Linear-quadratic Model Research Articles

Equivalent Uniform Dose (EUD) and the Evaluation of Cell Survival in Spatially Fractionated Radiotherapy (SFRT)

SFRT has shown promise as a treatment modality to decrease normal tissue sparing without compromising tumor coverage, i.e., an increase in the therapeutic window compared to more conventional uniform radiation therapy (RT). The aim of this work is to examine and test several alternative bio-dosimetric parameters for the prediction of cell survival for normal-tissue and tumor cell lines irradiated in vitro with uniform and microbeam radiotherapy (MRT). A bespoke tungsten collimator with 50 parallel, 50 µm wide slits and 400 µm slit spacing was mounted into an x-ray cabinet. Human fibroblast (MRC5) and two human tumor cell lines (LN18 and A549) were irradiated with a range of doses (< 10 Gy) for uniform and MRT (50um slits, 400um center spacing) using kV X-rays. Average, mean and valley dose as useful predictive metrics of cell survival are compared to the equivalent uniform dose (EUD) with biological parameters estimated from uniform-dose experiments. We find that EUD, with linear-quadratic (LQ) model parameters, is more predictive for survival after SFRT than maximum, minimum or average dose. The maximum and average doses are correlated very poorly with in vitro cell survival. The difference in cell survival between uniform and MRT irradiation as a function of EUD is cell-type and dose dependent. The report results suggest that MRT is more effective at cell killing of tumor-cell lines than uniform irradiation for both tumor cell lines. However, MRT is less effective at killing normal tissue cells than uniform irradiation. EUD is a superior predictor of in vitro cell survival than other metrics sometimes used in the SFRT literature, including mean dose, maximum dose, and valley dose. The reported studies provide some evidence that SFRT may increase the therapeutic ratio by producing spatial dose distributions that effectively reduce normal-tissue damage with little or no change in biological damage to tumor cells. Additional studies are needed to further extend and generalize our results and to test our conclusions against a larger dose range, low and high linear energy transfer (LET) radiations and additional cell lines.

Radio-Immune Response Model for Radiotherapy Plans with Heterogeneous Dose Distribution

In order to model the immune response in tumor of the patients under radiotherapy for cancer. Characteristics of the numerical model and preliminary application are presented. Immune response was modelled by 4 set of ordinary difference equations (ODE) as a function of biomedical variables including the amount of tumor antigen naturally released by tumor, the activation of cytotoxic T-lymphocytes (CTL) by radiation, immune suppression by tumor volume and the use of immunotherapy drugs. The effect of heterogeneous radiation dose distribution is also considered by hyperbolic tangent function to account for the immunogenic response of tissue under highly heterogeneous dose distribution intentionally modulated in spatially fractionated radiotherapy. Boundary behaviors of the model were investigated for tumors with different biomedical characteristics and under different treatment conditions. The developed model was applied to the tumor volume change in a mouse with 67NR tumors after radiation of 10 Gy to full or half volume of tumor and a clinical patient treated for sarcoma three times over 4 years. Tumor growth is exponential at early phase, slow down over time with increasing immune response and eventually reaches an equilibrium condition (known as terminal tumor volume) for tumors with little to no immune suppression capability (ISC) even in the lack of radiation treatment. Breaking-through the equilibrium for tumor to grow exponentially happens when ISC is larger than the bifurcation threshold, analytically calculated from the proposed model. Tumor with ISC close to the bifurcation threshold can show complex growth behavior depending on the treatment condition and it should be carefully considered for the optimal treatment. Tumor volume change over 30 days period on mouse was modeled well with this model. Full dose irradiation reduced the tumor volume faster in the first 10 days but half volume irradiation reduced the tumor volume faster at later stage due to the improved immune response which cannot be modelled with traditional linear quadratic model. Tumor volume on a patient retreated three times over 4 years was also accurately estimated. The proposed immune response model is capable to estimate tumor volume response under full or partial volume irradiation considering the complex immune characteristics of the tissue.

Design of Active Disturbance Rejection Controller for Trajectory-Following of Autonomous Ground Electric Vehicles

In this paper, the concept of symmetry is utilized in the promising trajectory-following control design of autonomous ground electric vehicles—that is, the construction and the solution of active disturbance rejection controllers are symmetrical. This paper presents an active disturbance rejection controller (ADRC) for improving the trajectory-following performance of autonomous ground electric vehicles (AGEV) with an advanced active front steering system. Since AGEV trajectory dynamics are inherently affected by complex traffic conditions, various driving maneuvers, and other road environment, the main control objective is to deal with the AGEV trajectory control challenges of system uncertainties, system nonlinearities, and external disturbance. First, the vehicle dynamics trajectory-following model and its state space representation system are established. Then, the augmented control-oriented vehicle-trajectory-following system with dynamic error is developed. The resulting active disturbance rejection controller of the vehicle-trajectory-following system is finally designed using the trajectory performance index and active disturbance compensation, and the stability of the active disturbance rejection controller is also analyzed and derived via Lyapunov stability theory. The effectiveness of the proposed controller is validated through double lane change and serpentine maneuvers under the co-simulation platform of MATLAB/Simulink-Carsim®. Simulation results show that the designed controller provides enhanced vehicle-trajectory-following performance compared to the linear quadratic regulator controller (LQR) and model predictive controller (MPC). It will provide a certain guidance for the controller engineering design of the AGEV trajectory-following system.

Optimal coalition splitting with heterogenous strategies

PurposeThe authors characterize the conditions under which a country may eventually split and when it splits within an infinite horizon multi-stage differential game.Design/methodology/approachIn contrast to the existing literature, the authors do not assume that after splitting, players will adopt Markovian strategies. Instead, the authors assume that while the splitting country plays Markovian, the remaining coalition remains committed to the collective control of pollution and plays open-loop.FindingsWithin a full linear-quadratic model, the authors characterize the optimal strategies. The authors later compare with the outcomes of the case where the splitting country and the remaining coalition play both Markovian. The authors highlight several interesting results in terms of the implications for long-term pollution levels and the duration of coalitions under heterogenous strategies as compared to Markovian behavior.Originality/valueIn this paper, the authors have illustrated the richness of the simplications of enlarging the set of strategies in terms of the emergence of coalitions, their duration and the implied welfare levels per player. Varying only three parameters (the technological gap, pollution damage and coalition payoff share distribution across players), the authors have been able to generate, among other findings, quite different rankings of welfare per player depending on whether the remaining coalitions after split play Markovian or stay precommited to the pre-splitting period decisions.

The dose-related plateau effect of surviving fraction in normal tissue during the ultra-high-dose-rate radiotherapy

Objective. Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared with conventional dose-rate radiotherapy. The transient hypoxia may be a vital explanation for sparing the normal tissue. The heterogeneity of oxygen distribution for different doses and dose rates in the different radiotherapy schemes are analyzed. With these results, the influence of doses and dose rates on cell survival are evaluated in this work. Approach. The two-dimensional reaction–diffusion equations are used to describe the heterogeneity of the oxygen distribution in capillaries and tissue. A modified linear quadratic model is employed to characterize the surviving fraction at different doses and dose rates. Main results. The reduction of the damage to the normal tissue can be observed if the doses exceeds a minimum dose threshold under the ultra-high-dose-rate radiation. Also, the surviving fraction exhibits the ‘plateau effect’ under the ultra-high dose rates radiation, which signifies that within a specific range of doses, the surviving fraction either exhibits minimal variation or increases with the dose. For a given dose, the surviving fraction increases with the dose rate until tending to a stable value, which means that the protection in normal tissue reaches saturation. Significance. The emergence of the ‘plateau effect’ allows delivering the higher doses while minimizing damage to normal tissue. It is necessary to develop appropriate program of doses and dose rates for different irradiated tissue to achieve more efficient protection.

PO83: Utilization of a Virtual Clinical Trial to Characterize Sensitivity of the Linear-Quadratic Model

PO83: Utilization of a Virtual Clinical Trial to Characterize Sensitivity of the Linear-Quadratic Model

Maximum principle for partially observed leader–follower stochastic differential game

AbstractThis paper deals with the optimal control problem for partially observed leader–follower stochastic differential game. By virtue of the classical variational method and Girsanov's theorem, the stochastic maximum principles for the follower under one type of partially observed case and for the leader under the complete information structure are derived. As applications, two partially observed cases are considered for the linear–quadratic models. Then by the stochastic filtering technique, the optimal feedback controls for the follower and the leader are represented by the new stochastic Riccati equations.

RADIOTHERAPY BED MODEL MULTIOBJECTIVE PARETO-INTERIOR DUAL-OPTIMIZATION FOR PROSTATE CANCER HYPERFRACTIONATED TREATMENT PLANNING AND ISODOSELINES INVENTION

In a previous publication, constrained evolutionary algorithms for IN-VITRO-BED-LQ model (Linear Quadratic Biological Effective Dose Model) in prostate cancer Hyperfractionation radiotherapy TPO were optimized with Pareto-Multiobjective (PMO) methods. This study improves the research with a further comparative IN-VIVO-BED-LQ model optimization followed by a precision-refinement with Interior Optimization (IO) methods. Complex software is developed based on hyperfractionation constraints, but with in vivo main parameters dataset, and IO programming. Results with software design algorithmic method take in handle subroutines functions and matrix-algebra method for setting constraints and 3D IO surfaces. Results with 3D Interior Optimization by using the Genetic Algorithms (GA) previous numbers show get very good precision with new-invention of isodoselines sharp determination. Solutions dataset is shortly compared with previous in vitro study. Findings prove comparative PMO 2D imaging charts and numerical values of PMO prostate cancer hyperfractionated TPO parameters. Applications for prostate tumors radiotherapy planning, especially with new Surfactal-Isodoselines, brain prostate metastases and stereotactic radiosurgery treatments are briefed.

L1 Adaptive Control for Marine Structures

Nowadays, many maritime structures require precise dynamic positioning (DP) of the constructive elements that compose them. In addition, the use of preconstructed elements that are later moved to the final location has become widespread. These operations have not been automated with the risks involved in carrying out the complex operations required. To minimize these operational risks and to perform a correct DP of floating structures, a new approach based on the L1 adaptive control technique is proposed. As an example of application, a proposed L1 adaptive controller was implemented in the dynamic positioning of a floating caisson. Several simulations of the system with wave disturbances were carried out, and the results were compared with those obtained by applying other classical and advanced control techniques, such as linear quadratic Gaussian control (LQG) and model predictive control (MPC). It was concluded that the proposed L1 adaptive controller performs correct dynamic positioning and reduces the tension generated on the lines concerning the other advanced control techniques with which it was compared. This reduction in line tension leads to an important improvement due to the possibility of reducing the size of the actuators or reducing their number, with the important economic and safety repercussions that these actions entail.

A new linear quadratic regulator model to mitigate frequency disturbances in the power system during cyber-attack

&lt;span lang="EN-US"&gt;This paper proposes a new model integrating a linear quadratic regulator (LQR) controller to mitigate frequency disturbances in the power system during cyber-attack, called as linear quadratic regulator to mitigate frequency disturbances (LQRMFD). As we know, most of the existing models have a common problem with achieving significant performances in mitigating dynamic response parameters, such as frequency deviation and settling time. However, the key aspect of LQRMFD is to mitigate the above issues with remarkable performance improvements. An uncommon and stable power system model has been considered in LQRMFD first to reach such a goal. A numerical problem has been solved to derive a certain characteristic equation, where the Routh-Hurwitz array criterion is applied for determining the stability of such a power system. After that, a state-space equation is developed from the power system to activate the LQR controller. Thus, achieving diversity and eliminating the redundancy of the power system considered can be obtained in LQRMFD. To evaluate the performance of LQRMFD, a series of experiments was conducted using the MATLAB-Simulink tool. Rigorous comparisons were also made among the results of LQRMFD, self-implemented and existing models. Furthermore, a detailed analysis was reported among those models to find the performance improvement of LQRMFD in percentage.&lt;/span&gt;

Automated walk-over-weigh system to track daily body mass and growth in grazing steers

Body weight is a critical component for monitoring animal body mass, body condition, nutritional status, and health. However, traditional methods of collecting body weight are stressful, costly, and logistically impractical with cattle on extensive landscapes. Remote systems capable of collecting individual animal body weight provide a potential solution, but automatic systems may collect spurious weight measurements. The objectives of this study were to (1) describe the utility of using a remote weight capture system, (2) develop methods for identifying and removing spurious measurements, and (3) cross-validate automatically collected weights with static chute collected weights. Beef steers (n = 10) were tagged with electronic Radio Frequency Identification tags and grazed for 286 days in an improved pasture (±11.54 ha) containing Bermuda (Cynodon dactylon) and Tall Fescue (Festuca arundinacea) and inter-seeded with Annual Ryegrass (Secale cereale). A walk-over-weigh (WOW) system was designed from a platform scale connected to a TruTest® scale head and paired with a computer to save data files. In total, 5,466 raw weights associated with individuals were collected (0 kg < weight < 1,000 kg). We assessed the use of whole herd and individual means ± 1 standard deviation calculated either daily or over the entire trial to identify potential outliers. Additionally, 3 data smoothing methods were tested: a linear quadratic model, cubic splines, and polynomial regression. Each method was evaluated for total weight events recorded, event frequency, measured body mass and average daily gain. Further, accuracy and precision were calculated using cross-validation with paired chute weights (n = 8). Whole herd means ± 1 SD identified the fewest spurious data points and showed a stronger relationship with paired chute weights (R2 = 0.90) whereas individual daily means ± 1 SD identified the most and exhibited a weaker relationship (R2 = 0.68). Repeated quadratic regression models provided the best results, identifying 3,759 clean weight points and providing an R2 = 0.96 between paired chute and WOW measurements. A real-time simulation analysis found that both individual and the herd means ± 1 SD performed similarly with an average of 30% of data classified as spurious and removed from the analysis, resulting in agreement (R2 = 0.93 for both individual and herd means) between chute and WOW weight measurements. These results indicate the utility of using a simple WOW system to collect data for measuring individual animal body mass and associated metrics, which has implications on making management and marketing decisions in near real-time.

Optimal control in linear-quadratic stochastic advertising models with memory

This paper deals with a class of optimal control problems which arises in advertising models with Volterra Ornstein-Uhlenbeck process representing the product goodwill. Such choice of the model can be regarded as a stochastic modification of the classical Nerlove-Arrow model that allows to incorporate both presence of uncertainty and empirically observed memory effects such as carryover or distributed forgetting. We present an approach to solve such optimal control problems based on an infinite dimensional lift which allows us to recover Markov properties by formulating an optimization problem equivalent to the original one in a Hilbert space. Such technique, however, requires the Volterra kernel from the forward equation to have a representation of a particular form that may be challenging to obtain in practice. We overcome this issue for Hölder continuous kernels by approximating them with Bernstein polynomials, which turn out to enjoy a simple representation of the required type. Then we solve the optimal control problem for the forward process with approximated kernel instead of the original one and study convergence. The approach is illustrated with simulations.

A machine learning approach to predict cellular mechanical stresses in response to chemical perturbation

Mechanical stresses generated at the cell-cell level and cell-substrate level have been suggested to be important in a host of physiological and pathological processes. However, the influence various chemical compounds have on the mechanical stresses mentioned above is poorly understood, hindering the discovery of novel therapeutics, and representing a barrier in the field. To overcome this barrier, we implemented two approaches: 1) monolayer boundary predictor and 2) discretized window predictor utilizing either stepwise linear regression or quadratic support vector machine machine learning model to predict the dose-dependent response of tractions and intercellular stresses to chemical perturbation. We used experimental traction and intercellular stress data gathered from samples subject to 0.2 or 2 μg/mL drug concentrations along with cell morphological properties extracted from the bright-field images as predictors to train our model. To demonstrate the predictive capability of our machine learning models, we predicted tractions and intercellular stresses in response to 0 and 1 μg/mL drug concentrations which were not utilized in the training sets. Results revealed the discretized window predictor trained just with four samples (292 images) to best predict both intercellular stresses and tractions using the quadratic support vector machine and stepwise linear regression models, respectively, for the unseen sample images.

Radiobiological Meta-Analysis of the Response of Prostate Cancer to Different Fractionations: Evaluation of the Linear-Quadratic Response at Large Doses and the Effect of Risk and ADT.

The purpose of this work was to investigate the response of prostate cancer to different radiotherapy schedules, including hypofractionation, to evaluate potential departures from the linear-quadratic (LQ) response, to obtain the best-fitting parameters for low-(LR), intermediate-(IR), and high-risk (HR) prostate cancer and to investigate the effect of ADT on the radiobiological response. We constructed a dataset of the dose-response containing 87 entries/16,536 patients (35/5181 LR, 32/8146 IR, 20/3209 HR), with doses per fraction ranging from 1.8 to 10 Gy. These data were fit to tumour control probability models based on the LQ model, linear-quadratic-linear (LQL) model, and a modification of the LQ (LQmod) model accounting for increasing radiosensitivity at large doses. Fits were performed with the maximum likelihood expectation methodology, and the Akaike information criterion (AIC) was used to compare the models. The AIC showed that the LQ model was superior to the LQL and LQmod models for all risks, except for IR, where the LQL model outperformed the other models. The analysis showed a low α/β for all risks: 2.0 Gy for LR (95% confidence interval: 1.7-2.3), 3.4 Gy for IR (3.0-4.0), and 2.8 Gy for HR (1.4-4.2). The best fits did not show proliferation for LR and showed moderate proliferation for IR/HR. The addition of ADT was consistent with a suppression of proliferation. In conclusion, the LQ model described the response of prostate cancer better than the alternative models. Only for IR, the LQL model outperformed the LQ model, pointing out a possible saturation of radiation damage with increasing dose. This study confirmed a low α/β for all risks.

Establishment and validation of a calibration curve for dicentric chromosome induced by 6MV X-ray.

Radiation during radiotherapy and nuclear accidents is currently one of the biggest concerns for the international community. Biological dosimetry examines the amount of damage caused by radiation at the cellular level by quantifying a radiation biomarker. In particular, the dicentric chromosome assay is a biodosimetric technique that can quantify radiation damage by correlating radiation dose exposure with the frequency of dicentric chromosomes in the peripheral lymphocytes extracted from exposed individuals. This study aims to present of the reference dose-response calibration curve for biodosimetry laboratory of Mashhad University of Medical Sciences (north-east of Iran). In all, 40 samples of peripheral blood from four healthy volunteers were irradiated at doses of 0-5 Gray in a customised water phantom using a 6MV X-rays at dose rate of 2Gy/min from a linear accelerator. The irradiated samples were cultured and analysed according to the International Atomic Energy Agency Cytogenetic Dosimetry Protocol (2011) with some modifications. Linear-quadratic model curve fitting and further statistical analysis were done using Chromosome Aberration Calculation Software Version 2.0 and Dose Estimate (Version 5.2). The curve equation obtained was ${Y}_{dic}=0.0533{D}^2+0.0231D+0.0001$ and was in the range of other studies. Validation of the calibration curve was done by estimating the dose of blind samples.

Similar additive effects of doxorubicin in combination with photon or proton irradiation in soft tissue sarcoma models.

High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue to result in high local recurrence rates often occurring within the treatment field. This strongly indicates the need of optimized treatment protocols taking the vast heterogeneity of STS into account, thereby fostering personalized treatment approaches. Here, we used preclinical STS models to investigate the radiation response following photon (X) or proton (H) irradiation alone and in combination with different treatment schedules of Dox. As preclinical models, fibrosarcoma (HT-1080), undifferentiated pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma (RD) cell lines were used; the latter two are mutated for TP53. The cellular response regarding clonogenic survival, apoptosis, cell-cycle distribution, proliferation, viability, morphology, and motility was investigated. The different STS cell types revealed a dose-dependent radiation response with reduced survival, proliferation, viability, and motility whereas G2/M phase arrest as well as apoptosis were induced. RD cells showed the most radiosensitive phenotype; the linear quadratic model fit could not be applied. In combined treatment schedules, Dox showed the highest efficiency when applied after or before and after radiation; Dox treatment only before radiation was less efficient. GCT cells were the most chemoresistant cell line in this study most probably due to their TP53 mutation status. Interestingly, similar additive effects could be observed for X or H irradiation in combination with Dox treatment. However, the additive effects were determined more frequently for X than for H irradiation. Thus, further investigations are needed to specify alternative drug therapies that display superior efficacy when combined with H therapy.

Development of a SiC semiconductor-based dosimeter for evaluating clinical dose distribution in carbon ion cancer therapy fields

Dosimeters with excellent energy resolution are required to improve quality control and assurance (QA/QC) for heavy-ion cancer therapy, in which multiple species of ions are expected to be used. The conventional ionization chamber that is widely used for QA/QC generally does not support quality discrimination for different radiation species, and several types of energy-dispersive dosimeters are being studied for this application, including silicon semiconductors on insulator devices. Other wide bandgap semiconductors with good radiation hardness, including SiC and diamond, are being studied for use in cancer therapy ion fields. In this study, a 4H-SiC Schottky barrier diode was used for energy-dispersive dosimetry in the clinical carbon therapy field at Gunma University Medical Center for Heavy Ion Beam Medicine. The relative biological effectiveness was estimated from the linear energy transfer spectra for a pristine carbon beam with an energy of 290 MeV/n and a spread-out Bragg peak beam using the linear-quadratic model. The results showed that the SiC-based dosimeter could be used in the detailed characterization of the clinical dose distribution of carbon ion cancer therapy fields.

Relative Biological Effectiveness (RBE) of [64Cu]Cu and [177Lu]Lu-NOTA-panitumumab F (ab')2 radioimmunotherapeutic agents vs. γ-radiation for decreasing the clonogenic survival in vitro of human pancreatic ductal adenocarcinoma (PDAC) cells

IntroductionOur objective was to compare [64Cu]Cu-NOTA-panitumumab F(ab')2 and [177Lu]Lu-NOTA-panitumumab F(ab')2 radioimmunotherapy (RIT) agents for decreasing the clonogenic survival fraction (SF) in vitro of EGFR-positive human pancreatic ductal adenocarcinoma (PDAC) cell lines and estimate the relative biological effectiveness (RBE) vs. γ-radiation (XRT). MethodsEGFR-positive PDAC cell lines (AsPC-1, PANC-1, MIAPaCa-2, Capan-1) and EGFR-knockout PANC-1 EGFR KO cells were treated in vitro for 18 h with (0–19.65 MBq; 72 nmols/L) of [64Cu]Cu-NOTA-panitumumab F(ab′)2 or [177Lu]Lu-NOTA-panitumumab F(ab′)2 or XRT (0–8 Gy) followed by clonogenic assay. The SF was determined after culturing single treated cells for 14 d. Cell fractionation studies were performed for cells incubated with 1 MBq (72 nmols/L) of [64Cu]Cu-NOTA-panitumumab F(ab′)2 or [177Lu]Lu-NOTA-panitumumab F(ab′)2 for 1, 4, or 24 h to estimate the time-integrated activity (Ã) on the cell surface, cytoplasm, nucleus and medium. Radiation absorbed doses in the nucleus were calculated by multiplying à by S-factors calculated by Monte Carlo N Particle (MCNP) modeling using monolayer cell culture geometry. The SF of PDAC cells was plotted vs. dose and fitted to a linear quadratic model to estimate the dose required to decrease the SF to 0.1 (D10). The D10 for RIT agents were compared to XRT to estimate the RBE. DNA double-strand breaks (DSBs) caused by [64Cu]Cu-NOTA-panitumumab F(ab′)2 or [177Lu]Lu-NOTA-panitumumab F(ab′)2 continuous exposure for 5 h or 20 h were probed by immunofluorescence for γ-H2AX. Relative EGFR expression of PDAC cells was assessed by flow cytometry (scored + to +++) and cell doubling times for untreated cells were determined. ResultsThe D10 for [64Cu]Cu-NOTA-panitumumab F(ab′)2 ranged from 9.1 Gy (PANC-1) to 39.9 Gy (Capan-1). The D10 for [177Lu]Lu-NOTA-panitumumab F(ab′)2 ranged from 11.7 Gy (AsPC-1) to 170.8 Gy (Capan-1). The D10 for XRT ranged from 2.5 Gy (Capan-1) to 6.7 Gy (PANC-1 EGFR KO). D10 values were not correlated with EGFR expression over a relatively narrow range (++ to +++) or with cell doubling times. Based on D10 values, PANC-1 EGFR KO cells were 1.6-fold less sensitive than PANC-1 cells to [64Cu]Cu-NOTA-panitumumab F(ab′)2 and 1.9-fold less sensitive to [177Lu]Lu-NOTA-panitumumab F(ab′)2. The RBE for [64Cu]Cu-NOTA-panitumumab F(ab′)2 ranged from 0.06 for Capan-1 cells to 0.45 for PANC-1 cells. The RBE for [177Lu]Lu-NOTA-panitumumab F(ab′)2 ranged from 0.015 for Capan-1 cells to 0.28 for AsPC-1 cells. DNA DSBs were detected in PDAC cells exposed to [64Cu]Cu-NOTA-panitumumab F(ab′)2 or [177Lu]Lu-NOTA-panitumumab F(ab′)2 but were not correlated with the SF of the cells. ConclusionsWe conclude that at the same dose delivered to the cell nucleus [64Cu]Cu-NOTA-panitumumab F(ab′)2 and [177Lu]Lu-NOTA-panitumumab F(ab′)2 were less radiobiologically effective than XRT for decreasing the SF of human PDAC cells, but [64Cu]Cu-NOTA-panitumumab F(ab′)2 was more cytotoxic than [177Lu]Lu-NOTA-panitumumab F(ab′)2 except for AsPC-1 cells which were more sensitive to [177Lu]Lu-NOTA-panitumumab F(ab′)2. Advances in knowledge and implications for patient careThis study demonstrates that higher radiation doses may be required for RIT than XRT to achieve radiobiologically equivalent effects when used to treat PDAC.

Boost modalities in cervical cancer: dosimetric comparison between intracavitary BT vs. intracavitary + interstitial BT vs. SBRT.

Purpose / objectiveThis study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses.Materials and methods24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/β of 10 (EQD210) and 3 (EQD23), respectivelyResultsA total of 72 plans were investigated. In the first normalization, the mean EQD23−D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%.ConclusionThe key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC.

Research on road tracking and anti-roll game control scheme of commercial vehicle based on Nash equilibrium

In view of the problem that the active suspension conflicts with the road tracking system while resisting roll when the commercial vehicle encounters emergency road conditions in the process of unmanned driving, this article is based on the Nash non-cooperative open-loop feedback game theory, taking the road tracking system, and the active anti-roll system as the participants of the game. An interactive control scheme which can not only accurately steer but also take into account the vertical roll stability is proposed. Firstly, the coupled model of Horizontal pendulum-anti-roll for commercial vehicles is established and extended to the vehicle-road three-degree of freedom closed model. Then, based on the derivation of the linear quadratic optimal control model (LQ), the non-cooperative open-loop Nash game theory is used to obtain the interactive optimal control afferent the road tracking system and the active anti-roll system. Finally, the experimental scheme is verified by hardware in the loop experiment. The results show that the interactive control scheme of road tracking and anti-roll based on Nash non-cooperative game for commercial vehicles allows the vehicle to take the vertical stability into account while turning actively, thus ensuring the safety and stability of the vehicle during driving.