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Objective: Hypersensitivity towards proton versus photon irradiation was demonstrated in homologous recombination repair (HRR)-deficient cell lines. Hence, combined treatment concepts targeting HRR provide a rational for potential pharmaceutical exploitation. The HSP90 inhibitor ganetespib (STA-9090) downregulates a multitude of HRR-associated proteins and sensitizes for certain chemotherapeutics. Thus, the radiosensitizing effect of HSP90-inhibiting ganetespib was investigated for reference photon irradiation and proton irradiation at a proximal and distal position in a spread-out Bragg peak (SOBP).Methods: A549 and FaDu cells were treated with low-dose (2 nM resp. 1 nM) ganetespib and irradiated with 200 kV photons. Proton irradiation was performed at a proximal and a distal position within a SOBP, with corresponding dose-averaged linear-energy transfer (LETD) values of 2.1 and 4.5 keV/µm, respectively. Cellular survival data was fitted to the linear-quadratic model to calculate relative biological effectiveness (RBE) and the dose-modifying factor (DMF). Additionally, A549 cells were treated with increasing doses of ganetespib and investigated by flow cytometry, immunoblotting, and immunofluorescence microscopy to investigate cell cycle distribution, Rad51 protein levels, and γH2AX foci, respectively.Results: Low-dosed ganetespib significantly sensitized both cancer cell lines exclusively for proton irradiation at both investigated LETD, resulting in increased RBE values of 10-40%. In comparison to photon irradiation, the fraction of cells in S/G2/M phase was elevated in response to proton irradiation with 10 nM ganetespib consistently reducing this population. No changes in cell cycle distribution were detected in unirradiated cells by ganetespib alone. Protein levels of Rad51 are downregulated in irradiated A549 cells by 10 nM and also 2 nM ganetespib within 24 h. Immunofluorescence staining demonstrated similar induction and removal of γH2AX foci, irrespective of irradiation type or ganetespib administration.Conclusion: Our findings illustrate a proton-specific sensitizing effect of low-dosed ganetespib in both employed cell lines and at both investigated SOBP positions. We provide additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To present the technical details of the runner‐up model in the open knowledge‐based planning (OpenKBP) challenge for the dose–volume histogram (DVH) stream. The model was designed to ensure simple and reproducible training, without the necessity of costly advanced generative adversarial network (GAN) techniques. Methods: The model was developed based on the OpenKBP challenge dataset, consisting of 200 and 40 head‐and‐neck patients for training and validation, respectively. The final model is a U‐Net with additional ResNet blocks between up‐ and down convolutions. The results were obtained by training the model with AdamW with the One Cycle scheduler. The loss function is a combination of the L1 loss with a feature loss, which uses a pretrained video classifier as a feature extractor. The performance was evaluated on another 100 patients in the OpenKBP test dataset. The DVH metrics of the test data were evaluated, where D0.1cc, and Dmean were calculated for the organs at risk (OARs) and D1%, D95%, and D99% were computed for the target structures. DVH metric differences between predicted and true dose are reported in percentage. Results: The model achieved 2nd and 4th place in the DVH and dose stream of the OpenKBP challenge, respectively. The dose and DVH score were 2.62 ± 1.10 and 1.52 ± 1.06, respectively. Mean dose differences for the different structures and DVH parameters were within ±1%. Conclusion: This straightforward approach produced excellent results. It incorporated One Cycle Learning, ResNet, and feature‐based losses, which are common computer vision techniques. [ABSTRACT FROM AUTHOR]

Purpose: Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose-volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose-volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART).Methods and Materials: The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose-volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression.Results: The treated EBRT volumes varied for the different techniques with ~2500 cm3 for 3D conformal radiotherapy (3D-CRT), ~2000 cm3 for EMBRACE‑I VMAT, and ~1800 cm3 for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose-volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V40Gy < 250 cm3, rectum V40Gy < 80% and bladder V40Gy < 80-90%.Conclusion: This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose-volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found. [ABSTRACT FROM AUTHOR]

To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects. [ABSTRACT FROM AUTHOR]

Background: The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics.Methods: Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches.Conclusions: Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners. [ABSTRACT FROM AUTHOR]

Background: Dosimetric effects of inaccuracies of output factors (OFs) implemented in treatment planning systems (TPSs) were investigated. Materials and methods: Modified beam models (MBM) for which the OFs of small fields (down to 1 × 1 cm2) were increased by up to 12% compared to the original beam models (OBM) were created for two TPSs. These beam models were used to recalculate treatment plans of different complexity. Treatment plans using stereotactic 3D-conformal (s3D-CRT) for brain metastasis as well as VMAT plans for head and neck and prostate cancer patients were generated. Dose distributions calculated with the MBM and the OBM were compared to measured dose distributions acquired using film dosimetry and a 2D-detector-array. For the s3D-CRT plans the calculated and measured dose at the isocenter was evaluated. For VMAT, gamma pass rates (GPRs) were calculated using global gamma index with 3%/3 mm, 2%/3 mm, 1%/3 mm and 2%/2 mm with a 20% threshold. Contribution of small fields to the total fluence was expressed as the ratio (F) of fluence trough leaf openings smaller than 2 cm to the total fluence. Results: Using film dosimetry for the s3D-CRT plans, the average of the ratio of calculated dose to measured dose at the isocenter was 1.01 and 1.06 for the OBM and MBM model, respectively. A significantly lower GPR of the MBM compared to the OBM was only found for the localized prostate cases (F = 12.4%) measured with the 2D-detector-array and an acceptance criterion of 1%/3 mm. Conclusion: The effects of uncertainties in small field OFs implemented in TPSs are most pronounced for s3D-CRT cases and can be clearly identified using patient specific quality assurance. For VMAT these effects mainly remain undetected using standard patient specific quality assurance. Using tighter acceptance criteria combined with an analysis of the fluence generated by small fields can help identifying inaccuracies of OFs implemented in TPSs. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: For commercially available linear accelerators (Linacs), the electron energies of flattening filter free (FFF) and flattened (FF) beams are either identical or the electron energy of the FFF beam is increased to match the percentage depth dose curve (PDD) of the FF beam (in reference geometry). This study focuses on the primary dose components of FFF beams for both kinds of settings, studied on the same Linac. Methods: The measurements were conducted on a VersaHD Linac (Elekta, Crawley, UK) for both FF and FFF beams with nominal energies of 6 and 10 MV. In the clinical setting of the VersaHD, the energy of FFFM (Matched) beams is set to match the PDDs of the FF beams. In contrast the incident electron beam of the FFFU beam was set to the same energy as for the FF beam. Half value layers (HVLs) and a dual parameter beam quality specifier (DPBQS) were determined. Results: For the 6 MV FFFM beam, HVL and DPBQS values were very similar compared to those of the 6 MV FF beam, while for the 10 MV FFFM and FF beams, only %dd(10)x and HVL values were comparable (differences below 1.5%). This shows that matching the PDD at one depth does not guarantee other beam quality dependent parameters to be matched. For FFFU beams, all investigated beam quality specifiers were significantly different compared to those for FF beams of the same nominal accelerator potential. The DPBQS of the 6 MV FF and FFFM beams was equal within the measurement uncertainty and was comparable to published data of a machine with similar TPR20,10 and %dd(10)x. In contrast to that, the DPBQS's two parameters of the 10 MV FFFM beam were substantially higher compared to those for the 10 MV FF beam. Conclusions: PDD-matched FF and FFF beams of both nominal accelerator potentials were observed to have similar HVL values, indicating similarity of their primary dose components. Using the DPBQS revealed that the mean attenuation coefficient was found to be the same within the uncertainty of 0.8% for 6 MV FF and 6 MV FFFM beams, while for 10 MV beams, they differed by 6.4%. This shows that the DPBQS can provide a differentiation of photon beam characteristics that would remain hidden by the use of a single beam quality specifier, such as %dd(10)x or HVL. [ABSTRACT FROM AUTHOR]

Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). Material and methods.For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT1/MR1at week 2 and CT2/MR2at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy, CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies. Results.Dosimetric evaluation of recalculated plans on CT1and CT2showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D2%for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D2%reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D2%decreased by up to 8 Gy while D98%increased by 1.2 Gy. Conclusion.ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: Helium ions (4He) may supplement current particle beam therapy strategies as they possess advantages in physical dose distribution over protons. To assess potential clinical advantages, a dose calculation module accounting for relative biological effectiveness (RBE) was developed and integrated into the treatment planning system Hyperion. Methods: Current knowledge on RBE of 4He together with linear energy transfer considerations motivated an empirical depth-dependent "zonal" RBE model. In the plateau region, a RBE of 1.0 was assumed, followed by an increasing RBE up to 2.8 at the Bragg-peak region, which was then kept constant over the fragmentation tail. To account for a variable proton RBE, the same model concept was also applied to protons with a maximum RBE of 1.6. Both RBE models were added to a previously developed pencil beam algorithm for physical dose calculation and included into the treatment planning system Hyperion. The implementation was validated against Monte Carlo simulations within a water phantom using -index evaluation. The potential benefits of 4He based treatment plans were explored in a preliminary treatment planning comparison (against protons) for four treatment sites, i.e., a prostate, a base-of-skull, a pediatric, and a head-and-neck tumor case. Separate treatment plans taking into account physical dose calculation only or using biological modeling were created for protons and 4He. Results: Comparison of Monte Carlo and Hyperion calculated doses resulted in a γmean of 0.3, with 3.4% of the values above 1 and γ1% of 1.5 and better. Treatment plan evaluation showed comparable planning target volume coverage for both particles, with slightly increased coverage for 4He. Organ at risk (OAR) doses were generally reduced using 4He, some by more than to 30%. Improvements of 4He over protons were more pronounced for treatment plans taking biological effects into account. All OAR doses were within tolerances specified in the QUANTEC report. Conclusions: The biological 4He model proposed above is a first approach matching biological data published so far. The advantage of 4He seems to lie in the reduction of dose to surrounding tissue and to OARs. Nevertheless, additional biological experiments and treatment planning studies with larger patient numbers and more tumor indications are necessary to study the possible benefits of helium ion beam therapy in detail. [ABSTRACT FROM AUTHOR]

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Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The purpose of the study was to examine the energy dependence of Gafchromic EBT radiochromic dosimetry films, in order to assess their potential use in intensity-modulated radiotherapy (IMRT) verifications. Materials and methods: The film samples were irradiated with doses from 0.1 to 12Gy using photon beams from the energy range 1.25MeV to 25MV and the film response was measured using a flat-bed scanner. The samples were scanned and the film responses for different beam energies were compared. Results: A high uncertainty in readout of the film response was observed for samples irradiated with doses lower than 1Gy. The relative difference exceeds 20% for doses lower than 1Gy while for doses over 1Gy the measured film response differs by less than 5% for the whole examined energy range. The achieved uncertainty of the experimental procedure does not reveal any energy dependence of Gafchromic EBT film response in the investigated energy range. Conclusions: Gafchromic EBT film does not show any energy dependence in the conditions typical for IMRT but the doses measured for pre-treatment plan verifications should exceed 1Gy. [Copyright &y& Elsevier]

Copyright of Zeitschrift für Medizinische Physik is the property of Elsevier GmbH, Urban & Fischer Verlag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Recent developments in radiation therapy such as intensity modulated radiotherapy (IMRT) or dose painting promise to provide better dose distribution on the tumor. For effective application of these methods the exact positioning of the patient and the localization of the irradiated organ and surrounding structures is crucial. Especially with respect to the treatment of the prostate, ultrasound (US) allows for differentiation between soft tissue and was therefore applied by various repositioning systems, such as BAT or Clarity. The authors built a new system which uses 3D US at both sites, the CT room and the intervention room and applied a 3D/3D US/US registration for automatic repositioning. Methods: In a first step the authors applied image preprocessing methods to prepare the US images for an optimal registration process. For the 3D/3D registration procedure five different metrics were evaluated. To find the image metric which fits best for a particular patient three 3D US images were taken at the CT site and registered to each other. From these results an US registration error was calculated. The most successful image metric was then applied for the US/US registration process. The success of the whole repositioning method was assessed by taking the results of an ExacTrac system as golden standard. Results: The US/US registration error was found to be 2.99 ± 1.54 mm with respect to the mutual information metric by Mattes (eleven patients) which revealed to be the most suitable of the assessed metrics. For complete repositioning chain the error amounted to 4.15 ± 1.20 mm (ten patients). Conclusions: The authors developed a system for patient repositioning which works automatically without the necessity of user interaction with an accuracy which seems to be suitable for clinical application. [ABSTRACT FROM AUTHOR]

Background and purpose: In the next few years the number of facilities providing ion beam therapy with scanning beams will increase. An auditing process based on an end-to-end test (including CT imaging, planning and dose delivery) could help new ion therapy centres to validate their entire logistic chain of radiation delivery. An end-to-end procedure was designed and tested in both scanned proton and carbon ion beams, which may also serve as a dosimetric credentialing procedure for clinical trials in the future. The developed procedure is focused only on physical dose delivery and the validation of the biological dose is out of scope of the current work. Materials and methods: The audit procedure was based on a homogeneous phantom that mimics the dimension of a head (20×20×21cm3). The phantom can be loaded either with an ionisation chamber or 20 alanine dosimeters plus 2 radiochromic EBT films. Dose verification aimed at measuring a dose of 10Gy homogeneously delivered to a virtual-target volume of 8×8×12cm3. In order to interpret the readout of the irradiated alanine dosimeters additional Monte Carlo simulations were performed to calculate the energy dependent detector response of the particle fluence in the alanine detector. A pilot run was performed with protons and carbon ions at the Heidelberg Ion Therapy facility (HIT). Results: The mean difference of the absolute physical dose measured with the alanine dosimeters compared with the expected dose from the treatment planning system was −2.4±0.9% (1σ) for protons and −2.2±1.1% (1σ) for carbon ions. The measurements performed with the ionisation chamber indicate this slight underdosage with a dose difference of −1.7% for protons and −1.0% for carbon ions. The profiles measured by radiochromic films showed an acceptable homogeneity of about 3%. Conclusions: Alanine dosimeters are suitable detectors for dosimetry audits in ion beam therapy and the presented end-to-end test is feasible. If further studies show similar results, this dosimetric audit could be implemented as a credentialing procedure for clinical proton and carbon beam delivery. [ABSTRACT FROM AUTHOR]

Purpose: To investigate robust margin strategies in intensity modulated proton therapy to account for interfractional organ motion in prostate cancer. Methods and Materials: For 9 patients, one planning computed tomography (CT) scan and daily and weekly cone beam CTs (CBCTs) were acquired and coregistered. The following planning target volume (PTV) approaches were investigated: a clinical target volume (CTV) delineated on the planning CT (CTVct) plus 10-mm margin (PTV10mm); a reduced PTV (PTVRed): CTVct plus 5 mm in the left-right (LR) and anterior-posterior (AP) directions and 8 mm in the inferior-superior (IS) directions; and a PTVHull method: the sum of CTVct and CTVs from 5 CBCTs from the first week plus 3 mm in the LR and IS directions and 5 mm in the AP direction. For each approach, separate plans were calculated using a spot-scanning technique with 2 lateral fields. Results: Each approach achieved excellent target coverage. Differences were observed in volume receiving 98% of the prescribed dose (V98%) where PTVHull and PTVRed results were superior to the PTV10mm concept. The PTVHull approach was more robust to organ motion. The V98% for CTVs was 99.7%, whereas for PTVRed and PTV10mm plans, V98% was 98% and 96.1%, respectively. Doses to organs at risk were higher for PTVHull and PTV10mm plans than for PTVRed, but only differences between PTV10mm and PTVRed were significant. Conclusions: In terms of organ sparing, the PTV10mm method was inferior but not significantly different from the PTVRed and PTVHull approaches. PTVHull was most insensitive to target motion. [Copyright &y& Elsevier]

Abstract: Background and purpose: The aim of this work was to compare the accuracy of different HU adjustments for CBCT-based dose calculation. Methods and materials: Dose calculation was performed on CBCT images of 30 patients. In the first two approaches phantom-based (Pha-CC) and population-based (Pop-CC) conversion curves were used. The third method (WAB) represents override of the structures with standard densities for water, air and bone. In ROI mapping approach all structures were overridden with average HUs from planning CT. All techniques were benchmarked to the Pop-CC and CT-based plans by DVH comparison and γ-index analysis. Results: For prostate plans, WAB and ROI mapping compared to Pop-CC showed differences in PTV Dmedian below 2%. The WAB and Pha-CC methods underestimated the bladder dose in IMRT plans. In lung cases PTV coverage was underestimated by Pha-CC method by 2.3% and slightly overestimated by the WAB and ROI techniques. The use of the Pha-CC method for head–neck IMRT plans resulted in difference in PTV coverage up to 5%. Dose calculation with WAB and ROI techniques showed better agreement with pCT than conversion curve-based approaches. Conclusions: Density override techniques provide an accurate alternative to the conversion curve-based methods for dose calculation on CBCT images. [Copyright &y& Elsevier]

Abstract: Background and purpose: Increase in positioning accuracy and treatment adaptation is supported by image guidance. The downside is the concomitant imaging dose. In this study, we report on the total dose picture for different styles of image guidance. Materials and methods: Dose was measured in the Alderson phantom using TLD’s. IGRT technology investigated included CBCT at the linac and simulator, multislice-CT and kV and MV planar imaging. Clinically used imaging protocols were applied and the total dose picture was assessed for four different sequences of imaging for a prostate and a head and neck treatment. Results: The different imaging geometries for the various imaging modalities resulted in fairly different dose distributions. Head and neck doses up to 100mGy and higher were found for portal imaging and multislice-CT. Depending on the IGRT sequence used maximum total dose varies between 120 and 1500mGy. In prostate maximum doses between 40 and 100mGy were found for portal imaging and CBCT at the linac. Here the maximum total dose varies between 120 and 2250mGy depending on the sequence used. Discussion: Factors like patient dimensions, age and sex can influence the applicability of presented values. Careful consideration of imaging dose especially for very intense imaging sequences is recommended. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study was to compare the dose calculation accuracy of advanced kernel-based methods and Monte Carlo algorithms in commercially available treatment planning systems. Materials and methods: Following dose calculation algorithms and treatment planning (TPS) systems were compared: the collapsed cone (CC) convolution algorithm available in Oncentra Masterplan, the XVMC Monte Carlo algorithm implemented in iPlan and Monaco, and the analytical anisotropic algorithm (AAA) implemented in Eclipse. Measurements were performed with a calibrated ionization chamber and radiochromic EBT type films in a homogenous polystyrene phantom and in heterogeneous lung phantoms. Single beam tests, conformal treatment plans and IMRT plans were validated. Dosimetric evaluations included absolute dose measurements, 1D γ-evaluation of depth–dose curves and profiles using 2mm and 2% dose difference criteria for single beam tests, and γ-evaluation of axial planes for composite treatment plans applying 3mm and 3% dose difference criteria. Results: Absolute dosimetry revealed no large differences between MC and advanced kernel dose calculations. 1D γ-evaluation showed significant discrepancies between depth–dose curves in different phantom geometries. For the CC algorithm γ mean values were 0.90±0.74 vs. 0.43±0.41 in heterogeneous vs. homogeneous conditions and for the AAA γ mean values were 1.13±0.91 vs. 0.41±0.28, respectively. In general, 1D γ results obtained with both MC TPS were similar in both phantoms and on average equal to 0.5 both for profiles and depth–dose curves. The results obtained with the CC algorithm in heterogeneous phantoms were slightly better in comparison to the AAA algorithm. The 2D γ-evaluation results of IMRT plans and four-field plans showed smaller mean γ-values for MC dose calculations compared to the advanced kernel algorithms (γ mean for four-field plan and IMRT obtained with Monaco MC were 0.28 and 0.5, respectively, vs. 0.40 and 0.54 for the AAA). Conclusion: All TPS investigated in this study demonstrated accurate dose calculation in homogenous and heterogeneous phantoms. Commercially available TPS with Monte Carlo option performed best in heterogeneous phantoms. However, the difference between the CC and the MC algorithms was found to be small. [Copyright &y& Elsevier]

Abstract: Purpose: To test the feasibility of a new inverse planning technology based on the Hybrid Inverse treatment Planning and Optimisation (HIPO) algorithm for image-guided cervical cancer brachytherapy in comparison to conventional manual optimisation as applied in recent clinical practice based on long-term intracavitary cervical cancer brachytherapy experience. Materials and methods: The clinically applied treatment plans of 10 tandem/ring (T/R) and 10 cases with additional needles (T/R + N) planned with PLATO v14.3 were included. Standard loading patterns were manually optimised to reach an optimal coverage with 7Gy per fraction to the High Risk CTV and to fulfil dose constraints for organs at risk. For each of these patients an inverse plan was retrospectively created with Oncentra GYN v0.9.14. Anatomy based automatic source activation was based on the topography of target and organs. The HIPO algorithm included individual gradient and modification restrictions for the T/R and needle dwell times to preserve the spatial high-dose distribution as known from the long-term clinical experience in the standard cervical cancer brachytherapy and with manual planning. Results: HIPO could achieve a better target coverage (V100) for all T/R and 7 T/R + N patients. Changes in the shape of the overdose volume (V200/400) were limited. The D2cc per fraction for bladder, rectum and sigmoid colon was on average lower by 0.2Gy, 0.4Gy, 0.2Gy, respectively, for T/R patients and 0.6Gy, 0.3Gy, 0.3Gy for T/R + N patients (a decrease from 4.5 to 4Gy per fraction means a total dose reduction of 5Gy EQD2 for a 4-fraction schedule). In general the dwell times in the additional needles were lower compared to manual planning. The sparing factors were always better for HIPO plans. Additionally, in 7 T/R and 7 T/R + N patients all three D0.1cc, D1cc and D2cc for vagina wall were lower and a smaller area of vagina was covered by the reference dose in HIPO plans. Overall loading times in the tandem, the ring and the needles, as well as dose distribution, were largely preserved with adaptations performed due to specific topographical variations, in particular in lateral and caudal directions. Conclusions: Inverse planning based on the HIPO algorithm can produce treatment plans for cervical cancer brachytherapy which are comparable to plans based on manual optimisation as applied in clinical practice. It is essential to take into account the spatial dose distribution in addition to the DVH-based constraints. The proposed inverse planning concept is feasible for improving the therapeutic ratio and limiting substantial high-dose regions around needles. [Copyright &y& Elsevier]

Abstract: Purpose: To determine dosimetric properties of unflattened megavoltage photon beams. Materials and methods: Dosimetric data including depth dose, profiles, output factors and phantom scatter factors from three different beam qualities provided by Elekta Precise linacs, operated with and without flattening filter were examined. Additional measurements of leaf transmission, leakage radiation and surface dose were performed. In flattening filter free (FFF) mode a 6-mm thick copper filter was placed into the beam to stabilize it. Results: Depths of dose maxima for flattened and unflattened beams did not deviate by more than 2mm and penumbral widths agreed within 1mm. In FFF mode the collimator exchange effect was found to be on average 0.3% for rectangular fields. Between maximum and minimum field size head scatter factors of unflattened beams showed on average 40% and 56% less variation for 6 and 10MV beams than conventional beams. Phantom scatter factors for FFF beams differed up to 4% from the published reference data. For field sizes smaller than 15cm, surface doses relative to the dose at d max increased for unflattened beams with maximum differences of 7% at 6MV and 25% at 10MV for a 5×5cm2 field. For a 30×30cm2 field, relative surface dose decreased by about 10% for FFF beams. Leaf transmission on the central axis was 0.3% and 0.4% lower for unflattened 6 and 10MV beams, respectively. Leakage radiation was reduced by 52% for 6MV and by 65% for 10MV unflattened beams. Conclusions: The results of the study were independently confirmed at two radiotherapy centres. Phantom scatter reference data need to be reconsidered for medical accelerators operated without a flattening filter. [Copyright &y& Elsevier]

Abstract: Purpose: To compare different dose–volume histogram (DVH) parameter concepts used for rectum and urethra. Methods and Materials: Thirty-eight postplan CT scans were used to contour the rectum with only one outer contour and as a wall structure. DVH analysis included dose to absolute and relative volumes of both contour types, from RD0.1cc to RD10cc and from RDmax to RD30, respectively. Volume parameters are reported (RV50–RV300) in cubic centimeters and percentages. The analysis of urethral dose parameters was based on 55 CTs with a urethral catheter. Relative (UD100 to UDmax) and absolute volume parameters (UD0.5cc to UD0.1cc, UV100, UV150) were evaluated, and also correlated to prostate parameters. The analysis was repeated for 10 MRI-based interstitial high-dose rate cases. Results: The correlation between organ and wall results was high for RD1, RD2cc, and RD0.1cc, with differences of <5%. DVH parameters reporting dose to a relative volume (e.g., RD10) or a relative volume related to a certain dose (e.g., RV100 [%]) are sensitive to the number of contoured slices. Dmax has a high uncertainty due to the sampling algorithm. RV100 (145Gy) of 1.5cc is similar to an RD2cc of 130Gy. The urethral UD10 and UD0.1cc correlate with a mean difference of 1%. The ratios of UD5/UD30, UD10/UD30, and UD5/UD10 were 1.12, 1.09, and 1.03, respectively. The correlation between D90 and D10 for prostate to urethra UD10 was poor. Conclusions: Only absolute volume parameters are stable in relation to different contouring concepts. When delineating the outer rectum contour, only RD2cc and RD0.1cc can be used. RV100 in cc correlates to RD2cc. Reporting UD5, UD10, and UD30 together is redundant. Additional information is given when reporting UV100 or UV150. [Copyright &y& Elsevier]

Abstract: Purpose: Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. Methods and materials: Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2Gy fractions (EQD2, α/β =3Gy), in 0.1, 1.0 and 2.0cm3 (D 0.1cc, D 1cc, D 2cc) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose–response analyses, the logit model was applied. Results: Mean follow-up was 18months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1cm3 volume (anterior wall). Mean values D 0.1cc, D 1cc, and D 2cc were 81±13, 70±9 and 66±8Gy, respectively. The ED50 values for VRS⩾3 and for LENT/SOMA⩾2 significantly increased with decreasing volumes. D 2cc was higher in patients with VRS⩾3 compared to VRS<3 (72±6 vs 62±7Gy; p <0.001) and in symptomatic vs asymptomatic patients (72±6 vs 63±8Gy; p <0.001). VRS correlated with the LENT/SOMA score. Conclusions: Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose–effect and volume–effect. DVH parameters could be established. [Copyright &y& Elsevier]