In vivo imaging of nanoparticle-labeled CAR T cells.

Metastatic osteosarcoma has a poor prognosis with a 2-y, event-free survival rate of ∼15 to 20%, highlighting the need for the advancement of efficacious therapeutics. Chimeric antigen receptor (CAR) T-cell therapy is a potent strategy for eliminating tumors by harnessing the immune system. However, clinical trials with CAR T cells in solid tumors have encountered significant challenges and have not yet demonstrated convincing evidence of efficacy for a large number of patients. A major bottleneck for the success of CAR T-cell therapy is our inability to monitor the accumulation of the CAR T cells in the tumor with clinical-imaging techniques. To address this, we developed a clinically translatable approach for labeling CAR T cells with iron oxide nanoparticles, which enabled the noninvasive detection of the iron-labeled T cells with magnetic resonance imaging (MRI), photoacoustic imaging (PAT), and magnetic particle imaging (MPI). Using a custom-made microfluidics device for T-cell labeling by mechanoporation, we achieved significant nanoparticle uptake in the CAR T cells, while preserving T-cell proliferation, viability, and function. Multimodal MRI, PAT, and MPI demonstrated homing of the T cells to osteosarcomas and off-target sites in animals administered with T cells labeled with the iron oxide nanoparticles, while T cells were not visualized in animals infused with unlabeled cells. This study details the successful labeling of CAR T cells with ferumoxytol, thereby paving the way for monitoring CAR T cells in solid tumors.

Artificial intelligence-based radiomics in bone tumors: Technical advances and clinical application.

Radiomics is the extraction of predefined mathematic features from medical images for predicting variables of clinical interest. Recent research has demonstrated that radiomics can be processed by artificial intelligence algorithms to reveal complex patterns and trends for diagnosis, and prediction of prognosis and response to treatment modalities in various types of cancer. Artificial intelligence tools can utilize radiological images to solve next-generation issues in clinical decision making. Bone tumors can be classified as primary and secondary (metastatic) tumors. Osteosarcoma, Ewing sarcoma, and chondrosarcoma are the dominating primary tumors of bone. The development of bone tumor model systems and relevant research, and the assessment of novel treatment methods are ongoing to improve clinical outcomes, notably for patients with metastases. Artificial intelligence and radiomics have been utilized in almost full spectrum of clinical care of bone tumors. Radiomics models have achieved excellent performance in the diagnosis and grading of bone tumors. Furthermore, the models enable to predict overall survival, metastases, and recurrence. Radiomics features have exhibited promise in assisting therapeutic planning and evaluation, especially neoadjuvant chemotherapy. This review provides an overview of the evolution and opportunities for artificial intelligence in imaging, with a focus on hand-crafted features and deep learning-based radiomics approaches. We summarize the current application of artificial intelligence-based radiomics both in primary and metastatic bone tumors, and discuss the limitations and future opportunities of artificial intelligence-based radiomics in this field. In the era of personalized medicine, our in-depth understanding of emerging artificial intelligence-based radiomics approaches will bring innovative solutions to bone tumors and achieve clinical application.

Case 326: Intra-Articular Osteoid Osteoma.

HISTORY: A 15-year-old male patient presented with a 3-week history of inner left thigh pain provoked by activity and experienced occasionally at rest. The patient denied nighttime pain, fever, or chills. Laboratory investigation revealed the following normal values: hemoglobin level of 15.6 g/dL (normal range, 13-16 g/dL), platelet count of 240 × 103/µL (normal range, 140-440 × 103/µL), and total leukocyte count of 7100 cells/µL (normal range, 4500-11 000 cells/µL). The percentage of neutrophils was considered low at 44% (normal range, 54%-62%), and the percentage of eosinophils was slightly high at 3.7% (normal range, 0%-3%). An anteroposterior radiograph of the left hip is shown. Physical therapy was initiated, with no improvement after 2 weeks of therapy. The patient was referred to an orthopedist for further evaluation. At physical examination, the patient endorsed marked left hip pain with hip flexion to 90°, limited internal and external rotation (5° and 15°, respectively), and antalgic gait favoring the left leg. Hip MRI and further serologic analysis were requested for further evaluation. Although the serologic testing was performed at an outside laboratory, the physician reported positive immunoglobulin-G Lyme titers, normal C-reactive protein level, and normal erythrocyte sedimentation rate. Pelvic CT was requested. The patient was prescribed a course of doxycycline (100 mg twice daily for 28 days), with reported resolution of symptoms 2 weeks after initiation of treatment. Three weeks later, the patient presented to our department with recurrent left hip pain, which was similar in severity compared with the initial presentation. A second MRI examination of the left hip was performed 4 months after the initial presentation.

Impact of Surveillance Imaging in Detecting Local and Metastatic Lung Recurrences Among Patients with Sarcomas of the Extremities: A Systematic Review and Meta-analysis.

BACKGROUND: The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas. PATIENTS AND METHODS: A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I2 statistics. Sensitivity analysis was assessed using influence plots and Baujat plots. RESULTS: Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging. CONCLUSION: The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions.

BACKGROUND: Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies. METHODS: Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time. RESULTS: Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points. CONCLUSION: Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

Imaging Assessment of the Efficacy of Chemotherapy in Primary Malignant Bone Tumors: Recent Advances in Qualitative and Quantitative Magnetic Resonance Imaging and Radiomics.

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Spectral CT assists differentiation of osteoblastic bone metastasis from bone island in newly diagnosed cancer patients.

OBJECTIVES: To investigate measurements derived from plain and enhanced spectral CT in differentiating osteoblastic bone metastasis (OBM) from bone island (BI). MATERIALS AND METHODS: From January to November 2020, 73 newly diagnosed cancer patients with 201 bone lesions (OBM = 92, BI = 109) having received spectral CT were retrospectively enrolled. Measurements including CT values of 40-140 keV, slope of the spectral curve, effective atomic number (Zeff), water (calcium) density, calcium (water) density, and Iodine (calcium) density were derived from manually segmented lesions on plain and enhanced spectral CT, and then analyzed using Student t-test and Pearson's correlation. Multivariate analysis was performed to build models (plain spectral model, enhanced spectral CT model, and combined model) for the discrimination of OBM and BI with performance evaluated using receiver operator characteristics curve and DeLong test. RESULTS: All features were significantly different between the BI group and OBM group (all p < 0.05), highly correlated with the corresponding features between plain and enhanced spectral CT both in OBM (r: 0.392-0.763) and BI (r: 0.430-0.544). As for the model performance, the combined model achieved the best performance (AUC = 0.925, 95% CI: 0.879 to 0.957), which significantly outperformed the plain spectral CT model (AUC = 0.815, 95% CI: 0.754 to 0.866, p < 0.001) and enhanced spectral CT model (AUC = 0.901, 95% CI: 0.852 to 0.939, p = 0.024) in differentiating OBM and BI. CONCLUSION: In addition to plain spectral CT measurements, enhanced spectral CT measurements would further significantly benefit the differential diagnosis. CLINICAL RELEVANCE STATEMENT: Measurements derived either from plain or enhanced spectral CT could provide additional valuable information to improve the differential diagnosis between OBM and BI in newly diagnosed cancer patients. KEY POINTS: • We intend to investigate plain and enhanced spectral CT measurements in differentiating OBM from BI. • Both plain and enhanced spectral CT help in discriminating OBM and BI in newly diagnosed cancer patients. • Enhanced spectral CT measurements further improve plain spectral CT measurements-based differential diagnosis.

Automatic detection, segmentation, and classification of primary bone tumors and bone infections using an ensemble multi-task deep learning framework on multi-parametric MRIs: a multi-center study.

OBJECTIVES: To develop an ensemble multi-task deep learning (DL) framework for automatic and simultaneous detection, segmentation, and classification of primary bone tumors (PBTs) and bone infections based on multi-parametric MRI from multi-center. METHODS: This retrospective study divided 749 patients with PBTs or bone infections from two hospitals into a training set (N = 557), an internal validation set (N = 139), and an external validation set (N = 53). The ensemble framework was constructed using T1-weighted image (T1WI), T2-weighted image (T2WI), and clinical characteristics for binary (PBTs/bone infections) and three-category (benign/intermediate/malignant PBTs) classification. The detection and segmentation performances were evaluated using Intersection over Union (IoU) and Dice score. The classification performance was evaluated using the receiver operating characteristic (ROC) curve and compared with radiologist interpretations. RESULT: On the external validation set, the single T1WI-based and T2WI-based multi-task models obtained IoUs of 0.71 ± 0.25/0.65 ± 0.30 for detection and Dice scores of 0.75 ± 0.26/0.70 ± 0.33 for segmentation. The framework achieved AUCs of 0.959 (95%CI, 0.955-1.000)/0.900 (95%CI, 0.773-0.100) and accuracies of 90.6% (95%CI, 79.7-95.9%)/78.3% (95%CI, 58.1-90.3%) for the binary/three-category classification. Meanwhile, for the three-category classification, the performance of the framework was superior to that of three junior radiologists (accuracy: 65.2%, 69.6%, and 69.6%, respectively) and comparable to that of two senior radiologists (accuracy: 78.3% and 78.3%). CONCLUSION: The MRI-based ensemble multi-task framework shows promising performance in automatically and simultaneously detecting, segmenting, and classifying PBTs and bone infections, which was preferable to junior radiologists. CLINICAL RELEVANCE STATEMENT: Compared with junior radiologists, the ensemble multi-task deep learning framework effectively improves differential diagnosis for patients with primary bone tumors or bone infections. This finding may help physicians make treatment decisions and enable timely treatment of patients. KEY POINTS: • The ensemble framework fusing multi-parametric MRI and clinical characteristics effectively improves the classification ability of single-modality models. • The ensemble multi-task deep learning framework performed well in detecting, segmenting, and classifying primary bone tumors and bone infections. • The ensemble framework achieves an optimal classification performance superior to junior radiologists' interpretations, assisting the clinical differential diagnosis of primary bone tumors and bone infections.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

OBJECTIVE: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. METHODS: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. RESULTS: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement. CONCLUSION: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. CLINICAL RELEVANCE STATEMENT: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. KEY POINTS: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

A retrospective external validation study of the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) for the management of solitary central cartilage tumours of the proximal humerus and around the knee.

OBJECTIVES: This study aimed to externally validate the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) recommendations for differentiation/follow-up of central cartilage tumours (CCTs) of the proximal humerus, distal femur, and proximal tibia and to propose BACTIP adaptations if the results provide new insights. METHODS: MRIs of 123 patients (45 ± 11 years, 37 men) with an untreated CCT with MRI follow-up (n = 62) or histopathological confirmation (n = 61) were retrospectively/consecutively included and categorised following the BACTIP (2003-2020 / Ghent University Hospital/Belgium). Tumour length and endosteal scalloping differences between enchondroma, atypical cartilaginous tumour (ACT), and high-grade chondrosarcoma (CS II/III/dedifferentiated) were evaluated. ROC-curve analysis for differentiating benign from malignant CCTs and for evaluating the BACTIP was performed. RESULTS: For lesion length and endosteal scalloping, ROC-AUCs were poor and fair-excellent, respectively, for differentiating different CCT groups (0.59-0.69 versus 0.73-0.91). The diagnostic performance of endosteal scalloping and the BACTIP was higher than that of lesion length. A 1° endosteal scalloping cut-off differentiated enchondroma from ACT + high-grade chondrosarcoma with a sensitivity of 90%, reducing the potential diagnostic delay. However, the specificity was 29%, inducing overmedicalisation (excessive follow-up). ROC-AUC of the BACTIP was poor for differentiating enchondroma from ACT (ROC-AUC = 0.69; 95%CI = 0.51-0.87; p = 0.041) and fair-good for differentiation between other CCT groups (ROC-AUC = 0.72-0.81). BACTIP recommendations were incorrect/unsafe in five ACTs and one CSII, potentially inducing diagnostic delay. Eleven enchondromas received unnecessary referrals/follow-up. CONCLUSION: Although promising as a useful tool for management/follow-up of CCTs of the proximal humerus, distal femur, and proximal tibia, five ACTs and one chondrosarcoma grade II were discharged, potentially inducing diagnostic delay, which could be reduced by adapting BACTIP cut-off values. CLINICAL RELEVANCE STATEMENT: Mostly, Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) assesses central cartilage tumours of the proximal humerus and the knee correctly. Both when using the BACTIP and when adapting cut-offs, caution should be taken for the trade-off between underdiagnosis/potential diagnostic delay in chondrosarcomas and overmedicalisation in enchondromas. KEY POINTS: • This retrospective external validation confirms the Birmingham Atypical Cartilage Tumour Imaging Protocol as a useful tool for initial assessment and follow-up recommendation of central cartilage tumours in the proximal humerus and around the knee in the majority of cases. • Using only the Birmingham Atypical Cartilage Tumour Imaging Protocol, both atypical cartilaginous tumours and high-grade chondrosarcomas (grade II, grade III, and dedifferentiated chondrosarcomas) can be misdiagnosed, excluding them from specialist referral and further follow-up, thus creating a potential risk of delayed diagnosis and worse prognosis. • Adapted cut-offs to maximise detection of atypical cartilaginous tumours and high-grade chondrosarcomas, minimise underdiagnosis and reduce potential diagnostic delay in malignant tumours but increase unnecessary referral and follow-up of benign tumours.

Intra-articular Osteoid Osteomas: Imaging Manifestations and Mimics.

Osteoid osteoma (OO) is the third most prevalent benign bone neoplasm in children. Although it predominantly affects the diaphysis of long bones, OO can assume an intra-articular location in the epiphysis or the intracapsular portions of bones. The most common location of intra-articular OO is the hip joint. The presentation of intra-articular OOs often poses a diagnostic enigma, both from clinical and radiologic perspectives. Initial symptoms are often vague and nonspecific, characterized by joint pain, stiffness, and limited range of motion, which frequently contributes to a delayed diagnosis. Radiographic findings range from normal to a subtle sclerotic focus, which may or may not have a lucent nidus. In contrast to their extra-articular counterparts, intra-articular lesions have distinct features at MRI, including synovitis, joint effusion, and bone marrow edema-like signal intensity. While CT remains the standard for identifying the nidus, even CT may be inadequate in visualizing it in some cases, necessitating the use of bone scintigraphy or fluorine 18-labeled sodium fluoride PET/CT for definitive diagnosis. Radiologists frequently play a pivotal role in suggesting this diagnosis. However, familiarity with the unique imaging attributes of intra-articular OO is key to this endeavor. Awareness of these distinctive imaging findings of intra-articular OO is crucial for avoiding diagnostic delay, ensuring timely intervention, and preventing unnecessary procedures or surgeries resulting from a misdiagnosis. The authors highlight and illustrate the different manifestations of intra-articular OO as compared with the more common extra-articular lesions with respect to clinical presentation and imaging findings. ©RSNA, 2024 Supplemental material is available for this article.

Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Can Differentiate Between Atypical Cartilaginous Tumors and High-Grade Chondrosarcoma: Correlation With Histological Vessel Characteristics.

OBJECTIVE: To differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma of the major long bones using intravoxel incoherent motion (IVIM) and Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI), and explore the correlation of quantitative parameters with hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density (MVD). METHOD: Between September 2016 and March 2022, 35 patients (17 atypical cartilaginous tumors, 18 high-grade chondrosarcoma) underwent MRI examination and pathological confirmation at our hospital. First, IVIM-derived parameters ( D , D* , and f ), and DCE-MRI parameters ( Ktrans , Kep , and V e ) were measured, and intraclass correlation efficient (ICC) and Mann-Whitney U test were performed. Second, receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Finally, Spearman's correlation analysis was performed between the quantitative parameters of IVIM-DWI and DCE-MRI and the immunohistochemical factors HIF-1α, VEGF, and MVD in chondrosarcoma tissue. RESULTS: D in atypical cartilaginous tumors was significantly higher than that in high-grade chondrosarcoma ( P = 0.003), whereas D* , Ktrans , and K ep in atypical cartilaginous tumors were significantly lower than those in high-grade chondrosarcoma (all P < 0.001). Ktrans demonstrated the highest area under the curve (AUC) of 0.979. The D* , Ktrans , and K ep were positively correlated with HIF-1α, VEGF, and MVD (all P < 0.001), whereas D had no correlation with HIF-1α, VEGF, and MVD ( P = 0.113, 0.077, 0.058, respectively). CONCLUSION: The IVIM-DWI quantitative parameters ( D , D* ) and DCE-MRI quantitative parameters ( Ktrans , Kep ) are helpful to differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma and could be imaging biomarkers to reflect the expressions of HIF-1α, VEGF, and angiogenesis of chondrosarcoma.

Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Neoplastic and Non-neoplastic Bone Lesions of the Knee.

Numerous anatomical variants are described around the knee, many of which look like bony lesions, so it is important to know them to avoid unnecessary complementary tests and inadequate management. Likewise, several alterations in relation to normal development can also simulate bone lesions.However, numerous pathologic processes frequently affect the knee, including traumatic, inflammatory, infectious, and tumor pathology. Many of these entities show typical radiologic features that facilitate their diagnosis. In other cases, a correct differential diagnosis is necessary for proper clinical management.Despite the availability of increasingly advanced imaging techniques, plain radiography is still the technique of choice in the initial study of many of these pathologies. This article reviews the radiologic characteristics of tumor and nontumor lesions that may appear around the knee to make a correct diagnosis and avoid unnecessary complementary radiologic examinations and inadequate clinical management.

Preoperative prediction of histopathological grading in patients with chondrosarcoma using MRI-based radiomics with semantic features.

BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.

Predictors of pulmonary metastases on chest computed tomography in children and adolescents with osteosarcoma-tips for qualifying patients for thoracotomy.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies. METHODS: Sixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified. RESULTS: All applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72-92%), positive predictive value (81-90%) and accuracy (74-79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables. CONCLUSIONS: The multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.

Histograms of computed tomography values in differential diagnosis of benign and malignant osteogenic lesions.

BACKGROUND: The use of histogram analysis of computed tomography (CT) values is a potential method for differentiating between benign osteoblastic lesions (BOLs) and malignant osteoblastic lesions (MOLs). PURPOSE: To explore the diagnostic efficacy of histogram analysis in accurately distinguishing between BOLs and MOLs based on CT values. MATERIAL AND METHODS: A total of 25 BOLs and 25 MOLs, which were confirmed through pathology or imaging follow-up, were included in this study. FireVoxel software was used to process the lesions and obtain various histogram parameters, including mean value, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy value, and percentiles ranging from 1st to 99th. Statistical tests, such as two independent-sample t-tests and the Mann-Whitney U test with Bonferroni correction, were employed to compare the differences in histogram parameters between BOLs and MOLs. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of each parameter. RESULTS: Significant differences were observed in several histogram parameters between BOLs and MOLs, including the mean value, coefficient of variation, skewness, and various percentiles. Notably, the 25th percentile demonstrated the highest diagnostic efficacy, as indicated by the largest area under the curve in the ROC curve analysis. CONCLUSION: Histogram analysis of CT values provides valuable diagnostic information for accurately differentiating between BOLs and MOLs. Among the different parameters, the 25th percentile parameter proves to be the most effective in this discrimination process.

Does A Single Osteotomy Technique for Frozen Autograft (Pedicled Freezing) in Patients With Malignant Bone Tumors of the Long Bones Achieve Union and Local Tumor Control?

BACKGROUND: Biological reconstruction by replanting the resected tumor-bearing segment is preferred by some surgeons when caring for a patient with a bone sarcoma. Frozen autografts are advantageous because they are cost-effective, provide an excellent fit, permit the maintenance of osteoinductive and osteoconductive properties, and are not associated with transmission of viral disease. The pedicle frozen autograft technique, in which only one osteotomy is made for the freezing procedure, keeping the affected segment in continuity with the host bone and soft tissue instead of two osteotomies, maintains the affected segment with the host bone and soft tissue. This could restore blood flow more rapidly in a frozen autograft than in a free-frozen autograft with two osteotomies. QUESTIONS/PURPOSES: (1) In what proportion of patients was union achieved by 6 months using this technique of frozen autografting? (2) What complications were observed in a small series using this approach? (3) What was the function of these patients as determined by Musculoskeletal Tumor Society (MSTS) score? (4) What proportion of patients experienced local recurrence? METHODS: Between 2014 and 2017, we treated 87 patients for primary sarcomas of the femur, tibia, or humerus. Of those, we considered patients who could undergo intercalary resection and showed a good response to neoadjuvant chemotherapy as potentially eligible for this technique. Based on these criteria, 49% (43 patients) were eligible; a further 9% (eight) were excluded because of inadequate bone quality (defined as cortical thickness less than 50% by CT assessment). We retrospectively studied 32 patients who were treated with a single metaphyseal osteotomy, the so-called pedicle freezing technique, which uses liquid nitrogen. There were 20 men and 12 women. The median age was 18 years (range 13 to 48 years). The median follow-up duration was 55 months (range 48 to 63 months). Patients were assessed clinically and radiologically regarding union (defined in this study as bony bridging of three of four cortices by 6 months), the proportion of patients experiencing local recurrence, the occurrence of nononcologic complications, and MSTS scores. RESULTS: Three percent (one of 32) of the patients had nonunion (no union by 9 months). The median MSTS score was 90%, with no evidence of metastases at the final follow-up interval. Nine percent (three of 32) of our patients died. The local recurrence rate was 3.1% (one of 32 patients). The mean restricted disease-free survival time at 60 months (5 years) was 58 months (95% CI 55 to 62 months). Twenty-five percent of patients (eight of 32) experienced nononcologic complications. This included superficial skin burns (two patients), superficial wound infection (two patients), deep venous thrombosis (one patient), transient nerve palsy (two patients), and permanent nerve palsy (one patient). CONCLUSION: This treatment was reasonably successful in patients with sarcomas of the femur, tibia, and humerus who could undergo an intercalary resection, and this treatment did not involve the epiphysis and upper metaphysis. It avoids a second osteotomy site as in prior reports of freezing techniques, and union was achieved in all but one patient. There were few complications or local recurrences, and the patients' function was shown to be good. This technique cannot be used in all long-bone sarcomas, but we believe this is a reasonable alternative treatment for patients who show a good response to neoadjuvant chemotherapy, those in whom intercalary resection is feasible while retaining at least 2 cm of the subchondral area, and in those who have adequate bone stock to withstand the freezing process. Experienced surgeons who are well trained on the recycling technique in specialized centers are crucial to perform the technique. Further study is necessary to see how this technique compares with other reconstruction options. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?

BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.