Search Results (614)

Objectives: Primary bone tumors such as osteosarcoma and chondrosarcoma are rare but aggressive malignancies that require early and accurate diagnosis. Although X-ray radiography is a widely accessible imaging modality, detecting small or multi lesions remains challenging. Existing deep learning models are often trained on small, single-center datasets and lack generalizability, limiting their clinical effectiveness. Methods: We propose the YOLOv11-MTB, a novel enhancement to YOLOv11 integrating multi-scale Transformer-based attention, boundary-aware feature fusion, and receptive field augmentation to improve detection of small and multi-focal lesions. The model is trained and evaluated on two multi-center datasets, including the BTXRD dataset containing annotated radiographs with lesion types and bounding boxes. Results: YOLOv11-MTB achieves state-of-the-art performance on bone tumor detection tasks. It attains a mean average precision (mAP) of 79.6% on the BTXRD dataset, outperforming existing methods. In clinically relevant categories, the model achieves small-lesion mAP of 55.8% and multi-lesion mAP of 63.2%. Conclusions: The proposed YOLOv11-MTB framework demonstrates promising generalization and accuracy for primary bone tumor detection in radiographic images. Its performance in detecting small and multiple lesions suggests potential for clinical application. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Transforming growth factor-β (TGF-β) is a key protein family member that includes activins, inhibins, and bone morphogenetic proteins (BMPs). It is essential in numerous biological processes, such as chemotaxis, apoptosis, differentiation, growth, and cell migration. TGF-β receptors initiate signaling through two primary pathways: the canonical pathway involving Smad proteins and non-canonical pathways that utilize alternative signaling mechanisms. When TGF-β signaling is disrupted, it has been shown to contribute to the development of various diseases, including cancer. Initially, TGF-β effectively inhibits the cell cycle and promotes apoptosis. However, its role can transition to facilitating tumor growth and metastasis as the disease progresses. Moreover, TGF-β drives cancer progression through epithelial–mesenchymal transition (EMT), modulation of factor expression, and evasion of immune responses. This complexity establishes the need for further research, particularly into pharmacological agents targeting TGF-β, which are emerging as promising therapeutic options. Current clinical and preclinical studies are making significant strides toward mitigating the adverse effects of TGF-β. This underscores the critical importance of understanding its underlying mechanisms to enhance treatment effectiveness and improve survival rates for cancer patients. Full article

Osteosarcoma (OS), the most common primary bone cancer of mesenchymal origin in children and young adolescents, remains a challenge due to metastasis and resistance to chemotherapy. It displays severe aneuploidy and a high mutation frequency which drive tumor initiation and progression; however, recent studies have highlighted the role of epigenetic modifications as a key driver of OS pathogenesis, independent of genetic mutations. DNA and RNA methylation, histone modifications and non-coding RNAs are among the major epigenetic modifications which can modulate the expression of oncogenes. Abnormal activity of these mechanisms contributes to gene dysregulation, metastasis and immune evasion. Therapeutic targeting against these epigenetic mechanisms, including inhibitors of DNA and RNA methylation as well as regulators of RNA modifications, can enhance tumor suppressor gene activity. In this review, we examine recent studies elucidating the role of epigenetic regulation in OS pathogenesis and discuss emerging drugs or interventions with potential clinical utility. Understanding of tumor- specific epigenetic alterations, coupled with innovative therapeutic strategies and AI-driven biomarker discovery, could pave the way for personalized therapies based on the molecular profile of each tumor and improve the management of patients with OS. Full article

Mitochondria are critical for cellular energy, and while large deletions in their genome (mtDNA) are linked to primary mitochondrial diseases, their significance in cancer is less understood. Given cancer’s metabolic nature, investigating mtDNA deletions in tumors at various stages could provide insights into disease origins and treatment responses. In this study, we analyzed 148 bone marrow samples from 129 pediatric patients with B-cell (B-ALL) and T-cell (T-ALL) acute lymphoblastic leukemia at diagnosis, remission, and relapse using long-range PCR, next-generation sequencing, and the Splice-Break2 pipeline. Both T-ALL and B-ALL exhibited significantly more mtDNA deletions than did the controls, with T-ALL showing a ~100-fold increase and B-ALL a ~15-fold increase. The T-ALL samples also exhibited larger deletions (median size > 2000 bp) and greater heterogeneity, suggesting increased mitochondrial instability. Clustering analysis revealed distinct deletion profiles between ALL subtypes and across disease stages. Notably, large clonal deletions were detected in some B-ALL remission samples, including one affecting up to 88% of mtDNA molecules, which points toward treatment-driven selection or toxicity. A multivariate analysis confirmed that disease type, timepoint, and WHO subtype significantly influenced mtDNA deletion metrics, while age and gender did not. These findings suggest that mtDNA deletion profiling could serve as a biomarker for pediatric ALL and may indicate mitochondrial toxicity contributing to late effects in survivors. Full article

Osteosarcoma is one of the most common primary bone malignancies, typically occurring around the knee. However, the forearm is a rare site, with tumors in the proximal ulna being extremely uncommon. Primary sarcoma in this location presents a surgical challenge due to the complex anatomy and limited reconstructive options. We report a rare case of a 19-year-old female with non-metastatic, high-grade giant cell-rich osteosarcoma involving the right proximal ulna. To our knowledge, this is only the second reported adult case of this histological subtype in this location. The patient was treated at a specialized oncology center with neoadjuvant and adjuvant chemotherapy, along with wide intra-articular resection for local tumor control. Reconstruction was achieved using a novel, customized 3D-printed articulating cement spacer mold with plate osteosynthesis. Artificial elbow ligamentous reconstruction was performed using FiberTape and FiberWire sutures passed through drill holes, and the triceps tendon was reattached to the cement mold using an endobutton. This cost-effective and personalized surgical approach allowed successful joint reconstruction while maintaining elbow stability and function. Our case highlights a feasible reconstructive option for rare and anatomically challenging osteosarcoma presentations, contributing to the limited literature on proximal ulna giant cell-rich osteosarcoma. Full article

Background: Potent androgen receptor pathway inhibitors induce small cell neuroendocrine prostate cancer (SCNC), a highly aggressive subtype of metastatic androgen deprivation-resistant prostate cancer (ARPC) with limited treatment options and poor survival rates. Patients with metastases in the liver have a poor prognosis relative to those with bone metastases alone. The mechanisms that underlie the different behavior of ARPC in bone vs. liver may involve factors intrinsic to the tumor cell, tumor microenvironment, and/or systemic factors, and identifying these factors is critical to improved diagnosis and treatment of SCNC. Metabolic reprogramming is a fundamental strategy of tumor cells to colonize and proliferate in microenvironments distinct from the primary site. Understanding the metabolic plasticity of cancer cells may reveal novel approaches to imaging and treating metastases more effectively. Methods: Using magnetic resonance (MR) imaging and spectroscopy, we interrogated the physiological and metabolic characteristics of SCNC patient-derived xenografts (PDXs) propagated in the bone and liver, and used correlative biochemical, immunohistochemical, and transcriptomic measures to understand the biological underpinnings of the observed imaging metrics. Results: We found that the influence of the microenvironment on physiologic measures using MRI was variable among PDXs. However, the MR measure of glycolytic capacity in the liver using hyperpolarized ¹³C pyruvic acid recapitulated the enzyme activity (lactate dehydrogenase), cofactor (nicotinamide adenine dinucleotide), and stable isotope measures of fractional enrichment of lactate. While in the bone, the congruence of the glycolytic components was lost and potentially weighted by the interaction of cancer cells with osteoclasts/osteoblasts. Conclusion: While there was little impact of microenvironmental factors on metabolism, the physiological measures (cellularity and perfusion) are highly variable and necessitate the use of combined hyperpolarized ¹³C MRI and multiparametric (anatomic, diffusion-, and perfusion- weighted) ¹H MRI to better characterize pre-treatment tumor characteristics, which will be crucial to evaluate treatment response. Full article

Background: Dental eruption pathways could be influenced by several factors, both general and local, with different prevalence and morbidity. This study aims to report our experience of pediatric impacted teeth due to local factors, with the exclusion of the third molars, illustrating their prevalence, diagnostic and therapeutic pathways, and treatment outcomes. Methods: The inclusion criteria were minor age (<18 years) and the presence of impacted teeth due to a local cause, excluding wisdom teeth. The complete diagnostic and therapeutic procedures and their outcomes were described. The relationship between the treatment and the outcomes was assessed with a chi-square test. Results: One hundred twelve patients with a single impaction were included in the study. The local causes of single impaction were: 63 odontogenic cysts (57%), 24 supernumerary teeth (21%), 17 odontogenic tumors (15%), and eight primary bone lesions (7%). During the follow-up period, 83 teeth erupted spontaneously 12–36 months following surgery (74%), 12 were extracted during surgery (11%), and 17 needed orthodontic traction to achieve their aesthetic and functional position (15%). The relationship between mini-invasive surgery and spontaneous eruption was significant (p < 0.00001). Conclusions: Within the limitations of this study, mini-invasive surgical treatment preceded by a correct diagnosis may lead to a spontaneous eruption of permanent teeth, avoiding further orthodontic intervention and premature loss of permanent teeth. Full article

Immune checkpoints such as PD-1/PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT play critical roles in regulating anti-tumor immunity and are exploited by hematological malignancies to evade immune surveillance. While classic Hodgkin lymphoma (HL) demonstrates notable responsiveness to immune checkpoint inhibitors (ICIs), which is attributed to genetic alterations like chromosome 9p24.1 amplification, the responsiveness of non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and multiple myeloma (MM) remain inconsistent and generally modest. In NHL, the heterogeneous immune microenvironment, particularly variations in tumor-infiltrating lymphocytes and PD-L1 expression, drives differential ICI outcomes. AML shows limited responsiveness to monotherapy, but the combination of monotherapy with hypomethylating agents yield encouraging results, particularly in selected patient subsets. Conversely, MM trials have largely failed, potentially due to genetic polymorphisms influencing checkpoint signaling pathways and the inherently immunosuppressive bone marrow microenvironment. Both intrinsic tumor factors (low tumor mutational burden, impaired antigen presentation, IFN-γ pathway alterations) and extrinsic factors (immunosuppressive cells and alternative checkpoint upregulation) contribute significantly to primary and acquired resistance mechanisms. Future strategies to overcome resistance emphasize combination therapies, such as dual checkpoint blockade, epigenetic modulation, and reprogramming the tumor microenvironment, as well as biomarker-driven patient selection, aiming for precision-based, tailored immunotherapy across hematological malignancies. Full article

Background/Objectives: This study evaluates whether combining ⁶⁸Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models. Methods: We analyzed data from 93 high-risk PCa patients who underwent ⁶⁸Ga-PSMA-11 PET/CT and received primary treatment at a single center. Two predictive models were developed: a logistic regression (LR) model and an ML derived probabilistic graphical model (PGM) based on a naïve Bayes framework. Both models were compared against each other and against the CAPRA risk score. The models’ input variables were selected based on statistical analysis and domain expertise including a literature review and expert input. A decision tree was derived from the PGM to translate its probabilistic reasoning into a transparent classifier. Results: The five key input variables were as follows: binarized CAPRA score, maximal intraprostatic PSMA uptake intensity (SUVmax), presence of bone metastases, nodal involvement at common iliac bifurcation, and seminal vesicle infiltration. The PGM achieved superior predictive performance with a balanced accuracy of 0.73, sensitivity of 0.60, and specificity of 0.86, substantially outperforming both the LR (balanced accuracy: 0.50, sensitivity: 0.00, specificity: 1.00) and CAPRA (balanced accuracy: 0.59, sensitivity: 0.20, specificity: 0.99). The decision tree provided an explainable classifier with CAPRA as a primary branch node, followed by SUVmax and specific PET-detected tumor sites. Conclusions: Integrating ⁶⁸Ga-PSMA-11 imaging biomarkers with clinical parameters, such as CAPRA, significantly improves models to predict progression in patients with high-risk PCa undergoing primary treatment. The PGM offers superior balanced accuracy and enables risk stratification that may guide personalized treatment decisions. Full article

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40–50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. Overall, 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era. Conclusions: The pattern of metastatic spread in MCC differs among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median overall survival (OS) of 8 months (range 12.75–4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care. Full article

Artificial Intelligence (AI) has emerged as a transformative force in orthopedic oncology, offering significant advances in the diagnosis, classification, and prediction of treatment response for primary malignant bone tumors (PBT). Through machine learning and deep learning techniques, AI leverages computational algorithms and large datasets to enhance medical imaging interpretation and support clinical decision-making. The integration of radiomics with AI enables the extraction of quantitative features from medical images, allowing for precise tumor characterization and the development of personalized therapeutic strategies. Notably, convolutional neural networks have demonstrated exceptional capabilities in pattern recognition, significantly improving tumor detection, segmentation, and differentiation. This narrative review synthesizes the evolving applications of AI in PBTs, focusing on early tumor detection, imaging analysis, therapy response prediction, and histological classification. AI-driven radiomics and predictive models have yielded promising results in assessing chemotherapy efficacy, optimizing preoperative imaging, and predicting treatment outcomes, thereby advancing the field of precision medicine. Innovative segmentation techniques and multimodal imaging models have further enhanced healthcare efficiency by reducing physician workload and improving diagnostic accuracy. Despite these advancements, challenges remain. The rarity of PBTs limits the availability of robust, high-quality datasets for model development and validation, while the lack of standardized imaging protocols complicates reproducibility. Ethical considerations, including data privacy and the interpretability of complex AI algorithms, also warrant careful attention. Future research should prioritize multicenter collaborations, external validation of AI models, and the integration of explainable AI systems into clinical practice. Addressing these challenges will unlock AI’s full potential to revolutionize PBT management, ultimately improving patient outcomes and advancing personalized care. Full article

Background: Primary malignant bone tumors among adolescent patients are most commonly associated with burdensome surgeries that can severely affect young patients’ early life. To this day, despite available autologous tissue donor sites, cement spacers or endoprostheses are still most commonly used as a form of reconstruction of post-resection defects. Methods: The study group includes 20 adolescent patients diagnosed with Osteosarcoma or Ewing Sarcoma involving the upper limbs. The inclusion criteria were as follows: primary malignant bone tumors sensitive to neoadjuvant chemotherapy, tumors not infiltrating major blood vessels and nerves, and the appliance of the microsurgical free flap as a reconstructive method. Poor tumor response to neodajuvant chemotherapy or patients with incomplete follow-up were excluded from this study. To achieve the functional reconstruction of post-resection defects, fibula free flaps were applied. In cases of resection, including the metaphysis of a long bone, a modification of the flap harvest was applied in order to prevent arthrodesis. The MSTS (Musculoskeletal Tumor Society Scoring System) scale was used as a functional outcome measurement tool. Results: The reported outcomes of this study prove the efficiency of the treatment’s approach of combining the resection of the tumor with subsequent microsurgical restoration with the use of autologous tissues. The average score on the MSTS scale, which assesses the functional outcome, was 26.8/30 points, which indicates great motor outcomes. There were no reports of local recurrence during follow-up. Conclusions: Patients with primary malignant bone tumors in the upper limbs can benefit from microsurgical techniques, which are highly customized; effective; and give sufficient functionality following extensive resection. Full article