Comprehensive investigation of lateral dose profile and output factor measurements in small proton fields from different delivery techniques

Background and purpose: As a part of the commissioning and quality assurance in proton beam therapy, lateral dose profiles and output factors have to be acquired. Such measurements can be performed with point detectors and are especially challenging in small fields or steep lateral penumbra regions as the detector's volume effect may lead to perturbations. To address this issue, this work aims to quantify and correct for such perturbations of six point detectors in small proton fields created via three different delivery techniques. Methods: Lateral dose profile and output measurements of three proton beam delivery techniques (pencil beam scanning, pencil beam scanning combined with collimators, passive scattering with collimators) were performed using high-resolution EBT3 films, a PinPoint 3D 31022 ionization chamber, a microSilicon diode 60023 and a microDiamond detector 60019 (all PTW Freiburg, Germany). Detector specific lateral dose response functions K(x,y) acting as the convolution kernel transforming the undisturbed dose distribution D(x,y) into the measured signal profiles M(x,y) were applied to quantify perturbations of the six investigated detectors in the proton fields and correct the measurements. A signal theoretical analysis in Fourier space of the dose distributions and detector's K(x,y) was performed to aid the understanding of the measurement process with regard to the combination of detector choice and delivery technique. Results: Quantification of the lateral penumbra broadening and signal reduction at the fields center revealed that measurements in the pencil beam scanning fields are only compromised slightly even by large volume ionization chambers with maximum differences in the lateral penumbra of 0.25 mm and 4% signal reduction at the field center. In contrast, radiation techniques with collimation are not accurately represented by the investigated detectors as indicated by a penumbra broadening up to 1.6 mm for passive scattering with collimators and 2.2 mm for pencil beam scanning with collimators. For a 3 mm diameter collimator field, a signal reduction at field center between 7.6% and 60.7% was asserted. Lateral dose profile measurements have been corrected via deconvolution with the corresponding K(x,y) to obtain the undisturbed D(x,y). Corrected output ratios of the passively scattered collimated fields obtained for the microDiamond, microSilicon and PinPoint 3D show agreement better than 0.9% (one standard deviation) for the smallest field size of 3 mm. Conclusion: Point detector perturbations in small proton fields created with three delivery techniques were quantified and found to be especially pronounced for collimated small proton fields with steep dose gradients. Among all investigated detectors, the microSilicon diode showed the smallest perturbations. The correction strategies based on detector's K(x,y) were found suitable for obtaining unperturbed lateral dose profiles and output factors. Approximation of K(x,y) by considering only the geometrical averaging effect has been shown to provide reasonable prediction of the detector's volume effect. The findings of this work may be used to guide the choice of point detectors in various proton fields and to contribute toward the development of a code of practice for small field proton dosimetry.</p

Validating a double Gaussian source model for small proton fields in a commercial Monte-Carlo dose calculation engine

Purpose: The primary fluence of a proton pencil beam exiting the accelerator is enveloped by a region of secondaries, commonly called “spray”. Although small in magnitude, this spray may affect dose distributions in pencil beam scanning mode e.g., in the calculation of the small field output, if not modelled properly in a treatment planning system (TPS). The purpose of this study was to dosimetrically benchmark the Monte Carlo (MC) dose engine of the RayStation TPS (v.10A) in small proton fields and systematically compare single Gaussian (SG) and double Gaussian (DG) modeling of initial proton fluence providing a more accurate representation of the nozzle spray. Methods: The initial proton fluence distribution for SG/DG beam modeling was deduced from two-dimensional measurements in air with a scintillation screen with electronic readout. The DG model was either based on direct fits of the two Gaussians to the measured profiles, or by an iterative optimization procedure, which uses the measured profiles to mimic in-air scan-field factor (SF) measurements. To validate the DG beam models SFs, i.e. relative doses to a 10 × 10 cm2 field, were measured in water for three different initial proton energies (100MeV, 160MeV, 226.7MeV) and square field sizes from 1×1cm2 to 10×10cm2 using a small field ionization chamber (IBA CC01) and an IBA ProteusPlus system (universal nozzle). Furthermore, the dose to the center of spherical target volumes (diameters: 1cm to 10cm) was determined using the same small volume ionization chamber (IC). A comprehensive uncertainty analysis was performed, including estimates of influence factors typical for small field dosimetry deduced from a simple two-dimensional analytical model of the relative fluence distribution. Measurements were compared to the predictions of the RayStation TPS. Results: SFs deviated by more than 2% from TPS predictions in all fields <4×4cm2 with a maximum deviation of 5.8% for SG modeling. In contrast, deviations were smaller than 2% for all field-sizes and proton energies when using the directly fitted DG model. The optimized DG model performed similarly except for slightly larger deviations in the 1×1cm2 scan-fields. The uncertainty estimates showed a significant impact of pencil beam size variations (±5%) resulting in up to 5.0% standard uncertainty. The point doses within spherical irradiation volumes deviated from calculations by up to 3.3% for the SG model and 2.0% for the DG model. Conclusion: Properly representing nozzle spray in RayStation's MC-based dose engine using a DG beam model was found to reduce the deviation to measurements in small spherical targets to below 2%. A thorough uncertainty analysis shows a similar magnitude for the combined standard uncertainty of such measurements

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures

BackgroundIn radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment.Materials and methodsOrgan doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al.ResultsOut-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs.ConclusionThe complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up

Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown

Mopeia Virus–related Arenavirus in Natal Multimammate Mice, Morogoro, Tanzania

A serosurvey involving 2,520 small mammals from Tanzania identified a hot spot of arenavirus circulation in Morogoro. Molecular screening detected a new arenavirus in Natal multimammate mice (Mastomys natalensis), Morogoro virus, related to Mopeia virus. Only a small percentage of mice carry Morogoro virus, although a large proportion shows specific antibodies

Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events

Technical Note: Investigating interplay effects in pencil beam scanning proton therapy with a 4D XCAT phantom within the RayStation treatment planning system

Purpose: Pencil beam scanning (PBS) for moving targets is known to be impacted by interplay effects. Four-dimensional computed tomography (4DCT)-based motion evaluation is crucial for understanding interplay and developing mitigation strategies. Availability of high-quality 4DCTs with variable breathing traces is limited. Purpose of this work is the development of a framework for interplay analysis using 4D-XCAT phantoms in conjunction with time-resolved irradiation patterns in a commercial treatment planning system (TPS). Four-dimensional dynamically accumulated dose distributions (4DDDs) are simulated in an in-silico study for a PBS liver treatment. Methods: An XCAT phantom with 50 phases, varying linearly in amplitude each by 1 mm, was combined with the RayStation TPS (7.99.10). Deformable registration was used with time-resolved dose calculation, mapping XCAT phases to motion signals. To illustrate the applicability of the method a two-field liver irradiation plan was used. A variety sin4 type motion signals, varying in amplitude (1–20 mm), period (1.6–5.2 s) and phase (0–2π) were applied. Either single variable variations or random combinations were selected. The interplay effect within a clinical target (5 cm diameter) was characterized in terms of homogeneity index (HI5), with and without five paintings. In total 2092 scenarios were analyzed within RayStation. Results: A framework is presented for interplay research, allowing for flexibility in determining motion management techniques, increasing reproducibility, and enabling comparisons of different methods. A case study showed the interplay effect was correlated with amplitude and strongly affected by the starting phase, leading to large variance. The average of all scenarios (single fraction) resulted in HI5 of 0.31 (±0.11), while introduction of five times layered repainting reduced this to 0.11(±0.03). Conclusion: The developed framework, which uses the XCAT phantom and RayStation, allows detailed analysis of motion in context of PBS with comparable results to clinical cases. Flexibility in defining motion patterns for detailed anatomies in combination with time-resolved dose calculation, facilitates investigation of optimal treatment and motion mitigation strategies.</p