Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.

BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status. METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 ( http://keyan.deepwise.com/ ), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA). RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram. CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.

Value of Dual-Energy Computed Tomography for Diagnosing Cervical Lymph Node Metastasis in Patients With Papillary Thyroid Cancer.

OBJECTIVE: The objective of this study was to determine the value of dual-energy computed tomography (DECT) for the diagnosis of cervical lymph node metastasis in papillary thyroid cancer. METHODS: The normalized iodine concentration (NIC) and the slope of the spectral Hounsfield unit curve (λHU) in the arterial and venous phases were measured using iodine-overlay images and spectral curves. Quantitative DECT data and qualitative conventional CT data were analyzed by radiologists. RESULTS: The best qualitative parameter for lymph node metastasis detection was obvious node enhancement, and the best quantitative parameter for detection was arterial-phase NIC, which showed high sensitivity, specificity, and accuracy values at an optimal threshold of 25.8%. The best combination of qualitative and quantitative parameters consisted of obvious enhancement and arterial-phase NIC; this combination showed a sensitivity of 90.8% and a specificity of 80.5%. CONCLUSIONS: The DECT quantitative parameters NIC and λHU can be an additional tool to diagnose cervical lymph node metastasis.

[Digital breast tomosynthesis in diagnosis of dense breast lesions].

OBJECTIVE: To evaluate the value of digital breast tomosynthesis (DBT) in diagnosis of dense breast lesions. METHODS: Clinical and pathological data of 163 patients (58 benign lesions, 122 malignant lesions, and 180 lesions in total) with breast lesions undergoing surgical treatment in Shaoxing Central Hospital from January 2017 to December 2018 were retrospectively analyzed. The lesions were classified into non-homogeneous dense gland type and extremely dense gland type according to BI-RADS creterion. Breast MRI and DBT examinations were performed before the surgery. ROC curve was generated and the diagnostic efficacy of two examination methods for dense breast lesions was evaluated with pathological results as the gold standard. The detection rate, diagnostic accuracy of benign and malignant breast lesions were compared between two methods using chi-square test. The accuracy of lesion size preoperatively evaluated by MRI and DBT was analyzed by Pearson correlation. RESULTS: The detection rate and diagnostic accuracy for benign breast lesions by MRI were higher than those by DBT (91.4% vs. 75.9%, χ2=5.098, P<0.05 and 89.7% vs. 67.2%, χ2=8.617, P<0.01). But there were no significant differences in detection rate and accuracy for malignant lesions by MRI and DBT (98.4% vs. 95.1%, χ2=2.068, P>0.05 and 94.3% vs. 91.8%, χ2=0.569, P>0.05). The areas under the ROC curves of MRI, DBT based on BI-RADS classification were 0.910 and 0.832, respectively (Z=1.860, P>0.05). The sensitivities of MRI, DBT to breast lesions were 93.3% and 86.7%, and the specificities were 68.3% and 79.1%. DBT and MRI measurements were positively correlated with pathological measurements (r=0.887 and 0.949, all P<0.01). CONCLUSIONS: DBT can effectively diagnose benign and malignant breast lesions under dense gland background, and it has similar diagnostic efficacy with MRI for breast malignant lesions.

[Stretched-exponential and mono-exponential diffusion-weighted imaging for assessing the aggressiveness of prostate cancer: A histogram analysis].

OBJECTIVE: To assess the value of stretched-exponential and mono-exponential diffusion-weighted imaging (DWI) in predicting the aggressiveness of PCa. METHODS: This retrospective study included 36 cases of PCa with 48 lesions in the peripheral zone diagnosed by DWI with b-values of 0, 500, 1000, and 2000 s/mm2. We reconstructed the apparent diffusion coefficient (ADC), distributed diffusion coefficient (DDC) and α maps on the post-processing workstation, performed a histogram analysis on the largest slice of PCa on T2WI and Spearman's rank-order analysis on the correlation of the histogram variables with Gleason grade grouping (GG). Then, we assessed the values of the histogram variables in differentiating low-grade from high-grade PCa using the receiver operating characteristic (ROC) curve. RESULTS: The percentile and mean ADCs and DDCs were correlated with GG (ρ: 0.392－0.641) but not the α value, skewnesses and kurtosises (ρ: 0.055－0.266). High-grade PCa exhibited significantly lower 10th-, 25th-, 50th- and 75th-percentile and mean ADCs (490 ± 141, 591 ± 137, 695 ± 137, 781 ± 139 and 888 ± 135 mm2/s) and DDCs (420 ± 146, 534 ± 167, 666 ± 182, 787 ± 190 and 912 ± 175 mm2/s) than low-grade PCa (ADCs: 636 ± 74, 727 ± 86, 825 ± 85, 907 ± 85 and 975 ± 117 mm2/s; DDCs: 542 ± 80, 666 ± 93, 806 ± 108, 910 ± 110 and 1023 ± 105 mm2/s), but there were no statistically significant differences between low- and high-grade PCa in the α value (0.67 ± 0.042 vs 0.64 ± 0.036), kurtosises (ADC 0.105 vs 0.078; DDC －0.027 vs －0.401) or skewnesses (ADC －0.042 vs 0.067; DDC －0.058 vs 0.162). Both 10th-percentile ADCs and DDCs showed a higher efficiency than the mean ones in differentiating high- from low-grade PCa, though with no statistically significant difference (P > 0.05). CONCLUSIONS: Histogram variables DDCs and ADCs, rather than the α value, can be used to predict the aggressiveness of PCa, even more efficiently at the 10th percentile than on the mean.

MRI characteristics of intraductal papilloma.

BACKGROUND: Intraductal papilloma (IDP) is the most common pathological finding in women with pathological nipple discharge. Magnetic resonance imaging (MRI) has shown potential for characterizing breast tumors; however, MRI findings of IDPs are inconclusive, and certain diagnostic standards are lacking. PURPOSE: To characterize the MRI features of IDP from a relatively large cohort. MATERIAL AND METHODS: We retrospectively reviewed from 358 women with IDPs that were confirmed by histopathology. The clinical and imaging findings in 70 patients who underwent preoperative MRI were analyzed. MRI analyses included morphology and dynamic contrast-enhanced MRI. RESULTS: In 70 patients, 77 IDPs were detected on MRI, which revealed the following three patterns: small luminal mass papillomas; tumor-like papillomas; and MRI-occult papillomas. Fourteen IDPs involved small, oval, smooth, and contrast-enhanced masses at the posterior end of the enlarged duct corresponding to small luminal mass papillomas. Seven IDPs had large diameters along the direction of the breast duct, indicating the typical MRI findings for IDP. Of 47 tumor-like papillomas, 16 cases showed large diameters along the direction of the breast duct and close to the nipple (within 4 cm), seven cases resembled invasive breast cancer on MRI, and the remaining 24 were (24/47) undistinguishable from other benign breast diseases. Sixteen IDPs were MRI-occult papillomas that could not be distinguished from the surrounding benign disease by either contrast-enhanced MRI or fat-suppressed T2-weighted MRI. CONCLUSION: Small luminal mass papillomas or tumor-like papillomas with the largest diameters along the direction of the breast duct and close to the nipple (within 4 cm) might be the typical MRI findings for IDPs.

Differentiation of gastric true leiomyoma from gastric stromal tumor based on biphasic contrast-enhanced computed tomographic findings.

UNLABELLED: The objective of this study was to identify the computed tomographic criteria that differentiate gastric true leiomyoma from gastric stromal tumor. MATERIALS AND METHODS: Computed tomographic images of gastric true leiomyoma (n = 11) and gastric stromal tumor (n=30) were reviewed. The location, contour, growth pattern, enhancement pattern, necrosis, and ulceration were analyzed. Long diameter (LD), short diameter (SD), LD/SD ratio, and enhancement degree were measured and calculated. The Fisher exact test, grouped t test, rank sum test, and receiver operating characteristic curve were analyzed. Sensitivity and specificity were also calculated. RESULTS: Cardial location, round/ovoid contour, intraluminal growth, homogeneous enhancement, absence of necrosis, less than 3.35 cm in LD and less than 2.3 cm in SD, enhancement degree of less than 12.5 Hounsfield units in the arterial phase versus less than 31.5 Hounsfield units in the portal venous phase were found to be significant variables for differentiating gastric true leiomyoma from gastric stromal tumor (P < 0.05). CONCLUSIONS: These 9 computed tomographic criteria are helpful to differentiate gastric true leiomyoma from gastric stromal tumor.

Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic resonance and upconverted luminescence imaging.

Insufficient or excess drug doses, due to unknown actual drug concentrations at the focus, are one of the main causes of chemotherapy failure for cancers. In this regard, the real-time monitoring of the release of anticancer drugs from nanoparticle drug delivery systems is of crucial importance, but it remains a critical and unsolved challenge. Herein, we report the proposal and development of a novel concept of real-time monitoring of NIR-triggered drug release in vitro and in vivo by using simultaneous upconverted luminescence (UCL) and magnetic resonance (MR) imaging. Such a monitoring strategy features the high sensitivity of UCL and the high-resolution, noninvasiveness, and tissue-depth-independence of MR imaging. The dual-mode real-time and quantitative monitoring of drug release can be applied to determine online the drug concentrations in vivo in the tissue regions of interest and, therefore, to avoid insufficient or excess drug dosings.

Magnetic resonance imaging based on radiomics for differentiating T1-category nasopharyngeal carcinoma from nasopharyngeal lymphoid hyperplasia: a multicenter study.

PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.

Induction sintilimab and chemotherapy followed by concurrent chemoradiotherapy for locally advanced esophageal cancer: a proof-of-concept, single-arm, multicenter, phase 2 trial.

Background: Concurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control. Methods: We did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046). Findings: Seventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3-35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%-90.7%), which was much higher than that in concurrent chemoradiation only (71.3%) in previous studies. Vascular normalization and hypoxia alleviation were observed in both biopsy specimens and perfusion CT. Interpretation: The addition of induction immunotherapy to standard concurrent chemoradiotherapy could improve radiosensitivity for locally advanced esophageal cancer as non-surgical treatment. New treatment combination led to higher local control rate through promoting vascular normalization and alleviating hypoxia. Our findings suggest that induction immunotherapy followed by concurrent chemoradiotherapy could be a potential option in future treatment. Funding: National Natural Science Foundation of China and Shanghai Rising-Star Program.

Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression and Metastasis.

Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (•OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert •OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Rattle-structured multifunctional nanotheranostics for synergetic chemo-/radiotherapy and simultaneous magnetic/luminescent dual-mode imaging.

Most hypoxic tumors are insensitive to radiation, which is a major obstacle in the development of conventional radiotherapy for tumor treatment. Some drugs, such as cisplatin (CDDP), have been extensively used both as an anticancer drug and clinically as a radiosensitizer to enhance radiotherapy. Herein, we develop rattle-structured multifunctional up-conversion core/porous silica shell nanotheranostics (UCSNs) for delivering CDDP to tumors for synergetic chemo-/radiotherapy by CDDP radiosensitization and magnetic/luminescent dual-mode imaging. UCSNs had a dynamic light scattering diameter of 79.1 nm and excellent water dispersity and stability. In vitro studies showed that CDDP loaded in UCSNs (UCSNs-CDDP) was more effective than free CDDP as a radiosensitizer. After injection, UCSNs-CDDP also demonstrated unambiguously enhanced radiotherapy efficacy in vivo. Our report aims at presenting a novel strategy in biomedical nanotechnology that allows simultaneous dual-mode imaging and localized therapy via synergetic chemo-/radiotherapy, which may achieve optimized therapeutic efficacy in cancer treatment.

Ultrasound-enhanced cascade chemodynamic tumor nanotherapy with lactic acid-enabled hydrogen peroxide self-production.

Chemodynamic therapy (CDT) is an effective therapeutic modality for cancer treatment with the action of a catalytic Fenton-like chemoreactive process. To furnish sufficient hydrogen peroxide (H2O2) for CDT, catalysts similar to superoxide dismutase are designed to be in cooperation with nanoplatforms. In this work, we rationally integrate lactate oxidase (LOD) with ultrasmall superparamagnetic iron oxide nanoparticles (USPION) to achieve high efficiency of the cascade Fenton reaction for efficient tumor therapy. During the sequential reaction, LOD converts lactic acid into H2O2 and pyruvate (PA) in situ, and then USPION with peroxidase-like activity generates large amounts of toxic hydroxyl radicals (˙OH) under the action of H2O2. Moreover, the reaction effectively utilizes the excess lactic acid of the tumor microenvironment (TME) as a new target of cancer treatment. To further achieve high-performance tumor treatment, ultrasound has been introduced for augmenting this specific chemoreactive tumor therapy, which can affect cancer cells mainly through sonoporation, cavitation, and thermal effect. With the effects of ultrasound irradiation, this work has constructed an efficient oncology treatment system for tumors. Moreover, the presence of USPION is highly desirable for contrast-enhanced T1-weighted MRI for monitoring the therapeutic process of cancer in real time.

Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging.

Here we report the design and controlled synthesis of monodisperse and precisely size-controllable UCNP@mSiO(2) nanocomposites smaller than 50 nm by directly coating a mesoporous silica shell (mSiO(2)) on upconversion nanocrystals NaYF(4):Tm/Yb/Gd (UCNPs), which can be used as near-infrared fluorescence and magnetic resonance imaging (MRI) agents and a platform for drug delivery as well. Some key steps such as transferring hydrophobic UCNPs to the water phase by using cetyltrimethylammonium bromide (CTAB), removal of the excess amount of CTAB, and temperature-controlled ultrasonication treatment should be adopted and carefully monitored to obtain uniform upconversion core/mesoporous silica shell nanocomposites. The excellent performance of the core-shell-structured nanocomposite in near-infrared fluorescence and magnetic resonance imaging was also demonstrated.

A uniform sub-50 nm-sized magnetic/upconversion fluorescent bimodal imaging agent capable of generating singlet oxygen by using a 980 nm laser.

Upconverting nanoparticles (UCNPs) with fascinating properties hold great potential as nanotransducers for solving the problems that traditional photodynamic therapy (PDT) has been facing. In this report, by using well-selected bifunctional gadolinium (Gd)-ion-doped UCNPs and water-soluble methylene blue (MB) combined with the water-in-oil reverse microemulsion technique, we have succeeded in developing a new kind of UCNP/MB-based PDT drug, NaYF(4):Er/Yb/Gd@SiO(2)(MB), with a particle diameter less than 50 nm. Great efforts have been made to investigate the drug-formation mechanism and provide detailed physical and photochemical characterizations and the potential structure optimization of the as-designed PDT drug. We envision that such a PDT drug will become a potential theranostic nanomedicine for future near-infrared laser-triggered photodynamic therapy and simultaneous magnetic/optical bimodal imaging.

Prediction Breast Molecular Typing of Invasive Ductal Carcinoma Based on Dynamic Contrast Enhancement Magnetic Resonance Imaging Radiomics Characteristics: A Feasibility Study.

Objective: To investigate the feasibility of radiomics in predicting molecular subtype of breast invasive ductal carcinoma (IDC) based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: A total of 303 cases with pathologically confirmed IDC from January 2018 to March 2021 were enrolled in this study, including 223 cases from Fudan University Shanghai Cancer Center (training/test set) and 80 cases from Shaoxing Central Hospital (validation set). All the cases were classified as HR+/Luminal, HER2-enriched, and TNBC according to immunohistochemistry. DCE-MRI original images were treated by semi-automated segmentation to initially extract original and wavelet-transformed radiomic features. The extended logistic regression with least absolute shrinkage and selection operator (LASSO) penalty was applied to identify the optimal radiomic features, which were then used to establish predictive models combined with significant clinical risk factors. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis were adopted to evaluate the effectiveness and clinical benefit of the models established. Results: Of the 223 cases from Fudan University Shanghai Cancer Center, HR+/Luminal cancers were diagnosed in 116 cases (52.02%), HER2-enriched in 71 cases (31.84%), and TNBC in 36 cases (16.14%). Based on the training set, 788 radiomic features were extracted in total and 8 optimal features were further identified, including 2 first-order features, 1 gray-level run length matrix (GLRLM), 4 gray-level co-occurrence matrices (GLCM), and 1 3D shape feature. Three multi-class classification models were constructed by extended logistic regression: clinical model (age, menopause, tumor location, Ki-67, histological grade, and lymph node metastasis), radiomic model, and combined model. The macro-average areas under the ROC curve (macro-AUC) for the three models were 0.71, 0.81, and 0.84 in the training set, 0.73, 0.81, and 0.84 in the test set, and 0.76, 0.82, and 0.83 in the validation set, respectively. Conclusion: The DCE-MRI-based radiomic features are significant biomarkers for distinguishing molecular subtypes of breast cancer noninvasively. Notably, the classification performance could be improved with the fusion analysis of multi-modal features.

Redox chemistry-enabled stepwise surface dual nanoparticle engineering of 2D MXenes for tumor-sensitive T1 and T2 MRI-guided photonic breast-cancer hyperthermia in the NIR-II biowindow.

With the fast advent of two-dimensional (2D) MXenes, several therapeutic paradigms based on 2D MXenes flourish, but a generic strategy for MXene functionalization to achieve theranostic functionalities and desirable performance is still lacking. In this work, we report a facile and efficient stepwise surface-functionalization strategy to achieve distinct tumor microenvironment (TME)-responsive T1 and T2 magnetic resonance (MR) imaging-guided photothermal breast-cancer hyperthermia in the second near-infrared (NIR-II) biowindow. This approach is based on the stepwise growth of superparamagnetic Fe3O4 and paramagnetic MnOx nanocomponents onto the large surface of ultrathin 2D niobium carbide (Nb2C) MXene nanosheets (Fe3O4/MnOx-Nb2C) by making full use of the redox status/chemistry of the 2D MXene surface. Such a surface-nanoparticle engineering strategy endows Fe3O4/MnOx-Nb2C composite nanosheets with a series of properties that include high photothermal-conversion efficiency in the NIR-II biowindow (1064 nm, η 30.9%) for effective photothermal tumor eradication without further reoccurrence. It also allows TME-responsive T1- and T2-weighted MR imaging and high biocompatibility for guaranteeing further potential clinical transformation. This work not only makes the efficient diagnostic T1- and T2-weighted MR imaging-guided photonic hyperthermia of breast cancer possible, but also broadens the biomedical applications of MXene-based nanoplatforms by developing novel surface-engineering strategies to construct 2D Nb2C MXene-based composite multifunctional nanoplatforms.

Multifunctional mesoporous composite nanocapsules for highly efficient MRI-guided high-intensity focused ultrasound cancer surgery.

Bloodless surgical knife: Nano-biotechnology has been introduced into imaging-guided high-intensity focused ultrasound (HIFU) cancer surgery by adopting engineered multifunctional manganese-based mesoporous composite nanocapsules as the contrast agents for T(1)-weighted magnetic resonance imaging (MRI) and simultaneously as synergistic agents for MRI-guided HIFU cancer surgery.

The longitudinal associations between bone mineral density and appendicular skeletal muscle mass in Chinese community-dwelling middle aged and elderly men.

BACKGROUND: The present study aimed to investigate longitudinal associations between bone mineral densities (BMDs) and appendicular skeletal muscle (ASM) mass in different regions of the body using three different indicators, in Chinese community-dwelling middle-aged and elderly men. METHODS: A total of 1,343 men aged ≥ 40 years from a Chinese community were assessed at baseline (2014-2016), one-year follow-up (2016-2017; n = 648), two-year follow-up (2017-2018; n = 407), and three-year follow up (2018-2019; n = 208). At all the four time-points, measurements included ASM mass and BMDs for all regions of the body using dual-energy X-ray absorptiometry. A questionnaire was completed by patients and biochemical markers were assessed. We applied three different indicators to define ASM mass or lean mass respectively, including the appendicular skeletal muscle index (ASM adjusted by height, ASMI, according to the Asian Working Group for Sarcopenia), skeletal muscle index (ASM adjusted by weight, SMI, according to the International Working Group on Sarcopenia), and the appendicular skeletal muscle/body mass index (ratio of ASM and Body mass index (BMI), ASM/BMI, according to the Foundation for the National Institutes of Health). After adjusting for potential confounders, the generalized additive mixed model (GAMM) was used to analyze the trend in ASM mass over time, and to test the association between ASM mass and regional and whole-body BMDs. RESULTS: The incidence of low lean mass was 8.2% defined by ASMI, 16.3% defined by SMI, and 8.3% defined by ASM/BMI. There was a linear relationship between BMDs and ASM mass, and ASMI, ASM/BMI, and SMI gradually decreased with time. After adjusting for covariances, GAMM analysis determined longitudinal associations between BMDs and ASM mass by three indicators respectively: the skull BMD was negatively associated with ASM mass. For each unit increase in skull BMD, ASMI decreased by 0.28 kg/m2 (95% confidence interval (CI) [-0.39 to -0.16]), ASM/BMI decreased by 0.02 m2 (95% CI [-0.03 to -0.00]), and SMI decreased by 0.01% (95% CI[-0.01 to -0.00]). The remaining parameters (including whole-body mean BMD, thoracic spinal BMD, lumbar spinal BMD, hip BMD, femoral neck BMD, pelvic BMD, left arm BMD, right arm BMD, left leg BMD, right leg BMD) were positively correlated with ASM mass. The ASMI increased by 3.07 kg/m2for each unit increase in the femoral neck BMD (95% CI [2.31-3.84]). The ASM/BMI increased by 0.22 m2for each unit increase in the left arm BMD (95% CI [0.12-0.33]), and the SMI increased by 0.05% per unit increase in the left arm BMD (95% CI [0.02-0.08]). CONCLUSIONS: Compared to ASMI and ASM/BMI, SMI was more sensitive to screen for the low lean mass. Skull BMD was negatively associated with ASM mass, while BMDs throughout the rest of the body were positively correlated with ASM mass among the middle-aged and elderly Chinese men.