Osteosarcoma After Total Knee Arthroplasty: A Case Report.

CASE: A 79-year-old woman presented with a periprosthetic fracture 8 years after a total knee arthroplasty (TKA). Radiographs demonstrated tibial implant loosening with severe osteolysis. A high-grade osteosarcoma around the prosthesis was diagnosed, and a supracondylar femoral amputation was performed. After 2 years, no complications have occurred. CONCLUSIONS: A malignant tumor around a TKA is extremely rare. Surgeons should remain vigilant with patients who present with rapidly progressive or very aggressive implant loosening with osteolysis. Owing to its complexity and potentially devastating prognosis, treatment should be guided by a specialist multidisciplinary team. Complex limb salvage procedures or amputation is usually required.

[Osteosarcoma Secondary to Polyostotoic Fibrous Dysplasia of the Ribs].

Sarcomatous transformation of fibrous dysplasia is extremely rare. We present the case of a 54-yearold man with multiple rib masses, multiple enlarged lymph nodes throughout the body, and multiple osteolytic lesions on computed tomography( CT). A positron emission tomography( PET) scan showed abnormal enhancement in each. A needle biopsy of the right supraclavicular fossa lymph node revealed sarcoidosis. Considering the possibility of malignancy associated with sarcoidosis, a rib tumor resection and mediastinal lymph node biopsy were performed to confirm the diagnosis of the rib lesion. The pathology results showed that the rib mass was a low-grade central osteosarcoma and the mediastinal lymph node was sarcoidosis. The distribution of the lesions was consistent with osteosarcoma secondary to multiple fibrous bone dysplasia. As the osteosarcoma was low grade, the patient was followed up. Three years after surgery, there was no increase in residual disease.

Can FDG-PET assess the response to chemotherapy and predict tissue necrosis in osteosarcoma and Ewing sarcoma?

INTRODUCTION: Osteosarcoma (OS) and Ewing sarcoma (ES) represent the pediatric population's most common malignant bone tumors. 18-Fluorodeoxyglucose positron emission tomography has been shown to be effective in both the diagnostic and staging phases of cancer treatment. In recent years, some studies have also explored the possibility that FDG-PET could have a prognostic role.

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.

DECIDE: A decoupled semantic and boundary learning network for precise osteosarcoma segmentation by integrating multi-modality MRI.

Automated Osteosarcoma Segmentation in Multi-modality MRI (AOSMM) holds clinical significance for effective tumor evaluation and treatment planning. However, the precision of AOSMM is challenged by the diverse characteristics of multi-modality MRI and the inherent heterogeneity and boundary ambiguity of osteosarcoma. While numerous methods have made significant strides in automated osteosarcoma segmentation, they primarily focused on the use of a single MRI modality and overlooked the potential benefits of integrating complementary information from other MRI modalities. Furthermore, they did not adequately model the long-range dependencies of complex tumor features, which may lead to insufficiently discriminative feature representations. To this end, we propose a decoupled semantic and boundary learning network (DECIDE) to achieve precise AOSMM with three functional modules. The Multi-modality Feature Fusion and Recalibration (MFR) module adaptively fuses and recalibrates multi-modality features by exploiting their channel-wise dependencies to compute low-rank attention weights for effectively aggregating useful information from different MRI modalities, which promotes complementary learning between multi-modality MRI and enables a more comprehensive tumor characterization. The Lesion Attention Enhancement (LAE) module employs spatial and channel attention mechanisms to capture global contextual dependencies over local features, significantly enhancing the discriminability and representational capacity of intricate tumor features. The Boundary Context Aggregation (BCA) module further enhances semantic representations by utilizing boundary information for effective context aggregation while also ensuring intra-class consistency in cases of boundary ambiguity. Substantial experiments demonstrate that DECIDE achieves exceptional performance in osteosarcoma segmentation, surpassing state-of-the-art methods in terms of accuracy and stability.

Can conventional magnetic resonance imaging at presentation predict chemoresistance in osteosarcoma?

OBJECTIVES: Histological tumour necrosis is the current indicator for the response of osteosarcoma after neoadjuvant chemotherapy. Chemoresistant tumours require close monitoring and adjustment of treatment. Characteristics of tumours on baseline MRI may be able to predict response to chemotherapy. The aim is to identify which baseline MRI findings can help predict chemoresistant osteosarcoma. METHODS: Baseline MRI before giving neoadjuvant chemotherapy of 95 patients during 2008-2021 was reviewed by 2 musculoskeletal radiologists. Histological necrosis from surgical specimens was the reference standard. MRIs were reviewed for tumour characteristics (tumour volume, maximum axial diameter, central necrosis, haemorrhage, fluid-fluid level), peritumoural bone and soft tissue oedema, and other parameters including intra-articular extension, epiphyseal involvement, neurovascular involvement, pathologic fracture, and skip metastasis. The cut-off thresholds were generated by receiver operating characteristic curves which then tested for diagnostic accuracy. RESULTS: Two-third of patients were chemoresistance (histological necrosis <90%). Tumour volume >150 mL, maximum axial diameter >7.0 cm, area of necrosis >50%, presence of intra-articular extension, and peritumoural soft tissue oedema >6.5 cm significantly predicted chemoresistance, particularly when found in combination. Tumour volume >150 mL and maximum axial diameter >7.0 cm could be used as an independent predictor (multivariable analysis, P-value = .025, .045). CONCLUSIONS: Findings on baseline MRI could help predicting chemoresistant osteosarcoma with tumour size being the strongest predictor. ADVANCES IN KNOWLEDGE: Osteosarcomas with large size, large cross-sectional diameter, large area of necrosis, presence of intra-articular extension, and extensive peritumoural soft tissue oedema were most likely to have a poor response to neoadjuvant chemotherapy.

The significance of surveillance imaging in children with Ewing sarcoma and osteosarcoma.

Primary bone tumors in children and adolescents, while rare, pose significant challenges in diagnosis and management. Children treated for Ewing sarcoma and osteosarcoma are offered a 5-year follow-up program after end of treatment, including radiological surveillance of primary location of tumor and the lungs. There is no consensus regarding how often and how the children should be followed with radiological imaging. This retrospective descriptive study of 69 patients (34 with Ewing sarcoma and 35 with osteosarcoma) investigated the consequences of abnormal findings in 1279 follow-up images. Nine relapses were detected, 4 in the Ewing group (3 local and 1 pulmonary) and 5 in the osteosarcoma group (1 local and 4 pulmonary). Of these, only two patients exhibited symptomatic relapses, with the remainder identified through imaging. The positive predictive value for relapse detection was 0.44 in the Ewing group, and 0.5 in the osteosarcoma group. In the Ewing sarcoma patient image follow-up program, the probability of anomaly detection was 12% (95% CI, 10-15). For osteosarcoma patients, the likelihood was 6% (95% CI, 4-8). Our data indicates that abnormal findings on follow-up images rarely represents relapse of tumor. As the surveillance protocol differs between the patient groups, wherein Ewing sarcoma patients primarily are monitored through MRI while osteosarcoma patients are predominantly tracked via X-rays, there is an increased occurrence of incidental findings in the first group. However, it is imperative to interpret imaging data in conjunction with clinical information, avoiding isolated reliance on imaging results when making treatment decisions.

Ct-based intratumoral and peritumoral radiomics for predicting prognosis in osteosarcoma: A multicenter study.

PURPOSE: To evaluate the performance of CT-based intratumoral, peritumoral and combined radiomics signatures in predicting prognosis in patients with osteosarcoma. METHODS: The data of 202 patients (training cohort:102, testing cohort:100) with osteosarcoma admitted to the two hospitals from August 2008 to February 2022 were retrospectively analyzed. Progression free survival (PFS) and overall survival (OS) were used as the end points. The radiomics features were extracted from CT images, three radiomics signatures（RSintratumoral, RSperitumoral, RScombined）were constructed based on intratumoral, peritumoral and combined radiomics features, respectively, and the radiomics score (Rad-score) were calculated. Kaplan-Meier survival analysis was used to evaluate the relationship between the Rad-score with PFS and OS, the Harrell's concordance index (C-index) was used to evaluate the predictive performance of the radiomics signatures. RESULTS: Finally, 8, 6, and 21 features were selected for the establishment of RSintratumoral, RSperitumoral, and RScombined, respectively. Kaplan-Meier survival analysis confirmed that the Rad-scores of the three RSs were significantly correlated with the PFS and OS of patients with osteosarcoma. Among the three radiomics signatures, RScombined had better predictive performance, the C-index of PSF prediction was 0.833 in the training cohort and 0.814 in the testing cohort, the C-index of OS prediction was 0.796 in the training cohort and 0.764 in the testing cohort. CONCLUSIONS: CT-based intratumoral, peritumoral and combined radiomics signatures can predict the prognosis of patients with osteosarcoma, which may assist in individualized treatment and improving the prognosis of osteosarcoma patients.

The clinical significance of indeterminate pulmonary nodules in patients with primary bone sarcoma: a systematic review.

OBJECTIVE: To report the incidence of indeterminate pulmonary nodules (IPN) and the rate of progression of IPNs to metastasis in patients with primary bone cancers. We also aimed to evaluate clinical or radiological parameters that may identify IPNs more likely to progress to metastatic disease and their effect on overall or event-free survival in patients with primary bone sarcoma. METHODS: A systematic search of the electronic databases Medline, Embase, and Cochrane Library was undertaken for eligible articles on IPNs in patients with primary bone sarcomas, published in the English language from inception of the databases to 2023. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was utilized to evaluate risk of bias in included studies. RESULTS: Six studies, involving 1667 patients, were included in this systematic review. Pooled quantitative analysis found the rate of incidence of IPN to be 18.1% (302 out of 1667) and the rate of progression to metastasis to be 45.0% (136 out of 302). Nodule size (more than 5 mm diameter), number (more than or equal to 4), distribution (bilaterally distributed), incomplete calcification, and lobulated margins were associated with an increased likelihood of IPNs progressing to metastasis, however, their impact on overall or event-free survival remains unclear. CONCLUSION: The risk of IPNs progressing to metastasis in patients with primary bone sarcoma is non-negligible. Large IPNs have a high risk to be an actual metastasis. We suggest that IPNs in these patients be followed up for a minimum of 2 years with CT imaging at 3, 6, and 12 month intervals, particularly for nodules measuring >5 mm in average diameter. ADVANCES IN KNOWLEDGE: This is the first systematic review on IPNs in patients with primary bone sarcomas only and proposes viable management strategies for such patients.

FDG-Avid Periprosthetic Particle Disease Mimicking Osteosarcoma Recurrence.

ABSTRACT: A 24-year-old man with a history of osteosarcoma presented with swelling in his right thigh for more than 1 year. 18 F-FDG PET/CT demonstrated increased FDG uptake in multiple juxtacortical masses around the prosthesis, which highly suggested the possibility of osteosarcoma recurrence. A biopsy was performed, and the pathology confirmed the diagnosis of particle disease. The current case indicates that particle disease should be considered when interpreting the PET/CT images with high FDG uptake around the prosthesis.

Imaging diagnosis and differential diagnosis of extraskeletal osteosarcoma.

OBJECTIVE: The aim of this study was to investigate the clinical, imaging and pathological features of extraskeletal osteosarcoma (EOS) and to improve the understanding of this disease and other similar lesions. METHODS: The data for 11 patients with pathologically confirmed extraosseous osteosarcoma, including tumour site and size and imaging and clinical manifestations, were analysed retrospectively. RESULTS: Six patients were male (60%), and 5 were female (40%); patient age ranged from 23 to 76 years (average age 47.1 years). Among the 11 patients, 7 had clear calcifications or ossification with different morphologies, and 2 patients showed a massive mature bone tumour. MRI showed a mixed-signal mass with slightly longer T1 and T2 signals in the tumour parenchyma. Enhanced CT and MRI scans showed enhancement in the parenchyma. Ten patients had different degrees of necrosis and cystic degeneration in the mass, 2 of whom were complicated with haemorrhage, and MRI showed "fluid‒fluid level" signs. Of the 11 patients, five patients survived after surgery, and no obvious recurrence or metastasis was found on imaging examination. One patient died of lung metastasis after surgery, and 2 patients with open biopsy died of disease progression. One patient died of respiratory failure 2 months after operation. 2 patients had positive surgical margins, and 1 had lung metastasis 6 months after operation and died 19 months after operation. Another patient had recurrence 2 months after surgery. CONCLUSION: The diagnosis of EOS requires a combination of clinical, imaging and histological examinations. Cystic degeneration and necrosis; mineralization is common, especially thick and lumpy mineralization. Extended resection is still the first choice for localized lesions. For patients with positive surgical margins or metastases, adjuvant chemoradiotherapy is needed.

Cemento-ossifying fibroma transforming to osteosarcoma.

Ossifying fibroma is a type of fibro-osseous lesion categorised into cemento-ossifying fibroma and juvenile ossifying fibroma. Malignant transformation of fibro-osseous lesions is documented especially for fibrous dysplasia, but scarcity is seen when we search for malignant transformation of ossifying fibroma. Thus, we are presenting an extremely rare case of cemento-ossifying fibroma transforming into osteosarcoma with long sequential radiographic details.

Evaluation of response to neoadjuvant chemotherapy in osteosarcoma using dynamic contrast-enhanced MRI: development and external validation of a model.

OBJECTIVE: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. METHODS: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). RESULTS: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. CONCLUSION: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy.

OBJECTIVES: A novel clinically translatable iron oxide nanoparticle (IOP) is currently being tested in phase 2 clinical trials as a magnetic resonance imaging (MRI) contrast agent for hepatocellular carcinoma diagnosis. The purpose of our study is to evaluate if this IOP can detect activation of tumor-associated macrophages (TAMs) due to CD47 mAb-targeted immunotherapy in 2 mouse models of osteosarcoma. MATERIALS AND METHODS: The toxicity, biodistribution, and pharmacokinetics of IOP were evaluated in 77 female and 77 male rats. Then, 24 female BALB/c mice with intratibial murine K7M2 tumors and 24 female NOD scid gamma mice with intratibial human 143B osteosarcoma xenografts were treated with either CD47 mAb (n = 12) or control antibody (n = 12). In each treatment group, 6 mice underwent MRI scans before and after intravenous infusion of either IOP or ferumoxytol (30 mg Fe/kg). Tumor T2* values and TAM markers F4/80, CD80, CD206, and Prussian blue staining were compared between different experimental groups using exact 2-sided Wilcoxon rank sum tests. RESULTS: Biodistribution and safety evaluations of IOP were favorable for doses of less than 50 mg Fe/kg body weight in female and male rats. Both IOP and ferumoxytol caused negative enhancement (darkening) of the tumor tissue. Both murine and human osteosarcoma tumors treated with CD47 mAb demonstrated significantly shortened T2* relaxation times after infusion of IOP or ferumoxytol compared with controls (all P 's < 0.05). Higher levels of F4/80 + CD80 + were found in murine and human osteosarcomas treated with CD47 mAb compared with sham-treated controls (all P 's < 0.05). In addition, murine CD47 mAb-treated tumors after infusion of either IOP or ferumoxytol showed significantly higher numbers of Prussian blue-positive cells compared with controls ( P < 0.05). There was no significant difference of F4/80 + CD206 + cells among any of the groups (all P 's > 0.05). CONCLUSIONS: Iron oxide nanoparticle-enhanced MRI can be used to diagnose CD47 mAb-mediated TAM-activation in osteosarcomas.

Tracked ultrasound registration for intraoperative navigation during pediatric bone tumor resections with soft tissue components: a porcine cadaver study.

PURPOSE: Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model. METHODS: First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire. RESULTS: Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work. CONCLUSION: The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.

Self-supervised tumor segmentation and prognosis prediction in osteosarcoma using multiparametric MRI and clinical characteristics.

BACKGROUND AND OBJECTIVE: Osteosarcoma has a high mortality among malignant bone tumors. MRI-based tumor segmentation and prognosis prediction are helpful to assist doctors in detecting osteosarcoma, evaluating the patient's status, and improving patient survival. Current intelligent diagnostic approaches focus on segmentation with single-parameter MRI, which ignores the nature of MRI resulting in poor performance, and lacks the connection with prognosis prediction. Besides, osteosarcoma is a rare disease, and their few labeled data may lead to model overfitting. METHODS: We propose a three-stage pipeline for segmentation and prognosis prediction of osteosarcoma to assist doctors in diagnosis. First, we propose the Multiparameter Fusion Contrast Learning (MPFCLR) algorithm to share pre-training weights for the segmentation model using unlabeled data. Then, we construct a multiparametric fusion network (MPFNet), which fuses the complementary features from multiparametric MRI (CE-T1WI, T2WI). It can automatically segment tumor and necrotic regions. Finally, a fusion nomogram is constructed by segmentation masks and clinical characteristics (volume, tumor spread) to predict the patient's prognostic status. RESULTS: Our experiments used data from 136 patients at the Second Xiangya Hospital in China. According to experiments, the MPFNet achieves 84.19 % mean DSC and 84.56 % mean F1-score in segmenting tumor and necrotic regions, surpassing existing models and single-parameter MRI input for osteosarcoma segmentation. Besides, MPFCLR improves the segmentation performance and convergence speed. In prognosis prediction, our fusion nomogram (C-index: 0.806, 95 %CI: 0.758-0.854) is better than radiomics (C-index: 0.753, 95 %CI: 0.685-0.841) and clinical (C-index: 0.794, 95 %CI: 0.735-0.854) nomograms in predictive performance. Compared to the comparison models, our model is closest to the prediction model based on physician annotations. Moreover, it can accurately distinguish the patients' prognostic status with good or poor. CONCLUSION: Our proposed solution can provide references for clinicians to detect osteosarcoma, evaluate patient status, and make personalized decisions. It can reduce delayed treatment or overtreatment and improve patient survival.

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.