•Development and comparison of two classifiers, random forest and linear discriminant, for distinguishing between radiation pneumonitis (RP) and immune-related pneumonitis (CIP) in lung cancer ...patients receiving radiotherapy(RT) and immune checkpoint inhibitors (ICIs).•Identification of four most discriminating features, including Long Run Low Gray Level Emphasis, Median, Joint Average, and Busyness, that contribute to the classification of CIP and RP.•Demonstration of the potential of CT radiomics signatures in accurately diagnosing and distinguishing between different types of pneumonitis in lung cancer patients undergoing RT and ICIs.•Highlighting the need for further characterization of the relationship between radiomics features and pathologic features to enhance the understanding of disease pathology in patients receiving RT and ICIs.
To develop a CT-based model to classify pneumonitis etiology in patients with non-small cell lung cancer(NSCLC) after radiotherapy(RT) and Immune checkpoint inhibitors(ICIs).
We retrospectively identified 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + thoracic RT only, the training cohort, n = 100), and RT + ICIs (the test cohort, n = 30). Clinical and CT radiomics features were described and compared between different groups. We constructed a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier by CT radiomics to discern pneumonitis etiology.
The patients in RT + ICIs group have more high grade (grade 3–4) pneumonitis compared to patients in ICIs only or RT only group (p < 0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RT-related pneumonitis(RP) and ICI-related pneumonitis(CIP), resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. The RF classifier showed favorable discrimination between RP and CIP with an area under the receiver operating curve (AUC) of 0.859 (95 %CI: 0.788-0.929) in the training cohort and 0.851 (95 % CI: 0.700–1) in the test cohort. The LDA classifier achieved an AUC of 0.881 (95 %CI: 0.815–0.947) in the training cohort and 0.842 (95 %CI: 0.686–0.997) in the test cohort. Our analysis revealed four principal CT-based features shared across both models:original_glrlm_LongRunLowGrayLevelEmphasis, wavelet-HLL_firstorder_Median, wavelet-LLL_ngtdm_Busyness， and wavelet-LLL_glcm_JointAverage.
CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after RT alone, ICIs alone or RT + ICIs.
Aiming at the problems of insufficient extraction of asynchronous motor fault features by traditional deep learning algorithms and poor diagnosis of asynchronous motor faults in robust noise ...environments, this paper proposes an end-to-end fault diagnosis method for asynchronous motors based on IInception-CBAM-IBiGRU. The method first uses a signal-to-grayscale image conversion method to convert one-dimensional vibration signals into two-dimensional images and initially extracts shallow features through two-dimensional convolution; then the Improved Inception (IInception) module is used as a residual block to learning features at different scales with a residual structure, and extracts its important feature information through the Convolutional Block Attention Module (CBAM) to extract important feature information and adjust the weight parameters; then the feature information is input to the Improved Bi-directional Gate Recurrent Unit (IBiGRU) to extract its timing features further; finally, the fault identification is achieved by the SoftMax function. The primary hyperparameters in the model are optimized by the Weighted Mean Of Vectors Algorithm (INFO). The experimental results show that the method is effective in fault diagnosis of asynchronous motors, with an accuracy rate close to 100%, and can still maintain a high accuracy rate under the condition of low noise ratio, with good robustness and generalization ability.
Purpose
Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the ...efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity.
Methods
We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS).
Results
Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (
p
= 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%–56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7–13.1 months) with ICI alone versus 13.8 months (95%CI 9.5–18.1 months) with ICI plus radiotherapy (hazard ratio HR 0.556;
p
= 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (
p
= 0.016), patients with ECOG PS = 0 (
p
= 0.048), and patients with 1–2 metastatic sites (
p
= 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm.
Conclusion
Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.
Pre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell ...migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.
Sixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1-14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.
With a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3-4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.
Anti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.
Chemoradiation therapy (CRT) of locally advanced esophageal cancer (LAEC), although improving outcomes of patients, still results in 50% of local failure. An early prediction could identify patients ...at high risk of poor response for individualized adaptive treatment. We aimed to investigate physiological changes in LAEC using diffusion and perfusion magnetic resonance imaging (MRI) for early prediction of treatment response. In the study, 115 LAEC patients treated with CRT were enrolled (67 in the discovery cohort and 48 in the validation cohort). MRI scans were performed before radiotherapy (pre‐RT) and at week 3 during RT (mid‐RT). Gross tumor volume (GTV) of primary tumor was delineated on T2‐weighted images. Within the GTV, the hypercellularity volume (VHC) and high blood volume (VHBV) were defined based on the analysis of ADC and fractional plasma volume (Vp) histogram distributions within the tumors in the discovery cohort. The median GTVs were 28 cc ± 2.2 cc at pre‐RT and 16.7 cc ± 1.5 cc at mid‐RT. Respectively, VHC and VHBV decreased from 4.7 cc ± 0.7 cc and 5.7 cc ± 0.7 cc at pre‐RT to 2.8 cc ± 0.4 cc and 3.5 cc ± 0.5 cc at mid‐RT. Smaller VHC at mid‐RT (area under the curve AUC = 0.67, P = .05; AUC = 0.66, P = .05) and further decrease in VHC at mid‐RT (AUC = 0.7, P = .01; AUC = 0.69, P = .03) were associated with longer progression‐free survival (PFS) in both discovery and validation cohort. No significant predictive effects were shown in GTV and VHBV at any time point. In conclusion, we demonstrated that VHC represents aggressive subvolumes in LAEC. Further analysis will be carried out to confirm the correlations between the changes in image‐phenotype subvolumes and local failure to determine the radiation‐resistant tumor subvolumes, which may be useful for dose escalation.
This study investigated physiological changes in locally advanced esophageal cancer (LAEC) using diffusion and perfusion magnetic resonance imaging (MRI) for early prediction of treatment response to chemoradiotherapy (CRT). We found that large hypercellularity volumes (VHC) delineated on diffusion‐weighted images (DWI) at 3 weeks after initiation of radiotherapy (RT) and increasing volumes in VHC during RT were associated with a worse prognosis. It indicated that tumor subvolumes containing hypercellularity represented radiation‐resistant tumor subvolumes and provided patients and doctors with an effective tool for determining further dose escalation.
Radiotherapy is a frequently utilized therapeutic modality in the treatment of esophageal cancer (EC). Even though extensive studies are carried out in radiotherapy for EC, the design of the clinical ...target volume and the radiation dose is not satisfactorily uniform. Radiotherapy acts as a double-edged sword on the immune system; it has both an immunostimulatory effect and an immunosuppressive effect. Radiation-induced lymphopenia and its potential association with tumor control and survival outcomes remain to be understood. The advent of immunotherapy has renewed the focus on preserving a pool of functioning lymphocytes in the circulation. In this review, we summarize the potential impact mechanisms of radiotherapy on peripheral blood lymphocytes and the prognostic role of radiation-induced lymphopenia in patients with EC. We also propose the concept of organs-at-risk of lymphopenia and discuss potential strategies to mitigate its effects on patients with EC. From an immunological perspective, we put forward the hypothesis that optimizing radiation modalities, radiation target volume schemes, and radiation doses could help to reduce radiation-induced lymphopenia risks and maximize the immunomodulatory role of radiotherapy. An optimized radiotherapy plan may further enhance the feasibility and effectiveness of combining immunotherapy with radiotherapy for EC.
The variability and unpredictability of immune checkpoint inhibitors (ICIs) in treating brain metastases (BMs) in patients with advanced non-small cell lung cancer (NSCLC) is the main concern. We ...assessed the utility of novel imaging biomarkers (radiomics) for discerning patients with NSCLC and BMs who would derive advantages from ICIs treatment.
Data clinical outcomes and pretreatment magnetic resonance images (MRI) were collected on patients with NSCLC with BMs treated with ICIs between June 2019 and June 2022 and divided into training and test sets. Metastatic brain lesions were contoured using ITK-SNAP software, and 3748 radiomic features capturing both intra- and peritumoral texture patterns were extracted. A clinical radiomic nomogram (CRN) was built to evaluate intracranial progression-free survival, progression-free survival, and overall survival. The prognostic value of the CRN was assessed by Kaplan-Meier survival analysis and log-rank tests.
In the study, a total of 174 patients were included, and 122 and 52 were allocated to the training and validation sets correspondingly. The intratumoral radiomic signature, peritumoral radiomic signature, clinical signature, and CRN predicted intracranial objective response rate. Kaplan-Meier analyses showed a significantly longer intracranial progression-free survival in the low-CRN group than in the high-CRN group (
< 0.001). The CRN was also significantly associated with progression-free survival (
< 0.001) but not overall survival.
Radiomics biomarkers from pretreatment MRI images were predictive of intracranial response. Pretreatment radiomics may allow the early prediction of benefits.
Abstract Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a ...hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer’s disease model, we demonstrate silencing of mutant APP swe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.
The dynamic event-triggered fault detection problem for discrete networked control systems with time-delay is investigated in this paper. Firstly, for reducing the triggering times, a new dynamic ...event-trigged is proposed. Secondly, an observer is constructed on the controller node to generate fault residual, and the mathematical model of the closed-loop systems is established by analyzing the sequence of the transmission signal. Thirdly, by constructing a suitable Lyapunov-Krasovskii functional, the sufficient stability conditions for the closed-loop networked control systems are derived. The computing method of the observer gain matrix, the controller gain matrix and the minimal disturbance repression index is provided. Finally, a casy study on the dynamic cart is employed to illustrate the merits of the proposed approach.
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