Risk Constraints Research Articles

Feasibility and Toxicity of Full-Body Volumetric Modulated Arc Therapy Technique for High-Dose Total Body Irradiation.

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Decentralized Bilateral Risk-based Self-healing Strategy for Power Distribution Network with Potentials from Central Energy Stations

Owing to potential regulation capacities from flexible resources in energy coupling, storage, and consumption links, central energy stations (CESs) can provide additional support to power distribution network (PDN) in case of power disruption. However, existing research has not explicitly revealed the emergency response of PDN with leveraging multiple CESs. This paper proposes a decentralized self-healing strategy of PDN to minimize the entire load loss, in which multi-area CESs' potentials including thermal storage and building thermal inertia, as well as the flexible topology of PDN, are reasonably exploited for service recovery. For sake of privacy preservation, the co-optimization of PDN and CESs is realized in a decentralized manner using adaptive alternating direction method of multipliers (ADMM). Furtherly, bilateral risk management with conditional value-at-risk (CVaR) for PDN and risk constraints for CESs is integrated to deal with uncertainties from outage duration. Case studies are conducted on a modified IEEE 33-bus PDN with multiple CESs. Numerical results illustrate that the proposed strategy can fully utilize the potentials of multi-area CESs for coordinated load restoration. The effectiveness of the performance and behaviors' adaptation against random risks is also validated.

Financial Hedging of Operational Risk Constraints: A General Framework

Financial Hedging of Operational Risk Constraints: A General Framework

Exploring risk and loss potential of Bali cattle farming: A review

The availability of beef is still polemic, and the direction of the national beef self-sufficiency policy has not been able to cover the gap between the demand for community beef consumption and local cattle resources. Cattle farming was faced with business risk constraints that occurred in its production process. This research aimed to explore the potential risks of Bali cattle farming as well as the impact of the losses that it will be caused by the risks. Exploration of potential risks and losses was carried out using descriptive methods, in which scientific articles on internet database searches were carried out, starting from searching the database, screening, selecting, and reviewing, to reporting descriptive research results. Investigating the risks and potential losses in the Bali cattle business, two main things were found: risks in production and marketing activities. Production activities faced many problems with pregnancy failure, availability of food, disease, work accidents, death, and cattle theft. Meanwhile, marketing activities often arise from uncertainty over price constraints, modes of transportation and distribution, consumer income and purchasing power.

Multi-objective risk-constrained optimal performance of hydrogen-based multi energy systems for future sustainable societies

Hydrogen is one of the leading energy sources under special consideration due to its sustainability and technological development. The main concept of integrated energy system is applied in this article. The goal is to maintain a coordination between hydrogen cycle where hydrogen is produced and converted with renewable energy (RE). Three energy storage for charging/discharging hydrogen, hot and cold water are employed enhance the energy efficiency. The demand-side energy system could rely on this combination that enables the increase in wind and solar energy utilization and uses it to generate hydrogen in future smart cities. This paper uses a scenario-based stochastic optimization to model the associated uncertainties. The epsilon-constraint and max-min fuzzy methods are used as multi-objective approach to satisfy environmental and economic goals, simultaneously. To analyze the associated risk imposed by multiple uncertain parameters, the downside risk constraint (DRC) is implemented to render several risk-averse strategies to the decision-maker based on various constraint level. The results show that the final solution in risk neutral strategy satisfies both emission and operation costs. The ultimate associated risk in conservative strategy will tend to zero at the 4.2% operation cost increment and 3% emission reduction.

Risk Assessment of Industrial Energy Hubs and Peer-to-Peer Heat and Power Transaction in the Presence of Electric Vehicles

The peer-to-peer (P2P) strategy as a new trading scheme has recently gained attention in local electricity markets. This is a practical framework to enhance the flexibility and reliability of energy hubs, specifically for industrial prosumers dealing with high energy costs. In this paper, a Norwegian industrial site with multi-energy hubs (MEHs) is considered, in which they are equipped with various energy sources, namely wind turbines (WT), photovoltaic (PV) systems, combined heat and power (CHP) units (convex and non-convex types), plug-in electric vehicles (EVs), and load-shifting flexibility. The objective is to evaluate the importance of P2P energy transaction with on-site flexibility resources for the industrial site. Regarding the substantial peak power charge in the case of grid power usage, this study analyzes the effects of P2P energy transaction under uncertain parameters. The uncertainties of electricity price, heat and power demands, and renewable generations (WT and PV) are challenges for industrial MEHs. Thus, a stochastically based optimization approach called downside risk constraint (DRC) is applied for risk assessment under the risk-averse and risk-neutral modes. According to the results, applying the DRC approach increased by 35% the operation cost (risk-averse mode) to achieve a zero-based risk level. However, the conservative behavior of the decision maker secures the system from financial losses despite a growth in the operation cost.

Risk preference interactions between individual farmers and small farmer groups: Experimental evidence from rural Ethiopia

AbstractThe understanding of risk preference interactions among poor farmers in developing countries has important policy implications, as many programs that aim to alleviate poverty and address risk constraints are provided on a collective basis. We conduct a randomized field experiment in the drought‐prone parts of Northern Ethiopia and elicit from poor, vulnerable farmers their hypothetical willingness to pay using individual and group lottery games. Analyzing the certainty equivalent ratios (CERs), we find that farmer groups are more risk averse than individual farmers. When the risk of the lottery is high, the group CER is primarily determined by the most‐risk‐averse farmer of the group, and to a lesser extent, by the least. The median farmer contributes to the group CER only when the lottery risk is moderate. After participating in the group elicitation, individual farmers also become as risk averse as the group on average. Specifically, the median and the least‐risk‐averse farmers become significantly more risk averse while the most‐risk‐averse farmer is unaffected. Our results show that policymakers should carefully consider how social interactions in rural communities affect individual and group risk preference and whether social interactions also affect the participation and effectiveness of development programs.

Four-Dimensional Computed Tomography Ventilation Image-Guided Lung Functional Avoidance Radiation Therapy: A Single-Arm Prospective Pilot Clinical Trial

The primary objective of this prospective pilot trial was to assess the safety and feasibility of lung functional avoidance radiation therapy (RT) with 4-dimensional (4D) computed tomography (CT) ventilation imaging. Patients with primary lung cancer or metastatic disease to the lungs to receive conventionally fractionated RT (CFRT) or stereotactic body RT (SBRT) were eligible. Standard-of-care 4D-CT scans were used to generate ventilation images through image processing/analysis. Each patient required a standard intensity modulated RT plan and ventilation image guided functional avoidance plan. The primary endpoint was the safety of functional avoidance RT, defined as the rate of grade ≥3 adverse events (AEs) that occurred ≤12 months after treatment. Protocol treatment was considered safe if the rates of grade ≥3 pneumonitis and esophagitis were <13% and <21%, respectively for CFRT, and if the rate of any grade ≥3 AEs was <28% for SBRT. Feasibility of functional avoidance RT was assessed by comparison of dose metrics between the 2 plans using the Wilcoxon signed-rank test. Between May 2015 and November 2019, 34 patients with non-small cell lung cancer were enrolled, and 33 patients were evaluable (n=24 for CFRT; n=9 for SBRT). Median follow-up was 14.7 months. For CFRT, the rates of grade ≥3 pneumonitis and esophagitis were 4.2% (95% confidence interval, 0.1%-21.1%) and 12.5% (2.7%-32.4%). For SBRT, no patients developed grade ≥3 AEs. Compared with the standard plans, the functional avoidance plans significantly (P < .01) reduced the lung dose-function metrics without compromising target coverage or adherence to standard organs at risk constraints. This study, representing one of the first prospective investigations on lung functional avoidance RT, demonstrated that the 4D-CT ventilation image guided functional avoidance RT that significantly reduced dose to ventilated lung regions could be safely administered, adding to the growing body of evidence for its clinical utility.

Risk-embedded scheduling of a CCHP integrated with electric vehicle parking lot in a residential energy hub considering flexible thermal and electrical loads

Climate change has detrimental impacts on the environment and sustainability, leading to employing alternative energy systems such as combined cooling, heat and power (CCHP). The concept of integrated energy systems (IES) allows the coordination of several components, such as electric vehicles (EV), to serve various demands simultaneously. This paper focuses on coordinating the CCHP and electric vehicle parking lot (EVPL) integrated with photovoltaic (PV) technology as renewable energy (RE). The residential energy hub (REH) is modeled to integrate these components to meet the demands and minimize REH’s operating costs and carbon emissions. EVPL functions as dynamic electrical storage besides serving EVs. Stochastic programming is used to model RE, EV, loads, and electricity price uncertainties. Demand response (DR) is applied for shiftable electrical loads. The thermodynamic model of heating and cooling loads is developed with flexibility as integrated demand response (IDR) based on the building’s desired temperature. The emission cost model with penalty factors enforces REH to use less-pollutant energy sources. Subsequently, a risk-aversion strategy, namely downside risk constraint (DRC), is implemented to diminish the associated risk as the consequence of uncertainties for the decision-maker. Different constraint level is applied to provide various conservative decision-making strategies for the operator. Summer and winter scenarios with and without DR and flexible thermal loads were used to evaluate the model’s accuracy. The scheduling problem is solved in IEEE 33-bus test system. The results reveal that the DR could reduce the operation cost by 5% in summer and 8% in winter. Moreover, zero risk for summer and winter is gained at the cost of 10.4% and 3.1% increment in operating costs.

Does Limited Liability Reduce Leveraged Risk?: The Case of Loan Portfolio Management

Return–risk models are the two pillars of modern portfolio theory, which are widely used to make decisions in choosing the loan portfolio of a bank. Banks and other financial institutions are subjected to limited-liability protection. However, in most of the model formulation, limited liability is not taken into consideration. Accordingly, to address this, we have, in this article, analyzed the effect of including it in the model formulation. We formulate four models, two of which are maximizing the expected return with risk constraint, including and excluding limited liability, and other two of which are minimizing of risk with threshold level of return with and without limited liability. Our theoretical results show that the solutions of the models with limited liability produce better results than the others, in both minimizing risk and maximizing expected return. More specifically, the portfolios that included limited liability are less risky as compared to the portfolios that did not include limited liability. Finally, an illustrative example is presented to support the theoretical results obtained.

Risk-based pavement maintenance planning considering budget and pavement deterioration uncertainty

Although some parameters are uncertain in pavement Maintenance and Rehabilitation (M&R) planning, most of the literature has considered these parameters deterministic. Likewise, minimizing risk has been an immense concern as a significant amount of money should be spent on the M&R of pavement networks. To this end, this study aims to propose a new approach to consider risk and uncertainty in a pavement M&R optimization problem. A Multistage Stochastic Integer Programming including risk constraints is applied for the problem modeling. Conditional Value at Risk index is applied to minimize the mentioned variables and avoid unacceptable risks. Subsequently, a case study is used to analyze the proposed technique’s effectiveness. The results indicate that the total pavement M&R agency cost equals 6.33 billion Tomans considering a confidence level of 95%. Furthermore, the proposed approach can detect the optimal value of the annual budget for pavement network M&R, which is 1.96 billion Tomans for the case study. Applying preventive maintenance can compensate for the negative effects of risk on projects. Therefore, the proposed approach can help decision-makers, policymakers, and transport agencies to analyze and control risk in the pavement M&R optimization problems and determine the optimal M&R budget.

Pesticide risk constraints to achieving Sustainable Development Goals in China based on national modeling

Pesticides applied worldwide to meet food demand is recognized as a key threat to the Sustainable Development Goals (SDGs) set by the United Nations. Studies on pesticide risks employ different ingredients, methods or specific environments, which makes it difficult to quantify the scale of the problem. Furthermore, the complex influences and hotspots of long-term pesticide usage remain unclear. Herein, we present a national-scale study of four typical pesticides in China, the world’s largest pesticide user. The spatiotemporal changes in legacy and risk of pesticides over 30 years were analyzed using a modified fugacity model approach coupled with comprehensive ingredient database. Pesticide risk in mainland China might last until 2075 due to the previous legacy, although the usage has declined since 2014. The use of target pesticides was estimated as 2.38 × 105 tonnes in 2017, and about 6.59 × 103 tonnes discharged into the ocean from major basins. Risk areas expanded from 47% in 1991 to 79% in 2017, with 30% at high risk. Of the risk areas, 31% were highly populated while 3% had high biodiversity. 7% of mainland China suffered from both limited water resource and high pesticide risk. It is shown that the improper substitution with lower toxicity pesticides would make the proportion of high-risk regions unexpectedly increased from 18% to 44% due to the longer half-lives of the alternatives. Pesticides pose risks to environmental and human health, and the tailored assessment tool will be vital in contributing towards future pesticide management and meeting sustainability targets in China.

Does Compromising Target Coverage Impact Overall Survival when Treating Oligometastatic Disease with Stereotactic Ablative Radiotherapy (SABR)?

<h3>Purpose/Objective(s)</h3> SABR may improve survival in patients with oligometastases, but for some lesions, safe delivery of SABR may require a reduction in delivered dose or target coverage. This study assessed the association between target coverage compromise and oncologic and survival outcomes through a secondary analysis of the SABR-COMET Phase II Randomized Trial. <h3>Materials/Methods</h3> Patients with a controlled primary malignancy and 1 to 5 oligometastases were randomized (1:2) between standard of care (SOC) treatment and SOC plus SABR. In patients receiving SABR, the target dose coverage was reduced to meet organ at risk (OAR) constraints, if necessary. The D99 value (minimum dose received by the hottest 99% of the planning target volume [PTV]) was used as a measure of PTV coverage for each treatment plan, and the relationship between the coverage compromise index (CCI, defined as D99/prescription dose) and patient outcomes were assessed. <h3>Results</h3> Sixty-two patients in the SABR arm had dosimetric information available and a total of 109 lesions were evaluated. The mean CCI per lesion was 0.96 (95% CI, 0.56-1.61). Of the 109 lesions evaluated, 29.4% (n = 32) required coverage compromise (CCI <0.9). Adrenal metastases required coverage compromise in 100% of analyzed lesions (n = 7). CCI was not significantly associated with lesional control, adverse events, overall survival (OS), or progression-free survival (PFS). <h3>Conclusion</h3> Target compromise was required in a substantial minority of cases, but PTV coverage was not associated with OS, progression-free survival, or lesional control. This suggests that OAR constraints used for SABR treatments in the oligometastatic setting should continue to be prioritized during planning.

Optimizing Carbon Capture and Sequestration Chains from Industrial Sources Under Seismic Risk Constraints

Optimizing Carbon Capture and Sequestration Chains from Industrial Sources Under Seismic Risk Constraints

Risk bounded nonlinear robot motion planning with integrated perception & control

Robust autonomy stacks require tight integration of perception, motion planning, and control layers, but these layers often inadequately incorporate inherent perception and prediction uncertainties, either ignoring them altogether or making questionable assumptions of Gaussianity. Robots with nonlinear dynamics and complex sensing modalities operating in an uncertain environment demand more careful consideration of how uncertainties propagate across stack layers. We propose a framework to integrate perception, motion planning, and control by explicitly incorporating perception and prediction uncertainties into planning so that risks of constraint violation can be mitigated. Specifically, we use a nonlinear model predictive control based steering law coupled with a decorrelation scheme based Unscented Kalman Filter for state and environment estimation to propagate the robot state and environment uncertainties. Subsequently, we use distributionally robust risk constraints to limit the risk in the presence of these uncertainties. Finally, we present a layered autonomy stack consisting of a nonlinear steering-based distributionally robust motion planning module and a reference trajectory tracking module. Our numerical experiments with nonlinear robot models and an urban driving simulator show the effectiveness of our proposed approaches.

Stereotactic Body Radiation Therapy Plus Anti-PD1/IL8 Therapy for Advanced Solid Tumors

<h3>Purpose/Objective(s)</h3> Anti-PD-(L)1 immunotherapy improves outcomes for patients across various cancers; however, many patients do not benefit. Previous studies combining multi-site stereotactic body radiation therapy (SBRT) with anti-PD1 have demonstrated feasibility and showed increased interferon signaling after SBRT. Elevated levels of serum IL8 (sIL8) associate with lack of response to anti-PD1 and we have observed that elevated IL8 is strongly associated with lack of response to immunotherapy and SBRT combinations. BMS-986253 is a fully human neutralizing antibody that binds to sIL8. The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors, chiefly melanoma (MEL) and renal cell carcinoma (RCC). <h3>Materials/Methods</h3> This is a phase 1 open label single arm study which will include safety and efficacy cohorts. Patients will receive SBRT to 1-4 metastatic sites in 3 or 5 fractions with a total dose of 30-50 Gy depending on anatomic subsite and dose/fractionation. SBRT treatment planning parameters and organ at risk constraints are based on NRG BR-001 study results. SBRT will be followed by nivolumab (480mg q4 weeks) and IV BMS-986253 (2400mg q2 weeks) within seven days of completing SBRT. In the initial safety portion of the clinical trial, we will include 30 patients with advanced/metastatic solid tumors. The primary endpoint of dose limiting toxicity will be assessed by continual Bayesian monitoring. The toxicities will be attributed to combination of SBRT/immunotherapy as opposed to individual components. After completion of the safety phase, an efficacy phase will be launched. To detect a lower bound of 20% for response rate with a one-sided confidence interval, 20 patients are required. Translational correlatives include paired biopsies pre/post SBRT to interrogate gene expression changes using scRNAseq and bulk RNAseq, TCRseq, PBMC profiling for IL8 gene expression, serum IL8 levels before/during/after combination treatment, and T cell radiomics analyses of irradiated metastases to correlate with clinical outcomes. <h3>Results</h3> The phase I trial is active and recruiting patients. <h3>Conclusion</h3> Blocking IL8 in conjunction with anti-PD1 therapy and SBRT is a rational, biomarker-driven approach that may overcome resistance and broaden immunotherapy benefit in patients for whom anti-PD1 therapy is inadequate. This trial is registered at ClinicalTrials.gov, NCT04572451.

Comparison of Short Term Clinical and Dosimetric Outcomes of Fast Forward vs. Hypofractionated Radiotherapy for Early Breast Cancer – A Single Center Experience

<h3>Purpose/Objective(s)</h3> To share the experience of planning, dosimetric evaluation and delivery of ultra-hypofractionated (fast forward-FF) versus hypofractionated (HF) radiotherapy in breast cancers treated at our center. <h3>Materials/Methods</h3> 60 patients (average age 44 years- range 32-65 years) of early [T1, T2N0] breast cancer (BC) treated between October 2020 and October 2021 were included. Plans of 15 patients of left BC by FF, left BC by HF, right BC by FF and right BC by HF were evaluated in terms of coverage and organs at risk (OAR) constraints. Patients were planned by field within field [FIF] planning for phase I (42.5 Gy/16# for HF and 26 Gy/5# for FF). Boost plans were generated by FIF/electron/conformal planning to a dose of 10-16 Gy @ 2 Gy/fraction. Deep inspiratory breath hold (DIBH) was used for left sided BC patients who were able to hold breath. PTV coverage goal was V95 more than or equal to 95%, V105 <7%, V107 < 2%. Constraints for FF were – lung V8<15%, heart V1.5<30%, V7<5%. Constraints for HF plans were – lung V20<20%, heart avg <3 Gy. 15 right sided BC patients were treated with FF and 15 by HF plans. For left sided BC, plans were generated for dosimetric comparison between FF and HF plans, but all patients were treated by HF plans. <h3>Results</h3> For left sided BC cases, high heart dose was seen in those with more heart volume, precordial location of boost volume and patients unable to do DIBH. All patients treated by FF had grade I skin reaction and 1/15 had wet desquamation in inframammary fold. Among patients treated by HF, majority patients had dry desquamation, 3/45 had wet desquamation in folds. Edema developed in FF by 2-3^rd fraction and by 7-9^th fraction in HF. Edema was milder in HF. The edema and skin changes resolved in 2-3 weeks. At 3 and 6 months, mild skin discoloration and minimal induration at post op site was seen which was similar in those treated by FF and HF. <h3>Conclusion</h3> Adequate coverage and OAR constraints can be met for FF as for HF plans. Radiation dermatitis is milder in FF arm and the edema is milder in the HF arm. Radiation of early breast cancer by FF is executable at independent centers with diligent planning with tight constraints and precise delivery.

A Survey of Pediatric Clinical Trial Radiotherapy Dose Constraints

<h3>Purpose/Objective(s)</h3> Radiation therapy normal tissue dose constraints are critical when treating children with cancer due to the vulnerability of developing organs to toxicity and the many years over which these effects can evolve. Guidelines in international clinical trials have been instrumental in shaping how treatment plans are designed; however, consistency among organs at risk (OARs) constraints has not been previously evaluated. In this study we identify the variations in OAR-specific dose constraints within pediatric trials both in the United States (US) and in Europe. <h3>Materials/Methods</h3> All US pediatric trials from the COG website were included up until 1/1/2020 along with a sampling of European trials accessible in the Netherlands. Dose constraints were identified and built into an interactive web application with filters to display data by OAR, protocol, dose, volume, and fractionation scheme. Dose constraints were compared between pediatric US and European trials by graphical intercomparison and by comparing high dose constraints (maximum dose [Dmax] or dose to a volume ≤ 20%) and by dose metrics that were commonly used across protocols. <h3>Results</h3> Sixty-five trials were included with the US trials (53) represented by the COG/CCG/POG and the European trials (12) represented by the SIOP, EURAMOS, GPOH, DCOG, and EpSSG. Thirty-three separate OARs were found with high variability within the trials for each OAR, ranging from different maximum tolerable doses to variations of volumetric dose constraints. Seven organs had 10 to 18 different constraints and included serial organs such as the spinal cord, optic chiasm, optic nerves, and brainstem as well as parallel organs including the lungs, liver, and heart. An example of dose variability can be seen with the spinal cord Dmax constraint ranging from 50 Gy to V59 < 10%, the optic nerves constraint ranging from a Dmax of 45 Gy to 60 Gy, the heart V30 constraint ranging from 40-100%, and the kidney D50% constraint ranging from 8-24 Gy. When comparing high dose tolerances between US and European trials, US constraints were higher for four OARs—bladder (V70 < 20% vs Dmax < 60), lungs (V20 < 20% vs Dmax < 18), mandible (V77 < 1cc vs Dmax < 60), and spinal cord (V57 < 10% vs Dmax < 54); lower for four OARs—brainstem (V63 < 10% vs V64 < 10%), heart (Dmax < 30 vs Dmax < 30.6), kidneys (Dmax < 15 vs Dmax < 19.8), and liver (Dmax < 15 vs Dmax < 23.4); and identical in four OARs—brain, optic chiasm, optic nerves, and bowel. <h3>Conclusion</h3> Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs. Continued focus on standardization of OAR dose constraints and risk profiles are essential to improving clinical trial consistency and improving understanding of dose-response in the pediatric population.

Online Adaptive MR-Guided Radiotherapy (MRgRT) in UltraCentral (UC) Lung Lesions: Cumulative Delivered Dose as Assessed with Rigid Fusion (RF) Analysis Shows Significant Improvement in Clinically Relevant Parameters

<h3>Purpose/Objective(s)</h3> MRgRT is used to treat UC lung lesions. Adaption is triggered if the original plan does not meet criteria of target coverage or organs at risk (OAR) constraints on recontoured anatomy of the day. Current MRgRT software does not provide composite dose delivered over the complete course, partly because daily anatomy changes make accurate spatial dose accumulation difficult. Previous approaches used DVH point averages to approximate doses from full course. We aimed to more accurately quantify true delivered dose via rigid fusion (RF) of fractional doses and hypothesize that treatment with adaptive MRgRT has superior cumulative doses than non-adaptive treatment. <h3>Materials/Methods</h3> We conducted a single institution analysis of patients receiving 60 Gy in 8 fractions with adaptive MRgRT to UC lesions (per HILUS) between 2/2020 – 1/2022. We created composite doses from ‘delivered' treatment plans and ‘predicted' treatment plans. For the ‘delivered' plans, dose for clinically treated plan (adapted or non-adapted based on daily plan quality) was exported for each fraction with MR contoured anatomy of the day. Using a third-party image registration software, we performed RF for each adaptive fraction focused on aligning two regions: (1) tumor and (2) proximal airway, to separately determine local cumulative dose to those sites. For fractions that were not adapted, the initial plan was fused to daily MR. For the ‘predicted' treatment plan, initial plan dose was RF to primary tumor location for each MR contoured anatomy of the day and then summed for composite dose. <h3>Results</h3> Eleven consecutive patients with UC lesions were treated with online adaptive MRgRT. Eight (73%) patients had primary lung tumors. Median distance from proximal airway: 0 mm (0-6). Median number of adapted fractions was 7 (6-8). Differences between cumulative delivered and predicted plan dose on daily anatomy GTV D100%, PTV D95%, and Proximal Airway D0.03cc (PA0.03cc) were all statistically significant (p<0.01). The delivered dose had improvement in GTV D100% versus the initial plan (p<0.01), PTV D95% and PA0.03cc were not significant. Median follow up was 7.4 months. No grade 3+ acute or late toxicity was reported. <h3>Conclusion</h3> Online adaptive MRgRT resulted in composite delivered doses from treatment on par with initial plan dosimetric quality and significantly outperforms doses delivered with non-adapted treatment. The adapted plan coverage superiority over the non-adapted plan is explained by the ‘feathering' of dose that creates a 60 Gy isodose line while respecting OAR, which is underappreciated with just simple summing of changes via adaptive plan DVH values. This is the first ever plan evaluation study of its kind for MRgRT and aids in establishing dosimetric superiority of daily online adaptation.

Real-Time Online Adaptive Magnetic Resonance Image Guided Stereotactic Body Radiation Therapy with or without Elective Nodal Irradiation for Inoperable Pancreas Cancer Patients

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) to patients with inoperable pancreas cancer has shown promising outcomes. Dose escalated SBRT is usually challenging given the associated risks to nearby organs. This study aims to report treatment outcomes and adverse events of Real-time Online Adaptive Magnetic Resonance-Guided SBRT (MRgSBRT). <h3>Materials/Methods</h3> This IRB approved retrospective study included inoperable pancreas cancer patients who were treated consecutively with MRgSBRT from 2020 to 2021. Most patients (89%) received 50Gy prescribed to gross tumor volume (GTV), two patients (11%) received 40 Gy to GTV. Ten patients (56%) received elective nodal irradiation (ENI) to celiac and super mesenteric lymph nodes, & 8 patients (44%) did not receive ENI. Planning Target Volume (PTV) received a median dose of 35 Gy (range 25-50 Gy) and 40 Gy (range 40-50 Gy), in patients with, and without ENI respectively. PTV was defined as 3 mm expansion of either GTV, or a clinical target volume encompassing GTV and ENI areas when treated. Real-time Online Adaptive MRgSBRT was utilized in 59% of the treated fractions (53 of 90 fractions), while gated MRgSBRT was utilized in all fractions (100%). Real-time Online Adaptive MRgSBRT was utilized whenever the predicted radiation plan did not meet the organs at risk (OARs) constraints based on daily anatomic variations. Reoptimized plans were generated after re-contouring OARs within a 3 cm ring, & verifying GTV & PTV, & always met OARs constraints. All patients were treated twice weekly. <h3>Results</h3> The study included 18 eligible patients with median age of 72.5 years (range 56-85). Patients had local-regional advanced (44%), borderline (33%) & metastatic (22%) diseases. At a median follow up of 10 months from MRgSBRT (range 2-17 months), in patients with & without ENI local-regional progression was 20% versus 67% (p 0.12 Fisher's Exact Test), distant progression was 30% versus 67% (p 0.3), & overall survival was 80% and 37.5% (p 0.14) respectively. Of those who developed disease progression, first site of progression was distant metastases (75%), versus regional nodal progression (75%) in patients with & without ENI respectively. In the non-ENI group, 50%, 12.5%, 12.5%, & 25% were dead of disease (DOD), dead without disease progression (DWODP), alive with disease (AWD), & alive without disease progression (AWODP) respectively. In the ENI group, 10%, 10%, 60%, & 20% were DOD, DWODP, AWD, & AWODP respectively. Median follow up from diagnosis was 19 months (range 6-103 months). Acute & chronic toxicities were uncommon, & included grade 1-2 nausea (22%), fatigue (17%), & abdominal discomfort (11%). No grades 3-5 toxicities were reported. <h3>Conclusion</h3> Real-time Online Adaptive MRgSBRT is a feasible, & safe approach with minimal treatment related toxicities & promising local-regional control in a cohort of advanced pancreas cancer patients. ENI is safe & shows a trend for improved local-regional control. Larger controlled prospective trials are recommended.