Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis.

BACKGROUND: Recently, a platform of T-cell replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using post-transplant cyclophosphamide (Cy) has shown high reproducibility and acceptable safety profile. METHOD: This prospective cohort analysis allowed us to collect data on infections among 70 consecutive recipients of haplo-HSCT affected by various hematologic malignancies. RESULTS: After a median follow-up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [CI] 59-81) at 100 days and 77% (95% CI 67-87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus-virus-associated cystitis was 19% (13/70). Cumulative incidence of bacterial and fungal infections at 1 year were 63% (95% CI 51-75) and 12% (95% CI 4-19), respectively. Of note, only 1 invasive fungal infection occurred beyond 1 year after transplant (day +739). CONCLUSION: In conclusion, despite a high rate of viral infections in the early period, present data suggest a satisfactory infectious profile after T-cell replete haplo-HSCT using post-transplant Cy. These results may help clinicians to improve both prophylactic and therapeutic antimicrobial strategies in this emerging haploidentical setting.

Virtual 4DCT generated from 4DMRI in gated particle therapy: phantom validation and application to lung cancer patients.

Objective. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved. To support the clinical practice based on 4D computed tomography (CT), 4D magnetic resonance imaging (MRI) acquisitions can be exploited. The purpose of this study was to validate a method for virtual 4DCT generation from 4DMRI data for lung cancers on a porcine lung phantom, and to apply it to lung cancer patients in PT.Approach. Deformable image registration was used to register each respiratory phase of the 4DMRI to a reference phase. Then, a static 3DCT was registered to this reference MR image set, and the virtual 4DCT was generated by warping the registered CT according to previously obtained deformation fields. The method was validated on a physical phantom for which a ground truth 4DCT was available and tested on lung tumor patients, treated with gated PT at end-exhale, by comparing the virtual 4DCT with a re-evaluation 4DCT. The geometric and dosimetric evaluation was performed for both proton and carbon ion treatment plans.Main results. The phantom validation exhibited a geometrical accuracy within the maximum resolution of the MRI and mean dose deviations, with respect to the prescription dose, up to 3.2% for targetD95%, with a mean gamma pass rate of 98%. For patients, the virtual and re-evaluation 4DCTs showed good correspondence, with errors on targetD95%up to 2% within the gating window. For one patient, dose variations up to 10% at end-exhale were observed due to relevant inter-fraction anatomo-pathological changes that occurred between the planning and re-evaluation CTs.Significance. Results obtained on phantom data showed that the virtual 4DCT method was accurate, allowing its application on patient data for testing within a clinical scenario.

Determination of ion recombination and polarity effects for the PTW Advanced Markus ionization chamber in synchrotron based scanned proton and carbon ion beams.

The aim of this work was the investigation of the ion recombination and polarity factors (ksat ad kpol) for a PTW Advanced Markus ionization chamber exposed to proton and carbon ion beams at the Centro Nazionale di Adroterapia Oncologica. Measurements with protons were specifically dedicated for ocular treatments, in the low energy range and for small, collimated scanning fields. For both protons and carbon ions, several measurements were performed by delivering a 2D single energy layer of 3x3 cm2 and homogeneous, biologically-optimized SOBPs. Data were collected at different depths in water, by varying the voltage values of the ionization chamber and for two different dose rates (the nominal one and one reduced to 20% of it). The ksat-values were determined from extrapolation of the saturation curves. Furthermore kpol-values were calculated using the recommendations from the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Results showed that the Advanced Markus performs optimally in this clinical scenario characterized by small treatment volumes and high dose gradients although for both particle types, but particularly for carbon ions, a charge multiplication effect up to 1.7% occurs at voltage higher than 150 V. For protons, both the ion recombination and polarity corrections were always smaller than 0.3%, for all the analysed cases and adopted dose rates, so not affecting the dosimetric measurements for clinical routine. For carbon ions the polarity effect can be neglected while ion recombination has to be carefully calculated and cannot be neglected since corrections even higher than 1% can be found, especially at high LET measuring points.

Dosimetric effect of variable rectum and sigmoid colon filling during carbon ion radiotherapy to sacral chordoma.

PURPOSE: Carbon ion radiotherapy (CIRT) is sensitive to anatomical density variations. We examined the dosimetric effect of variable intestinal filling condition during CIRT to ten sacral chordoma patients. METHODS: For each patient, eight virtual computed tomography scans (vCTs) were generated by varying the density distribution within the rectum and the sigmoid in the planning computed tomography (pCT) with a density override approach mimicking a heterogeneous combination of gas and feces. Totally full and empty intestinal preparations were modelled. In addition, five different intestinal filling conditions were modelled by a mixed density pattern derived from two combined and weighted Gaussian distributions simulating gas and feces respectively. Finally, a patient-specific mixing proportion was estimated by evaluating the daily amount of gas detected in the cone beam computed tomography (CBCT). Dose distribution was recalculated on each vCT and dose volume histograms (DVHs) were examined. RESULTS: No target coverage degradation was observed at different vCTs. Rectum and sigma dose degradation ranged respectively between: [-6.7; 21.6]GyE and [-0.7; 15.4]GyE for D50%; [-377.4; 1197.9] and [-95.2; 1027.5] for AUC; [-1.2; 10.7]GyE and [-2.6; 21.5]GyE for D1%. CONCLUSIONS: Variation of intestinal density can greatly influence the penetration depth of charged particle and might compromise dose distribution. In particular cases, with large clinical target volume in very close proximity to rectum and sigmoid colon, it is appropriate to evaluate the amount of gas present in the daily CBCT images even if it is totally included in the reference planning structures.

Determination of ion recombination and polarity effect correction factors for a plane-parallel ionization Bragg peak chamber under proton and carbon ion pencil beams.

Within the dosimetric characterization of particle beams, laterally-integrated depth-dose-distributions (IDDs) are measured and provided to the treatment planning system (TPS) for beam modeling or used as a benchmark for Monte Carlo (MC) simulations. The purpose of this work is the evaluation, in terms of ion recombination and polarity effect, of the dosimetric correction to be applied to proton and carbon ion curves as a function of linear energy transfer (LET). LET was calculated with a MC code for selected IDDs. Several regions of Bragg peak (BP) curve were investigated. The charge was measured with the plane-parallel BP-ionization chamber mounted in the Peakfinder as a field detector, by delivering a fixed number of particles at the maximum flux. The dose rate dependence was evaluated for different flux levels. The chamber was connected to an electrometer and exposed to un-scanned pencil beams. For each measurement the chamber was supplied with {±400, +200, +100} V. Recombination and polarity correction factors were then calculated as a function of depth and LET in water. Three energies representative of the clinical range were investigated for both particle types. The corrected IDDs (IDD k s) were then compared against MC. Recombination correction factors were LET and energy dependent, ranging from 1.000 to 1.040 (±0.5%) for carbon ions, while nearly negligible for protons. Moreover, no corrections need to be applied due to polarity effect being <0.5% along the whole IDDs for both particle types. IDD k s showed a better agreement than uncorrected curves when compared to MC, with a reduction of the mean absolute variation from 1.2% to 0.9%. The aforementioned correction factors were estimated and applied along the IDDs, showing an improved agreement against MC. Results confirmed that corrections are not negligible for carbon ions, particularly around the BP region.

Characterization of a commercial scintillation detector for 2-D dosimetry in scanned proton and carbon ion beams.

INTRODUCTION: Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. METHODS AND MATERIALS: The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. RESULTS: Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. CONCLUSION: Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing.

Awareness of medical radiation exposure among patients: A patient survey as a first step for effective communication of ionizing radiation risks.

INTRODUCTION: The European Directive 2013/59/EURATOM requires patient radiation dose information to be included in the medical report of radiological procedures. To provide effective communication to the patient, it is necessary to first assess the patient's level of knowledge regarding medical exposure. The goal of this work is to survey patients' current knowledge level of both medical exposure to ionizing radiation and professional disciplines and communication means used by patients to garner information. MATERIAL AND METHODS: A questionnaire was designed comprised of thirteen questions: 737 patients participated in the survey. The data were analysed based on population age, education, and number of radiological procedures received in the three years prior to survey. RESULTS: A majority of respondents (56.4%) did not know which modality uses ionizing radiation. 74.7% had never discussed with healthcare professionals the risk concerning their medical radiological procedures. 70.1% were not aware of the professionals that have expertise to discuss the use of ionizing radiation for medical purposes, and 84.7% believe it is important to have the radiation dose information stated in the medical report. CONCLUSION: Patients agree with new regulations that it is important to know the radiation level related to the medical exposure, but there is little awareness in terms of which modalities use X-Rays and the professionals and channels that can help them to better understand the exposure information. To plan effective communication, it is essential to devise methods and adequate resources for key professionals (medical physicists, radiologists, referring physicians) to convey correct and effective information.

Dosimetric characterization of carbon fiber stabilization devices for post-operative particle therapy.

PURPOSE: The aim of this study was to evaluate the dosimetric impact caused by recently introduced carbon fiber reinforced polyetheretherketone (CF/PEEK) stabilization devices, in comparison with conventional titanium (Ti) implants, for post-operative particle therapy (PT). METHODS: As a first step, protons and carbon ions Spread-Out Bragg Peaks (SOBPs) were delivered to CF/PEEK and Ti screws. Transversal dose profiles were acquired with EBT3 films to evaluate beam perturbation. Effects on image quality and reconstruction artifacts were then investigated. CT scans of CF/PEEK and Ti implants were acquired according to our clinical protocol and Hounsfield Unit (HU) mean values were evaluated in three regions of interest. Implants and artifacts were then contoured in the sample CT scans, together with a target volume to simulate a spine tumor. Dose calculation accuracy was assessed by comparing optimized dose distributions with Monte Carlo simulations. In the end, the treatment plans of nine real patients (seven with CF/PEEK and two with Ti stabilization devices) were retrospectively analyzed to evaluate the dosimetric impact potentially occurring if improper management of the spine implant was carried out. RESULTS: As expected, CF/PEEK screw caused a very slight beam perturbation in comparison with Ti ones, leading to a lower degree of dose degradation in case of contouring and/or set-up uncertainties. Furthermore, CF/PEEK devices did not determine appreciable HU artifacts on CT images thus improving image quality and, as a final result, dose calculation accuracy. CONCLUSIONS: CF/PEEK spinal fixation devices resulted dosimetrically more suitable than commonly-used Ti implants for post-operative PT.

Contrasting the grain boundary-affected performance of zinc and indium oxide transparent conductors.

Zinc oxide-based transparent conductors have long been advanced for their potential as low-cost, earth-abundant replacements for the indium oxide-based materials that currently dominate in practical applications. However, this potential has yet to be realized because of the difficulties in producing zinc oxide thin films with the necessary high levels of electrical conductivity and environmental stability that are readily achieved using indium oxide. To better understand the fundamental reasons for this, polycrystalline zinc and indium oxide thin films were prepared across a range of deposition temperatures using the technique of spray pyrolysis. Electrical transport measurements of these samples both as a function of temperature and UV irradiation were correlated with film morphology to illustrate that the different grain boundary behaviour of these two materials is one of the key reasons for their divergent performance. This is a critical challenge that must be addressed before any substantial increase in the adoption of ZnO-based transparent conductors can take place.