Risk adaptive planning with biology-based constraints may lead to higher tumor control probability in tumors of the canine brain: A planning study.

BACKGROUND: Classical radiation protocols are guided by physical dose delivered homogeneously over the target. Protocols are chosen to keep normal tissue complication probability (NTCP) at an acceptable level. Organs at risk (OAR) adjacent to the target volume could lead to underdosage of the tumor and a decrease of tumor control probability (TCP). The intent of our study was to explore a biology-based dose escalation: by keeping NTCP for OAR constant, radiation dose was to be maximized, allowing to result in heterogeneous dose distributions. METHODS: We used computed tomography datasets of 25 dogs with brain tumors, previously treated with 10x4 Gy (40 Gy to PTV D50). We generated 3 plans for each patient: A) original treatment plan with homogeneous dose distribution, B) heterogeneous dose distribution with strict adherence to the same NTCPs as in A), and C) heterogeneous dose distribution with adherence to NTCP <5%. For plan comparison, TCPs and TCP equivalent doses (homogenous target dose which results in the same TCP) were calculated. To enable the use of the generalized equivalent uniform dose (gEUD) metric of the tumor target in plan optimization, the calculated TCP values were used to obtain the volume effect parameter a. RESULTS: As intended, NTCPs for all OARs did not differ from plan A) to B). In plan C), however, NTCPs were significantly higher for brain (mean 2.5% (SD±1.9, 95%CI: 1.7,3.3), p<0.001), optic chiasm (mean 2.0% (SD±2.2, 95%CI: 1.0,2.8), p=0.010) compared to plan A), but no significant increase was found for the brainstem. For 24 of 25 of the evaluated patients, the heterogenous plans B) and C) led to an increase in target dose and projected increase in TCP compared to the homogenous plan A). Furthermore, the distribution of the projected individual TCP values as a function of the dose was found to be in good agreement with the population TCP model. CONCLUSION: Our study is a first step towards risk-adaptive radiation dose optimization. This strategy utilizes a biologic objective function based on TCP and NTCP instead of an objective function based on physical dose constraints.

Pesticide risk assessment in European agriculture: Distribution patterns, ban-substitution effects and regulatory implications.

This study estimates the risks of agricultural pesticides on non-target organisms and the environment by combining detailed pesticide application data for 2015 with the Danish risk indicator Pesticide Load. We quantify and map the pesticide load of 59 pesticides on 28 crops and pastures in the EU. Furthermore, we investigate how recent bans on 14 pesticides in the EU could reduce pesticide use and load. Key findings show that the highest pesticide loads per hectare occur in Cyprus and the Netherlands due to high application rates and a high proportion of vegetable production. Chlorpyrifos caused the highest pesticide load per hectare on more than half of the assessed crops before its ban. The ban of 14 pesticides between 2018 and 2023 potentially reduced pesticide loads by 94%, but unobserved substitution effects could offset pesticide load reductions. Although bans on active substances are justified to control certain endpoint risks, our results highlight the potential weaknesses of bans that merely shift risks. These findings contribute to the ongoing scientific and societal discourse on efficiently mitigating pesticides' impacts on non-target organisms and the environment. However, to improve the evaluation of pesticide use, it is vital to enhance the reporting on detailed pesticide use for individual crop-pesticide combinations.

Monte Carlo model for ion mobility and diffusion for characteristic electric fields in nanodosimetry.

The quantification of the effects of space radiation for manned spaceflight can be approximated by nanodosimetric measurements. For the development of nanodosimetric detectors, a Monte Carlo model for ion mobility and diffusion for characteristic electric fields is presented. This model can be used to describe the interactions of ions in their parent gas based solely on commonly known input parameters, such as the ionization potential, kinetic diameter, molar mass, and polarizability of the gas. A model for approximating the resonant charge exchange cross section has been proposed, requiring only the ionization energy and mass of the parent gas as input parameters. The method proposed in this work was tested against experimental drift velocity data for a wide range of gases (helium, neon, nitrogen, argon, krypton, carbon monoxide, carbon dioxide, oxygen, propane). The transverse diffusion coefficients were compared to experimental values for helium, nitrogen, neon, argon, and propane gas. With the Monte Carlo code and resonant charge exchange cross section approximation model presented in this work, it is now possible to calculate an estimate of the drift velocities, transverse diffusion, and thus the ion mobility of ions in their parent gas. This is essential for further nanodosimetric detector development, as those parameters are often not well known for the gas mixtures used in nanodosimetry.

European astronaut radiation related cancer risk assessment using dosimetric calculations of organ dose equivalents.

An illustrative sample mission of a Mars swing-by mission lasting one calendar year was chosen to highlight the application of European risk assessment software to cancer (all solid cancer plus leukaemia) risks from radiation exposures in space quantified with organ dose equivalent rates from model calculations based on the quantity Radiation Attributed Decrease of Survival (RADS). The relevant dose equivalent to the colon for radiation exposures from this Mars swing-by mission were found to vary between 198 and 482 mSv. These doses depend on sex and the two other factors investigated here of: solar activity phase (maximum or minimum); and the choice of space radiation quality factor used in the calculations of dose equivalent. Such doses received at typical astronaut ages around 40 years old will result in: the probability of surviving until retirement age (65 years) being reduced by a range from 0.38% (95%CI: 0.29; 0.49) to 1.29% (95%CI: 1.06; 1.56); and the probability of surviving cancer free until retirement age being reduced by a range from 0.78% (95%CI: 0.59; 0.99) to 2.63% (95%CI: 2.16; 3.18). As expected from the features of the models applied to quantify the general dosimetric and radiation epidemiology parameters, the cancer incidence risks in terms of surviving cancer free, are higher than the cancer mortality risks in terms of surviving, the risks for females are higher than for males, and the risks at solar minimum are higher than at solar maximum.

Sustainable livelihood capital and climate change adaptation in Pakistan's agriculture: Structural equation modeling analysis in the VIABLE framework.

This study aims to assess the role of sustainable livelihood capital, the mediation of investments and farming purposes, and the moderation of climatic and non-climatic factors in the adaptation process, particularly in the aspects of Crop, Farm, Irrigation, and Economic Management. Moreover, guided by the VIABLE (Values and Investments for Agent-Based Interaction and Learning in Environmental Systems) framework, we analyze stakeholders' actions, priorities, and goals in the climate change adaptation process. A structured questionnaire was designed based on a five-point Likert scale covering the concepts of livelihood capital, climate change adaptation, investment priorities, farming constraints, and farmers' decision-making factors. Field data were collected from 800 farmers during December 2021 to February 2022 in the irrigated agricultural regions in the Indus Plain of the Punjab and Sindh provinces, Pakistan. We employed the Partial Least Square Structural Equation Modeling approach to the VIABLE framework (VIABLE-SEM) to analyze the collected data. The results confirm livelihood capital as the most significant determinant (beta = 0.57, effect size = 0.503) for farmers' adaptation strategies in the Indus plain. Other variables, such as the principal purpose of farming, available investment options, natural and human constraints, appear less important. We identified 13 significant viability pathways that show investment priorities, farming purposes, and constraints faced by the farmers in climate change adaptation. The study also found that non-climatic factors negatively influence (beta = -0.156) the relationship between capital and adaptation, while climatic factors positively influence (beta = 0.050) this relationship. Interestingly, the presence of these influencing factors increases the adaptive capacity of farmers. These findings have important implications for policymakers and researchers in designing and implementing effective climate change adaptation strategies in the agricultural sector of Pakistan.

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

Background: In 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 methods: Organ 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. Results: Out-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. Conclusion: The 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.

Quality assessment of automatically planned O-Ring linac SBRT plans for pelvic lymph node metastases, finding the optimal minimum target size by comparison with robotic SBRT.

PURPOSE: The purpose of this study is to assess the quality of automatic planned O-Ring Halcyon linac SBRT plans for pelvic lymph node metastases and to establish an absolute PTV volume threshold as a plan quality prediction criterion. Compliance of the plans to institutional SBRT plan evaluation criteria and differences in plan quality and treatment delivery times between Halcyon Linac and CyberKnife robotic SBRT were evaluated. METHODS: Twenty-one CyberKnife treatment plans were replanned for Halcyon. Prescription doses range was 26-40 Gy in mean three fractions. The mean/median planning target volume was 4.0/3.6 cm3 . Institutional criteria for the plan evaluation were: New Conformity Index (NCI), Conformity Index (CI), Modified Gradient Index (MGI), selectivity index reciprocal (PIV/TVPIV ), and the target coverage by prescription isodose (%PIV). Statistical analysis based on the receiver operating characteristic (ROC) curve was used to determine a plan quality predictor threshold of the PTV volume. Comparative analysis of normal tissue complication probabilities (NTCP) was used to assess the risk of toxicity in healthy tissues. RESULTS: Seventy-one percent (n = 15)/95% (n = 20) of Halcyon and 81% (n = 17)/100% (n = 21) of CK plans fulfilled all ideal/tolerance criteria. For PTVs above a found optimal threshold of 2.6 cm3 (71%, n = 15), no statistically significant difference was observed between the CI, NCI, PIV/TVPIV , and MGI indexes of both groups, while the coverage (%PIV) was statistically but not clinically significantly different between cohorts. Significantly shorter delivery times are expected with Halcyon. No significant differences in NTCP were observed. CONCLUSION: All but one automatically optimized Halcyon treatment plans demonstrated ideal or acceptable performance. PTV threshold of 2.6 cm3 can be used as decision criteria in clinical settings. The results of our study demonstrated the promising performance of the Halcyon for pelvic SBRT, although plan-specific QA is required to verify machine performance during plan delivery.

Exploring the benefits of inoculated cowpeas under different climatic conditions in Namibia.

Cowpeas (Vigna uniculata L. Walp) are grown by many smallholder farmers in sub-Saharan Africa for food and their ability to fix nitrogen even under stress. Their performance depends on the indigenous rhizobial strains that live in symbiotic association with the roots; it can be enhanced if the seeds are inoculated with more effective ones. Data of the effectiveness of the technique under a variety of climatic conditions is rare. Here, we thus use a model to upscale two field experiments conducted in Namibia to include different climate change scenarios. The simulations show that non-inoculated cowpeas have mean yields of 0.5 t/ha and inoculated cowpeas 1 t/ha. If climatic conditions are favorable (cool and wet), estimated yield differences increase to over 1 t/ha. In dry years (< 200 mm), the average yield difference is only 0.1 t/ha. In the far future (2080-2100), instances of dry and hot years will increase. Using inoculated cowpea seeds instead of non-inoculated ones thus does not benefit farmers as much then as in the near future (2030-2050). In conclusion, using cowpea seeds inoculated with an efficient rhizobial strain can significantly increase yields under varying climatic conditions, but yield advantages decrease markedly in very dry and hot years.

Rights and duties of genetic counsellors in Germany related to relatives at risk: comparative thoughts on the German Genetic Diagnostics Act.

Genetic testing has familial implications. Counsellors find themselves in (moral) conflict between medical confidentiality (towards the patient) and a potential right or even duty to warn at-risk relatives. Legal regulations vary between countries. English literature about German law is scarce. We reviewed the literature of relevant legal cases, focussing on German law, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This article aims to familiarise counsellors with their responsibilities, compare the situation between countries and point out legally unresolved areas.According to the German Genetic Diagnostics Act (Gendiagnostikgesetz) in case of an 'avoidable or treatable' genetic disorder, geneticists ought to confine themselves to the obligated advice to the patient. Whether a breach of the duty of confidentiality can be justified in exceptional cases by 'necessity as justification' for actively informing relatives at risk remains legally unclear. In case of a 'neither avoidable nor treatable' genetic disease, geneticists should also refrain from actively informing relatives as the justifiable state of emergency does not permit to break the duty of confidentiality.

Amniotic fluid content in children with kidney and urinary tract anomalies determines pre- and postnatal development.

BACKGROUND: Renal oligohydramnios (ROH) describes an abnormally low volume of amniotic fluid (AF) during pregnancy. ROH is mostly caused by congenital fetal kidney anomalies. The ROH diagnosis frequently implies an increased risk of peri- and postnatal fetal mortality and morbidity. The present study aimed to evaluate the impact of ROH on pre-and postnatal development in children with congenital kidney anomalies. METHODS: This retrospective study included 168 fetuses with anomalies in the kidney and urinary tract. Based on the amount of AF measured by ultrasound, patients were divided into three groups: normal amniotic fluid (NAF), amniotic fluid in the lower normal range (LAF), and ROH. These groups were compared with respect to prenatal sonographic parameters, perinatal outcomes, and postnatal outcomes. RESULTS: Among the 168 patients with congenital kidney anomalies, 26 (15%) had ROH, 132 (79%) had NAF, and 10 (6%) had LAF. Of the 26 families affected by ROH, 14 (54%) decided to terminate pregnancy. Of 10 live-born children in the ROH group, 6 (60%) survived the observation time; of these, 5/6 presented with chronic kidney disease, stages I-III, at their last examination. The main differences in postnatal development between the ROH group and the NAF and LAF groups were: restricted height and weight gain, respiratory issues, complicated feeding, and the presence of extrarenal malformations. CONCLUSIONS: ROH is not a mandatory indicator of severe postnatal kidney function impairment. However, children with ROH have complicated peri-and postnatal periods, due to the presence of concomitant malformations, which must be considered in prenatal care. A higher resolution version of the Graphical abstract is available as Supplementary information.

Towards sustainable human space exploration-priorities for radiation research to quantify and mitigate radiation risks.

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon's orbit, return to the Moon's surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit.

A stakeholders' pathway towards a future land use and food system in Germany.

Food systems contribute considerably to greenhouse gas (GHG) emissions and influence land use. In Germany, many strategies have been proposed by policy-makers to reduce negative impacts and make the food system more sustainable. It is unclear how close the suggested policies, when bundled, will bring the food and land use system towards the targeted goals; and what stakeholders from non-policy-making organizations consider realistic changes in the German food system. We thus surveyed different stakeholder groups on their opinions about realistic changes in the food and land use system in Germany up to 2050, developed four stakeholder pathways, and used an accounting tool to determine the effect of each pathway on indicators such as land use, GHG emissions, and biodiversity conservation potential. The assessment showed that GHG emissions from agricultural activities and land use are reduced from 66 to - 2-22 TgCO2e by 2050, while the area where natural processes predominate increases from 19 to 27-32%, and the resilience of the food system is not negatively influenced. The change is caused mainly by a diet-change-induced reduction of livestock production and agricultural area transformation into areas with higher carbon sequestration rates. If followed, the common stakeholder pathway (based on all stakeholder responses) would thus lead towards a sustainable food and land use system, but only if the underlying assumption of a drastic diet change towards more plant-based products comes true. Stakeholders from the academic and public sectors were more likely to assume that such a change was realistic than stakeholders from the private sector.

Furthering climate-smart farming with the introduction of floating agriculture in Bangladeshi wetlands: Successes and limitations of an innovation transfer.

Although floating farming, a climate-smart practice, is a response to climate change challenges facing agriculture in wetland areas, the adoption of floating agriculture in Bangladesh wetland areas (also known as Haor) is slow. The purpose of our study was to identify the factors that motivate and barriers that inhibit the adoption of floating agriculture in the Haor region in Bangladesh's Kishoreganj district. To achieve our purpose, we used Roger's five-stage innovation-decision theory. We collected data from a sample of 120 Haor rural farmers using a quantitative questionnaire answered via a personal interview. We used a binary logistic regression to identify the factors that predict farmers' motivational actions in adopting floating agriculture. In addition, we rank ordered the data to identify the obstacles that prohibit farmers from implementing floating agriculture. The results demonstrate that education, training related to floating agriculture, credit received, communication behavior, trialability and observability, and complexity in practicing floating agriculture motivate farmers to adopt floating agriculture. The results also show that climatic factors (e.g., high waves and excessive rainfall, aquatic plant scarcity) and non-climatic factors (e.g., inadequate demonstration plots, conflict, and political power abuse) inhibit adoption of floating agriculture. Our study provides suggestions for increasing farmers' adoption of floating agriculture in wetland areas.

Intrafraction Prostate Motion Management for Ultra-Hypofractionated Radiotherapy of Prostate Cancer.

Purpose: Determine the time-dependent magnitude of intrafraction prostate displacement and a cutoff for the tracking decision. Methods: Nine patients with localized prostate cancer were treated with ultra-hypofractionated radiotherapy (CyberKnife) with fiducial markers. Exact tract kV/kV imaging was used with an average interval of 19−92 s. A Gaussian distribution was calculated for the x-, y-, and z-directions (σx,y,z). The variation of prostate motion (µσ) was obtained by averaging the patients' specifics, and the safety margin was calculated to be MAB = WYm + WBSs. Results: The calculated PTV safety margins were as follows: at 40 s: 0.55 mm (L/r), 0.85 mm (a/p), and 1.05 mm (s/i); at 60 s: 0.9 mm (L/r), 1.35 mm (a/p), and 1.55 mm (s/i); at 100 s: 1.5 mm (L/r), 2.3 mm (a/p), and 2.6 mm (s/i); at 150 s: 1.9 mm (L/r), 3.1 mm (a/p), and 3.6 mm (s/i); at 200 s: 2.2 mm (L/r), 3.8 mm (a/p), and 4.2 mm (s/i); and at 300 s: 2.6 mm (L/r), 5.3 mm (a/p), and 5.6 mm (s/i). A tracking cutoff of 2.5 min seemed reasonable. In order to achieve an accuracy of < 1 mm, tracking with < 50 s intervals was necessary. Conclusions: For ultra-hypofractionated radiotherapy of the prostate with treatment times > 2.5 min, intrafraction motion management is recommended.

Chronic Kidney Disease and Pregnancy. Guideline of the DGGG, OEGGG, DGfN (S2k Level, AWMF Registry No. 015 - 090).

Aim As diagnostic and therapeutic options have improved in recent years, women with limited renal function of varying etiologies are now able to become pregnant. Depending on the extent of disease and the patients' comorbidities, the care of these women can be especially challenging. This guideline aims to improve the interdisciplinary care offered to pregnant women with kidney disease. Methods A selective literature search was carried out. This S2k guideline was then compiled using a structured consensus-based process which included representatives from different medical specialties and professional societies. Recommendations Recommendations for the care of pregnant women with renal disease were developed to cover preconception counseling, the recording of risks, special aspects of prenatal care and prenatal screening, as well as the specific treatment options for the underlying disease in women wanting to have children and pregnant women.

A concept for anisotropic PTV margins including rotational setup uncertainties and its impact on the tumor control probability in canine brain tumors.

Objective.In this modelling study, we pursued two main goals. The first was to establish a new CTV-to-PTV expansion which considers the closest and most critical organ at risk (OAR). The second goal was to investigate the impact of the planning target volume (PTV) margin size on the tumor control probability (TCP) and its dependence on the geometrical setup uncertainties. The aim was to achieve a smaller margin expansion close to the OAR while allowing a moderately larger expansion in less critical areas further away from the OAR and whilst maintaining the TCP.Approach.Imaging data of radiation therapy plans from pet dogs which had undergone radiation therapy for brain tumor were used to estimate the clinic specific rotational setup uncertainties. A Monte-Carlo methodology using a voxel-based TCP model was used to quantify the implications of rotational setup uncertainties on the TCP. A combination of algorithms was utilized to establish a computational CTV-to-PTV expansion method based on probability density. This was achieved by choosing a center of rotation close to an OAR. All required software modules were developed and integrated into a software package that directly interacts with the Varian Eclipse treatment planning system.Main results.Several uniform and non-isotropic PTVs were created. To ensure comparability and consistency, standardized RT plans with equal optimization constraints were defined, automatically applied and calculated on these targets. The resulting TCPs were then computed, evaluated and compared.Significance.The non-isotropic margins were found to result in larger TCPs with smaller margin excess volume. Further, we presented an additional application of the newly established CTV-to-PTV expansion method for radiation therapy of the spinal axis of human patients.

Experimental Validation of an Analytical Program and a Monte Carlo Simulation for the Computation of the Far Out-of-Field Dose in External Beam Photon Therapy Applied to Pediatric Patients.

Background: The out-of-the-field absorbed dose affects the probability of primary second radiation-induced cancers. This is particularly relevant in the case of pediatric treatments. There are currently no methods employed in the clinical routine for the computation of dose distributions from stray radiation in radiotherapy. To overcome this limitation in the framework of conventional teletherapy with photon beams, two computational tools have been developed-one based on an analytical approach and another depending on a fast Monte Carlo algorithm. The purpose of this work is to evaluate the accuracy of these approaches by comparison with experimental data obtained from anthropomorphic phantom irradiations. Materials and Methods: An anthropomorphic phantom representing a 5-year-old child (ATOM, CIRS) was irradiated considering a brain tumor using a Varian TrueBeam linac. Two treatments for the same planned target volume (PTV) were considered, namely, intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). In all cases, the irradiation was conducted with a 6-MV energy beam using the flattening filter for a prescribed dose of 3.6 Gy to the PTV. The phantom had natLiF : Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs) in its 180 holes. The uncertainty of the experimental data was around 20%, which was mostly attributed to the MCP-N energy dependence. To calculate the out-of-field dose, an analytical algorithm was implemented to be run from a Varian Eclipse TPS. This algorithm considers that all anatomical structures are filled with water, with the exception of the lungs which are made of air. The fast Monte Carlo code dose planning method was also used for computing the out-of-field dose. It was executed from the dose verification system PRIMO using a phase-space file containing 3x109 histories, reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1 ) on all voxels scoring more than 50% of the maximum dose. The standard statistical uncertainty of out-of-field voxels in the Monte Carlo simulation did not exceed 5%. For the Monte Carlo simulation the actual chemical composition of the materials used in ATOM, as provided by the manufacturer, was employed. Results: In the out-of-the-field region, the absorbed dose was on average four orders of magnitude lower than the dose at the PTV. For the two modalities employed, the discrepancy between the central values of the TLDs located in the out-of-the-field region and the corresponding positions in the analytic model were in general less than 40%. The discrepancy in the lung doses was more pronounced for IMRT. The same comparison between the experimental and the Monte Carlo data yielded differences which are, in general, smaller than 20%. It was observed that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT. Conclusions: The proposed computational methods for the routine calculation of the out-of-the-field dose produce results that are similar, in most cases, with the experimental data. It has been experimentally found that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT for a given PTV.

Validation of a Monte Carlo Framework for Out-of-Field Dose Calculations in Proton Therapy.

Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments. Unfortunately, no method exists in clinics for the computation of the out-of-field dose distributions in proton therapy. To help overcome this limitation, a computational tool has been developed based on the Monte Carlo code TOPAS. The purpose of this work is to evaluate the accuracy of this tool in comparison to experimental data obtained from an anthropomorphic phantom irradiation. An anthropomorphic phantom of a 5-year-old child (ATOM, CIRS) was irradiated for a brain tumor treatment in an IBA Proteus Plus facility using a pencil beam dedicated nozzle. The treatment consisted of three pencil beam scanning fields employing a lucite range shifter. Proton energies ranged from 100 to 165 MeV. A median dose of 50.4 Gy(RBE) with 1.8 Gy(RBE) per fraction was prescribed to the initial planning target volume (PTV), which was located in the cerebellum. Thermoluminescent detectors (TLDs), namely, Li-7-enriched LiF : Mg, Ti (MTS-7) type, were used to detect gamma radiation, which is produced by nuclear reactions, and secondary as well as recoil protons created out-of-field by secondary neutrons. Li-6-enriched LiF : Mg,Cu,P (MCP-6) was combined with Li-7-enriched MCP-7 to measure thermal neutrons. TLDs were calibrated in Co-60 and reported on absorbed dose in water per target dose (µGy/Gy) as well as thermal neutron dose equivalent per target dose (µSv/Gy). Additionally, bubble detectors for personal neutron dosimetry (BD-PND) were used for measuring neutrons (>50 keV), which were calibrated in a Cf-252 neutron beam to report on neutron dose equivalent dose data. The Monte Carlo code TOPAS (version 3.6) was run using a phase-space file containing 1010 histories reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1) on all voxels scoring more than 50% of the maximum dose. The primary beam was modeled following a Fermi-Eyges description of the spot envelope fitted to measurements. For the Monte Carlo simulation, the chemical composition of the tissues represented in ATOM was employed. The dose was tallied as dose-to-water, and data were normalized to the target dose (physical dose) to report on absorbed doses per target dose (mSv/Gy) or neutron dose equivalent per target dose (µSv/Gy), while also an estimate of the total organ dose was provided for a target dose of 50.4 Gy(RBE). Out-of-field doses showed absorbed doses that were 5 to 6 orders of magnitude lower than the target dose. The discrepancy between TLD data and the corresponding scored values in the Monte Carlo calculations involving proton and gamma contributions was on average 18%. The comparison between the neutron equivalent doses between the Monte Carlo simulation and the measured neutron doses was on average 8%. Organ dose calculations revealed the highest dose for the thyroid, which was 120 mSv, while other organ doses ranged from 18 mSv in the lungs to 0.6 mSv in the testes. The proposed computational method for routine calculation of the out-of-the-field dose in proton therapy produces results that are compatible with the experimental data and allow to calculate out-of-field organ doses during proton therapy.

Retrospective evaluation of a robust hybrid planning technique established for irradiation of breast cancer patients with included mammary internal lymph nodes.

BACKGROUND: The irradiation of breast cancer patients with included internal mammary lymph nodes challenges radiation planning with regard to robustness and protection of OARs. In this publication, a feasible hybrid radiation technique is presented with a retrospective dosimetric and radiobiological analysis of patient data of our institute from 2016 to 2020 and robustness analysis. METHODS: The proposed hybrid irradiation technique consists of two IMRT tangents and two partial VMAT fields. The retrospective dosimetric and radiobiological evaluation are made for 217 patient treatments (right- and left-sided). The robustness is evaluated regarding an artificial swelling from 0.4 to 1.5 cm for a random example patient and compared to a pure VMAT planning technique with use of a virtual bolus. The out of field stray dose is calculated for a selected patient plan and compared to alternative radiation techniques. RESULTS: The coverage D95% of the PTVEval (with breast swelling of 1.5 cm) changes for the hybrid plan from 96.1 to 92.1% of prescribed dose and for the pure VMAT plan from 94.3 to 87%. The retrospective dosimetric evaluation of patient irradiations reveals a Dmean for total lung 6.5 ± 0.9 Gy (NTCP[Semenenko 2008] 2.8 ± 0.5%), ipsilateral lung 10.9 ± 1.5 Gy, contralateral lung 2.2 ± 0.6 Gy, heart 2.1 ± 1.1 Gy (ERR[Schneider 2017] 0.02 ± 0.17%) and contralateral breast 1.7 ± 0.6 Gy. The scatter dose of the hybrid irradiation technique is higher than for pure VMAT and lower than for pure IMRT irradiation. CONCLUSIONS: The feasibility of the proposed planning technique is shown by treating many patients with this technique at our radiotherapy department. The hybrid radiation technique shows a good sparing of the OARs in the retrospective analysis and is robust with regards to a breast swelling of up to 1.5 cm. The slightly higher stray dose of the hybrid technique compared to a pure VMAT technique originates from higher number of MUs and lower conformity.

Investigation of the effect of air gap size on the spatial resolution in proton- and helium radio- and tomography.

PURPOSE: Proton computed (transmission) tomography (pCT) refers to the process of imaging an object by letting protons pass through it, while measuring their energy after, and their position and (optionally) direction both before and after their traversal through that object. The so far experimental technique has potential to improve treatment planning of proton therapy by enabling the direct acquisition of a proton stopping power map of tissue, thus removing the need to obtain it by converting X-ray CT attenuation data and thereby eliminating uncertainties which arise in the mentioned conversion process. The image reconstruction in pCT requires accurate estimates of the proton trajectories. In experimental pCT detector setups where the direction of the protons is not measured, the air gap between the detector planes and the imaged object worsens the spatial resolution of the image obtained. In this work we determined the mean proton paths and the corresponding spatial uncertainty, taking into account the presence of the air gap. METHODS: We used Monte Carlo simulations of radiation transport to systematically investigate the effect of the air gap size between detector and patient on the spatial resolution of proton (ion) computed tomography for protons with an energy of 200MeV and 250MeV as well as for helium ions (He-4) with an energy of 798MeV. For the simulations we used TOPAS which itself is based on Geant4. RESULTS: For all particles, which are detected at the same entrance and exit coordinate, the average ion path and the corresponding standard deviation was computed. From this information, the dependence of the spatial resolution on the air gap size and the angular confusion of the particle beam was inferred. CONCLUSION: The presence of the airgap does not pose a problem for perfect fan beams. In realistic scenarios, where the initial angular confusion is around 5mrad and for typical air gap sizes up to 10cm, using an energy of 200MeV a spatial resolution of about 1.6mm can be achieved. Using protons with E=250MeV a spatial resolution of about 1.1mm and using helium ions (He-4) with E=798MeV even a spatial resolution below 0.7mm respectively is attainable.