DataSheet_1_Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases.pdf

Background and objectiveFor patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions.MethodsIn this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS).ResultsFor the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan–Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided PConclusionsThis study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.</p

SMC changes viewed with immunofluorescent staining (a) and analysis result of SMC content (b).

<p>(<b>c</b>) Detailed micrograph of alpha-actin staining in Group CE on day 30. **<i>P</i><0.01, ***<i>P</i><0.0001. Original magnification ×200.</p

Inner diameter changes measured by intravenous digital subtraction angiography imaging.

<p>(<b>a</b>) Anteroposterior aortography shows inner diameters of incubated aorta in each group. (<b>b</b>) Profile plots of inner diameter changes in three groups. (<b>c</b>) Aneurysm sample with a diameter of 9.2 mm harvested from Group CE on day 30. AAA: abdominal aortic aneurysm; AN: aneurysm neck. *<i>P</i><0.01, compared to Group C and the Sham Group, ^†<i>P</i><0.05, compared to Group E. Baseline: normal aorta diameter just above and proximal to the incubated segment.</p

Micrographs of PSR-stained sections viewed with conventional light and circularly polarized light (a) and semiquantitative analysis of type I and type III collagen content (b).

<p>*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.0001. All micrographs were viewed at magnification ×200, except for entire aorta ring viewed with polarized light (×20).</p

Volumes of brain glioma calculated by MRI scan.

<p>A Curve shows the volume of tumors on different days after transplantation. B, D, F, and H are images of T1 weighted signal. C, E, G, and I are images of T2 weighted signal. First day (B and C), 5 days (D and E), 10 days (F and G) and 14 days (H and I) after transplantation are shown.</p

Expressions of P-gp and MRP1 after LIUS sonication.

<p>Down-regulation of P-gp and MRP1 proteins of C6 cells in vitro post-sonication (P-gp and MRP1) and pre-sonication (P-gp-con and MRP1-con) are shown by immunofluorency assay (A). Scale bar = 10 nm. The bands show that the expressions of P-gp and MRP1 of rat brain glioma at mRNA level reducing significantly after LIUS sonication. The analysis of bands shows integrated density value of P-gp and MRP1 post-sonication at mRNA level by RT-PCR assay (B). *<i>P</i><0.05 compared with the control group. The expressions of protein levels of P-gp and MRP1 of rat brain glioma are shown by immunohistochemistry pre- and post- LIUS sonication. The expressions of P-gp and MRP1 reduce after LIUS sonication. The analysis of bands of mean optical density shows a significant down-regulation after LIUS sonication (C). *<i>P</i><0.05 compared with the control group. Scale bar = 20 nm.</p

Inhibitory rates of C6 cells induced by Doxorubicin or/and LIUS sonication measured by CCK-8 assay.

<p>A. Treated by Doxorubicin (DOX) at different concentrations. *<i>P</i><0.05compared with control group. B. Treatment at the combination of ultrasound (142 mW/cm², 30 s) and Doxorubicin (DOX) at different concentrations. *<i>P</i><0.01 compared with control group. C. Comparison of C6 cells inhibitory rates after treated by Doxorubicin (DOX) and the combination of sonication and DOX. *<i>P</i><0.05 compared with DOX group at the same concentration.</p

Phosphorylation of Akt, ERK and eNOS in ischemic muscle following injections of 2HP-β-CD or PBS.

<p>Muscle tissue homogenates from 2HP-β-CD-treated (filled) and PBS-treated (open) mice at post-operative day 28 were subjected to western blot using antibodies against phospho-Akt and total Akt (A), phospho-ERK and total ERK (B), and phospho-eNOS and total eNOS (C) as described in “Materials and Methods”. The quantitative analyses of band densities are also shown. Data represent the mean ± S.E.M. (<i>n</i> = 5 mice per group). * <i>p</i> < 0.05, versus the PBS-treated control mice.</p

The influence on the expressions of PI3K\Akt\NF-κB signal pathways related proteins by DOX treatment and LIUS sonication separately or in combination shown by immunohistochemistry.

<p>PI3K-p110 delta, Akt, pAkt and NF-κB p65 signal proteins reduce significantly in rat brain glioma after LIUS sonication and DOX treated separately or in combination (A). B shows the analysis of the proteins by mean optical density. *<i>P</i><0.05 compared with the control group. † <i>P</i><0.05 compared with the DOX treated group. ‡ <i>P</i><0.05 compared with the LIUS sonicated group. Scale bar = 10 nm.</p

Apoptosis and membrane permeability of C6 cells and astrocytes are induced by LIUS sonication detected by TUNEL assay and propidium iodide (PI) staining.

<p>A. The number of apoptotic C6 cells. B. The number of apoptotic astrocytes. *<i>P</i><0.05 compared with the control group (without sonication both in A and B). C. The number of astrocytes and C6 cells positively stained by PI staining. *<i>P</i><0.05 compared with astrocytes.</p