Development and Validation of a Computed Tomography-Based Radiomics Signature to Predict Response to Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

Importance: Neoadjuvant therapies have been shown to decrease tumor burden, increase resection rate, and improve the outcomes among patients with locally advanced gastric cancer (GC). However, not all patients are equally responsive; therefore, differentiating potential respondents from nonrespondents is clinically important. Objective: To use pretreatment computed tomography (CT)-pixelated feature-difference extraction techniques to identify diagnostically relevant features that could predict patients' response to neoadjuvant chemotherapy at diagnosis. Design, Setting, and Participants: This multicenter cohort study included patients with locally advanced GC who were treated from January 2010 to July 2017 at 2 hospitals in southern China (training cohort) and 1 hospital in northern China (external validation cohort). Their clinicopathological data, pretreatment CT images, and pathological reports were retrieved and analyzed. Data analysis was conducted from December 2017 to May 2021. Exposures: All patients underwent 2 to 4 cycles of fluorouracil in combination with a platinum-based neoadjuvant chemotherapy regimen. All gastrectomies were performed according to the Japanese Classification of Gastric Carcinoma (14th edition) guidelines. Main Outcomes and Measures: Reliability of clinicopathological and radiomics-based features were assessed with area under receiver operating characteristic curve (AUC) and Mann-Whitney U test. Results: A total of 323 patients (242 [74.9%] men; median [range] age, 58 [24-82] years) were included in the study, with 250 patients (77.4%) in the training cohort and 73 (22.6%) in the validation cohort. The baseline pretreatment characteristics of the training and validation cohorts were well-balanced. The number of respondents in the training and validation cohort was 122 (48.8%) and 40 (54.8%), respectively, and the number of nonrespondents was 128 (51.2%) and 33 (45.2%), respectively. No clinicopathological variables were significantly associated with treatment response. Using radiomics, 20 low-intercorrelated features from a total of 7477 features were used to construct a radiomics signature that demonstrated significant association with treatment response. Good discrimination performance of the radiomics signature for predicting treatment response in the training (AUC, 0.736; 95% CI, 0.675-0.798) and external validation (AUC, 0.679; 95% CI, 0.554-0.803) cohorts was observed. Decision curve analysis confirmed the clinical utility of the radiomics signature. Conclusions and Relevance: In this study, the proposed radiomics signature showed potential as a clinical aid for predicting the response of patients with locally advanced GC before treatment, thereby allowing timely planning for effective treatments for potential nonrespondents.

Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts.

PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts. MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1.5T whole-body MRI system. Gaussian-DWI-derived apparent diffusion coefficient (ADC), D, D*, and f, and non-Gaussian-DWI-derived MD, MK, DDC, and α were calculated and compared between the control (n = 6) and sorafenib-treated groups (n = 10) with respect to each timepoint using Mann-Whitney or Wilcoxon signed-rank test. Results were validated by pathology. RESULTS: Compared to baseline, ADC and D at 1 hour posttreatment (P = 0.005 and P = 0.013, respectively) and MD and DDC at 3 hours posttreatment (P = 0.009 and P = 0.005, respectively) significantly decreased and remained lower through 12 hours of follow-up (P = 0.005-0.022), followed by recovery to baseline levels at 24 hours posttreatment (P = 0.139-0.646). MK significantly increased at 1 hour posttreatment (P = 0.013) and remained higher through 24 hours of follow-up (P = 0.009-0.028). No significant differences were found in D*, f, and α at different timepoints (P = 0.188-0.714). Light microscopy did not reveal abnormal findings until 3 hours posttreatment, when central patchy necrosis was observed; more prominent diffuse necrosis was observed at 24 hours. Electron microscopy revealed swollen mitochondria at 1 hour posttreatment and accumulation of intracellular autophagosomes from 3 to 24 hours posttreatment. CONCLUSION: Multiparametric DWI might evaluate therapeutic effects of sorafenib in HCC, where metrics of ADC, D, and MK could potentially serve as imaging biomarkers for monitoring therapeutic effects as early as 1 hour after treatment. Level of Evidence 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:248-256.

Texture analysis of intermediate-advanced hepatocellular carcinoma: prognosis and patients' selection of transcatheter arterial chemoembolization and sorafenib.

Transcatheter arterial chemoembolization (TACE) and sorafenib combination treatment for unselected hepatocellular carcinoma (HCC) is controversial. We explored the potential of texture analysis for appropriate patient selection. There were 261 HCCs included (TACE group: n = 197; TACE plus sorafenib (TACE+Sorafenib) group n = 64). We applied a Gabor filter and wavelet transform with 3 band-width responses (filter 0, 1.0, and 1.5) to portal-phase computed tomography (CT) images of the TACE group. Twenty-one textural parameters per filter were extracted from the region of interests delineated around tumor outline. After testing survival correlations, the TACE group was subdivided according to parameter thresholds in receiver operating characteristic curves and compared to TACE+Sorafenib group survival. The Gabor-1-90 (filter 0) was most significantly correlated with TTP. The TACE group was accordingly divided into the TACE-1 (Gabor-1-90 ≤ 3.6190) and TACE-2 (Gabor-1-90 > 3.6190) subgroups; TTP was similar in the TACE-1 subgroup and TACE+Sorafenib group, but shorter in the TACE-2 subgroup. Only wavelet-3-D (filter 1.0) correlated with overall survival (OS), and was used for subgrouping. The TACE-5 (wavelet-3-D ≤ 12.2620) subgroup and the TACE+Sorafenib group showed similar OS, while the TACE-6 (wavelet-3-D > 12.2620) subgroup had shorter OS. Gabor-1-90 and wavelet-3-D were consistent.Independent of tumor number or size, CT textural parameters are correlated with TTP and OS. Patients with lower Gabor-1-90 (filter 0) and wavelet-3-D (filter 1.0) should be treated with TACE and sorafenib. Texture analysis holds promise for appropriate selection of HCCs for this combination therapy.

In vitro labeling of mesenchymal stem cells with superparamagnetic iron oxide by means of microbubble-enhanced US exposure: initial experience.

PURPOSE: To investigate the feasibility of magnetically labeling stem cells with superparamagnetic iron oxide (SPIO) by means of microbubble-enhanced ultrasonographic (US) exposure (MUE) and to study the effects of this approach--without secondary transfection agents--on the viability, proliferation activity, and differentiation capability of MUE-labeled stem cells. MATERIALS AND METHODS: Institutional review board approval was obtained for this study. Human mesenchymal stem cells (MSCs) ([1 to 2] x 10(6)/mL) were studied in four experiment groups: sham exposure to US with microbubbles and SPIO (group A), exposure to US with SPIO but without microbubbles (group B), exposure to US with microbubbles and SPIO (group C), and sham exposure to US without SPIO or microbubbles (group D). Intracellular iron uptake was analyzed qualitatively at light and electron microscopy. The viability and proliferation activity of MSCs were evaluated. The adipogenic and osteogenic differentiation capability of the labeled MSCs was also evaluated. Ninety-five percent confidence intervals were derived for assessment of differences in cell viability and proliferation activity between groups C and D. RESULTS: Light and electron microscopy revealed intracytoplasmic iron uptake and nearly 100% cell labeling efficiency. The MUE-labeled MSCs had unaltered viability and uncompromised proliferation activity compared with the nonlabeled MSCs. Similar to the nonlabeled MSCs, the MUE-labeled MSCs differentiated into adipogenic and osteogenic lineages. CONCLUSION: Initial study results show that stem cells can be effectively labeled with SPIO by using MUE without secondary transfection agents and thus that MUE labeling is an appealing alternative cell-labeling approach that warrants investigation for intracellular magnetic labeling of stem cells. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531081974/-/DC1.