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Previously undescribed molecular mechanisms of resistance will emerge with the increased use of cyclin-dependent kinase 4/6 inhibitors in clinical settings. To identify genomic aberrations in circulating tumor DNA associated with treatment resistance in palbociclib-treated metastatic breast cancer (MBC) patients, we collected 35 pre- and post-treatment blood samples from 16 patients with estrogen receptor-positive (ER + ) MBC, including 9 with inflammatory breast cancer (IBC). Circulating cell-free DNAs (cfDNAs) were isolated for sequencing using a targeted panel of 91 genes. Our data showed that FBXW7 and CDK6 were more frequently altered in IBC than in non-IBC, whereas conversely, PIK3CA was more frequently altered in non-IBC than in IBC. The cfDNA samples collected at follow-up harbored more mutations than baseline samples. By analyzing paired samples, we observed a higher percentage of patients with mutations in RB1 , CCNE1 , FBXW7 , EZH2 , and ARID1A , but a lower proportion of patients with mutated TSC2 at the post-treatment stage when they developed progression. Moreover, acquisition of CCNE1 mutations or loss of TSC2 mutations after treatment initiation conferred an unfavorable prognosis. These data provide insights into the relevance of novel genomic alterations in cfDNA to palbociclib resistance in MBC patients. Future large-scale prospective studies are warranted to confirm our findings.

Introduction: Radiation therapy technologists (RTTs) are exposed to high stress levels which may lead to burnout, which could be further increased by the current pandemic. The aim of our study was to assess burnout and stress among Italian RTTs before and during the pandemic., Methods: The Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) and the Italian Federation of Scientific Radiographers Societies (FASTeR) proposed a national online survey, including the Maslach Burnout Inventory assessing emotional exhaustion (EE), depersonalisation (DP), and personal accomplishment (PA) to RTTs before and during the pandemic. Multivariate regression analyses and χ 2 tests were used for data analysis., Results: We obtained 367 answers, 246 before and 121 during the pandemic. RTTs before and during the pandemic showed high EE and DP, intermediate PA. Median EE was 37 (interquartile range [IQR] 31-46] before and 37 (IQR 30-43) during the pandemic, median DP was 16 (IQR 13-21) and 15 (IQR 12-20), respectively. PA was 31 (IQR 28-34) and 32 (IQR 28-34), respectively. Through multivariate analysis, being female and having children led to higher EE scores before and during the pandemic (p≤0.026). Only the presence of workplace stress management courses was related to lower DP before and being female was related to higher DP during the pandemic (p<0.001). Being female, having children, and working with paediatric patients were related to lower PA before and during the pandemic (p≤0.015)., Conclusion: Our study highlighted high burnout levels for RTTs regardless of the pandemic. Future interventions aimed at preventing burnout should be implemented in their work environment, independently of the impact of exceptional events., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To assess the dosimetric advantages of apertures in intracranial single fraction proton radiosurgery., Materials and Methods: Six neuroma and 10 meningioma patients were investigated. For each patient, six plans were computed, with two spot spacing and three aperture settings (no apertures, 5 and 8 mm margin between aperture and clinical target volume [CTV]). All plans were optimized on the CTV with the same beam arrangement and the same single-field robust optimization (2 mm setup errors, 3.5% range uncertainties). Robustness analysis was performed with 0.5 and 1.0 mm systematic setup errors and 3.5% range uncertainties. CTV coverage in the perturbed scenarios and healthy brain tissue sparing in the surrounding of the CTV were compared., Results: Meningiomas were larger and at a shallow depth than neuromas. In neuromas, spot spacing did not affect OAR doses or the robustness of CTV coverage and the apertures reduced brain dose without any significant impact on CTV robustness. In meningiomas, smaller spot spacing produced a reduction in brain V5Gy and improved robustness of CTV coverage; in addition, an 8 mm margin aperture reduced low and medium brain tissue doses without affecting robustness in the 0.5 mm perturbed scenario. A 5 mm margin aperture caused a reduction of plan robustness., Conclusion: The optimal use of apertures is a trade-off between sparing of low and medium dose to the healthy brain and robustness of target coverage, also depending on size and depth of the lesion., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: Interventional radiotherapy (IRT, brachytherapy and intra-operative radiotherapy) is a complex treatment approach that requires a multi-professional approach. The aim of this work was to assess the role of radiation therapy technologist (RTT) in IRT team, with a special focus on brachytherapy as well as to define more appropriate ways to improve skills and training to promote cooperation of multi-professional team., Material and Methods: A nationwide survey consisting of 16 questions was proposed between April and May 2020, with collaboration between the Italian Association of Radiation Therapy and Medical Physics Technologists (AITRO) and the Interventional Radiotherapy Study Group of Italian Association of Radiotherapy and Clinical Oncology (AIRO). The survey was sent through the AITRO contact list to RTTs' contacts from all Italian radiotherapy (RT) departments., Results: A total of 37 answered questionnaires returned (36% of all contacts reached), each from different center. 23 centers (62%) presented with dedicated team for IRT treatments, while 15 centers (41%) had dedicated RTT staff. The majority of RTT (86%) did not consider undergraduate training adequate to acquire the skills required to work in IRT departments or units., Conclusions: This survey underlines the need of additional education and training for RTTs that should focus on treatment management optimization in development of an IRT multi-professional team. Specific updates could be the key to develop further collaboration and to improve cancer patient care., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

Purpose: To perform the validation of the GPU-based (Graphical Processing Unit based) proton Monte Carlo (MC) dose engine implemented in a commercial TPS (RayStation 10B) and to report final dose calculation times for clinical cases., Materials and Methods: 440 patients treated at the Proton Therapy Center of Trento, Italy, between 2018 and 2019 were selected for this study. 636 approved plans with 3361 beams computed with the clinically implemented CPU-MC dose engine (version 4.2 and 4.5), were used for the validation of the new algorithm. For each beam, the dose was recalculated using the new GPU-MC dose engine with the initial CPU computation settings and compared to the original CPU-MC dose. Beam dose difference distributions were studied to ensure that the two dose distributions were equal within the expected fluctuations of the MC statistical uncertainty (s) of each computation. Plan dose distributions were compared with respect to the dosimetric indices D 98 , D 50 and D 1 of all ROIs defined as targets. A complete assessment of the computation time as a function of s and dose grid voxel size was done., Results: The median over all mean beam dose differences between CPU- and GPU-MC was -0.01% and the median of the corresponding standard deviations was close to (√2s) both for simulations with an s of 0.5% and 1.0% per beam. This shows that the two dose distributions can be considered equal. All the DVH indices showed an average difference below 0.04%. About half of the plans were computed with 1.0% statistical uncertainty on a 2 mm dose calculation grid, for which the median computation time was 5.2 s. The median computational speed for all plans in the study was 8.4 million protons/second., Conclusion: A validation of a clinical MC algorithm running on GPU was performed on a large pool of patients treated with pencil beam scanning proton therapy. We demonstrated that the differences with the previous CPU-based MC were only due to the intrinsic statistical fluctuations of the MC method, which translated to insignificant differences on plan dose level. The significant increase in dose calculation speed is expected to facilitate new clinical workflows., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

To implement a multi-field-optimization (MFO) technique for treating patients with high-Z implants in pencil beam scanning proton-therapy and generate treatment plans that avoids small implants. Two main issues were addressed: (i) the assessment of the optimal CT acquisition and segmentation technique to define the dimension of the implant and (ii) the distance of pencil beams from the implant (avoidance margin) to assure that it does not affect dose distribution. Different CT reconstruction protocols (by O-MAR or standard reconstruction and by 12 bit or 16 bit dynamic range) followed by thresholding segmentation were tested on a phantom with lead spheres of different sizes. The proper avoidance margin was assessed on a dedicated phantoms of different materials (copper/tantalum and lead), shape (square slabs and spheres) and detectors (two-dimensional array chamber and radio-chromic films). The method was then demonstrated on a head-and-neck carcinoma patient, who underwent carotid artery embolization with a platinum coil close to the target. Regardless the application of O-MAR reconstruction, the CT protocol with a full 16 bit dynamic range allowed better estimation of the sphere volumes, with maximal error around -5% in the greater sphere only. Except the configuration with a shallow target (which required a pre-absorber), particularly with a retracted snout, an avoidance margin of around 0.9-1.3 cm allowed to keep the difference between planned and measured dose below 5-10%. The patient plan analysis showed adequate plan quality and confirmed effective implant avoidance. Potential target under-dosage can be produced by patient misalignment, which could be minimized by daily alignment on the implant, identifiable on orthogonal kilovolt images. By implant avoidance MFO it was possible to minimize potential dose perturbation effects produced by small high-Z implants. An advantage of such approach lies in its potential applicability for any type of implant, regardless the precise knowledge of its composition.

Purpose: To develop normal tissue complication probability (NTCP) models for radiation-induced alopecia (RIA) in brain tumor patients treated with proton therapy (PT)., Methods and Materials: We analyzed 116 brain tumor adult patients undergoing scanning beam PT (median dose 54 GyRBE; range 36-72) for CTCAE v.4 grade 2 (G2) acute (≤90 days), late (>90 days) and permanent (>12 months) RIA. The relative dose-surface histogram (DSH) of the scalp was extracted and used for Lyman-Kutcher-Burman (LKB) modelling. Moreover, DSH metrics (Sx: the surface receiving ≥ X Gy, D 2% : near maximum dose, D mean : mean dose) and non-dosimetric variables were included in a multivariable logistic regression NTCP model. Model performances were evaluated by the cross-validated area under the receiver operator curve (ROC-AUC)., Results: Acute, late and permanent G2-RIA was observed in 52%, 35% and 19% of the patients, respectively. The LKB models showed a weak dose-surface effect (0.09 ≤ n ≤ 0.19) with relative steepness 0.29 ≤ m ≤ 0.56, and increasing tolerance dose values when moving from acute and late (22 and 24 GyRBE) to permanent RIA (44 GyRBE). Multivariable modelling selected S 21Gy for acute and S 25Gy , for late G2-RIA as the most predictive DSH factors. Younger age was selected as risk factor for acute G2-RIA while surgery as risk factor for late G2-RIA. D 2% was the only variable selected for permanent G2-RIA. Both LKB and logistic models exhibited high predictive performances (ROC-AUCs range 0.86-0.90)., Conclusion: We derived NTCP models to predict G2-RIA after PT, providing a comprehensive modelling framework for acute, late and permanent occurrences that, once externally validated, could be exploited for individualized scalp sparing treatment planning strategies in brain tumor patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The requirements of ITER neutral beam injectors (1 MeV, 40 A negative deuterium ion current for 1 h) have never been simultaneously attained; therefore, a dedicated Neutral Beam Test Facility (NBTF) was set up at Consorzio RFX (Padova, Italy). The NBTF includes two experiments: SPIDER (Source for the Production of Ions of Deuterium Extracted from Rf plasma), the full-scale prototype of the source of ITER injectors, with a 100 keV accelerator, to investigate and optimize the properties of the ion source; and MITICA, the full-scale prototype of the entire injector, devoted to the issues related to the accelerator, including voltage holding at low gas pressure. The present paper gives an account of the status of the procurements, of the timeline, and of the voltage holding tests and experiments for MITICA. As for SPIDER, the first year of operation is described, regarding the solution of some issues connected with the radiofrequency power, the source operation, and the characterization of the first negative ion beam.

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT 1 and IMPT 2 ) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HI IMPT2 = 0.11 vs. HI IMXT = 0.22 and CI IMPT2 = 0.96 vs. CI IMXT = 0.82, p  < .05). A significant relative skin risk reduction (RR = NTCP IMPT /NTCP IMXT ) was obtained with IMPT 2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Purpose: To present an advanced junction concept in craniospinal irradiation (CSI) by proton pencil beam scanning (PBS)., Materials and Methods: In PBS CSI, whole brain irradiation (WBI) is commonly delivered by opposed lateral-beams, whereas spine irradiation is delivered by posterior entrances. Since lateral-beams would cross a large portion of the patient at the shoulder level, the junction between WBI and spine irradiation cannot extend below that level, thus the size of the lateral-beams needs to be limited and the number of required isocenters can increase. To overcome such limitation, a pseudo-junction was introduced below the posterior fossa, to turn in this region the WBI beam arrangement to a single posterior beam pointed at the same isocenter, that was matched to the posterior spinal beam more caudally, below shoulder level, in the true-junction. After assessing robustness of the technique to range and setup uncertainties, twenty-three treated patients were reviewed to estimate the percentage that might benefit of being treated by two instead of three isocenters., Results: Target coverage at the junction levels resulted robust, with D95% > 95% on pseudo-junction and D95% > 90% on the true-junction. By the advanced junction concept, 91% of patients might by treated with only two isocenters, whereas, by the conventional method, 83% of patients required three isocenters., Conclusion: With the presented junction concept the number of isocenters can be reduced, with a consequent relevant reduction of treatment time, which is particularly valuable in the management of pediatric patients under anesthesia., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Proton therapy has proven to be effective and safe in the treatment of radioresistant skull base tumors such as chordomas. Thanks to the peculiar physical properties of the proton beam, radiation energy is delivered in a narrow space called the Bragg peak and the surrounding normal tissues receive a minimal amount of the radiation dose. This is important to lower the risk of radiation-induced damage, especially in children. However, local adverse effects in proximity to the target volume may occur. In particular, the development of moyamoya syndrome (MMS) has been rarely reported in children receiving proton beam therapy for brain tumors., Case Description: We report on a child who developed rapidly progressive MMS after proton beam therapy for a clivus chordoma. A combined indirect revascularization procedure by encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis was performed with good neuroradiologic and clinical outcome., Conclusions: Regardless of the presence of known risk factors for MMS, strict neuroimaging surveillance is indicated in all patients treated with radiotherapy including those receiving proton beam therapy. We suggest that an early revascularization procedure should be considered in patients with worsening symptoms and/or sign of neuroradiologic progression of cerebral vasculopathy. This management of MMS could lower the risk of permanent neurologic deficits and improve patients' quality of life., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To implement a new proton therapy planning method for the treatment of shallow lesions with PBS and to compare it to the standard method., Methods and Materials: In order to treat shallow lesions, a pre-absorber, usually called range-shifter (RS), is needed: it is used to degrade the beam energy and treat tumors shallower than the minimum range available. Its use is associated to dose calculation uncertainties and plan quality degradation which should be minimized. We studied five tumor localizations requiring RS and created three plans for each case: a) standard method with the RS close to the patient surface, b) with the RS used only for the shallow part of the tumor (when strictly needed) and completely retracted and c) as the b) approach but with the RS close to the patient. We called these two approaches 'Range Shifter Optimization' (RSO) techniques. We compared those plans in terms of dose distribution quality, delivery time and patient-specific-QA results., Results: In most cases a good dose reduction to OARs with no significant loss in terms of target coverage was obtained when the RSO techniques were used. Patient-specific-QA gave very good results in terms of γ-Passing-Rate (PR) (3%, 3 mm) for both RSO techniques (mean 98.09%), while the standard had some very low PR (minimum 81.09%). The delivery time increased (5.0 min on average per treatment) but was still acceptable in terms of patient compliance., Conclusion: We developed a new planning technique for shallow lesions and we demonstrated its superiority in terms of both plan quality and patient-specific-QA results with respect to the standard method. This technique is routinely used to treat patients in our center., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Proton therapy for the treatment of breast cancer is acquiring increasing interest, due to the potential reduction of radiation-induced side effects such as cardiac and pulmonary toxicity. While several in silico studies demonstrated the gain in plan quality offered by pencil beam scanning (PBS) compared to passive scattering techniques, the related dosimetric uncertainties have been poorly investigated so far., Methods: Five breast cancer patients were planned with Raystation 6 analytical pencil beam (APB) and Monte Carlo (MC) dose calculation algorithms. Plans were optimized with APB and then MC was used to recalculate dose distribution. Movable snout and beam splitting techniques (i.e. using two sub-fields for the same beam entrance, one with and the other without the use of a range shifter) were considered. PTV dose statistics were recorded. The same planning configurations were adopted for the experimental benchmark. Dose distributions were measured with a 2D array of ionization chambers and compared to APB and MC calculated ones by means of a γ analysis (agreement criteria 3%, 3 mm)., Results: Our results indicate that, when using proton PBS for breast cancer treatment, the Raystation 6 APB algorithm does not allow obtaining sufficient accuracy, especially with large air gaps. On the contrary, the MC algorithm resulted into much higher accuracy in all beam configurations tested and has to be recommended., Conclusions: Centers where a MC algorithm is not yet available should consider a careful use of APB, possibly combined with a movable snout system or in any case with strategies aimed at minimizing air gaps., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described., Methods: Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on., Results: In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets., Discussion: Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background and Purpose: Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described., Materials and Methods: Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed., Results: PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm., Conclusions: The reported methods allowed to effectively perform proton PBS CSI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To investigate the range errors made in treatment planning due to the presence of the immobilization devices along the proton beam path., Methods: The measured water equivalent thickness (WET) of selected devices was measured by a high-energy spot and a multi-layer ionization chamber and compared with that predicted by treatment planning system (TPS). Two treatment couches, two thermoplastic masks (both un-stretched and stretched) and one headrest were selected. At TPS, every immobilization device was modelled as being part of the patient. The following parameters were assessed: CT acquisition protocol, dose-calculation grid-sizes (1.5 and 3.0mm) and beam-entrance with respect to the devices (coplanar and non-coplanar). Finally, the potential errors produced by a wrong manual separation between treatment couch and the CT table (not present during treatment) were investigated., Results: In the thermoplastic mask, there was a clear effect due to beam entrance, a moderate effect due to the CT protocols and almost no effect due to TPS grid-size, with 1mm errors observed only when thick un-stretched portions were crossed by non-coplanar beams. In the treatment couches the WET errors were negligible (<0.3mm) regardless of the grid-size and CT protocol. The potential range errors produced in the manual separation between treatment couch and CT table were small with 1.5mm grid-size, but could be >0.5mm with a 3.0mm grid-size. In the headrest, WET errors were negligible (0.2mm)., Conclusions: With only one exception (un-stretched mask, non-coplanar beams), the WET of all the immobilization devices was properly modelled by the TPS., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this case report is to report on a dosimetric comparison between volumetric modulated arc therapy (RapidArc technique and active scanning proton therapy (single-field (SFO) and multifield (MFO) techniques) in a case of nasal cavity cancer recurrence., Case Report: A 72-year-old man, who received adjuvant radiotherapy for a carcinoma of the nasal cavity, experienced an unresectable local recurrence in the previous surgical bed. Hence, the patient was evaluated for reirradiation by comparing different modalities, with a total prescribed dose of 50 Gy in standard fractionation. RA plan was revealed to be equivalent to the MFO plan in terms of target dose coverage and conformity index. SFO plan was not able to respect a maximum dose of 9 Gy to nervous structures, in contrast to RA and MFO plans., Conclusions: In this challenging scenario, although a clear preference would be given to the MFO proton plan, the RA plan was revealed to be adequate for the clinical goal of target coverage and sparing of organs at risk.

Megavolt ITER Injector Concept Advancement is the full scale prototype of the heating and current drive neutral beam injectors for ITER, to be built at Consorzio RFX (Padova). The engineering design of its components is challenging: the total heat loads they will be subjected to (expected between 2 and 19 MW), the high heat fluxes (up to 20 MW/m(2)), and the beam pulse duration up to 1 h, set demanding requirements for reliable active cooling circuits. In support of the design, the thermo-hydraulic behavior of each cooling circuit under steady state condition has been investigated by using one-dimensional models. The final results, obtained considering a number of optimizations for the cooling circuits, show that all the requirements in terms of flow rate, temperature, and pressure drop are properly fulfilled.

Neutral Beam Injectors (NBI), which need to be strongly optimized in the perspective of DEMO reactor, request a thorough understanding of the negative ion source used and of the multi-beamlet optics. A relatively compact RF ion source, named NIO1 (Negative Ion Optimization 1), with 9 beam apertures for a total H(-) current of 130 mA, 60 kV acceleration voltage, is being installed at Padua, in Consorzio RFX, to provide a test bench for source optimizations in the framework of the accompanying activities in support to the ITER NBI test facility. NIO1 construction and status of the overall installation, including a high voltage deck and an optical cavity ring down spectrometer are here summarized and reported. Plasma and low voltage beam operations are discussed. Development of a sampling beam calorimeter (with small sampling holes, and a segmented cooling circuit) is also discussed.

Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.

Purpose: To compare helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) for prostate cancer irradiation while concomitantly boosting dominant intraprostatic lesions (DILs)., Methods and Materials: Treatment plans of seven patients were designed for HT and IMPT (pencil beam size: 3mm sigma). The prescribed median PTV/DIL doses were 71.4/100 Gy in 28 fractions, while satisfying "safe" dose constraints for organs at risks (OARs) including rectum, bladder, femoral heads, penile bulb and urethra. The planner could further reduce the dose to OARs if PTV/DIL constraints were reached., Results: IMPT achieved better dose conformity (CI=1.11 vs 1.31, p<0.05) and coverage (V95%=97.3% vs 95.3%, p<0.05) in PTV. Concerning DIL volumes, both techniques delivered the prescribed dose (D median: HT=100 Gy, IMPT=102.1 Gy) with similar dose conformity (CI: HT=1.49, IMPT=1.44) and same dose homogeneity, D99%, D1%, while satisfying the OARs constraints. Excepting urethra, the sparing of OARs was significantly better with IMPT; in general, the lower the dose, the greater the benefit of IMPT. Normal tissue complication probabilities for the rectum were in favor of IMPT with an absolute reduction of 3-8%, depending on the NTCP model (p<0.05)., Conclusions: Both techniques allowed delivering 100 Gy to DILs, while complying with the OARs constraints. IMPT was superior in sparing OARs for doses up to approximately 70 Gy, with larger benefit at lower doses., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation., Methods and Materials: Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC.To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter., Results: The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma)., Conclusions: From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.

Purpose: We estimated the potential advantage of remote positioning (RP) vs. in-room positioning (IP) for a proton therapy facility in terms of patient throughput., Materials and Methods: Monte Carlo simulations of facilities with one, two or three gantries were performed. A sensitivity analysis was applied by varying the imaging and setup correction system (ICS), the speed of transporters (for RP) and beam switching time. Possible advantages of using three couches (for RP) or of switching the beam between fields was also investigated., Results: For a single gantry facility, an average of 20% more patients could be treated using RP: ranging from +45%, if a fast transporter and slow ICS were simulated, to -14% if a slow transporter and fast ICS was simulated. For two gantries, about 10% more patients could be treated with RP, ranging from +32% (fast transporter, slow ICS) to -12% (slow transporter, fast ICS). The ability to switch beam between fields did not substantially influence the throughput. In addition, the use of three transporters showed increased delays and therefore a slight reduction of the fractions executables. For three gantries, RP and IP showed similar results., Conclusions: The advantage of RP vs. IP strongly depends on ICS and the speed of the transporters. For RP to be advantageous, reduced transport times are required. The advantage of RP decreases with increasing number of gantries., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT., Patients and Methods: We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions., Results: IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D(mean) reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V(20) reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints., Conclusion: Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 × 3 mm (up to 9 × 9 mm) does not compromise dosimetric results and allows a shorter delivery time.

A 60 kV ion source (9 beamlets of 15 mA each of H(-)) and plasma generators are being developed at Consorzio RFX and INFN-LNL, for their versatility in experimental campaigns and for training. Unlike most experimental sources, the design aimed at continuous operation. Magnetic configuration can achieve a minimum ∣B∣ trap, smoothly merged with the extraction filter. Modular design allows for quick substitution and upgrading of parts such as the extraction and postacceleration grids or the electrodes in contact with plasma. Experiments with a radio frequency plasma generator and Faraday cage inside the plasma are also described.

Purpose: To compare helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) on early stage prostate cancer treatments delivered with simultaneous integrated boost (SIB) in moderate hypofractionation., Material/methods: Eight patients treated with HT were replanned with two-field IMPT (2fIMPT) and five-field IMPT (5fIMPT), using a small pencil beam size (3 mm sigma). The prescribed dose was 74.3 Gy in 28 fractions on PTV1 (prostate) and PTV2 (proximal seminal vesicles), 65.5 Gy on PTV3 (distal seminal vesicles) and on the overlap between rectum and PTVs., Results: IMPT and HT achieved similar target coverage and dose homogeneity, with 5fIMPT providing the best results. The conformity indexes of IMPT were significantly lower for PTV1+2 and PTV3. Above 65 Gy, HT and IMPT were equivalent in the rectum, while IMPT spared the bladder and the penile bulb from 0 to 70 Gy. From 0 up to 60 Gy, IMPT dosimetric values were (much) lower for all OARs except the femur heads, where HT was better than 2fIMPT in the 25-35 Gy dose range. OARs mean doses were typically reduced by 30-50% by IMPT. NTCPs for the rectum were within 1% between the two techniques, except when the endpoint was stool frequency, where IMPT showed a small (though statistically significant) benefit., Conclusions: HT and IMPT produce similar dose distributions in the target volume. The current knowledge on dose-effect relations does not allow to quantify the clinical impact of the large sparing of IMPT at medium-to-low doses., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

A number of topics have been reviewed pertaining to hematologic problems in preoperative patients. Most if not all of the problems discussed can be evaluated reasonably well by history, physical examination, and a few simple laboratory tests. Because the morbidity arising from some of these abnormalities can be quite significant, evaluation and treatment should be completed prior to surgery whenever possible. It is also critical to recall that therapy for a number of hematologic problems involves the transfusion of blood or blood products. This therapy should not be taken lightly as both immediate reactions (fever, anaphalaxis, hemolysis) as well as delayed effects (allosensitization and viral infections) occur frequently. The prudent clinician should try to minimize his patients' exposure to these potentially toxic materials by using alternative therapies.