Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.

Determining bifurcations to explosive synchronization for networks of coupled oscillators with higher-order interactions.

We determine bifurcations from gradual to explosive synchronization in coupled oscillator networks with higher-order coupling using self-consistency analysis. We obtain analytic bifurcation values for generic symmetric natural frequency distributions. We show that nonsynchronized, drifting, oscillators are non-negligible and play a crucial role in bifurcation. As such, the entire natural frequency distribution must be accounted for, rather than just the shape at the center. We verify our results for Lorentzian- and Gaussian-distributed natural frequencies.

Exoskeleton-Assisted Rehabilitation and Neuroplasticity in Spinal Cord Injury.

Spinal cord injury (SCI) results in neurological deficits below the level of injury, causing motor dysfunction and various severe multisystem complications. Rehabilitative training plays a crucial role in the recovery of individuals with SCI, and exoskeleton serves as an emerging and promising tool for rehabilitation, especially in promoting neuroplasticity and alleviating SCI-related complications. This article reviews the classifications and research progresses of medical exoskeletons designed for SCI patients and describes their performances in practical application separately. Meanwhile, we discuss their mechanisms for enhancing neuroplasticity and functional remodeling, as well as their palliative impacts on secondary complications. The potential trends in exoskeleton design are raised according to current progress and requirements on SCI rehabilitation.

IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve.

BACKGROUND: The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. METHODS: A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION's CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. RESULTS: CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION's CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION's CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. CONCLUSION: IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.

Comparison of Edge of Lamina Block with Thoracic Paravertebral Block and Retrolaminar Block for Analgesic Efficacy in Adult Patients Undergoing Video-Assisted Thoracic Surgery: A Prospective Randomized Study.

Background: A novel ultrasound-guided paravertebral block, the edge laminar block (ELB) was reported recently. However, it was unclear how effective ELB was in comparison with traditional blocking methods. We conducted a trial to compare the analgesic efficacy of ELB with the thoracic paravertebral block (TPVB) and the retrolaminar block (RLB) in patients undergoing video-assisted thoracic surgery (VATS). Methods: We identified 90 patients who were scheduled for VATS and randomly assigned them to three groups: ELB group (Group E), TPVB group (Group T), and RLB group (Group R). Each group underwent ELB, TPVB, and RLB, respectively, under ultrasound guidance before general anesthesia induction. All patients received post-operative routine analgesia protocol. Our primary outcome was the extent of dermatomal sensory loss on the midclavicular, midaxillary, and scapular lines, measured using a pinprick 15 minutes after the nerve block. Secondary outcomes included the intraoperative dose of sufentanil, the numerical rating scale (NRS) scores assessed in the post-anesthesia care unit (PACU) and at 6, 12, and 24 hours post-operatively, and pethidine administrated as analgesic rescue dose. Results: The percentages of nerve block range reaching the midclavicular line, midaxillary line, and scapular line in Group E were 96.7%, 93.3%, 93.3%, and 60% in Group T and 30%, 56.7%, and 96.7% in Group R, respectively. Group E had wider dermatomal sensory loss on the midclavicular line and midaxillary line compared to Group R (P < 0.001) and had a wider range compared to Group T on the scapular line (P < 0.001). There was no significant difference in the intraoperative use of sufentanil in the three groups. Post-operative NRS scores at each time point were significantly lower in Group E than those in the other two groups (P < 0.01). Conclusion: ELB had a wider nerve block range and applied better post-operative analgesia in comparison with TPVB and RLB.

Postoperative Spinal 18 F-FDG PET Pseudoprogression Mimicking Malignancy.

ABSTRACT: A 60-year-old woman presented with left upper limb weakness. Spinal MRI revealed C2-C3 heterogeneous mass with no hypermetabolic foci on 18 F-FDG PET. Total resection was performed, and the pathology showed gliosis. Her limb weakness worsened 3 months after surgery. Spinal MRI revealed long intramedullary mass from medulla oblongata to C5, which showed obvious hypermetabolism under 18 F-FDG PET with an SUV max of 7.11, but 18 F-FET PET indicated mild hypermetabolism with an SUV max of 2.29. Malignancy was suspected, and C2-C4 biopsy was performed. The pathology results confirmed the diagnosis of gliosis, and the postoperative spinal 18 F-FDG PET results were considered pseudoprogression.

Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.

BACKGROUND: Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined. METHODS: The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate the cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data indicating a high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines. RESULTS: Differences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and their biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital. We further evaluated the clinical significance of the BM-index and identified 7 drugs that potentially target BMAECs. CONCLUSIONS: This study clarified possible cellular origins and drivers of metastatic LUAD at the single-cell level and laid a foundation for early detection of LUAD patients with a high risk of BM.

Efficient Construction of Symmetrical Diaryl Sulfides via a Supported Pd Nanocatalyst-Catalyzed C-S Coupling Reaction.

Aryl sulfides play an important role in pharmaceuticals, biologically active molecules and polymeric materials. Herein, a general and efficient protocol for Pd@COF-TB (a kind of Pd nanocatalyst supported by a covalent organic framework)/DIPEA-catalyzed one-pot synthesis of symmetrical diaryl sulfides through a C-S coupling reaction from aryl iodides and Na2S2O3 is developed. More importantly, the addition of N,N-diisopropylethylamine (DIPEA) can not only enhance the catalytic activity of a Pd@COF-TB nanocatalyst, but also effectively inhibit the formation of biphenyl byproducts, which are a product of Ullmann reaction. Besides, it has been confirmed that the aryl Bunte salts generated in situ from Na2S2O3 and aryl iodides are the sulfur sources involved in this C-S coupling reaction. With the strategy proposed in this work, a variety of symmetrical diaryl sulfides could be obtained in moderate to excellent yields with a high tolerance of various functional groups. Moreover, a possible mechanism of this Pd nanoparticle-catalyzed C-S coupling reaction is proposed based on the results of controlling experiments.

Tumor-Treating Fields in Glioblastomas: Past, Present, and Future.

Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of glioblastomas (GBMs), the most deadly primary brain cancer. According to on recent milestone randomized trials and subsequent observational data, TTFields therapy leads to substantially prolonged patient survival and acceptable adverse events. Clinical trials are ongoing to further evaluate the safety and efficacy of TTFields in treating GBMs and its biological and radiological correlations. TTFields is administered by delivering low-intensity, intermediate-frequency, alternating electric fields to human GBM function through different mechanisms of action, including by disturbing cell mitosis, delaying DNA repair, enhancing autophagy, inhibiting cell metabolism and angiogenesis, and limiting cancer cell migration. The abilities of TTFields to strengthen intratumoral antitumor immunity, increase the permeability of the cell membrane and the blood-brain barrier, and disrupt DNA-damage-repair processes make it a promising therapy when combined with conventional treatment modalities. However, the overall acceptance of TTFields in real-world clinical practice is still low. Given that increasing studies on this promising topic have been published recently, we conducted this updated review on the past, present, and future of TTFields in GBMs.

Multi-Omics Investigations Revealed Underlying Molecular Mechanisms Associated With Tumor Stiffness and Identified Sunitinib as a Potential Therapy for Reducing Stiffness in Pituitary Adenomas.

Purpose: Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients. Methods: RNA sequencing, whole-genome bisulfite sequencing, and whole exome sequencing were applied to identify transcriptomic, epigenomic, and genomic underpinnings among 11 soft and 11 stiff PA samples surgically resected from patients at Peking Union Medical College Hospital (PUMCH). GH3 cell line and xenograft PA model was used to demonstrate therapeutic effect of sunitinib, and atomic force microscopy (AFM) was used to detect the stiffness of tumors. Results: Tumor microenvironment analyses and immunofluorescence staining indicated endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) were more abundant in stiff PAs. Weighted gene coexpression network analysis identified the most critical stiffness-related gene (SRG) module, which was highly correlated with stiff phenotype, ECs and CAFs. Functional annotations suggested SRGs might regulate PA stiffness by regulating the development, differentiation, and apoptosis of ECs and CAFs and related molecular pathways. Aberrant DNA methylation and m6A RNA modifications were investigated to play crucial roles in regulating PA stiffness. Somatic mutation analysis revealed increased intratumoral heterogeneity and decreased response to immunotherapy in stiff tumors. Connectivity Map analysis of SRGs and pRRophetic algorithm based on drug sensitivity data of cancer cell lines finally determine sunitinib as a promising agent targeting stiff tumors. Sunitinib inhibited PA growth in vitro and in vivo, and also reduced tumor stiffness in xenograft PA models detected by AFM. Conclusion: This is the first study investigating the underlying mechanisms contributing to the stiffening of PAs, and providing novel insights into medication therapy for stiff PAs.

Skull modulated strategies to intensify tumor treating fields on brain tumor: a finite element study.

Tumor treating fields (TTFields) are a breakthrough in treating glioblastoma (GBM), whereas the intensity cannot be further enhanced, due to the limitation of scalp lesions. Skull remodeling (SR) surgery can elevate the treatment dose of TTFields in the intracranial foci. This study was aimed at exploring the characteristics of the skull modulated strategies toward TTFields augmentation. The simplified multiple-tissue-layer model (MTL) and realistic head (RH) model were reconstructed through finite element methods (FEM), to simulate the remodeling of the skull, which included skull drilling, thinning, and cranioplasty with PEEK, titanium, cerebrospinal fluid (CSF), connective tissue and autologous bone. Skull thinning could enhance the intensity of TTFields in the brain tumor, with a 10% of increase in average peritumoral intensity (API) by every 1 cm decrease in skull thickness. Cranioplasty with titanium accompanied the most enhancement of TTFields in the MTL model, but CSF was superior in TTFields enhancement when simulated in the RH model. Besides, API increased nonlinearly with the expansion of drilled burr holes. In comparison with the single drill replaced by titanium, nine burr holes could reach 96.98% of enhancement in API, but it could only reach 63.08% of enhancement under craniectomy of nine times skull defect area. Skull thinning and drilling could enhance API, which was correlated with the number and area of skull drilling. Cranioplasty with highly conductive material could also augment API, but might not provide clinical benefits as expected.

Effects of oncolytic viruses and viral vectors on immunity in glioblastoma.

Glioblastoma (GBM) is regarded as an incurable disease due to its poor prognosis and limited treatment options. Virotherapies were once utilized on cancers for their oncolytic effects. And they are being revived on GBM treatment, as accumulating evidence presents the immunogenic effects of virotherapies in remodeling immunosuppressive GBM microenvironment. In this review, we focus on the immune responses induced by oncolytic virotherapies and viral vectors in GBM. The current developments of GBM virotherapies are briefly summarized, followed by a detailed depiction of their immune response. Limitations and lessons inferred from earlier experiments and trials are discussed. Moreover, we highlight the importance of engaging the immune responses induced by virotherapies into the multidisciplinary management of GBM.

Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials.

Recurrence is a major concern for adult patients with glioblastomas (GBMs), and the prognosis remains poor. Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM (rGBM). Here, we review the results of clinical trials for the systematic therapy of rGBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1 (PD-1) inhibitors are promising agents for rGBM, while regorafenib is effective in both O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase (IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec (Toca 511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.

Oncogenesis, Microenvironment Modulation and Clinical Potentiality of FAP in Glioblastoma: Lessons Learned from Other Solid Tumors.

Currently, glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. Fibroblast activation protein (FAP) is a member of the dipeptidyl peptidase family, which has catalytic activity and is engaged in protein recruitment and scaffolds. Recent studies have found that FAP expression in different types of cells within the GBM microenvironment is typically upregulated compared with that in lower grade glioma and is most pronounced in the mesenchymal subtype of GBM. As a marker of cancer-associated fibroblasts (CAFs) with tumorigenic activity, FAP has been proven to promote tumor growth and invasion via hydrolysis of molecules such as brevican in the extracellular matrix and targeting of downstream pathways and substrates, such as fibroblast growth factor 21 (FGF21). In addition, based on its ability to suppress antitumor immunity in GBM and induce temozolomide resistance, FAP may be a potential target for immunotherapy and reversing temozolomide resistance; however, current studies on therapies targeting FAP are still limited. In this review, we summarized recent progress in FAP expression profiling and the understanding of the biological function of FAP in GBM and raised the possibility of FAP as an imaging biomarker and therapeutic target.

Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation.

Background: Glioblastoma (GBM) is the most common primary malignant intracranial tumor and closely related to metabolic alteration. However, few accepted prognostic models are currently available, especially models based on metabolic genes. Methods: The transcriptome data were obtained for all of the patients diagnosed with GBM from the Gene Expression Omnibus (GEO) (training cohort, n=369) and The Cancer Genome Atlas (TCGA) (validation cohort, n=152) with the following variables: age at diagnosis, sex, follow-up and overall survival (OS). Metabolic genes according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were contracted, and a Lasso regression model was constructed. Survival was assessed by univariate or multivariate Cox proportional hazards regression and Kaplan-Meier analysis, and an independent external validation was also conducted to examine the model. Results: There were 341 metabolic genes showed significant differences between normal brain and GBM tissues in both the training and validation cohorts, among which 56 genes were dramatically correlated to the OS of patients. Lasso regression revealed that the metabolic prognostic model was composed of 18 genes, including COX10, COMT, and GPX2 with protective effects, as well as OCRL and RRM2 with unfavorable effects. Patients classified as high-risk by the risk score from this model had markedly shorter OS than low-risk patients (P<0.0001), and this significant result was also observed in independent external validation (P<0.001). Conclusions: The prognosis of GBM was dramatically related to metabolic pathways, and our metabolic prognostic model had high accuracy and application value in predicting the OS of GBM patients.

Awareness of thyroid cancer among medical students: A questionnaire-based study.

To investigate whether medical students acquire enough knowledge about thyroid cancer (TC). It was a cross-sectional study in a Chinese medical college based on a questionnaire about the knowledge of TC and thyroid self-examination. Medical students enrolled were grouped into preclinical medical students (PMS) and clinical medical students (CMS) according to their grades. A total of 337 questionnaires were distributed and 274 effective responses were collected with 129 from PMS and 145 from CMS. The percentage of thyroid self-examination in CMS was higher than that of PMS (55.8% vs 11.6%, p < 0.001). Generally, CMS had better comprehension of TC, including prognosis (97.2% vs 64.5%, p < 0.001), diagnosis (95.6% vs 33.1%, p < 0.001), and surgery indications (82.1% vs 58.1%, p = 0.001). There was no significant difference between PMS and CMS on the acquaintance of the risk factors. However, more CMS stated that the below 5% of thyroid nodules might turn malignant (45.5% vs 6.5%, p < 0.001), and more CMS suggested that people without nodules should receive TC screening tests (62.1% vs 41.9%, p = 0.001). Medical education on TC was effective in teaching clinical knowledge. Medical school should focus more on preclinical general health education and clinical practices education in the future.

Optimal Therapies for Recurrent Glioblastoma: A Bayesian Network Meta-Analysis.

The optimal treatment of recurrent glioblastoma (GBM) remains controversial. Therefore, our study aimed to compare and rank active therapies in recurrent GBM. We performed a systematic review and a Bayesian network meta-analysis. We obtained a treatment hierarchy using the surface under the cumulative ranking curve and mean ranks. A cluster analysis was conducted to aggregate the separated results of three outcomes. The protocol was registered in PROSPERO (CRD42019146794). A total of 1,667 citations were identified, and 15 eligible articles with 17 treatments remained in the final network meta-analysis. Pairwise comparison showed no significant difference on the 6-month progression-free survival (6-m PFS) rate, objective response rate (ORR), and overall survival (OS). Among the reports, cediranib plus lomustine (CCNU) corresponded to the highest rates of grade 3-4 adverse events. Ranking and cluster analysis indicated that bevacizumab (BEV) plus CCNU and regorafenib had a higher efficacy on the ORR, 6-m PFS rate and OS, and that BEV monotherapy or BEV combined with active drug therapies was advantageous for the ORR and 6-m PFS rate. Additionally, tumor treatment fields (TTF) plus BEV showed a relatively higher SUCRA value in OS. According to ranking and cluster analysis, BEV plus CCNU and regorafenib are the primary recommendations for treatment. BEV monotherapy alone or combined with active drug therapies are recommended in patients with severe neurological symptoms. Advanced therapy, such as TTF and immunotherapy, remain to be investigated in future studies.

Role of traditional CHO PET parameters in distinguishing IDH, TERT and MGMT alterations in primary diffuse gliomas.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status are diagnostic, prognostic, predictive and therapeutic biomarkers for primary diffuse gliomas, and this study aimed to explore the relationship between choline (CHO) positron emission tomography (PET) parameters and these molecular alterations. METHODS: Twenty-eight patients who were histopathologically diagnosed with primary diffuse glioma and underwent presurgical CHO PET/CT were retrospectively analyzed, and IDH, TERT and MGMT alterations were examined. The volume of interest (VOI) was semiautomatically defined based on standardized uptake value (SUV) thresholds, and 5 traditional CHO parameters, namely, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion CHO uptake (TLC) and tumor-to-normal contralateral cortex activity ratio (T/N ratio), were calculated. Wilcoxon rank-sum tests and receiver operating characteristic (ROC) curves were applied to evaluate the differences and performances of the CHO parameters, and their capability to stratify patient prognosis was also evaluated. RESULTS: All 5 parameters were significantly higher in IDH-wildtype gliomas than in IDH-mutant gliomas (p = 0.0001-0.037), and SUVmax, SUVmean, TLC and the T/N ratio exhibited good performances in distinguishing the IDH status (areas under the ROC curve (AUCs) 0.856-0.918, accuracies 0.857-0.893) as well as stratifying patient prognosis. Although the differences and performances of the traditional parameters in distinguishing diverse TERT and MGMT statuses were moderate in the whole population, the T/N ratio and TLC displayed certain predictive value in discriminating the TERT status in the IDH-mutant and IDH-wildtype subgroups (p = 0.028-0.048, AUCs 0.857-0.860, accuracies 0.800-0.917, respectively). CONCLUSIONS: Traditional CHO PET parameters are capable of distinguishing IDH but not TERT or MGMT alterations in the whole population. In accordance with the clinical understanding of TERT promoter mutations, the T/N ratio and TLC can also discriminate the TERT status in IDH subgroups.

Radiotherapy in combination with systemic therapies for brain metastases: current status and progress.

Brain metastases (BMs) are the most common cause of intracranial neoplasms in adults with poor prognosis. Most BMs originate from lung cancer, breast cancer, or melanoma. Radiotherapy (RT), including whole brain radiotherapy (WBRT) and stereotactic radiation surgery (SRS), has been widely explored and is considered a mainstay anticancer treatment for BMs. Over the past decade, the advent of novel systemic therapies has revolutionized the treatment of BMs. In this context, there is a strong rationale for using a combination of treatments based on RT, with the aim of achieving both local disease control and extracranial disease control. This review focuses on describing the latest progress in RT as well as the synergistic effects of the optimal combinations of RT and systemic treatment modalities for BMs, to provide perspectives on current treatments.

Thin-Slice Magnetic Resonance Imaging-Based Radiomics Signature Predicts Chromosomal 1p/19q Co-deletion Status in Grade II and III Gliomas.

Objective: Chromosomal 1p/19q co-deletion is recognized as a diagnostic, prognostic, and predictive biomarker in lower grade glioma (LGG). This study aims to construct a radiomics signature to non-invasively predict the 1p/19q co-deletion status in LGG. Methods: Ninety-six patients with pathology-confirmed LGG were retrospectively included and randomly assigned into training (n = 78) and validation (n = 18) dataset. Three-dimensional contrast-enhanced T1 (3D-CE-T1)-weighted magnetic resonance (MR) images and T2-weighted MR images were acquired, and simulated-conventional contrast-enhanced T1 (SC-CE-T1)-weighted images were generated. One hundred and seven shape, first-order, and texture radiomics features were extracted from each imaging modality and selected using the least absolute shrinkage and selection operator on the training dataset. A 3D-radiomics signature based on 3D-CE-T1 and T2-weighted features and a simulated-conventional (SC) radiomics signature based on SC-CE-T1 and T2-weighted features were established using random forest. The radiomics signatures were validated independently and evaluated using receiver operating characteristic (ROC) curves. Tumors with IDH mutations were also separately assessed. Results: Four radiomics features were selected to construct the 3D-radiomics signature and displayed accuracies of 0.897 and 0.833, areas under the ROC curves (AUCs) of 0.940 and 0.889 in the training and validation datasets, respectively. The SC-radiomics signature was constructed with 4 features, but the AUC values were lower than that of the 3D signature. In the IDH-mutated subgroup, the 3D-radiomics signature presented AUCs of 0.950-1.000. Conclusions: The MRI-based radiomics signature can differentiate 1p/19q co-deletion status in LGG with or without predetermined IDH status. 3D-CE-T1-weighted radiomics features are more favorable than SC-CE-T1-weighted features in the establishment of radiomics signatures.