and 1.5 mm, D99 decreased by 1.0%, 3.6%, and 6.9%, and coverage by 0.2%, 0.8%, and 1.9%, respectively. For rotational yaw axis displacement, mean distance midpoint-target axis (4.2cm), D99 decreased by 0.3%, 1.2%, and 2.5%, and coverage by 0.1%, 0.2%, and 0.5%, respectively. Conclusions: Simulated target displacements showed that sensitivity of tumor dose to motion depends on both target volume and target location. Suggesting that patient- and target-specific thresholds may be implemented for optimizing the balance between dosimetric plan accuracy and treatment prolongation caused by out-of-tolerance motion.

The FLASH effect designates normal tissue sparing at ultra-high dose rate (UHDR, >40 Gy/s) compared to conventional dose rate (∼0.1 Gy/s) irradiation while maintaining tumour control and has the potential to improve the therapeutic ratio of radiotherapy (RT). UHDR high-energy electron (HEE, 4-20 MeV) beams are currently a mainstay for investigating the clinical potential of FLASH RT for superficial tumours. In the future very-high energy electron (VHEE, 50-250 MeV) UHDR beams may be used to treat deep-seated tumours. UHDR HEE treatment planning focused at its initial stage on accurate dosimetric modelling of converted and dedicated UHDR electron RT devices for the clinical transfer of FLASH RT. VHEE treatment planning demonstrated promising dosimetric performance compared to clinical photon RT techniques in silico and was used to evaluate and optimise the design of novel VHEE RT devices. Multiple metrics and models have been proposed for a quantitative description of the FLASH effect in treatment planning, but an improved experimental characterization and understanding of the FLASH effect is needed to allow for an accurate and validated modelling of the effect in treatment planning. The importance of treatment planning for electron FLASH RT will augment as the field moves forward to treat more complex clinical indications and target sites. In this review, TPS developments in HEE and VHEE are presented considering beam models, characteristics, and future FLASH applications.

RaySearch (AB, Stockholm) has released a module for CyberKnife (CK) planning within its RayStation (RS) treatment planning system (TPS). To create and validate beam models of fixed, Iris, and multileaf collimators (MLC) of the CK M6 for Monte Carlo (MC) and collapsed cone (CC) algorithms in the RS TPS. Measurements needed for the creation of the beam models were performed in a water tank with a stereotactic PTW 60018 diode. Both CC and MC models were optimized in RS by minimizing the differences between the measured and computed profiles and percentage depth doses. The models were then validated by comparing dose from the plans created in RS with both single and multiple beams in different phantom conditions with the corresponding measured dose. Irregular field shapes and off-axis beams were also tested for the MLC. Validation measurements were performed using an A1SL ionization chamber, EBT3 Gafchromic films, and a PTW 1000 SRS detector. Finally, patient-specific QAs with gamma criteria of 3%/1 mm were performed for each model. The models were created in a straightforward manner with efficient tools available in RS. The differences between computed and measured doses were within ±1% for most of the configurations tested and reached a maximum of 3.2% for measurements at a depth of 19.5-cm. With respect to all collimators and algorithms, the maximum averaged dose difference was 0.8% when considering absolute dose measurements on the central axis. The patient-specific QAs led to a mean result of 98% of points fulfilling gamma criteria. We created both CC and MC models for fixed, Iris, and MLC collimators in RS. The dose differences for all collimators and algorithms were within ±1%, except for depths larger than 9 cm. This allowed us to validate both models for clinical use.

BACKGROUND AND PURPOSE: Lung cancer radiotherapy increases the risk of cardiotoxicity and heart radiation dose is an independent predictor of poor survival. This study describes heart doses and strategies aiming to reduce exposure.MATERIALS AND METHODS: A systematic review of lung cancer dosimetry studies reporting heart doses published 2013-2020 was undertaken. Doses were compared according to laterality, region irradiated, treatment modality (stereotactic ablative body radiotherapy (SABR) and non-SABR), planning technique, and respiratory motion management.RESULTS: For 392 non-SABR regimens in 105 studies, the average MHD was 10.3 Gy (0.0-48.4) and was not significantly different between left and right-sided tumours. It was similar between IMRT and 3DCRT (10.9 Gy versus 10.6 Gy) and lower with particle beam therapy (proton 7.0 Gy; carbon-ion 1.9 Gy). Active respiratory motion management reduced exposure (7.4 Gy versus 9.3 Gy). For 168 SABR regimens in 35 studies, MHD was 4.0 Gy (0.0-32.4). Exposure was higher in central and lower lobe lesions (6.3 and 5.8 Gy respectively). MHD was lowest for carbon ions (0.5 Gy) compared to other techniques. Active respiratory motion management reduced exposure (2.4 Gy versus 5.0 Gy). Delineation guidelines and Dose Volume Constraints for the heart varied substantially.CONCLUSIONS: There is scope to reduce heart radiation dose in lung cancer radiotherapy. Consensus on planning objectives, contouring and DVCs for the heart may lead to reduced heart doses in the future. For IMRT, more stringent optimisation objectives may reduce heart dose. Active respiratory motion management or particle therapy may be considered in situations where cardiac dose is high.

Background Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its treatment planning for BC. To decrease this practice variation, it is essential to first gain insight into the current variation in RT treatment between institutes. This paper describes the development of the NABON Breast Cancer Audit-Radiotherapy (NBCA-R), a structural nationwide registry of BC RT data of all BC patients treated with at least surgery and RT. Methods A working group consisting of representatives of the BC Platform of the Dutch Radiotherapy Society selected a set of dose volume parameters deemed to be surrogate outcome parameters, both for tumour control and toxicity. Two pilot studies were carried out in six RT institutes. In the first pilot study, data were manually entered into a secured web-based system. In the second pilot study, an automatic Digital Imaging and Communications in Medicine (DICOM) RT upload module was created and tested. Results The NBCA-R dataset was created by selecting RT parameters describing given dose, target volumes, coverage and homogeneity, and dose to organs at risk (OAR). Entering the data was made mandatory for all Dutch RT departments. In the first pilot study (N = 1093), quite some variation was already detected. Application of partial breast irradiation varied from 0 to 17% between the 6 institutes and boost to the tumour bed from 26.5 to 70.2%. For patients treated to the left breast or chest wall only, the average mean heart dose (MHD) varied from 0.80 to 1.82 Gy; for patients treated to the breast/chest wall only, the average mean lung dose (MLD) varied from 2.06 to 3.3 Gy. In the second pilot study 6 departments implemented the DICOM-RT upload module in daily practice. Anonymised data will be available for researchers via a FAIR (Findable, Accessible, Interoperable, Reusable) framework. Conclusions We have developed a set of RT parameters and implemented registration for all Dutch BC patients. With the use of an automated upload module registration burden will be minimized. Based on the data in the NBCA-R analyses of the practice variation will be done, with the ultimate aim to improve quality of BC RT. Trial registration Retrospectively registered.

Contains fulltext : 207179.pdf (Publisher’s version ) (Closed access) PURPOSE: One of the major challenges in stereotactic body radiation therapy (SBRT) of renal cell carcinoma is internal motion during treatment. Previous literature has aimed to mitigate the effects of motion by expanding the treatment margins or respiratory tracking. Online magnetic resonance imaging (MRI)-guided radiation therapy has the potential to further improve the treatment of renal cell carcinoma by direct visualization of the tumor during treatment. The efficacy of 2 motion management techniques were assessed: tumor trailing and respiratory tracking. The simulation of a single-fraction, MRI-based SBRT was performed to quantify intrafraction motion and assess the efficacy of the different motion management strategies. METHODS AND MATERIALS: Fifteen patients were included in the study. At the beginning and end of the scanning protocol, 2 cine-MRI scans were acquired to assess cyclic respiratory motion. In addition, 3-dimensional spoiled gradient echo scans were acquired at 4 different time points to assess the slow drifts over 25 minutes. The systematic and random errors owing to intrafraction drift were calculated, as well as the random error induced by respiratory motion. The motion margins were calculated for tumor trailing and respiratory tracking and compared with the margin when no motion compensation would be performed to assess the relative efficacy of each technique. RESULTS: The largest respiratory tumor motion was observed along the caudo-cranial direction with a median 95% maximum amplitude of approximately 12 mm. SigmaDRIFT, sigmaDRIFT, and sigmaRESP were determined to be 1.0 mm 1.8 mm, and 3.8 mm, respectively. Without mechanical immobilization, intrafraction drift accounted for 75% of the total intrafraction motion margin for online midposition-based SBRT treatments. CONCLUSIONS: The contribution of intrafraction drift to the total internal motion margin is much larger than periodic respiratory motion. This makes tumor trailing a viable option to consider on the MRI linac because it allows for 3-dimensional MRI acquisitions during beam delivery, which simplifies the introduction of new techniques, such as dose accumulation and online intrafraction replanning.

Background: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting.Materials and methods: Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland-Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients.Results: Bland-Altman's analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort.Conclusion: The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches. (C) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objective. In preclinical radiotherapy with kilovolt (kV) x-ray beams, accurate treatment planning is needed to improve the translation potential to clinical trials. Monte Carlo based radiation transport simulations are the gold standard to calculate the absorbed dose distribution in external beam radiotherapy. However, these simulations are notorious for their long computation time, causing a bottleneck in the workflow. Previous studies have used deep learning models to speed up these simulations for clinical megavolt (MV) beams. For kV beams, dose distributions are more affected by tissue type than for MV beams, leading to steep dose gradients. This study aims to speed up preclinical kV dose simulations by proposing a novel deep learning pipeline. Approach. A deep learning model is proposed that denoises low precision (∼106 simulated particles) dose distributions to produce high precision (109 simulated particles) dose distributions. To effectively denoise the steep dose gradients in preclinical kV dose distributions, the model uses the novel approach to use the low precision Monte Carlo dose calculation as well as the Monte Carlo uncertainty (MCU) map and the mass density map as additional input channels. The model was trained on a large synthetic dataset and tested on a real dataset with a different data distribution. To keep model inference time to a minimum, a novel method for inference optimization was developed as well. Main results. The proposed model provides dose distributions which achieve a median gamma pass rate (3%/0.3 mm) of 98% with a lower bound of 95% when compared to the high precision Monte Carlo dose distributions from the test set, which represents a different dataset distribution than the training set. Using the proposed model together with the novel inference optimization method, the total computation time was reduced from approximately 45 min to less than six seconds on average. Significance. This study presents the first model that can denoise preclinical kV instead of clinical MV Monte Carlo dose distributions. This was achieved by using the MCU and mass density maps as additional model inputs. Additionally, this study shows that training such a model on a synthetic dataset is not only a viable option, but even increases the generalization of the model compared to training on real data due to the sheer size and variety of the synthetic dataset. The application of this model will enable speeding up treatment plan optimization in the preclinical workflow.

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, ‘improving efficiency’, ‘improving planning and delivery’, ‘improving imaging’, and ‘improving patient selection’.

Treatment planning is the process where the prescription of the radiation oncologist is translated into a deliverable treatment. With the complexity of contemporary radiotherapy, treatment planning cannot be performed without a computerized treatment planning system. Proton therapy (PT) enables highly conformal treatment plans with a minimum of dose to tissues outside the target volume, but to obtain the most optimal plan for the treatment, there are a multitude of parameters that need to be addressed. In this review areas of ongoing improvements and research in the field of PT treatment planning are identified and discussed. The main focus is on issues of immediate clinical and practical relevance to the PT community highlighting the needs for the near future but also in a longer perspective. We anticipate that the manual tasks performed by treatment planners in the future will involve a high degree of computational thinking, as many issues can be solved much better by e.g. scripting. More accurate and faster dose calculation algorithms are needed, automation for contouring and planning is required and practical tools to handle the variable biological efficiency in PT is urgently demanded just to mention a few of the expected improvements over the coming 10 years.

Background: In patients diagnosed with rectal cancer, dose escalation is currently being investigated in a large number of studies. Since there is little known on gross tumor volume (GTV) inter-fraction motion for rectal cancer, a wide variety in margins is used. Purpose of this study is to quantify GTV inter-fraction motion statistics on different timescales and to give estimates of planning target volume (PTV) margins. Material and methods: Thirty-two patients, diagnosed with rectal cancer, were included. To investigate motion from week-to-week, 16 patients underwent a pretreatment and five weekly MRIs, prior to a radiotherapy (RT) fraction of the chemoradiotherapy treatment. To investigate motion from day-to-day, the remaining 16 patients underwent five daily MRIs before each fraction in one week of RT. GTV was delineated on all scans according to guidelines. Scans were aligned on bony anatomy with the first MRI. For both datasets separately, GTV inter-fraction motion was determined based on center-of-gravity displacement. Therefrom, systematic and random errors were determined in left/right (LR), anterior/posterior and cranial/caudal (CC) direction. PTV margin estimates were calculated and evaluated on GTV coverage. Results: Systematic and random errors were found in the range of 2.3–4.8 mm and 1.5–3.3 mm from week-to-week, and 1.8–4.5 mm and 1.8–4.0 mm from day-to-day, respectively. On both timescales, similar motion patterns were found; the most motion was observed in CC whilst the least motion was observed in LR. On the week-to-week data more systematic and less random motion was observed compared to the day-to-day data. Overall, only slight differences in margin estimates were found. Derived PTV margin estimates were found to give adequate GTV coverage. Conclusion: GTV inter-fraction motion, on a week-to-week and day-to-day timescale, can be accounted for using motion statistics presented in this study.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) is the standard therapy for localized anal cancer (AC), but this treatment is associated with substantial toxicity. However, there is a lack of prospectively collected toxicity and patient reported outcome (PRO) data from larger cohorts. The purpose was to prospectively collect and determine agreement between physician assessed toxicity (CTCAE) and PRO during and after CRT and to compare IMRT, VMAT and proton-based planning in a subgroup of patients.MATERIAL AND METHODS: Patients, treated with CRT for AC, were included between 2015 and 2017. NCI-CTCAE v.4.0, EORTC QLQ-C30 and CR29 data were collected baseline, mid-therapy, end-of therapy and 2-4 weeks posttherapy. Treatment planning with 5- or 6-fixed field IMRT, 2 and 3 arc VMAT, and 3- and 4-field proton plans were compared.RESULTS: One-hundred patients were included. Both CTCAE and PROs related to acute toxicity reached a maximum at end of therapy. Incidences of PROs were markedly higher with only slight to fair agreement to CTCAE, (κ 13-37). Comparative planning revealed dosimetric equality of IMRT and VMAT plans, but superiority of proton plans.CONCLUSIONS: The high incidence of PRO scores and weak agreement to CTCAE suggest that PROs are important tools complementary to CTCAE in evaluating patient symptoms during and after CRT. Proton therapy has the potential to lower radiation doses to most organs at risk.

PURPOSE: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. RESULTS: The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). CONCLUSION: In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at www.cancerdata.org and will be updated whenever required. ispartof: RADIOTHERAPY AND ONCOLOGY vol:128 issue:1 pages:37-43 ispartof: location:Ireland status: published

INTRODUCTION: The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins.MATERIALS AND METHODS: In total, 1576 patients completing radical primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0-2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point's position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis.RESULTS: After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (p = 0.4) or the dose to LRs (p = 0.2) was detected between the groups. A difference in LC was found univariate between the centers (p = 0.03), but not in multivariate analysis (p = 0.4).CONCLUSIONS: No relation was found between the recurrences' distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.

Background and purpose: Planned doses are used as surrogate for the actually delivered dose in radiotherapy. We have estimated the delivered dose in a dose-escalation trial of locally advanced prostate cancer by statistical dose-accumulation and by DVH-summation, and compared to planned dose.Materials and method: Prescribed dose-escalation to the prostate was 67.5 Gy/25fr., corresponding to 81GyEQD2 assuming alpha/beta = 1.5. The 21 patients had three targets (i.e. CTV67.5 + 2 mm, CTV60 + 5 mm, CTV50 + 10 mm) irradiated by a simultaneous-integrated-boost technique. Analysis was based on 213 CT scans and 5-years of follow-up. For statistical dose-accumulation, we modelled 10000 possible treatment courses based on planned dose and deformation-vector-fields from contour-based registration. For DVH-summation we recalculated dose on repeat-CTs and estimated median D98%/EUD. Groups with/without disease recurrence were compared.Results: Discrepancies between planned and accumulated dose were mostly seen for CTV67.5, where under-dosage was found at different locations in the prostate in 12/21 patients. Delivered dose-escalation (D98%) was on average 73.9GyEQD2 (range: 68.3-78.7GyEQD2). No significant difference in accumulated-D98% was found in patients with (n = 8) and without (n = 13) recurrence (p > 0.05). Average D98%/EUD with statistical dose-accumulation vs DVH-summation was significantly different in CTV60, CTV50, rectum and bladder but not in CTV67.5.Conclusion: The planned dose escalation was not received by more than half-of-the patients. Robustness of the prostate target (CTV67.5) should therefore be better prioritized in these patients given the low toxicity profile. Estimates of delivered dose were less conservative for dose-accumulation due to interaction of random organ motion with the dose matrix. (C) 2018 Elsevier B.V. All rights reserved.

Background and purpose: Dynamic Wave Arc (DWA) is a system-specific noncoplanar arc technique that combines synchronized gantry-ring rotation with D-MLC optimization. This paper presents the clinical workflow, quality assurance program, and reports the geometric and dosimetric results of the first patient cohort treated with DWA. Methods and materials: The RayStation TPS was clinically integrated on the Vero SBRT platform for DWA treatments. The first 15 patients treated with DWA represent a broad range of treatment sites: breast boost, prostate, lung SBRT and bone metastases, which allowed us to explore the potentials and assess the limitations of the current DWA site-specific template solution. For the DWA verification a variety of QA equipment was used, from 3D diode array to an anthropomorphic end-to-end phantom. The geometric accuracy of each arc was verified with an independent orthogonal fluoroscopy method. Results: The average beam-on delivery time was 3 min, ranging from 1.22 min to 8.82 min. All patient QAs passed our institutional clinical criteria of gamma index. For both EBT3 film and Delta4 measurements, DWA planned versus delivered dose distributions presented an average agreement aboire 97%. An overall mean gantry-ring geometric deviation of-0.03 0.46 and 0.18 0.26 was obtained, respectively. Conclusion: For the first time, DWA has been translated into the clinic and used to treat various treatment sides. DWA has been successfully added to the noncoplanar rotational IMRT techniques arsenal, allowing additional flexibility in dose shaping while preserving dosimetrically robust delivery. (C) 2017 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 122 (2017) 347-351

Background: Delineation accuracy of the gross tumor volume (GTV) in radiotherapy planning for head and neck (H&N) cancer is affected by computed tomography (CT) artifacts from metal implants which obscure identification of tumor as well as organs at risk (OAR). This study investigates the impact of metal artifact reduction (MAR) in H&N patients in terms of delineation consistency and dose calculation precision in radiation treatment planning. Material and methods: Tumor and OAR delineations were evaluated in planning CT scans of eleven oropharynx patients with streaking artifacts in the tumor region preceding curative radiotherapy (RT). The GTV-tumor (GTV-T), GTV-node and parotid glands were contoured by four independent observers on standard CT images and MAR images. Dose calculation was evaluated on thirty H&N patients with dental implants near the treated volume. For each patient, the dose derived from the clinical treatment plan using the standard image set was compared with the recalculated dose on the MAR image dataset. Results: Reduction of metal artifacts resulted in larger volumes of all delineated structures compared to standard reconstruction. The GTV-T and the parotids were on average 22% (p 3 (range 0–32 cm3). Conclusions: Delineation of structures in the head and neck were affected by metal artifacts and volumes were generally larger and more consistent after reduction of metal artifacts, however, only small changes were observed in the dose calculations.

The purpose of this study was to develop a method enabling synthetic computed tomography (sCT) generation of the whole abdomen using magnetic resonance imaging (MRI) images of pediatric patients with abdominal tumors. The proposed method relies on an automatic atlas-based segmentation of bone and lungs followed by an MRI intensity to synthetic Hounsfield unit conversion. Separate conversion algorithms were used for bone, lungs and soft-tissue. Rigidly registered CT and T2-weighted MR images of 30 patients in treatment position and with the same field of view were used for the evaluation of the atlas and the conversion algorithms. The dose calculation accuracy of the generated sCTs was verified for volumetric modulated arc therapy (VMAT) and pencil beam scanning (PBS). VMAT and PBS plans were robust optimized on an internal target volume (ITV) against a patient set-up uncertainty of 5 mm. Average differences between CT and sCT dose calculations for the ITV V95% were 0.5% (min 0.0%; max 5.0%) and 0.0% (min -0.1%; max 0.1%) for VMAT and PBS dose distributions, respectively. Average differences for the mean dose to the organs at risk were

OBJECTIVE:: To assess the accuracy and efficiency of four different techniques, thus determining the optimum method for recalculating dose on cone beam CT (CBCT) images acquired during radiotherapy treatments.METHODS:: Four established techniques were investigated and their accuracy assessed via dose calculations: (1) applying a standard planning CT (pCT) calibration curve, (2) applying a CBCT site-specific calibration curve, (3) performing a density override and (4) using deformable registration. Each technique was applied to 15 patients receiving volumetric modulated arc therapy to one of three treatment sites, head and neck, lung and prostate. Differences between pCT and CBCT recalculations were determined with dose volume histogram metrics and 2.0%/0.1 mm gamma analysis using the pCT dose distribution as a reference.RESULTS:: Dose volume histogram analysis indicated that all techniques yielded differences from expected results between 0.0 and 2.3% for both target volumes and organs at risk. With volumetric gamma analysis, the dose recalculation on deformed images yielded the highest pass-rates. The median pass-rate ranges at 50% threshold were 99.6-99.9%, 94.6-96.0%, and 94.8.0-96.0% for prostate, head and neck and lung patients, respectively.CONCLUSION:: Deformable registration, HU override and site-specific calibration curves were all identified as dosimetrically accurate and efficient methods for dose calculation on CBCT images.ADVANCES IN KNOWLEDGE:: With the increasing adoption of CBCT, this study provides clinical radiotherapy departments with invaluable information regarding the comparison of dose reconstruction methods, enabling a more accurate representation of a patient's treatment. It can also integrate studies in which CBCT is used in image-guided radiation therapy and for adaptive radiotherapy planning processes.

Background: Dose-guided adaptive radiation therapy (DGART) is the systematic evaluation and adaptation of the dose delivery during treatment for an individual patient. The aim of this study is to define quantitative action levels for DGART by evaluating changes in 3D dose metrics in breast cancer and correlate them with clinical expert evaluation. Material and methods: Twenty-three breast cancer treatment plans were evaluated, that were clinically adapted based on institutional IGRT guidelines. Reasons for adaptation were variation in seroma, hematoma, edema, positioning or problems using voluntary deep inspiration breath hold. Sixteen patients received a uniform dose to the breast (clinical target volume 1; CTV1). Six patients were treated with a simultaneous integrated boost to CTV2. The original plan was copied to the CT during treatment (re-CT) or to the stitched cone-beam CT (CBCT). Clinical expert evaluation of the re-calculated dose distribution and extraction of dose-volume histogram (DVH) parameters were performed. The extreme scenarios were evaluated, assuming all treatment fractions were given to the original planning CT (pCT), re-CT or CBCT. Reported results are mean ± SD. Results: DVH results showed a mean dose (Dmean) difference between pCT and re-CT of -0.4 ± 1.4% (CTV1) and −1.4 ± 2.1% (CTV2). The difference in V95% was −2.6 ± 4.4% (CTV1) and −9.8 ± 8.3% (CTV2). Clinical evaluation and DVH evaluation resulted in a recommended adaptation in 17/23 or 16/23 plans, respectively. Applying thresholds on the DVH parameters: Dmean CTV, V95% CTV, Dmax, mean lung dose, volume exceeding 107% (uniform dose) or 90% (SIB) of the prescribed dose enabled the identification of patients with an assumed clinically relevant dose difference, with a sensitivity of 0.89 and specificity of 1.0. Re-calculation on CBCT imaging identified the same plans for adaptation as re-CT imaging. Conclusions: Clinical expert evaluation can be related to quantitative DVH parameters on re-CT or CBCT imaging to select patients for DGART.

Magnetic resonance imaging (MRI)-guided attenuation correction (AC) of positron emission tomography (PET) data and/or radiation therapy (RT) treatment planning is challenged by the lack of a direct link between MRI voxel intensities and electron density. Therefore, even if this is not a trivial task, a pseudo-computed tomography (CT) image must be predicted from MRI alone. In this work, we propose a two-step (segmentation and fusion) atlas-based algorithm focusing on bone tissue identification to create a pseudo-CT image from conventional MRI sequences and evaluate its performance against the conventional MRI segmentation technique and a recently proposed multi-atlas approach. The clinical studies consisted of pelvic CT, PET and MRI scans of 12 patients with loco-regionally advanced rectal disease. In the first step, bone segmentation of the target image is optimized through local weighted atlas voting. The obtained bone map is then used to assess the quality of deformed atlases to perform voxel-wise weighted atlas fusion. To evaluate the performance of the method, a leave-one-out cross-validation (LOOCV) scheme was devised to find optimal parameters for the model. Geometric evaluation of the produced pseudo-CT images and quantitative analysis of the accuracy of PET AC were performed. Moreover, a dosimetric evaluation of volumetric modulated arc therapy photon treatment plans calculated using the different pseudo-CT images was carried out and compared to those produced using CT images serving as references. The pseudo-CT images produced using the proposed method exhibit bone identification accuracy of 0.89 based on the Dice similarity metric compared to 0.75 achieved by the other atlas-based method. The superior bone extraction resulted in a mean standard uptake value bias of -1.5 +/- 5.0% (mean +/- SD) in bony structures compared to -19.9 +/- 11.8% and -8.1 +/- 8.2% achieved by MRI segmentation-based (water-only) and atlas-guided AC. Dosimetric evaluation using dose volume histograms and the average difference between minimum/maximum absorbed doses revealed a mean error of less than 1% for the both target volumes and organs at risk. Two-dimensional (2D) gamma analysis of the isocenter dose distributions at 1%/1 mm criterion revealed pass rates of 91.40 +/- 7.56%, 96.00 +/- 4.11% and 97.67 +/- 3.6% for MRI segmentation, atlas-guided and the proposed methods, respectively. The proposed method generates accurate pseudo-CT images from conventional Dixon MRI sequences with improved bone extraction accuracy. The approach is promising for potential use in PET AC and MRI-only or hybrid PET/MRI-guided RT treatment planning.

INTRODUCTION: Decreasing the radiation dose in the surgical area is important to lower the risk of wound complications when surgery and radiotherapy are combined for the treatment of spinal metastases. The purpose of this study was to compare the radiation dose in the surgical area for spinal metastases between single fraction external beam radiotherapy (EBRT), single fraction stereotactic body radiotherapy (SBRT) and single fraction SBRT with active sparing (SBRT-AS) of the posterior surgical area. METHODS: Radiotherapy treatment plans for EBRT, SBRT and SBRT-AS of the posterior surgical area were created for 13 patients with spinal metastases. A single fraction of 8Gy was prescribed to the spinal metastasis in the EBRT plan. For the SBRT treatment plans, a single fraction of 18Gy was prescribed to the metastasis and 8Gy to the rest of the vertebral body. For the SBRT plan with active sparing the dose in the designated surgical area was minimized without compromising the dose to the organs at risk. RESULTS: The median dose in the surgical area was 2.6Gy (1.6-5.3Gy) in the SBRT plan with active sparing of the surgical area compared to a median dose of 3.7Gy (1.6-6.3Gy) in the SBRT plan without sparing and 6.5Gy (3.5-9.1Gy) in the EBRT plans (p

To enable magnetic resonance (MR)-only radiotherapy and facilitate modelling of radiation attenuation in humans, synthetic-CT (sCT) images need to be generated. Considering the application of MR-guided radiotherapy and online adaptive replanning, sCT generation should occur within minutes. This work aims at assessing whether an existing deep learning network can rapidly generate sCT images to be used for accurate MR-based dose calculations in the entire pelvis. A study was conducted on data of 91 patients with prostate, rectal and cervical cancer who underwent external beam radiotherapy acquiring both CT and MRI for patients' simulation. Dixon reconstructed water, fat and in-phase images obtained from a conventional dual gradient-recalled echo sequence were used to generate sCT images. A conditional generative adversarial network (cGAN) was trained in a paired fashion on 2D transverse slices of 32 prostate cancer patients. The trained network was tested on the remaining patients to generate sCT images. For 30 patients in the test set, dose recalculations of the clinical plan were performed on sCT images. Dose distributions were evaluated comparing voxel-based dose differences, gamma and dose-volume histogram (DVH) analysis. The sCT generation required 5.6 s and 21 s for a single patient volume on a GPU and CPU, respectively. On average, sCT images resulted in a higher dose to the target of maximum 0.3%. Results suggest that accurate MR-based dose calculation using sCT images generated with a cGAN trained on prostate cancer patients is feasible for the entire pelvis. The sCT generation was sufficiently fast to be integrated into an MR-guided radiotherapy workflow., Accepted for publication in Physics in Medicine and Biology, in press (2018)

Purpose: This study automatically quantified calcifications in coronary arteries (CAC) and thoracic aorta (TAC) on breast planning computed tomography (CT) scans and assessed its reproducibility compared to manual scoring. Material and Methods: Dutch (n = 1199) and Singaporean (n = 1090) breast cancer patients with radiotherapy planning CT scan were included. CAC and TAC were automatically scored using deep learning algorithm. CVD risk categories were based on Agatson CAC: 0, 1–10, 11–100, 101–400 and >400. Reliability between automatic and manual scoring was assessed in 120 randomly selected CT scans from each population, with linearly weighted kappa for CAC categories and intraclass correlation coefficient for TAC. Results: Median age was higher in Dutch patients than Singaporean patients: 57 versus 52 years. CAC and TAC increased with age and were more present in Dutch patients than Singaporean patients: 24.2% versus 17.3% and 73.0% versus 62.2%, respectively. Reliability of CAC categories and TAC was excellent in the Netherlands (0.85 (95% confidence interval (CI) = 0.77–0.93) and 0.98 (95% CI = 0.96–0.98) respectively) and Singapore (0.90 (95% CI = 0.84–0.96) and 0.99 (95% CI = 0.98–0.99) respectively). Conclusions: CAC and TAC prevalence was considerable and increased with age. Deep learning software is a reliable method to automatically measure CAC and TAC on radiotherapy breast CT scans.

PURPOSE: To quantify intrafractional motion to determine population-based radiotherapy treatment margins for head-and-neck tumors. METHODS: Cine MR imaging was performed in 100 patients with head-and-neck cancer on a 3T scanner in a radiotherapy treatment setup. MR images were analyzed using deformable image registration (optical flow algorithm) and changes in tumor contour position were used to calculate the tumor motion. The tumor motion was used together with patient setup errors (450 patients) to calculate population-based PTV margins. RESULTS: Tumor motion was quantified in 84 patients (12/43/29 nasopharynx/oropharynx/larynx, 16 excluded). The mean maximum (95th percentile) tumor motion (swallowing excluded) was: 2.3 mm in superior, 2.4 mm in inferior, 1.8 mm in anterior and 1.7 mm in posterior direction. PTV margins were: 2.8 mm isotropic for nasopharyngeal tumors, 3.2 mm isotropic for oropharyngeal tumors and 4.3 mm in inferior-superior and 3.2 mm in anterior-posterior for laryngeal tumors, for our institution. CONCLUSIONS: Intrafractional head-and-neck tumor motion was quantified and population-based PTV margins were calculated. Although the average tumor motion was small (95th percentile motion

Purpose/Objective: Flank irradiation for Wilms' tumor (WT) is currently performed at our institute using a cone-beam computed tomography-guided volumetric modulated arc (VMATCBCT) workflow. By adding real-time magnetic resonance imaging (MRI) guidance to the treatment, safety margins could be reduced. The study purpose was to quantify the potential reduction of the planning target volume (PTV) margin and its dosimetric impact when using an MRI-guided intensity modulated radiation therapy (IMRTMRI) workflow compared to the VMATCBCT workflow. Material/Methods: 4D-CT, MRI and CBCT scans acquired during preparation and treatment of 15 patients, were used to estimate both geometric, motion and patient set-up systematic (∑) and random (σ) errors for VMATCBCT and IMRTMRI workflows. The mean PTV (PTVmean) expansion was calculated using the van Herk formula. Treatment plans were generated using five margin scenarios (PTVmean ± 0, 1 and 2 mm). Furthermore, the IMRTMRI plans were optimized with a 1.5T transverse magnetic field turned-on to realistically model an MRI-guided treatment. Plans were evaluated using dose-volume statistics (p Results: Analysis of ∑ and σ errors resulted in a PTVmean of 5 mm for the VMATCBCT and 3 mm for the IMRTMRI workflows in each orthogonal direction. Target coverage was unaffected by the margin decrease with a mean V95%=100% for all margin scenarios. For the PTVmean, an average reduction of the mean dose to the organs at risk (OARs) was achieved with IMRTMRI compared to VMATCBCT: 3.4 ± 2.4% (pppp Conclusions: Imaging data in children with WT demonstrated that the PTV margin could be reduced isotropically down to 2 mm when using the IMRTMRI compared to the VMATCBCT workflow. The former results in a dose reduction to the OARs while maintaining target coverage.

BACKGROUND AND PURPOSE:Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs.MATERIAL AND METHODS:Radiation oncologists at four Danish cancer centres delineated high, intermediate and elective dose CTVs (CTV1, CTV2 and CTV3, respectively) in a patient-case template (stage IV squamous cell carcinoma of the oropharynx), first using mainly anatomical margins (original standard) and then using concentric geometric expansion (new standard). Each centre made a dummy-run radiotherapy plan based on the delineated CTVs. The difference between the CTV contours and the radiotherapy plans was evaluated across the centres.RESULTS:Anatomy-based contours were significantly more heterogenous and showed larger volume differences between centres than geometric margins. Dice similarity coefficient increased by 0.29 and mean surface distance decreased by 4mm for CTV1. Use of consistent CTV volumes resulted in more consistent irradiated volumes between centres.CONCLUSION:Introduction of geometric margins resulted in more uniform CTV1 and CTV2 delineation. Geometric CTV expansion was easier, left less room for misinterpretation, and resulted in more uniform treatment plans with similar irradiated high and intermediate dose volumes across all centres.

Radiotherapy treatment planning of complex radiotherapy techniques, such as intensity modulated radiotherapy and volumetric modulated arc therapy, is a resource-intensive process requiring a high level of treatment planner intervention to ensure high plan quality. This can lead to variability in the quality of treatment plans and the efficiency in which plans are produced, depending on the skills and experience of the operator and available planning time. Within the last few years, there has been significant progress in the research and development of intensity modulated radiotherapy treatment planning approaches with automation support, with most commercial manufacturers now offering some form of solution. There is a rapidly growing number of research articles published in the scientific literature on the topic. This paper critically reviews the body of publications up to April 2018. The review describes the different types of automation algorithms, including the advantages and current limitations. Also included is a discussion on the potential issues with routine clinical implementation of such software, and highlights areas for future research.

To assess whether deformable registration between CT and MR images can be used to avoid patient immobilization, we compared registration accuracy in various scenarios, with and without immobilization equipment. Whereas both deformable registration and the use of immobilization equipment improved the registration accuracy, the combination gave, the best alignment. (C) 2015 Published by Elsevier Ireland Ltd.

BACKGROUND: Adaptive (ART) and image guided radiation therapy (IGRT) can improve target coverage and reduce unnecessary irradiation of organs at risk (OAR). The purpose of this study is to report the results of using mid-course imaging and a novel workflow with cone-beam computed tomography (CBCT) surveillance of dose to OAR to trigger adaptive replanning in head and neck radiotherapy. MATERIAL AND METHODS: Impact of radiation therapist (RTT) managed match protocol and mid-course imaging was assessed in two cohorts of consecutive patients receiving RT to the head and neck region, using computed tomography (CT) and CBCT-based dose verification respectively. In the CBCT cohort, patients at high risk of xerostomia received weekly dose surveillance, while low-risk patients received a mid-course CBCT review. For weekly surveillance, predicted total doses to parotid glands, spinal cord and brainstem were calculated. If predicted mean dose to parotid glands increased by >2 Gy or constraints to brainstem or spinal cord were exceeded, replanning was performed. RESULTS: None had replanning triggered by mid-course imaging. In the CBCT cohort, weekly surveillance of 40 patients yielded minimal reduction in mean dose to parotid glands of 0.65 Gy (range0.4-1 Gy ) for three patients. Patients were surveilled averagely 4.5 times during treatment. Time consumption per CBCT/week was 22 min (range 17-38). Number of patients needed to see to achieve any dose reduction to parotid glands was 13 or the equivalent of 22 working-hours. CONCLUSION: The tested dose surveillance algorithm resulted in a minimal dose reduction ( ≤1 Gy) to parotid glands for three of 40 patients. The proposed algorithm and workflow is thus not sustainable. Mid-course dose verification did not provide added benefit and can be safely omitted in the presence of closely monitored daily IGRT. Daily image guidance and match protocol is a safe and efficient method for identifying patients requiring adaptive replanning.

Background: Current state of the art radiotherapy planning of prostate cancer utilises magnetic resonance (MR) for soft tissue delineation and computed tomography (CT) to provide an electron density map for dose calculation. This dual scan workflow is prone to setup and registration error. This study evaluates the feasibility of an MR-only workflow and the validity of dose calculation from an MR derived pseudo CT. Material and methods: Thirty prostate cancer patients were CT and MR scanned. Clinical treatment plans were generated on CT using a single 18 MV arc volumetric modulated arc therapy (VMAT) with a prescription of 78 Gy/39 fractions. Dose was recalculated on pseudo CT and assuming uniform water density. Pseudo CT and uniform density based dose calculations were compared to CT dose calculations by gamma analysis. One patient was treated with a plan based solely on MR and pseudo CT including daily image guided radiotherapy (IGRT) performed by manual match of implanted gold markers. Results: A pseudo CT was generated for 29 of the 30 patients. Median gamma pass rates for 1%/1 mm passing criteria for dose calculated on pseudo CT when compared to CT were 100% for most evaluated structures. Dose calculated on uniform density also yielded high median pass rates, but with a higher occurrence of pass rates below 95%. Cases of pass rate below 95% on pseudo CT proved to originate from the presence of rectal air on CT, not represented by the pseudo CT. Treatment based on MR alone was successfully delivered to one patient, including manually performed daily IGRT. Conclusions: Median gamma pass rates were high for pseudo CT and proved superior to uniform density. Local differences in dose calculations were concluded not to have clinical relevance. Feasibility of the MR-only workflow was demonstrated through successful delivery of a treatment course planned based on MR alone.

Purpose: Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Gregoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. Method: For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. Results: This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. Conclusion: Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma. (C) 2017 Elsevier B.V. All rights reserved.

Background Pre-treatment magnetic resonance imaging (MRI) can give patient-specific evaluation of 25 suspected pathologically-involved volumes in the seminal vesicles (SV) in prostate cancer patients. By 26 targeting this suspicious volume we hypothesize that radiotherapy is more efficient without introducing more 27 toxicity. In this study we evaluate the concept of using MRI-defined target volumes in terms of tumor 28 control probability (TCP) and rectal normal tissue complication probability (NTCP). Materials and methods Twenty-one high-risk prostate cancer patients were included. Pre-treatment CT 30 images, T2 weighted (T2w) MRI and two multi-parametric MRI were acquired. Overlap between a 31 suspicious volume in the SV observed on T2w images and a suspicious volume observed on either multi-32 parametric MRI was assumed to reflect a true malignant region (named “MRI positive”). In addition the 33 entire SV on the CT-scan was delineated. Three treatment plans of 2Gyx39 fractions were generated per 34 patient: one covering the MRI positive volume in SV and prostate with margin of 11 mm to the MRI positive 35 in the SV and two plans covering prostate and SV using 11mm and 7mm SV margin, respectively. All plans 36 prescribed the same PTV mean dose. Rectal NTCP grade≥2 was evaluated with the Lyman-Kutcher-Burman 37 model and TCP was estimated by a logistic model using the combined MRI positive volume in SV and 38 prostate as region-of-interest. Results 14/21 patients were classified as MRI positive, 6 of which had suspicious volumes in all three MRI 40 modalities. On average TCP for the plan covering prostate and the MRI positive volume was 3% higher (up 41 to 11%) than the two other plans which was statistically significant. The increased TCP was obtained without 42 increasing rectal NTCP grade≥2. Conclusion Using functional MRI for individualized target delineation in the seminal vesicles may improve 44 the treatment outcome in radiotherapy of prostate cancer without increasing the rectal toxicity.

Objective To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Methods Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. Results A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81Gy (range, 0.25–2.02Gy) and 1.82Gy (range, 0.19–2.12Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02Gy (range, −0.11/+0.19Gy, p =0.102) (median difference of 1.1%, range −6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., −8.9%). Conclusions Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.

PURPOSE: To investigate the feasibility of using deformable registration in clinical practice to fuse MR and CT images of the head and neck for treatment planning.METHOD AND MATERIALS: A state-of-the-art deformable registration algorithm was optimized, evaluated, and compared with rigid registration. The evaluation was based on manually annotated anatomic landmarks and regions of interest in both modalities. We also developed a multiparametric registration approach, which simultaneously aligns T1- and T2-weighted MR sequences to CT. This was evaluated and compared with single-parametric approaches.RESULTS: Our results show that deformable registration yielded a better accuracy than rigid registration, without introducing unrealistic deformations. For deformable registration, an average landmark alignment of approximatively 1.7 mm was obtained. For all the regions of interest excluding the cerebellum and the parotids, deformable registration provided a median modified Hausdorff distance of approximatively 1 mm. Similar accuracies were obtained for the single-parameter and multiparameter approaches.CONCLUSIONS: This study demonstrates that deformable registration of head-and-neck CT and MR images is feasible, with overall a significanlty higher accuracy than for rigid registration.

Purpose To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. Methods and Materials Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. Results Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection ( P =.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity ( P =.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. Conclusions Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

Aims: Hypofractionation of postoperative radiotherapy for breast cancer has been evaluated in a number of large randomised clinical trials, but concerns remain over the late cardiac toxicity. In this study, we examined the predictions of the linear quadratic model on the estimated fraction size-corrected dose to the heart for four evidence-based hypofractionation regimens. Materials and methods: Dose plans for 60 left-sided breast cancer patients were analysed. All patients were planned with tangential fields for whole breast irradiation. Dose distributions were corrected to the equivalent dose in 2 Gy fractions (EQD(2)) using the linear quadratic model for five different fractionation schedules (50 Gy/25 fractions and four hypofractionation regimens) and for a range of alpha/beta. values (0-5 Gy). The mean EQD(2) to the heart (D-mean(EQD2)) and the volume receiving 40 Gy (V-40(Gy)EQD2), both as calculated from the EQD(2) dose distributions, were compared between schedules. Results: For alpha/beta = 3 Gy, V-40(Gy)EQD2 favours hypofractionation for 40 Gy/15 fractions, 39 Gy/13 fractions and 42.5 Gy/16 fractions, but not for 41.6 Gy/13 fractions. All of the hypofractionation schedules result in lower D-mean(EQD2) compared with normofractionation. These results hold as long as alpha/beta greater than or similar to 1.5 Gy. If the heart is blocked from the treatment beam, the fraction size-corrected dose is lower for the first three hypofractionation schedules, compared with normofractionation, even for alpha/beta = similar to 1 Gy. Conclusion: For standard tangential field whole breast irradiation, most of the examined hypofractionation schedules are estimated to spare the heart when compared with normofractionation. The dose to the heart, adjusted for fraction size using the linear quadratic model, will generally be lower after hypofractionated compared with normofractionated schedules, even for very low values of alpha/beta. (C) 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background: Autocontouring improves workflow in computed tomography (CT)-based dose planning, but could also potentially play a role for optimal use of daily cone beam CT (CBCT) in adaptive radiotherapy. This study aims to determine the accuracy of a deformable image registration (DIR) algorithm for organs at risk (OAR) in the neck region, when applied to CBCT. Material and methods: For 30 head and neck cancer (HNC) patients 14 OARs including parotid glands, swallowing structures and spinal cord were delineated. Contours were propagated by DIR from CT to the CBCTs of the first and last treatment fraction. An indirect approach, propagating contours to the first CBCT and from there to the last CBCT was also tested. Propagated contours were compared to manually corrected contours by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dose was recalculated on CBCTs and dosimetric consequences of uncertainties in DIR were reviewed. Results: Mean DSC values of ≥0.8 were considered adequate and were achieved in tongue base (0.91), esophagus (0.85), glottic (0.81) and supraglottic larynx (0.83), inferior pharyngeal constrictor muscle (0.84), spinal cord (0.89) and all salivary glands in the first CBCT. For the last CBCT by direct propagation, adequate DSC values were achieved for tongue base (0.85), esophagus (0.84), spinal cord (0.87) and all salivary glands. Using indirect propagation only tongue base (0.80) and parotid glands (0.87) were ≥0.8. Mean relative dose difference between automated and corrected contours was within ±2.5% of planed dose except for esophagus inlet (-4.5%) and esophagus (5.0%) for the last CBCT using indirect propagation. Conclusion: Compared to manually corrected contours, the DIR algorithm was accurate for use in CBCT images of HNC patients and the minor inaccuracies had little consequence for mean dose in most clinically relevant OAR. The method can thus enable a more automated segmentation of CBCT for use in adaptive radiotherapy. Radiotherapy is the primary treatment for most patients with squamous cell carcinoma of the head and neck and about 80% of all patients receive radiotherapy either alone or in combination with surgery and chemotherapy. Relatively high loco-regional control rates are obtained, but at the expense of substantial side effects, of which xerostomia and swallowing dysfunction are the most prominent [1–4 Jensen K, Jensen AB, Grau C. A cross sectional quality of life study of 116 recurrence free head and neck cancer patients. The first use of EORTC H&N35 in Danish. Acta Oncol 2006;45:28–37. Jensen K, Lambertsen K, Grau C. Late swallowing dysfunction and dysphagia after radiotherapy for pharynx cancer: frequency, intensity and correlation with dose and volume parameters. Radiother Oncol 2007;85:74–82. Jensen K, Overgaard M, Grau C. Morbidity after ipsilateral radiotherapy for oropharyngeal cancer. Radiother Oncol 2007;85:90–7. Mortensen HR, Overgaard J, Specht L, et al. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol 2012;103:69–75. ]. The observed morbidity is to a large extent due to inadvertent irradiation of normal tissues in the vicinity of the clinical target, including salivary glands and swallowing structures [5 Eisbruch A, Ten Haken RK, Kim HM, et al. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577–87. [CrossRef], [PubMed], [Web of Science ®] ,6 Langendijk JA, Doornaert P, Rietveld DH, et al. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol 2009;90:189–95. [CrossRef], [PubMed], [Web of Science ®] ]. The irradiation of normal structures are in part a result of applied margins around the clinical target to counteract multiple uncertainties, including daily setup errors, target definition, and interfraction changes in the anatomy. Several studies indicate that the anatomical changes in these patients over the course of treatment can be substantial [7–9 Barker JL, Garden AS, Ang KK, et al. Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system. Int J Radiat Oncol Biol Phys 2004;59:960–70. Castadot P, Lee JA, Geets X, et al. Adaptive radiotherapy of head and neck cancer. Semin Radiat Oncol 2010;20:84–93. Ricchetti F, Wu B, McNutt T, et al. Volumetric change of selected organs at risk during IMRT for oropharyngeal cancer. Int J Radiat Oncol Biol Phys 2011;80:161–8. ]. Repeated imaging and replanning, even with a single mid-treatment computed tomography (CT), can significantly improve tumor coverage and normal tissue sparing [10–12 Hansen EK, Bucci MK, Quivey JM, et al. Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;64:355–62. Schwartz DL, Garden AS, Thomas J, et al. Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a prospective trial. Int J Radiat Oncol Biol Phys 2012;83:986–93. Schwartz DL, Garden AS, Shah SJ, et al. Adaptive radiotherapy for head and neck cancer-dosimetric results from a prospective clinical trial. Radiother Oncol 2013;106:80–4. ]. Replanning requires repeated contouring of target volumes and normal tissues, which remains a time consuming task, even for experienced clinicians. There is a growing array of commercial software aimed at easing this burden by automatic contouring, utilizing novel deformable image registration (DIR) techniques to propagate one set of contours from an initial CT to fit the anatomy of a second CT [13 Elstrøm UV, Wysocka BA, Muren LP, et al. Daily kV cone-beam CT and deformable image registration as a method for studying dosimetric consequences of anatomic changes in adaptive IMRT of head and neck cancer. Acta Oncol 2010;49:1101–8. [Taylor & Francis Online], [Web of Science ®] ,14 Østergaard Noe K, De Senneville BD, Elstrøm UV, et al. Acceleration and validation of optical flow based deformable registration for image-guided radiotherapy. Acta Oncol 2008;47:1286–93. [Taylor & Francis Online], [Web of Science ®] ]. Such techniques have been found to reduce contouring time considerably [15 La Macchia M, Fellin F, Amichetti M, et al. Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer. Radiat Oncol 2012;7:160. [CrossRef], [PubMed], [Web of Science ®] ,16 Teguh DN, Levendag PC, Voet PW, et al. Clinical validation of atlas-based auto-segmentation of multiple target volumes and normal tissue (swallowing/mastication) structures in the head and neck. Int J Radiat Oncol Biol Phys 2011;81:950–7. [CrossRef], [PubMed], [Web of Science ®] ]. Today, in-room daily imaging with cone beam CT (CBCT) allows more convenient soft tissue volumetric information to be potentially utilized in an adaptive approach. Previous studies have shown that if the image quality is sufficiently optimized, it is possible to contour soft tissue organs at risk (OAR), including spinal cord, salivary glands and swallowing structures [17 Elstrøm UV, Muren LP, Petersen JB, et al. Evaluation of image quality for different kV cone-beam CT acquisition and reconstruction methods in the head and neck region. Acta Oncol 2011;50:908–17. [Taylor & Francis Online], [Web of Science ®] ]. With Hounsfield unit calibration, the segmented CBCT can subsequently be used for dose calculation, with an overall precision of 2–3% for clinically relevant dose-volume parameters compared to standard CT-based dose planning [18 Elstrøm U, Olsen S, Wysocka B, et al. Cone-beam CT-based radiotherapy planning of head and neck cancer. Radiother Oncol 2012;103. [CrossRef] ]. Combining DIR techniques with the daily CBCT imaging could potentially enable prospective monitoring of volumetric and dosimetric changes over the course of treatment, improving the possibilities for plan adaptation. Few studies concerning this have been published to date [19 Hou J, Guerrero M, Chen W, et al. Deformable planning CT to cone-beam CT image registration in head-and-neck cancer. Med Phys Apr 2011;38:2088–94. [CrossRef], [PubMed], [Web of Science ®] ]. If feasible, this approach may also replace the mid-treatment CT as an added benefit. The purpose of this study was to determine the contouring accuracy of a software solution for unsupervised segmentation of OARs in daily CBCTs of head and neck cancer (HNC) patients.

Item does not contain fulltext BACKGROUND AND PURPOSE: To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. MATERIALS AND METHODS: Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). RESULTS: ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. CONCLUSIONS: ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients.

The intra-fractional movement of the prostate constitutes a hindrance for the reduction of the planning target volume margin for prostate cancer patients. Monitoring the movement of the prostate during treatment is a promising but in most centres not feasible solution. However, the projection images of the pre-treatment cone-beam computed tomography (CBCT) provide information about the motion of the target immediately preceding the treatment. This motion information can be extracted from any standard CBCT scan which is available in many institutions. In this study we measure the motion of the prostate during the pre-treatment CBCT and investigate whether this motion is correlated with the intra-fractional movement of the prostate. Material and methods. Pre- and post-treatment CBCT scans were made during a number of the fractions (average 11 range 8-12) for 13 prostate cancer patients during the radiation treatment course. The displacement of the post-treatment CBCT scans relative to the pre-treatment position was used to assess the intra-fractional motion. Automated image analysis was used to track the 2D position of radiopaque markers in the projection images of the scans. The most probable 3D trajectory of the markers during the CBCT scan was estimated based on a probability density function which was established for each individual scan. Results. The accuracy of the tracking algorithm was found satisfactory and the motion of the markers during the CBCT scans was successfully extracted from the projection images. This motion was generally small and uncorrelated with the subsequent intra-fractional movement of the prostate. The correlation coefficients were 20.05, 0.07, and 20.05 in the LR, AP, and CC direction, respectively. Conclusion. It is tempting to exploit the pre-treatment CBCT to predict the intra-fractional movement of the prostate but, unfortunately, we have found no correlation between the intra-fractional movement and the motion of the prostate immediately prior to treatment.

Magnetic resonance imaging (MRI) is increasingly being used in the radiotherapy workflow because of its superior soft tissue contrast and high flexibility in contrast. In addition to anatomical and functional imaging, MRI can also be used to characterize the physiologically induced motion of both the tumor and organs-at-risk. Respiratory-correlated 4D-MRI has gained large interest as an alternative to 4D-CT for the characterization of respiratory motion throughout the thorax and abdomen. These 4D-MRI data sets consist of three spatial dimensions and the respiratory phase or amplitude over the fourth dimension (opposed to time-resolved 4D-MRI that represents time in the fourth dimension). Over the last 15 years numerous methods have been presented in literature. This review article provides a comprehensive overview of the various 4D-MRI techniques, and describes the differences in MRI data acquisition and 4D data set generation from a methodological point of view. The current status and future perspective of these techniques are highlighted, and the requirements for safe introduction into the clinic (e.g. method validation) are discussed.

We would like to compare the effectiveness of image-guided (IGRT) and intensity-modulated (IMRT) radiotherapy to spare the larynx in head and neck cancer patients. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Mean laryngeal and hypopharyngeal dose was compared between 11 patients treated with IMRT and 37 patients treated with IGRT. Mean laryngeal dose was, respectively, 41.2 Gy and 22.8 Gy for the IMRT and IGRT technique (p

Purpose To quantify the inter-fraction shape variation of the mesorectum for rectal cancer patients treated with 5 × 5 Gy in supine position and compare it to variation in prone position. Methods and materials For 28 patients a planning CT (pCT) and five daily cone-beam-CT (CBCT) scans were acquired in supine position. The mesorectal part of the CTV (MesoRect) was delineated on all scans. The shape variation was quantified by the distance between the pCT- and the CBCT delineations and stored in surface maps after online setup correction. Data were analyzed for male and female patients separately and compared to prone data. Results A large range of systematic, 1–8 mm (1SD), and random, 1–5 mm, shape variation was found, comparable to prone patients. Random-shape variation was comparable for male and female patients, while systematic variation was 3 mm larger for female patients. Conclusions Shape variation of the MesoRect is substantial, heterogeneous and different between male and female patients. Differences between supine and prone orientation, however, are small. Clinical margins should be differentiated in position along the cranio–caudal axis, in anterior–posterior direction and for gender. Margins should also be increased, even when online setup correction is used. Due to the small margin differences between prone and supine treatments, the setup choice should be determined on dose to the organs at risk.