Method For Evaluation Of Response Research Articles

Measurement of metabolite levels and treatment-induced changes in hepatic metastases of gastro-esophageal cancer using 7-T phosphorus magnetic resonance spectroscopic imaging.

Methods for early treatment response evaluation to systemic therapy of liver metastases are lacking. Tumor tissue often exhibits an increased ratio of phosphomonoesters to phosphodiesters (PME/PDE), which can be noninvasively measured by phosphorus magnetic resonance spectroscopy (31P MRS), and may be a marker for early therapy response assessment in liver metastases. However, with commonly used 31P surface coils for liver 31P MRS, the liver is not fully covered, and metastases may be missed. The objective of this study was to demonstrate the feasibility of 31P MRS imaging (31P MRSI) with full liver coverage to assess 31P metabolite levels and chemotherapy-induced changes in liver metastases of gastro-esophageal cancer, using a 31P whole-body birdcage transmit coil in combination with a 31P body receive array at 7 T. 3D 31P MRSI data were acquired in two patients with hepatic metastases of esophageal cancer, before the start of chemotherapy and after 2 (and 9 in patient 2) weeks of chemotherapy. 3D 31P MRSI acquisitions were performed using an integrated 31P whole-body transmit coil in combination with a 16-channel body receive array at 7 T, with a field of view covering the full abdomen and a nominal voxel size of 20-mm isotropic. From the 31P MRSI data, 12 31P metabolite signals were quantified. Prior to chemotherapy initiation, both PMEs, that is, phosphocholine (PC) and phosphoethanolamine (PE), were significantly higher in all metastases compared with the levels previously determined in the liver of healthy volunteers. After 2 weeks of chemotherapy, PC and PE levels remained high or even increased further, resulting in increased PME/PDE ratios compared with healthy liver tissue, in correspondence with the clinical assessment of progressive disease after 2 months of chemotherapy. The suggested approach may present a viable tool for early therapy (non)response assessment of tumor metabolism in patients with liver metastases.

Modeling PAH Mixture Interactions in a Human In Vitro Organotypic Respiratory Model.

One of the most significant challenges in human health risk assessment is to evaluate hazards from exposure to environmental chemical mixtures. Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants typically found as mixtures in gaseous and particulate phases in ambient air pollution associated with petrochemicals from Superfund sites and the burning of fossil fuels. However, little is understood about how PAHs in mixtures contribute to toxicity in lung cells. To investigate mixture interactions and component additivity from environmentally relevant PAHs, two synthetic mixtures were created from PAHs identified in passive air samplers at a legacy creosote site impacted by wildfires. The primary human bronchial epithelial cells differentiated at the air-liquid interface were treated with PAH mixtures at environmentally relevant proportions and evaluated for the differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response. Component additivity was evaluated across all endpoints using two independent action (IA) models with and without the scaling of components by toxic equivalence factors. Both IA models exhibited trends that were unlike the observed mixture response and generally underestimated the toxicity across dose suggesting the potential for non-additive interactions of components. Overall, this study provides an example of the usefulness of mixture toxicity assessment with the currently available methods while demonstrating the need for more complex yet interpretable mixture response evaluation methods for environmental samples.

Distributed real-time hybrid simulation method for dynamic response evaluation of floating wind turbines

Limited land and near coast spaces led to the development of floating wind turbine (FWT) farms in unlimited space of deep water with steady winds. Experimental evaluation of dynamic responses of FWT is essential to ensure its safe operation. However, due to laboratory limitations and scaling issues, realistic FWT responses are difficult to be replicated on scaled-down test specimens. To facilitate larger-scale testing of FWT and apply realistic wind and wave loads, distributed real-time hybrid simulation (dRTHS) method is proposed which combines the testing of FWT substructures at geographically distributed laboratories using wind tunnels and wave tanks. In this research, dRTHS experimental method for FWT is developed and its feasibility is verified through a series of virtual dRTHS (vdRTHS) and proof-of-the-concept partial dRTHS tests. The equation of motion of a prototype FWT structure under coupled aerodynamic and hydrodynamic loads was partitioned to represent the wind turbine tower and platform substructures, based on which substructural formulation was derived. During the vdRTHS, two distributed real-time controllers were used to simulate the physical testing of the two substructures tested in the wind tunnel and water tank, respectively, with interfacing data being transferred in real-time through a network. FWT responses from vdRTHS match well with those obtained from numerical simulations of the whole FWT model and the substructured models, demonstrating that the feasibility of the proposed dRTHS method. In addition, the substructuring approach, the vdRTHS testing platform, and the method to overcome network communication delay are effective in the vdRTHS resulting in reliable FWT dynamic responses under coupled loading conditions. Furthermore, the proposed dRTHS concept was verified through a partial distributed physical tests during which the wind turbine substructure was tested physically, while the platform substructure and the hydrodynamic loads were simulated numerically.

Blasting vibration effect and safety evaluation method of railway cross tunnels

The evolution characteristics of the peak particle velocity and frequency of an existing railway cross tunnel are systematically studied. The analysis results show that there is a difference in the blasting vibration response before and after the new tunnel face is built. In this paper, a set of blasting vibration response evaluation methods that can quantitatively consider the influence of frequency by means of dimensional analysis is introduced. In addition, relevant knowledge on topics such as wavelet packet analysis, signal processing, structural dynamics, and explosion mechanics is applied to research the influence of the frequency. The research results show that the influence of the frequency on the blasting vibration response can be quantitatively analyzed by quantifying the dynamic amplification factor. To resolve the insufficiency of field monitoring, the distribution of the blasting vibration response along the entire section of the existing tunnel is studied through numerical simulation. Based on the theory of distortion energy in material mechanics, a new idea for evaluating the blasting vibration response of a cross tunnel is proposed.

Dynamic performance of structures with clutching inertia‐damping system: Theoretical study

AbstractThis paper addresses performance limitations in passive clutching inertia devices due to the absence of flywheel deceleration damping. A solution introducing viscous damping to serve as the flywheel deceleration mechanism is proposed, thus forming the “CIDS” (Clutching Inertia‐Damping System). The study establishes a multi‐body motion analysis model for the CIDS within a single‐degree‐of‐freedom structure. Simulations investigate the impact of control force model parameters on the computation. The impact of additional damping on structural dynamic responses and the system's relative motion is thoroughly elucidated and revealed through dynamic simulations and multi‐body motion decomposition. The “ELS” (Equivalent Linear System) is introduced for the simplified performance assessment of CIDS. Expressions for equivalent damping and inertance are derived based on the equivalence of vibration period and energy in sinusoidal steady‐state vibration. The feasibility and accuracy of ELS for assessing CIDS's performance are validated through response analyses under harmonic and seismic excitations. Notably, displacement indicators exhibit higher precision than acceleration. When subjected to seismic excitation, selecting a more suitable excitation frequency to determine the corresponding equivalent damping can enhance the accuracy of ELS. Considering the frequency dependence of equivalent damping, a frequency‐domain‐based random response evaluation method is proposed. The influence of additional rotational damping, flywheel inertia, and structural natural period on random response is evaluated and analyzed. In CIDS with similar rotational damping and inertia, its control effect is related to the excitation. In summary, this study offers a structured framework for comprehending and evaluating the performance of CIDS, offering valuable insights into its potential engineering design, applications, and analysis.

Development of a dynamic demand response quantification and control framework for fan-coil air-conditioning systems based on prediction models

The air-conditioning demand response has gradually become an effective approach to reduce peak load of the national grid. However, with the increasing penetration of renewable energy generation sources, static performance evaluation of demand response that only fits one certain scenario cannot meet the demandsofthe times. To address this issue, a novel dynamic demand response quantification and control framework was built based on the secondary development of building energy simulation software and multilayer perceptron algorithm. In this framework, the demand response evaluation method can be used for different global temperature adjustment strategies under different external disturbances and internal loads, and the dynamic demand response control method could be further adopted for load reduction prediction and setpoint adjustment recommendation. The performance prediction model based on artificial neural network can predict the maximum load shedding during demand response period with an average absolute percentage error of 15 %, and the prediction error of load shedding intensity is ± 1 W/m2 for over 80 % of samples. Besides, the setpoint adjustment prediction model achieved an average absolute percentage error of 3 % while its prediction error is ± 0.25 °C for over 99 % of samples. The results prove that this research can provide reasonable suggestions for customers and load aggregators to achieve accurate control of setpoint adjustment in dynamic demand response conditions.

Comparison of different techniques for evaluation of cellular immunity to SARS-CoV-2 virus

Most techniques for evaluation of T-cell immunity are laborious and unsuitable for routine laboratory diagnostics, thus encouraging researchers to look for accessible and reproducible tests. The purpose of our study is to compare three methods aimed for evaluation of cellular immune response levels to the SARS-CoV-2 viral antigens in patients who have been ill and vaccinated against a new coronavirus infection. We have examined 26 persons who experienced mild or moderate COVID-19 (group 1); 19 people vaccinated twice with Sputnik V, who did not have clinical COVID-19 (group 2); 21 subjects who had COVID-19 and were twice vaccinated with Sputnik V (group 3), and 14 persons who had COVID-19 twice (group 4). Peripheral blood mononuclear cells were isolated by gradient centrifugation. The first tested technique was performed as follows: the mononuclear cells were incubated with the S-protein of the SARS-CoV-2 virus, and stained with fluorescently labeled antibodies. The percentage of CD8highCD107a was counted by means of BD FACS Canto II flow cytometer. When assessed by the ELISpot method with “Human IFN-γ ELISpot” kit, IFNγ production was stimulated by SARS-CoV-2 S-protein, or a mixture of SARS-CoV-2 protein peptides in the “Corona-T-test” kit. There were no significant differences in the levels of CD107a expression on CD8high cells between the groups 1, 2, 3, and 4, as well as in amounts of IFNγ producers against SARS-CoV-2 S-protein when using “Human IFN-γ ELISpot” kit. Production of IFN was significantly lower in group 3 (hybrid immunity), i.e., 317.29±19.04 pg/ml compared to groups 1 and 2 (post-infection and post-vaccination immunity), i.e., 454.95±20.32 and 470.77±26.24 pg /ml, respectively. The relative level of IFNγ -producing cells in group 2 was higher (22.34±3.77) versus 16.83±2.35 in group 1, and 15.46±1.83 in group 3, whereas the relative levels of IFNγ did not differ in these groups. Stimulation with full-length S-protein showed a significant reduction in the number of spots in group 4 (breakthrough immunity), i.e., 30.59±2.29 vs 58.97±4.47 in group 3. Stimulation with a mixture of SARS-CoV-2 peptides in group 4 vs group 3 revealed a significantly increased number of IFNγ -producing cells (86.72±7.20 versus 69.38±5.53) and higher IFNγ production (991.25±65.18 pg/ml versus 760.76±50.70 pg/ml). Appropriate relative values were as follows: 10.30±2.77 versus 8.61±2.66, and 68.10±9.41 versus 48.35±8.15, respectively. The results of three methods for evaluation of cellular immune response correlate positively with each other, but at different significance levels.

Response Evaluation after Neoadjuvant Chemotherapy for Resectable Gastric Cancer

Background: The method of response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer has been widely debated. An essential prerequisite is the ability to stratify patients into subsets of different long-term survival rates based on the response mode. Histopathological measures of regression have their limitations, and interest resides in CT-based methods that can be used in everyday settings. Methods: We conducted a population-based study (2007–2016) on 171 consecutive patients with gastric adenocarcinoma who were receiving NAC. Two methods of response evaluation were investigated: a strict radiological procedure using RECIST (downsizing), and a composite radiological/pathological procedure comparing the initial radiological TNM stage to the pathological ypTNM stage (downstaging). Clinicopathological variables that could predict the response were searched for, and correlations between the response mode and long-term survival rates were assessed. Results: RECIST failed to identify half of the patients progressing to metastatic disease, and it was unable to assign patients to subsets with different long-term survival rates based on the response mode. However, the TNM stage response mode did achieve this objective. Following re-staging, 48% (78/164) were downstaged, 15% (25/164) had an unchanged stage, and 37% (61/164) were upstaged. A total of 9% (15/164) showed a histopathological complete response. The 5-year overall survival rate was 65.3% (95% CI 54.7–75.9%) for TNM downstaged cases, 40.0% (95% CI 20.8–59.2%) for stable disease, and 14.8% (95% CI 6.0–23.6%) for patients with TNM progression, p < 0.001. In a multivariable ordinal regression model, the Lauren classification and tumor site were the only significant determinants of the response mode. Conclusions: Downsizing, as a method for evaluating the response to NAC in gastric cancer, is discouraged. TNM re-staging by comparing the baseline radiological CT stage to the pathological stage following NAC is suggested as a useful method that may be used in everyday situations.

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed therapy emerged as a treatment of peritoneal metastasis (PM) a decade ago. The response assessment of PIPAC is not uniform. This narrative review describes non-invasive and invasive methods for response evaluation of PIPAC and summarizes their current status. PubMed and clinicaltrials.gov were searched for eligible publications, and data were reported on an intention-to-treat basis. The peritoneal regression grading score (PRGS) showed a response in 18-58% of patients after two PIPACs. Five studies showed a cytological response in ascites or peritoneal lavage fluid in 6-15% of the patients. The proportion of patients with malignant cytology decreased between the first and third PIPAC. A computed tomography showed stable or regressive disease following PIPAC in 15-78% of patients. The peritoneal cancer index was mainly used as a demographic variable, but prospective studies reported a response to treatment in 57-72% of patients. The role of serum biomarkers of cancer or inflammation in the selection of candidates for and responders to PIPAC is not fully evaluated. In conclusion, response evaluation after PIPAC in patients with PM remains difficult, but PRGS seems to be the most promising response evaluation modality.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma

Background The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. Methods A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). Results For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). Conclusion RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.

Methods of constructing algorithms for comparative test statistical verification of mathematical models of bioobject responses to low-intensity stimuli

The paper presents the results of the construction of algorithms for comparative test statistical testing of mathematical models of responses of a bioobject to low-intensity stimuli, which is an oscillating function with relaxation. In addition, due to the hierarchically primary role of the mathematical model among the used means of this test, the possibility of determining the quality of the response evaluation method is substantiated.

Evaluation of F-18 FDG radiopharmaceuticals through Molecular Docking and radiation effects

Fluorodeoxyglucose (FDG), marked with the most used Positron Emission Tomography (PET) radiopharmaceutical Fluorine-18 (F-18), is a glucose analog and is taken to living cells through membrane glucose carriers. F-18 FDG involvement in tissue is proportional to glucose use. In many cancers, there is increased glucose use due to increased gluten expression and hexokinase activity. F-18 FDG PET is a proven method for diagnosis, staging, re-staging, and evaluation of treatment response in oncology. The purpose of this study is to find the effect of ionizing radiation on proteins in the mechanism of action of FDG and determine to Molecular mechanisms of F-18 FDG accumulation in metabolism. In the study, two different models were used together, the first method, the study was Molecular Docking method for modeling molecules deconstructed and the structure of FDG was energy minimized by utilizing the density functional theory, and the B3LYP functional was used with 6-311G basis set. The second method was the Monte Carlo method for modeling ionizing radiation interactive with the potential routes of FDG metabolism within the cell. It was determined that the Gibbs free energy (ΔG) change was compatible with the ionizing radiation factors for binding of FDG to the aphthous regions of Glucose-6-phosphate isomerase (G1), hexokinase (G2), and glucose transporter-1 (G3) were selected. In this study, the strong binding of FDG to protein influences the effect of radiation on the active site of enzymes. The G1 and G3 shown in the study interacted with only one charged amino acid FDG, and the absence of an aromatic residue around it can be considered among the results of this study as the cause of the low protective effect against ionizing radiation.

A Rate‐Dependent Constitutive Model of HTPB Propellant Based on Parallel Rheological Framework

AbstractNumerous studies have shown that highly strain‐rate dependent behavior is present in the mechanical properties of Hydroxyl‐terminated polybutadiene(HTPB)propellants, and many experts and scholars have attempted to develop constitutive models to describe such rate‐dependent properties of propellants. From the linear viscoelastic model to the Zhu‐Wang‐Tang model, the strain‐rate dependent properties of viscoelastic materials have been described to some extent. But due to the highly nonlinear mechanical behavior exhibited in propellant materials, the nonlinear behavior of propellants at different strain rates is difficult to be captured in the above constitutive models which are all based on linear elasticity. Therefore, in this paper, a nonlinear viscoelastic constitutive model was proposed based on the parallel rheological framework, in which the hyperelastic and viscoelastic flow laws were embedded. Because of the excellent ability to capture the nonlinear behavior of the material, the parallel rheological framework was used to predict the mechanical response at six sets of experiments with different rates. Surprisingly, this constitutive structure model performed good prediction of the mechanical properties of the material by comparison between theoretical calculations and experimental data. The constitutive model was verified by finite element method with numerical simulation software, and the robustness of the constitutive model was checked by a new set of experimental data. A good foundation was established for the accurate description of the propellant constitutive model strain‐rate dependent characteristics by the results of this paper, which could provide a new method for the rapid prediction and evaluation of the propellant mechanical response.

The Role of [68Ga]Ga-Pentixafor PET/CT or PET/MRI in Lymphoma: A Systematic Review.

Simple SummaryPreliminary evidence about the useful impact of [68Ga]Ga-Pentixafor PET/CT or PET/MRI in lymphoma is available but reveals heterogeneous findings. The aim of this systematic review was to analyze the published data about the role of [68Ga]Ga-Pentixafor PET/CT or PET/MRI in lymphoma and to focus on different lymphoma variants and clinical fields. [68Ga]Ga-Pentixafor PET may be considered a useful imaging method for staging and treatment response evaluation of several lymphomas, mainly FDG-not-avid variants. These findings may change the diagnostic flow-chart of lymphoma in the future.The aim of this systematic review was to investigate published data about the role of gallium-68 Pentixafor positron emission tomography/computed tomography ([68Ga]Ga-Pentixafor PET/CT) or PET/magnetic resonance imaging (PET/MRI) in patients affected by lymphoma. A comprehensive computer literature search of the Scopus, PubMed/MEDLINE, and Embase databases was conducted including articles indexed up to June 2022. In total, 14 studies or subsets in studies were eligible for inclusion. From the analyses of the selected studies, the following main findings have been found: (1) lymphomas can be considered [68Ga]Ga-Pentixafor avid diseases, also in cases of fluorine-18 fluorodeoxyglucose [18F]FDG-not avid forms such as lymphoplasmacytic lymphoma (LPL), chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL) and central nervous system lymphoma (CNSL); (2) among lymphomas, mantle cell lymphoma (MCL) and MZL are those with highest [68Ga]Ga-Pentixafor uptake; (3) [68Ga]Ga-Pentixafor PET/CT or PET/MRI is a useful tool for the staging and treatment response evaluation; (4) [68Ga]Ga-Pentixafor PET seems to have a better diagnostic performance than [18F]FDG PET in evaluating lymphomas. Despite several limitations affecting this analysis, especially related to the heterogeneity of the included studies, [68Ga]Ga-Pentixafor PET may be considered a useful imaging method for staging and treatment response evaluation of several lymphomas, especially MZL, CNSL and LPL.

Three-Dimensional Culture of Cartilage Tissue on Nanogel-Cross-Linked Porous Freeze-Dried Gel Scaffold for Regenerative Cartilage Therapy: A Vibrational Spectroscopy Evaluation.

This study presents a set of vibrational characterizations on a nanogel-cross-linked porous freeze-dried gel (NanoCliP-FD gel) scaffold for tissue engineering and regenerative therapy. This scaffold is designed for the in vitro culture of high-quality cartilage tissue to be then transplanted in vivo to enable recovery from congenital malformations in the maxillofacial area or crippling jaw disease. The three-dimensional scaffold for in-plate culture is designed with interface chemistry capable of stimulating cartilage formation and maintaining its structure through counteracting the dedifferentiation of mesenchymal stem cells (MSCs) during the formation of cartilage tissue. The developed interface chemistry enabled high efficiency in both growth rate and tissue quality, thus satisfying the requirements of large volumes, high matrix quality, and superior mechanical properties needed in cartilage transplants. We characterized the cartilage tissue in vitro grown on a NanoCliP-FD gel scaffold by human periodontal ligament-derived stem cells (a type of MSC) with cartilage grown by the same cells and under the same conditions on a conventional (porous) atelocollagen scaffold. The cartilage tissues produced by the MSCs on different scaffolds were comparatively evaluated by immunohistochemical and spectroscopic analyses. Cartilage differentiation occurred at a higher rate when MSCs were cultured on the NanoCliP-FD gel scaffold compared to the atelocollagen scaffold, and produced a tissue richer in cartilage matrix. In situ spectroscopic analyses revealed the cell/scaffold interactive mechanisms by which the NanoCliP-FD gel scaffold stimulated such increased efficiency in cartilage matrix formation. In addition to demonstrating the high potential of human periodontal ligament-derived stem cell cultures on NanoCliP-FD gel scaffolds in regenerative cartilage therapy, the present study also highlights the novelty of Raman spectroscopy as a non-destructive method for the concurrent evaluation of matrix quality and cell metabolic response. In situ Raman analyses on living cells unveiled for the first time the underlying physiological mechanisms behind such improved chondrocyte performance.

SO-11 Response evaluation after neoadjuvant chemotherapy for resectable gastric cancer: Downsizing vs downstaging

Response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer is debated. The aims of the present study were to investigate the value of strict radiologic methods, hence UICC-downstaging and RECIST, as mode of response evaluation following a MAGIC-style regimen of NAC applied to a large Western cohor. Further to explore a composite radiologic/pathologicdownstaging comparing radiologic stage at diagnosis (rTNM) to pathologic stage following chemotherapy (ypTNM). Population-based study (2007-2016) on 171 consecutive patients with gastric adenocarcinoma, receiving a MAGIC style neoadjuvant chemotehrapi (NAC). Three methods of response evaluation are investigated, two strict radiologic methodes; one comparing initialt rTNM-stage and radiologic stage following NAC (yrTNM) and one using RECIST (downsizing), and a composite radiologic/pathologic comparing initial rTNM-stage to pathologic ypTNM-stage (downstaging). Of 171 patients receiving NAC, 169 were available for response evaluation. For radiologic TNM response mode, 43% responded, 50% had stable disease and 7% progressed at CT. Crosstabulating yrTNM stage to ypTNM stage, 24% had concordant stages, with CT overstaging 38% and understaging 38% of the tumours, Cohen kappa ƙ=0,06 (95%CI 0,004-0,12). Similar patterns of discordance were found for T-stages and N-stages separately. For M-category, restaging CT detected 12 patients with carcinomatosis, with an additional 14 diagnosed with carcinomatosis only at operation. No patient developed parenchymal or extra abdominal metastases, and none developed locally non-resectable tumour during delivery of NAC. Restaging CT with response evaluation was not able to stratify patients into groups of different long-term survival rates based on response mode. RECIST failed to identify half of the patients progressing to metastatic disease, and were not able to assign patients to subsets with different long-term survival rates. The compositeTNM response mode, comparing initialt radiologic stage (rTNM) to the pathologic TNM stage (ypTNM) did achieve this objective. A totale of 78/164 (48%) were downstaged, 25/164 (15%) had stable disease and 61/164 (37%) were upstaged. Histopathologic complete response was found in 15/164 (9%). The 5-year overall survival was 65.3% (95% CI 54.7% - 75.9%) for responders, 40.0% (95 CI 20.8% - 59.2%) for stable disease and 14.8% (95% CI 6.0% - 23.6%) for patients with progression, p < 0.001. In a multivariable ordinal regression Lauren category and tumour location were the only significant determinants of response mode. Routine CT-scan following NAC is of limited value. Accuracy of CT staging compared to final pathologic stage is poor, and strict radiologic downstaging as measure of response evaluation is unreliable and unable to discriminate long-term survival rates based on response mode. RECIST as method of response evaluation following NAC in gastric cancer is also discouraged. Comparing CT-stage at diagnosis to pathologic stage following NAC appears as a useful method of response evaluation serving the every-day situation well.

Dynamic monitoring circulating tumor DNA in plasma samples by PEAC technology for patients with early-stage non–small cell lung cancer after surgery.

8547 Background: Local recurrence or distant metastasis after surgery is not rare for early-stage Non-Small Cell Lung Cancer (NSCLC) patients. Present clinicopathological parameters, such as TNM stages and pathological subtype, are limited effective, as Positive Predictive Value (PPV) is low while Negative Predictive Value (NPV) is high. In recent years, circulating tumor DNA (ctDNA) has emerged as a noninvasive method for early diagnosis, prognostic stratification, disease surveillance, and treatment response evaluation. We assessed whether circulating tumor DNA (ctDNA) detected by PEAC technology could be a biomarker for minimal residual disease (MRD) and prediction of postoperative relapse in early-stage NSCLC. Methods: We enrolled 132 NSCLC patients with EGFR, KRAS, NRAS, BRAF and PIK3CA mutations, and obtained plasma samples at five perioperative time points (before surgery, 3-7 days, 6-months, 12-months and 18-months after surgery). Using PEAC technology, somatic mutations in plasma samples were identified and utilized for ctDNA-based MRD analysis. Clinical follow-ups were collected. Results: Our data showed that 32.0% (8 of 25) of patients with positive preoperative ctDNA experienced postoperative relapse, compared with 7.2% (6 of 83) in ctDNA negative patients, demonstrating that preoperative ctDNA status is an effective prognosis factor for NSCLC. In time point of 3-7 days after surgery, plasma samples were obtained from 47 patients, of which 33.3% (2 of 6) with positive ctDNA experienced postoperative relapse, while only 4.9% (2 of 41) in ctDNA negative patients. The result suggests that ctDNA positive in plasma samples of 3-7 days after surgery might be a strong biomarker for MRD detection and relapse prediction. For ctDNA surveillance, plasma samples from 6-months, 12-months and 18-months after surgery were collected and detected. At any one of the three tests ctDNA is positive, 20.0% (8 of 40) patients experienced clinical relapse, while 5.1% (3 of 59) patients with ctDNA negative status at all times relapse. A total of 14 recurrence events had occurred, ctDNA positivity precedes radiological recurrence by a median of 150.5 days (90.5 – 182, P = 0.006). Conclusions: Perioperative ctDNA analysis using PEAC technology is effective in early detection of MRD and relapse prediction, and hence could benefit NSCLC patient management in clinical settings. Clinical trial information: NCT03465241.

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

Imaging for Multiple Myeloma according to the Recent International Myeloma Working Group Guidelines: Analysis of Image Acquisition Techniques and Response Evaluation in Whole-Body MRI according to MY-RADS

Multiple myeloma (MM) is a malignant hematologic disease caused by the proliferation of clonal plasma cells in the bone marrow, and its incidence is increasing in Korea. With the development of treatments for MM, the need for early diagnosis and treatment has emerged. In recent years, the International Myeloma Working Group (IMWG) has been constantly revising the laboratory and radiological diagnostic criteria for MM. In addition, as whole-body MRI (WBMR) has been increasing used in the diagnosis and treatment response evaluation of patients with MM, the Myeloma Response Assessment and Diagnosis System (MY-RADS) was created to standardize WBMR image acquisition techniques, image interpretation, and response evaluation methods. Radiologists need to have a detailed knowledge of the features of MM for accurate diagnosis. Thus, in this review article, we describe the imaging method for MM according to the latest IMWG guidelines as well as the image acquisition and response evaluation technique for WBMR according to MY-RADS.

Electroencephalographic Network Topologies Predict Antidepressant Responses in Patients With Major Depressive Disorder.

Medication therapy seems to be an effective treatment for major depressive disorder (MDD). However, although the efficacies of various medicines are equal or similar on average, they vary widely among individuals. Therefore, an understanding of methods for the timely evaluation of short-term therapeutic response and prediction of symptom improvement after a specific course of medication at the individual level at the initial stage of treatment is very important. In our present study, we sought to identify a neurobiological signature of the response to short-term antidepressant treatment. Related brain network analysis was applied in resting-state electroencephalogram (EEG) datasets from patients with MDD. The corresponding EEG networks were constructed accordingly and then quantitatively measured to predict the efficacy after eight weeks of medication, as well as to distinguish the therapeutic responders from non-responders. The results of our present study revealed that the corresponding resting-state EEG networks became significantly weaker after one week of treatment, and the eventual medication efficacy was reliably predicted using the changes in those network properties within the one-week medication regimen. Moreover, the corresponding resting-state networks at baseline were also proven to precisely distinguish those responders from other individuals with an accuracy of 96.67% when using the spatial network topologies as the discriminative features. These findings consistently provide a deeper neurobiological understanding of antidepressant treatment and a reliable and quantitative approach for personalized treatment of MDD.