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Purpose To compare photons, protons and carbon ions and their combinations for treatment of atypical and anaplastical skull base meningioma. Material and methods Two planning target volumes (PTVinitial/PTVboost) were delineated for 10 patients (prescribed doses 50 Gy(RBE) and 10 Gy(RBE)). Plans for intensity modulated photon (IMXT), proton (IMPT) and carbon ion therapy (12C) were generated assuming a non-gantry scenario for particles. The following combinations were compared: IMXT + IMXT/IMPT/12C; IMPT + IMPT/12C; and 12C + 12C. Plan quality was evaluated by target conformity and homogeneity (CI, HI), V95%, D2% and D50% and dose-volume-histogram (DVH) parameters for organs-at-risk (OAR). If dose escalation was possible, it was performed until OAR tolerance levels were reached. Results CI was worst for IMXT. HI < 0.05 ± 0.01 for 12C was significantly better than for IMXT. For all treatment options dose escalation above 60 Gy(RBE) was possible for four patients, but impossible for six patients. Compared to IMXT + IMXT, ion beam therapy showed an improved sparing for most OARs, e.g. using protons and carbon ions D50% was reduced by more than 50% for the ipsilateral eye and the brainstem. Conclusion Highly conformal IMPT and 12C plans could be generated with a non-gantry scenario. Improved OAR sparing favors both sole 12C and/or IMPT plans. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To identify modifying factors and dose–/volume–response relationships for the retina and optic nerve related to highly conformal hypofractionated radiotherapy. Patients and methods: Seventy-three patients undergoing hypofractionated stereotactic photon radiotherapy of choroidal melanoma were included in this retrospective study. The volumes of the optic nerve receiving doses of more than 7.5 or 12Gy, respectively, were defined. Optic nerve circumference included in the 30%, 40%, 50%, or 80% isodose (ON%) and retina included in 30% or 40% were determined as quantal effects. Univariate and multivariate analyses were performed for clinical variables as well as probit analysis to define EDx (doses where a positive response is expected in x% of the cases). Results: Median follow-up was 90.0 (interquartile range 69.0–98.0) months. Fifty-two (71%) and 49 (67%) patients developed radiation retinopathy and optic neuropathy (any grade). Age, length of follow-up and diabetes were significant parameters regarding retinopathy. Optic neuropathy was significantly influenced by age, length of follow-up, and ON30. The probability of optic neuropathy (any grade and grade ⩾2) significantly increases with the dose (p ranges from 0.0126 to 0.0211). Conclusion: Treatment planning should aim at minimizing encompassing isodoses particularly in the low dose region, without compromising PTV coverage. [Copyright &y& Elsevier]

Abstract: Purpose: Evaluation of dosimetric benefits of advanced radiotherapy techniques for the treatment of abdominal lesions during early childhood. Patients and methods: Treatment planning was performed for five Neuroblastoma (NBL) and four Wilms Tumor (WT) patients. Opposing fields (2F), photon intensity modulated radiotherapy (IMXT) and two proton techniques (passively scattered (PT) and scanned beams (IMPT)) were considered. Averaged dose-volume histograms, associated dosimetric parameters and a radiobiological model for the estimation of the therapy related carcinogenic effect were evaluated. Results: With respect to the 2F technique, both proton techniques enabled to reduce mean liver and kidney dose by 40–60%; Organ fractions irradiated at the level of the tolerance dose were reduced by 65% for kidneys and 75% for the liver in NBL patients and by additional 10% for WT patients. IMXT enabled to reduce parameters related to the steep high-dose gradient, e.g., V 15Gy for the kidneys was reduced by a factor 2–3 compared to 2F. V 12Gy was reduced by 40% in the liver. On the other side, the improvement of those parameters characterizing the low isodose domain was limited for IMXT. The risk for radiation-induced secondary cancer was doubled for IMXT and even more increased for PT if secondary neutrons were taken into account, while this risk remained the same or was reduced by IMPT with respect to 2F. Conclusions: Proton beams improved all dosimetric parameters for NBL and WT patients compared to photon techniques. This improvement was limited for IMXT mainly to parameters related to the steep high-dose gradient. Further research is needed to minimize uncertainties for secondary cancer estimations. [Copyright &y& Elsevier]

Abstract: Background and purpose: The aim of the present study was to investigate potential dosimetric benefits of proton therapy for hypofractionated stereotactic body radiotherapy (SBRT). Materials and method: Twelve patients undergoing hypofractionated SBRT at the Medical University Vienna were selected. Passively scattered protons (PT) and intensity modulated proton therapy (IMPT) were evaluated against a conformal photon technique (3D-CRT), assuming a fractionation of 3×15Gy, prescribed to the 65% isodose. For all treatment techniques shallow breathing with abdominal compression (SB+AC) was compared with a deep inspiration breath hold technique (DIBH). Treatment planning was done with XiO (CMS, USA). Target conformity, dose–volume histograms (DVH) and various associated dosimetric parameters were considered for the planning target volume (PTV), lung, heart and esophagus. Results: For both breathing conditions conformity indices were very similar. They were between 0.75 and 0.78 for IMPT and 3D-CRT and around 0.55 for PT using 2–3 beams. Irrespective of treatment modality, DVHs for the ipsilateral lung were improved with the DIBH technique. For the PT technique, the 2Gy isodose (V 2Gy) covered on average 7–9% less lung volume compared to 3D-CRT, for IMPT this reduction was more than 10%. Volumes covered the 4 and 6Gy isodoses were 2–4% smaller for IMPT, but very similar for PT and 3D-CRT. Both proton techniques achieved full sparing of the contralateral lung and superior sparing of the heart. Maximum doses to the heart and esophagus were on average around 3Gy for 3D-CRT and almost 0Gy for both proton techniques. For 3D-CRT average V 2Gy values for the heart could be reduced from 64% in shallow breathing to 34% in DIBH. V 2Gy for protons was negligible. Conclusions: Only small dosimetric differences were found between photons and protons for SBRT of lung lesions. Whether these small dosimetric benefits translate in reduced side effects or have the potential to improve local control rates remains to be demonstrated in clinical studies. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study was the clinical evaluation of an independent dose and monitor unit verification (MUV) software which is based on sophisticated semi-analytical modelling. The software was developed within the framework of an ESTRO project. Finally, consistent handling of dose calculation deviations applying individual action levels is discussed. Materials and methods: A Matlab-based software (“MUV”) was distributed to five well-established treatment centres in Europe (Vienna, Graz, Basel, Copenhagen, and Umeå) and evaluated as a quality assurance (QA) tool in clinical routine. Results were acquired for 226 individual treatment plans including a total of 815 radiation fields. About 150 beam verification measurements were performed for a portion of the individual treatment plans, mainly with time variable fluence patterns. The deviations between dose calculations performed with a treatment planning system (TPS) and the MUV software were scored with respect to treatment area, treatment technique, geometrical depth, radiological depth, etc. Results: In general good agreement was found between calculations performed with the different TPSs and MUV, with a mean deviation per field of 0.2±3.5% (1 SD) and mean deviations of 0.2±2.2% for composite treatment plans. For pelvic treatments less than 10% of all fields showed deviations larger than 3%. In general, when using the radiological depth for verification calculations the results and the spread in the results improved significantly, especially for head-and-neck and for thorax treatments. For IMRT head-and-neck beams, mean deviations between MUV and the local TPS were −1.0±7.3% for dynamic, and −1.3±3.2% for step-and-shoot IMRT delivery. For dynamic IMRT beams in the pelvis good agreement was obtained between MUV and the local TPS (mean: −1.6±1.5%). Treatment site and treatment technique dependent action levels between ±3% and ±5% seem to be clinically realistic if a radiological depth correction is performed, even for dynamic wedges and IMRT. Conclusion: The software MUV is well suited for patient specific treatment plan QA applications and can handle all currently available treatment techniques that can be applied with standard linear accelerators. The highly sophisticated dose calculation model implemented in MUV allows investigation of systematic TPS deviations by performing calculations in homogeneous conditions. [Copyright &y& Elsevier]

Abstract: Background and purpose: A strategy for national TLD audit programmes has been developed by the International Atomic Energy Agency (IAEA). It involves progression through three sequential dosimetry audit steps. The first step audits are for the beam output in reference conditions for high-energy photon beams. The second step audits are for the dose in reference and non-reference conditions on the beam axis for photon and electron beams. The third step audits involve measurements of the dose in reference, and non-reference conditions off-axis for open and wedged symmetric and asymmetric fields for photon beams. Through a co-ordinated research project the IAEA developed the methodology to extend the scope of national TLD auditing activities to more complex audit measurements for regular fields. Materials and methods: Based on the IAEA standard TLD holder for high-energy photon beams, a TLD holder was developed with horizontal arm to enable measurements 5cm off the central axis. Basic correction factors were determined for the holder in the energy range between Co-60 and 25MV photon beams. Results: New procedures were developed for the TLD irradiation in hospitals. The off-axis measurement methodology for photon beams was tested in a multi-national pilot study. The statistical distribution of dosimetric parameters (off-axis ratios for open and wedge beam profiles, output factors, wedge transmission factors) checked in 146 measurements was 0.999±0.012. Conclusions: The methodology of TLD audits in non-reference conditions with a modified IAEA TLD holder has been shown to be feasible. [Copyright &y& Elsevier]

Abstract: Background and purpose: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. Patients and methods: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group ‘DEF’) and 10 endometrial cancer patients treated postoperatively (group ‘POST’). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4Gy) were compared in terms of DVH and various target parameters. Results: At doses between 40 and 50.4Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. Conclusions: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing. [Copyright &y& Elsevier]

Abstract: Background and purpose: In 1990 the skin source measuring bridge was proposed as a tool to measure (1) the distance between the interstitial implant and the overlying skin during brachytherapy boost treatment as well as (2) the distances between the lateral source end and the exit point of the guide needle. The present study reports on the clinical experience using the source skin measuring bridge with respect to incidence and grade of teleangiectasia, and their relation to source skin distances and doses. Patients and methods: Two hundred and twenty-two breast cancer patients (229 breasts) treated between 1983 and 1996 with breast conserving therapy including a brachytherapy boost were scored on the occurrence of teleangiectasia. The minimum distance between the sources (above implant and laterally) and the skin surface were measured. Results: If no bridge was used the appearance of teleangiectasia in the epiderm above the implant is 77, 63 and 50% for boost doses of 25, 20 and 15Gy, respectively. For brachytherapy boost doses of 25 and 20Gy and distances smaller than 10mm between the implant and the overlying epiderm, as determined with the skin source measuring bridge, the appearance of teleangiectasia was 78 and 46%, respectively. When respecting provisional dosimetry to spare the skin for a boost dose of 15Gy, resulting in distances between 10 and 15mm for the implant overlying skin and distances between 5 and 10mm for the lateral skin, teleangiectasia can be reduced to a minimum (6.3% above and 3.3% laterally). While in a univariate analysis several parameters (use of the bridge, boost dose, boost modality, external beam therapy modality) were predictive factors, the use of the bridge remained the only significant variable in a multivariate analysis. Conclusions: The skin source measuring bridge reduces teleangiectasia after interstitial brachytherapy boost treatment. A hypothesis made previously relating teleangiectasia and source skin distances was verified and extended. Even when 3D planning is used, the bridge allows for a provisional calculation of the security margins between source positions and the skin at the time of BT implantation to assure a correct needle positioning from the beginning, instead of correcting dwell times later on to avoid unnecessary high skin doses. [Copyright &y& Elsevier]

Purpose: To construct and test a semi-analytical model describing the effects on Monitor Unit (MU) verification caused by scattering in the treatment head. The implementation of the model should be accomplished using a small set of experimental data. Furthermore, the model should include a geometry dependent estimation of the resulting uncertainty.Material and methods: The input required by the created model consists of basic treatment head geometry and 10 measured output factors in air (OFair) for square fields. It considers primary energy fluence, scattered radiation from an extra-focal source and from secondary collimators, as well as backscatter to the monitor chamber. Measurements and calculations were performed in open symmetric and asymmetric fields at points located both on and off the collimator axis, as well as at arbitrary treatment distances. The model has been verified for 19 photon beams in the range from 4 up to 50 MV, provided by nine different treatment units from six manufacturers.Results: The presented model provided results with errors smaller than 1% (2 S.D.) in typical clinical situations for all beams tested. In more exceptional situations, i.e. combinations of unconventional treatment head designs, very elongated fields, and dosimetry points far away from the isocenter, the total uncertainty increased to approximately 2%. The spread in the results was further analysed in order to create a method for predicting the uncertainties under different treatment conditions.Conclusions: A general head scatter model that is easy to implement has been developed and can be used as the basis for computerised MU verification. The model handles all commercially available treatment units adequately and also includes an estimation of the resulting uncertainty. [Copyright &y& Elsevier]

Purpose: To study local tumor control and radiogenic side effects after fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma.Patients and methods: Between June 1997 and March 2001, 90 patients suffering from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized with a modified stereotactic frame system (BrainLAB). For stabilization of the eye position a light source was integrated into the mask system in front of the healthy or the diseased eye. A mini-video camera was used for on-line eye movement control. Tumors included in the study were either located unfavorably with respect to macula and optical disc (<3 mm distance) or presented with a thickness >7 mm. Median tumor volume was 305±234 mm3 (range 70–1430 mm3), and mean tumor height was 5.4±2.3 mm (range 2.7–15.9 mm). Total doses of 70 (single dose 14 Gy @ 80% isodose) or 60 Gy (single dose 12 Gy @ 80% isodose) were applied in five fractions within 10 days. The first fractionation results in total dose (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding values for the second fractionation schedule are 135 and 180 Gy, respectively.Results: After a median follow-up of 20 months (range 1–48 months) local control was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and 37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases. Secondary enucleation was performed in seven patients (7.7%). Long term side effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and secondary neovascular glaucoma (8.8%).Conclusion: Fractionated LINAC based stereotactic photon beam therapy in conjunction with a dedicated eye movement control system is a highly effective method to treat unfavorably located uveal melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be sufficient to achieve good local tumor control. [Copyright &y& Elsevier]

Background and purpose: During the last years endovascular brachytherapy has been established as a new field in radiotherapy. In a recent recommendation of the EndoVAscular, Groupe Europe´en de Curiethe´rapie, European Society for Therapeutic Radiation Oncology, Working Group the reference isodose length (RIL) has been introduced as a central parameter for treatment planning. It is defined as the vessel length at the reference depth enclosed by the 90% isodose. The dose is normalized to 100% at the reference depth (i.e. lumen radius plus 1 mm into the vessel wall) at the central plane. In order to avoid a geographic miss the clinical target length has to be encompassed by the RIL.Material and methods: RILs are determined by Monte Carlo calculations and GafChromic film dosimetry for three endovascular brachytherapy devices currently in clinical use (192Ir seed ribbon, 32P wire source, 90Sr seed train). For all measurements, phantoms and devices the sensitive layer of GafChromic film is located in a plane at 2±0.1 mm parallel to the axis of the source delivery catheter. The EGSnrc code system is applied to calculate the dose profile at 2 and 3 mm distance from the source axis.Results: For the ten seed 192Ir source calculated RIL at 2 mm radial distance is 30.2 mm whereas the measured RIL is 33.5 mm. In case of a 20 mm 32P wire source with two steps the calculated RIL of 36.6 mm shows excellent agreement compared with the measured value of 36.2 mm. The calculated RIL of a 40 mm 90Sr seed train was 35.8 mm compared to a measured value of 34.8 mm.Conclusion: As a compromise between calculated and measured RIL values at 2 and 3 mm radial distances we propose to use a RIL of 30 mm for the 192Ir ten seed ribbon, 36 mm for the32P wire source with two steps and 35 mm for the 40 mm 90Sr seed train. These parameter values can be used to define the maximum intervention length for endovascular sources. [Copyright &y& Elsevier]

Highlights • Establish EBRT treatment planning compliance through a dummy-run (EMBRACE II). • Plan quality development after introducing novel EBRT planning concepts. • Individual feedback improves EBRT plan quality and inter-center consistency. Abstract Background and purpose The EMBRACE II study combines state-of-the-art Image-Guided Adaptive Brachytherapy in cervix cancer with an advanced protocol for external beam radiotherapy (EBRT) which specifies target volume selection, contouring and treatment planning. In EMBRACE II, well-defined EBRT is an integral part of the overall treatment strategy with the primary aim of improving nodal control and reducing morbidity. The EMBRACE II EBRT planning concept is based on improved conformality through relaxed coverage criteria for all target volumes. For boosting of lymph nodes, a simultaneous integrated boost and coverage probability planning is applied. Before entering EMBRACE II, institutes had to go through accreditation. Material and methods As part of accreditation, a treatment planning dummy-run included educational blocks and submission of an examination case provided by the study coordinators. Seventy-one centers submitted 123 EBRT dose distributions. Replanning was required if hard constraints were violated or planning concepts were not fully accomplished. Dosimetric parameters of original and revised plans were compared. Results Only 11 plans violated hard constraints. Twenty-seven centers passed after first submission. 27 needed one and 13 centers needed more revisions. The most common reasons for revisions were low conformality, relatively high OAR doses or insufficient lymph node coverage reduction. Individual feedback on planning concepts improved plan quality considerably, resulting in a median body V43Gy reduction of 158 cm3 from first plan submission to approved plan. Conclusion A dummy-run as applied in EMBRACE II, consisting of training and examination cases enabled us to test institutes' treatment planning capabilities, and improve plan quality. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the differences in treatment plan quality of IMRT and VMAT with and without flattening filter using Pareto optimal fronts, for two treatment sites of different anatomic complexity. Materials and Methods: Pareto optimal fronts (POFs) were generated for six prostate and head-and-neck cancer patients by stepwise reduction of the constraint (during the optimization process) of the primary organ-at-risk (OAR). 9-static field IMRT and 360°-single-arc VMAT plans with flattening filter (FF) and without flattening filter (FFF) were compared. The volume receiving 5Gy or more (V 5Gy) was used to estimate the low dose exposure. Furthermore, the number of monitor units (MUs) and measurements of the delivery time (T) were used to assess the efficiency of the treatment plans. Results: A significant increase in MUs was found when using FFF-beams while the treatment plan quality was at least equivalent to the FF-beams. T was decreased by 18% for prostate for IMRT with FFF-beams and by 4% for head-and-neck cases, but increased by 22% and 16% for VMAT. A reduction of up to 5% of V 5Gy was found for IMRT prostate cases with FFF-beams. Conclusions: The evaluation of the POFs showed an at least comparable treatment plan quality of FFF-beams compared to FF-beams for both treatment sites and modalities. For smaller targets the advantageous characteristics of FFF-beams could be better exploited. [Copyright &y& Elsevier]

Abstract: Purpose: To compare the dosimetric accuracy of advanced dose calculation algorithms for flattened (FF) and unflattened (FFF) photon beams. Material and methods: We compared the enhanced collapsed cone (eCC) algorithm implemented in OncentraMasterplan and the XVMC (MC) code in Monaco. Test plans were created for 10MV FF and FFF beams. Single beam tests were delivered to radiochromic films positioned within a solid water phantom and evaluated with 1D γ-index analysis. Conformal plans were verified with ion chambers in an anthropomorphic thorax phantom. IMRT plans were applied to the Delta4 system and evaluated with γ-criteria of 3% and 3mm. Results: 1D γ-index evaluation revealed significantly lower (p <0.05) average γmean -values of 0.46±0.22 for MC calculated FFF profiles compared to average values of 0.53±0.27 detected for FF beams. Respective values for eCC were 0.42±0.27/0.38±0.26 (FF/FFF). When considering off-axis profiles separately, we found significantly reduced average γmean -values for FFF and both algorithms (MC: 0.55±24 vs. 0.45±0.21, eCC: 0.41±0.24 vs. 0.35±0.22). No significant differences were detected on-axis. Absolute dosimetry in the anthropomorphic phantom revealed superior results for MC based dose calculation, with mean deviations of 0.8±0.8/0.0±1.0% compared to −0.1±1.7/−0.5±0.1.7% (FF/FFF) for the eCC algorithm. IMRT plans showed similar results for both linac modes. Conclusions: The dose calculation accuracy for unflattened beams was found to be at least as high as for flattened beams. The slightly improved dose calculation accuracy observed for off-axis profiles for single FFF beams did not directly translate into better verification results for composite IMRT plans. [Copyright &y& Elsevier]

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

• Quality assurance (QA) with phantoms was developed to test multicenter quantitative MRI (qMRI). • The QA framework was applied to the qMRI protocols of a trial for cervical cancer. • Consistent values for apparent diffusion coefficient and T2 were obtained between 15 institutes. • Dynamic contrast-enhanced MRI and T1 require institute-specific corrections of patient data. • Changes in qMRI protocols are allowed during a trial by repeating QA. A wide variation of MRI systems is a challenge in multicenter imaging biomarker studies as it adds variation in quantitative MRI values. The aim of this study was to design and test a quality assurance (QA) framework based on phantom measurements, for the quantitative MRI protocols of a multicenter imaging biomarker trial of locally advanced cervical cancer. Fifteen institutes participated (five 1.5 T and ten 3 T scanners). Each institute optimized protocols for T2, diffusion-weighted imaging, T1, and dynamic contrast-enhanced (DCE–)MRI according to system possibilities, institutional preferences and study-specific constraints. Calibration phantoms with known values were used for validation. Benchmark protocols, similar on all systems, were used to investigate whether differences resulted from variations in institutional protocols or from system variations. Bias, repeatability (%RC), and reproducibility (%RDC) were determined. Ratios were used for T2 and T1 values. The institutional protocols showed a range in bias of 0.88–0.98 for T2 (median %RC = 1%; %RDC = 12%), −0.007 to 0.029 × 10−3 mm2/s for the apparent diffusion coefficient (median %RC = 3%; %RDC = 18%), and 0.39–1.29 for T1 (median %RC = 1%; %RDC = 33%). For DCE a nonlinear vendor-specific relation was observed between measured and true concentrations with magnitude data, whereas the relation was linear when phase data was used. We designed a QA framework for quantitative MRI protocols and demonstrated for a multicenter trial for cervical cancer that measurement of consistent T2 and apparent diffusion coefficient values is feasible despite protocol differences. For DCE–MRI and T1 mapping with the variable flip angle method, this was more challenging. [ABSTRACT FROM AUTHOR]

Background and purpose Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. Material and methods Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. Results With equivalent Planning Target Volume (PTV) V 95% , D 2% , D 98% , and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy ( p  < 0.001) in D mean , 4.0% ( p  < 0.001) in V 60Gy , and 1.5% ( p  = 0.001) in V 75Gy , and for bladder D mean (0.9 Gy, p  < 0.001). Also the clinicians’ plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum D mean and V 60Gy of [−4,12] Gy and [−2,15]%, respectively. Conclusion Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning. [ABSTRACT FROM AUTHOR]

Under the umbrella of the European Network for Light Ion Therapy (ENLIGHT), the project on Union of Light Ion Centers in Europe (ULICE), which was funded by the European Commission (EC/FP7), was carried out from 2009 to 2014. Besides the two pillars on Transnational Access (TNA) and Networking Activities (NA), six work packages formed the pillar on Joint Research Activities (JRA). The current manuscript focuses on the objectives and results achieved within these research work packages: “Clinical Research Infrastructure”, “Biologically Based Expert System for Individualized Patient Allocation”, “Ion Therapy for Intra-Fractional Moving Targets”, “Adaptive Treatment Planning for Ion Radiotherapy”, “Carbon Ion Gantry”, “Common Database and Grid Infrastructures for Improving Access to Research Infrastructures”. The objectives and main achievements are summarized. References to either publications or open access deliverables from the five year project work are given. Overall, carbon ion radiotherapy is still not as mature as photon or proton radiotherapy. Achieved results and open questions are reflected and discussed in the context of the current status of carbon ion therapy and particle and photon beam therapy. Most research topics covered in the ULICE JRA pillar are topical. Future research activities can build upon these ULICE results. Together with the continuous increase in the number of particle therapy centers in the last years ULICE results and proposals may contribute to the further growth of the overall particle therapy field as foreseen with ENLIGHT and new joint initiatives such as the European Particle Therapy Network (EPTN) within the overall radiotherapy community. [ABSTRACT FROM AUTHOR]

Background and purpose During extended follow-up (of up to 15 years), approximately fifty percent of patients with choroidal melanoma will develop metastatic disease and eventually die. Thus, continuing research on prognostic factors, early detection and treatment is necessary. Height regression rates both after plaque brachytherapy and proton beam irradiation have been shown to have prognostic value. The purpose of this study was to analyze the influence of early tumor regression rate after treatment of choroidal melanoma with LINAC stereotactic fractionated radiotherapy (SFRT) as an independent risk factor for metastasis. Material and methods 256 patients with choroidal melanoma treated with LINAC SFRT were included. Follow-up included standardized echography yielding apical height, smallest and largest basal linear diameter, tumor volume and mean reflectivity. The influence of baseline measurements and of a longitudinal, normalized area under the curve coefficient (NAC) of the latter marker on metastasis risk was assessed. Results NAC for tumor thickness at months 3, 6, and 12 had a statistically significant ( p  < 0.001) non-linear effect on risk of metastasis. Additionally, ultrasonographic baseline tumor dimensions, but not internal reflectivity were found to be statistically significant risk factors for metastasis. Conclusions Our results demonstrate a non-linear influence of regression rate of choroidal melanoma as independent risk factor of metastatic disease after LINAC SFRT. These prove the clinical experience that, in comparison to rather slow regressions, very quick and very slow early tumor responses to LINAC SFRT are associated with a significantly higher metastasis risk. [ABSTRACT FROM AUTHOR]

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies. [ABSTRACT FROM AUTHOR]

Background and purpose Multimodal tissue characterization by combined MRI and PET has high clinical potential in the context of sub-target definition for dose painting and response assessment but its clinical exploration is yet limited. The aim of this study was to prove the potential and feasibility of hybrid PET/MRI to non-invasively measure tumor hypoxia, perfusion and microstructure at one stop in tumors of the uterine cervix during chemoradiotherapy. Material and methods Ten cervix cancer patients were subjected to simultaneous multiparametric PET/MRI with [ 18 F]fluoromisonidazole ([ 18 F]FMISO). Imaging was scheduled before, twice during and after chemoradiotherapy. Intra- and inter-time point analyses of the extracted parameters (i.e. ADC, K trans , A Brix , [ 18 F]FMISO-tumor to background ratio (TBR)) were performed. The [ 18 F]FMISO uptake- and ADC-spatio-temporal changes were assessed. Results Patient averaged ADC values increased from baseline to follow up (1.03 ± 0.11/1.30 ± 0.13 × 10 −3  mm 2 /s), while the TBR decreased (1.73 ± 0.24/1.36 ± 0.19), K trans dropped over time (0.17 ± 0.05/0.05 ± 0.05 min −1 ); for all above p  < 0.05. None of these parameters correlated significantly on a voxel-by-voxel basis. Low-ADC regions spatially varied over time. There was pronounced reduction of the [ 18 F]FMISO-avid volumes during treatment. Conclusions The suggested hybrid PET/MRI protocol to non-invasively investigate tumor hypoxia, perfusion and microstructure at one stop was feasible, revealing spatio-temporal response patterns that could be utilized for comprehensive sub-target definition for dose painting and response assessment. [ABSTRACT FROM AUTHOR]

• Review of similarities and distinct differences between the well-known quantity "linear energy transfer" and the microdosimetry quantity "lineal energy" • Clarify the differences between the widely used dose-averaged LET, its spatial distribution, and the density distribution of LET. • Description of the theoretical basis and link between radiobiological considerations and microdosimetry. • Discussion of the current lack of a complete understanding of the role of saturation on RBE and clinical response. • Review of the current state of research in experimental microdosimetry including future research needs to make it a mature procedure in a clinical context. In radiotherapy, radiation-quality should be an expression of the biological and physical characteristics of ionizing radiation such as spatial distribution of ionization or energy deposition. Linear energy transfer (LET) and lineal energy (y) are two descriptors used to quantify the radiation quality. These two quantities are connected and exhibit similar features. In ion-beam therapy (IBT), lineal energy can be measured with microdosimeters, which are specifically designed to cope with the high fluence of particles in clinical beams, while the quantification of LET is generally based on calculations. In pre-clinical studies, microdosimetric spectra are used for the indirect determination of relative biological effectiveness (RBE), e.g., using the microdosimetric kinetic model (MKM) or biophysical response functions. In this context it is important to consider saturation effects, which occur when the highest values of y become less biologically relevant compared to the relative contribution they make to the physical dose. Recent clinical data suggests that local tumor control and normal tissue effects can be linked to macroscopic and microscopic dosimetry parameters. In particular, positive clinical outcomes have been correlated to the highest LET values in the density distribution, and there is no evident link to the saturation discussed above. A systematic collection of microdosimetric information in combination with clinical data in retrospective studies may clarify the role of radiation quality at the highest LET. In the clinical setting, microdosimetry is not widely used yet, despite its potential to be linked with LET by experimentally-determined y values. Through this connection, both play an important role in complex therapy techniques such as intensity modulated particle therapy (IMPT), LET-painting and multi-ion optimization. This review summarizes the current state of microdosimetry for IBT and its potential, as well as research and development needed to make experimental microdosimetry a mature procedure in a clinical context. [ABSTRACT FROM AUTHOR]

• 3D printed 2D/3D range modulators (2D/3DRM) offer advantages for light ion beam therapy, also in combination with pencil-beam scanning (PBS). • We designed 2DRMs with Monte Carlo simulations and validated them on a dosimetric as well as on a microdosimetric scale for both H and C12 beams. • The equivalence of using a single spot vs. a larger plan delivered via PBS with an appropriate 2DRM based on microdosimetric spectra is shown. Particle therapy using pencil beam scanning (PBS) faces large uncertain- ties related to ranges and target motion. One possibility to improve existing mitigation strategies is a 2D range modulator (2DRM). A 2DRM offers faster irradiation times by reducing the number of layers and spots needed to create a spread-out Bragg peak. We have investigated the impact of 2DRM on microdosimetric spectra measured in proton and carbon ion beams. Two 2DRMs were designed and 3D printed, one for. 124.7 MeV protons and one for 238.6 MeV/u carbon ions. Their dosimetric validation was performed using Roos and PinPoint ionization chamber and EBT3 films. Monte Carlo simulations were done using GATE. A silicon-based solid-state microdosimeter was used to collect pulse-height spectra along three depths for two irradiation modalities, PBS and a single central beam. For both particle types, the original pin design had to be optimized via GATE simulations. The difference between the R80 of the simulated and measured depth dose curve was 0. 1 mm. The microdosimetric spectra collected with the two irradiation modalities overlap well. Their mean lineal energy values differ over all positions by 5. 2 % for the proton 2DRM and 2. 1 % for the carbon ion 2DRM. Radiation quality in terms of lineal energy was independent of the irradiation method. This supports the current approach in reference dosimetry, where the residual range is chosen as a beam quality index to select stopping power ratios. [ABSTRACT FROM AUTHOR]

Background and purpose To analyze treatment plan robustness and plan optimization strategies of 106 Ru eye plaque brachytherapy using a novel software tool. Materials and methods A treatment planning software was developed that allows to calculate dose–volume metrics. Plaque misplacements were simulated and evaluated with respect to the effect on tumor coverage and dose changes in critical structures. Two treatment plan optimization approaches were analyzed: (a) reducing plaque size and (b) shifting the plaque away from organs-at-risk (OAR). Results Maximum tumor sizes were identified which can be covered by the prescribed dose for different robustness levels (0–2 mm). For an apex height of 5 mm a 1 mm uncertainty yielded changes in D 2% to the lens of up to ±13 Gy in anterior and ±20 Gy to the optic nerve in posterior tumors. By reducing the plaque size D mean and D 2% to lens, optic nerve and macula were decreased by >60% for most simulated cases. Similarly, by shifting the plaque away from the lens dose reductions of 15%/mm in anterior and even 30%/mm in central tumors were achieved. Conclusion Critical structures in the treatment of uveal melanomas with 106 Ru plaques can benefit from the proposed, computational treatment plan optimization. [ABSTRACT FROM AUTHOR]

Background and purpose Target and organ movement motivate adaptive radiotherapy for cervix cancer patients. We investigated the dosimetric impact of margin concepts with different levels of complexity on both organ at risk (OAR) sparing and PTV coverage. Material and methods Weekly CT and daily CBCT scans were delineated for 10 patients. The dosimetric impact of organ shape variations were evaluated for four (isotropic) margin concepts: two static PTVs (PTV 6mm and PTV 15mm ), a PTV based on ITV of the planning CT and CBCTs of the first treatment week (PTV ART ITV ) and an adaptive PTV based on a library approach (PTV ART Library ). Results Using static concepts, OAR doses increased with large margins, while smaller margins compromised target coverage. ART PTVs resulted in comparable target coverage and better sparing of bladder (V40 Gy: 15% and 7% less), rectum (V40 Gy: 18 and 6 cc less) and bowel (V40 Gy: 106 and 15 cc less) compared to PTV 15mm . Target coverage evaluation showed that for elective fields a static 5 mm margin sufficed. Conclusion PTV ART Library achieved the best dosimetric results. However when weighing clinical benefit against workload, ITV margins based on repetitive movement evaluation during the first week also provide improvements over static margin concepts. [ABSTRACT FROM AUTHOR]

Background and purpose Advancements in imaging and dose delivery enable boosting of the dominant intraprostatic lesions (DIL), while maintaining organs-at-risk (OAR) tolerances. This study aimed to assess the feasibility of DIL boosting for volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT) and high dose rate brachytherapy (HDR-BT). Material and methods DILs were defined on multiparametric magnetic resonance imaging and fused with planning CT for twelve patients. VMAT, IMPT and HDR-BT plans were created for each patient with an EQD2 α / β DIL aimed at 111.6 Gy, PTV initial D pres was 80.9 Gy (EBRT) with CTV D 90% = 81.9 Gy (HDR-BT). Hard dose constraints were applied for OARs. Results Higher boost doses were achieved with IMPT compared to VMAT, keeping major OAR doses at similar levels. Patient averaged EQD2 α / β D 50% to DIL were 110.7, 114.2 and 150.1 Gy(IsoE) for VMAT, IMPT and HDR-BT, respectively. Respective rectal wall D mean were 30.5 ± 5.0, 16.7 ± 3.6, 9.5 ± 2.5 Gy(IsoE) and bladder wall D mean were 21.0 ± 5.5, 15.6 ± 4.3 and 6.3 ± 2.2 Gy(IsoE). Conclusions DIL boosting was found to be feasible with all investigated techniques. Although OAR doses were higher than for standard treatment approach, the risk levels were reasonably low. HDR-BT was superior to VMAT and IMPT, both in terms of OAR sparing and DIL boosting. [ABSTRACT FROM AUTHOR]

Purpose To systematically evaluate machine specific quality assurance (QA) for volumetric modulated arc therapy (VMAT) based on log files by applying a dynamic benchmark plan. Methods and materials A VMAT benchmark plan was created and tested on 18 Elekta linacs (13 MLCi or MLCi2, 5 Agility) at 4 different institutions. Linac log files were analyzed and a delivery robustness index was introduced. For dosimetric measurements an ionization chamber array was used. Relative dose deviations were assessed by mean gamma for each control point and compared to the log file evaluation. Results Fourteen linacs delivered the VMAT benchmark plan, while 4 linacs failed by consistently terminating the delivery. The mean leaf error (±1 SD) was 0.3 ± 0.2 mm for all linacs. Large MLC maximum errors up to 6.5 mm were observed at reversal positions. Delivery robustness index accounting for MLC position correction (0.8–1.0) correlated with delivery time (80–128 s) and depended on dose rate performance. Dosimetric evaluation indicated in general accurate plan reproducibility with γ mean (±1 SD) = 0.4 ± 0.2 for 1 mm/1%. However single control point analysis revealed larger deviations and attributed well to log file analysis. Conclusion The designed benchmark plan helped identify linac related malfunctions in dynamic mode for VMAT. Log files serve as an important additional QA measure to understand and visualize dynamic linac parameters. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Image-guided advanced photon and particle beam treatments are promising options for improving lung treatments. Extensive use of imaging increases the overall patient dose. The aim of this study was to determine the imaging dose for different IGRT solutions used in photon and particle beam therapy. Material and methods: Measurements were performed in an Alderson phantom with TLDs. Clinically applied protocols for orthogonal planar kV imaging, stereoscopic imaging, CT scout views, fluoroscopy, CT, 4D-CT and CBCT were investigated at five ion beam centers and one conventional radiotherapy department. The overall imaging dose was determined for a patient undergoing a lung tumor irradiation with institute specific protocols. Results: OAR doses depended on imaging modality and OAR position. Dose values were in the order of 1mGy for planar and stereoscopic imaging and 10–50mGy for volumetric imaging, except for one CBCT device leading to lower doses. The highest dose per exam (up to 150mGy to the skin) was recorded for a 3-min fluoroscopy. Discussion: Modalities like planar kV or stereoscopic imaging result in very low doses (∼1mGy) to the patient. Imaging a moving target during irradiation, low-dose protocols and protocol optimization can reduce the imaging dose to the patient substantially. [Copyright &y& Elsevier]

Purpose: The applicability of various detectors for small field dosimetry and whether there are differences in the detector response when irradiated with FF- and FFF-beams was investigated. Materials and methods: Output factors of 6 and 10MV FF- and FFF-beams were measured with 14 different online detectors using field sizes between 10×10 and 0.6×0.6cm2 at a depth of 5cm of water in isocentric conditions. Alanine pellets with a diameter of 5 and 2.5mm were used as reference dosimeters for field sizes down to 1.2×1.2 and 0.6×0.6cm2, respectively. The ratio of the relative output measured with the online detectors to the relative output measured with alanine was evaluated (referred to as dose response ratio). Results: The dose response ratios of two different shielded diodes measured with 10MV FF-beams deviated substantially by 2–3% compared to FFF-beams at a field size of 0.6×0.6cm2. This difference was less pronounced for 6MV FF- and FFF-beams. For all other detectors the dose response ratios of FF- and FFF-beams showed no significant difference. Conclusion: The dose response ratios of the majority of the detectors agreed within the measurement uncertainty when irradiated with FF- and FFF-beams. Of all investigated detectors, the microDiamond and the unshielded diodes would require only small corrections which make them suitable candidates for small field dosimetry in FF- and FFF-beams. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10Gy each in patients with centrally located choroidal melanoma. Materials and Methods: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6MV photon beams with 5 fractions at 10Gy each. Examinations were performed at baseline and every 3months in the first 2years, then every 6months until 5years and yearly thereafter. Median follow-up was 37.8months (IQR 19.2–49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. Results: Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10–13.70), 9.80mm (IQR 7.80–11.70), 4.53mm (IQR 3.33–6.43) and 253.8mm3 (IQR 127.5–477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p <0.001). The most common toxicities (any grade) were radiation retinopathy (n =39), optic neuropathy (n =32), radiogenic cataract (n =21), neovascular glaucoma (n =15) and dry eye syndrome (n =10). The 5year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. Conclusion: Hypofractionated stereotactic photon radiotherapy with a total dose of 50Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile. [Copyright &y& Elsevier]

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]

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: Background and purpose: In this paper, we investigate the possibility to use X-ray based real time 2D/3D registration for non-invasive tumor motion monitoring during radiotherapy. Materials and methods: The 2D/3D registration scheme is implemented using general purpose computation on graphics hardware (GPGPU) programming techniques and several algorithmic refinements in the registration process. Validation is conducted off-line using a phantom and five clinical patient data sets. The registration is performed on a region of interest (ROI) centered around the planned target volume (PTV). Results: The phantom motion is measured with an rms error of 2.56mm. For the patient data sets, a sinusoidal movement that clearly correlates to the breathing cycle is shown. Videos show a good match between X-ray and digitally reconstructed radiographs (DRR) displacement. Mean registration time is 0.5s. Conclusions: We have demonstrated that real-time organ motion monitoring using image based markerless registration is feasible. [Copyright &y& Elsevier]

Abstract: Background: To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT)±chemotherapy (ChT). Methods: Treatment schedule was EBRT with 45–50.4Gy±concomitant cisplatin chemotherapy plus 4×7Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90>85Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75Gy for rectum and sigmoid and 90Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings: One hundred and fifty-six consecutive patients (median age 58years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93±13Gy, D2cc 86±17Gy for bladder, 65±9Gy for rectum and 64±9Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3years was 95%; 98% for tumours 2–5cm, and 92% for tumours >5cm (p =0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3years was overall 74%, 83% for tumours 2–5cm, 70% for tumours >5cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3years was in total 68%, 72% for tumours 2–5cm, 65% for tumours >5cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1+2 and 11 grade 3+4 late events were observed in 143 patients. G1+2/G3+4 events for bladder were n =32/3, for rectum n =14/5, for bowel (including sigmoid) n =3/0, for vagina n =128/2, respectively. Interpretation: 3D conformal radiotherapy±chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. [Copyright &y& Elsevier]

Abstract: Background and purpose: In-room cone-beam CT (CBCT) imaging and adaptive treatment strategies are promising methods to decrease target volumes and to spare organs at risk. The aim of this work was to analyze the inter-observer contouring uncertainties of target volumes and organs at risks (oars) in localized prostate cancer radiotherapy using CBCT images. Furthermore, CBCT contouring was benchmarked against other image modalities (CT, MR) and the influence of subjective image quality perception on inter-observer variability was assessed. Methods and materials: Eight prostate cancer patients were selected. Seven radiation oncologists contoured target volumes and oars on CT, MRI and CBCT. Volumes, coefficient of variation (COV), conformity index (cigen), and coordinates of center-of-mass (COM) were calculated for each patient and image modality. Reliability analysis was performed for the support of the reported findings. Subjective perception of image quality was assessed via a ten-scored visual analog scale (VAS). Results: The median volume for prostate was larger on CT compared to MRI and CBCT images. The inter-observer variation for prostate was larger on CBCT (CIgen =0.57±0.09, 0.61 reliability) compared to CT (CIgen =0.72±0.07, 0.83 reliability) and MRI (CIgen =0.66±0.12, 0.87 reliability). On all image modalities values of the intra-observer reliability coefficient (0.97 for CT, 0.99 for MR and 0.94 for CBCT) indicated high reproducibility of results. For all patients the root mean square (RMS) of the inter-observer standard deviation (σ) of the COM was largest on CBCT with σ(x)=0.4mm, σ(y)=1.1mm, and σ(z)=1.7mm. The concordance in delineating OARs was much stronger than for target volumes, with average CIgen >0.70 for rectum and CIgen >0.80 for bladder. Positive correlations between CIgen and VAS score of the image quality were observed for the prostate, seminal vesicles and rectum. Conclusions: Inter-observer variability for target volume delineation in prostate cancer is larger for CBCT-based contouring compared to CT and MRI. This factor of influence needs to be considered when defining safety margins for CBCT-based Adaptive Radiotherapy (ART). [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: Introduction: Our aim was to implement standards for quality assurance of IGRT devices used in our department and to compare their performances with that of a CT simulator. Materials and methods: We investigated image quality parameters for three devices over a period of 16months. A multislice CT was used as a benchmark and results related to noise, spatial resolution, low contrast visibility (LCV) and uniformity were compared with a cone beam CT (CBCT) at a linac and simulator. Results: All devices performed well in terms of LCV and, in fact, exceeded vendor specifications. MTF was comparable between CT and linac CBCT. Integral nonuniformity was, on average, 0.002 for the CT and 0.006 for the linac CBCT. Uniformity, LCV and MTF varied depending on the protocols used for the linac CBCT. Contrast-to-noise ratio was an average of 51% higher for the CT than for the linac and simulator CBCT. No significant time trend was observed and tolerance limits were implemented. Discussion: Reasonable differences in image quality between CT and CBCT were observed. Further research and development are necessary to increase image quality of commercially available CBCT devices in order for them to serve the needs for adaptive and/or online planning. [Copyright &y& Elsevier]