Primary Malignant Bone Tumor Research Articles

COMPARATIVE ANALYSIS OF THE DIAGNOSTIC ACCURACY OF ENDOSTATIN AND VEGF SERUM LEVELS IN PATIENTS WITH BONE SARCOMAS

Introduction. Angiogenesis regulators are of particular interest as new serum markers in cancer patients, since they reflect the intensity of tumor growth and metastasis. Currently, many works are dedicated to the study of vascular endothelial growth factor (VEGF), which activates angiogenesis, and endostatin, which inhibits it. However, a comparative study of the diagnostic accuracy of serum levels of these two markers in patients with bone sarcomas has not been conducted yet. Аim. A comparative analysis of the diagnostic accuracy indicators and prognostic significance of VEGF and endostatin in the blood serum of patients with primary malignant bone tumors. Methods. During the study, the levels of endostatin and VEGF in blood serum samples from 123 patients with a newly diagnosed and morphologically verified bone sarcoma were measured. Patients were examined at the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Blokhin” of the Russian Ministry of Health from July 2001 to December 2022. Sixty age- and gender-matched healthy donors were included in the control group. Results. Median serum concentrations of endostatin and VEGF in the patient group were statistically significantly increased compared to the control group by 1.3 and 1.4 times, respectively (p < 0.01). Statistically significant differences in the serum concentrations of VEGF and endostatin depending on the T category and the tumor grade and stage were not identified. The cut-off value of VEGF was 279 pg/ml, and the cut-off value of endostatin was 121 ng/ml. With the same sensitivity of 75.6%, endostatin is characterized by higher specificity than VEGF (73.0 and 67.6%, respectively). The proportional hazards model characterizing the effect of serum VEGF and endostatin levels on overall and survival was not statistically significant. Conclusion. Endostatin in the blood serum of patients with bone tumors is more informative compared to VEGF; however, both markers are not predictors of overall and survival.

Shared decision making in primary malignant bone tumour surgery around the knee in children and young adults: protocol for a prospective study

BackgroundChildren and young adults needing surgery for a primary malignant bone tumour around the knee face a difficult, life-changing decision. A previous study showed that this population wants to be involved more in the decision-making process and that more involvement leads to less decisional stress and regret. Therefore, a well-designed and standardized decision-making process based on the principles of shared decision-making needs to be designed, implemented, and evaluated.MethodsWe developed a shared decision-making (SDM) model for this patient population, including an online decision aid (DA). This model has been implemented in the standard care of patients with a primary malignant bone tumour around the knee. Following implementation, we will analyse its effect on the decision-making process and the impact on patient experiences using questionnaires and interviews. Moreover, potential areas for improvement will be identified.DiscussionGiven the importance of involving patients and parents in surgical decision-making, particularly in life-changing surgery such as malignant bone tumour surgery, and given the lack of SDM models applicable for this purpose, we want to share our model with the international community, including our study protocol for evaluating and optimising the model. This study will generate valuable knowledge to facilitate the optimisation of current patient care for local treatment. The sharing of our implementation and study protocol can serve as an example for other centres interested in implementing SDM methods in an era characterized by more empowered patients and parents who desire autonomy and reliable and realistic information.

M2 macrophage exosome-derived Apoc1 promotes ferroptosis resistance in osteosarcoma by inhibiting ACSF2 deubiquitination.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. The aim of this study was to investigate the regulatory mechanisms of M2 macrophage exosomes (M2-Exos) in ferroptosis in OS. A mouse model was established to investigate the in vivo role of M2-Exos. We investigated their effects on ferroptosis in OS using erastin, a ferroptosis activator, and deferoxamine mesylate, an iron chelator. In vitro, we investigated whether the Apoc1/Acyl-CoA Synthetase Family Member 2 (ACSF2) axis mediates these effects, using shApoc1 and shACSF2. The mechanisms whereby Apoc1 regulates ACSF2 were examined using cyclohexanone, a protein synthesis inhibitor, and MG132, a proteasomal inhibitor. M2-Exos reversed the inhibitory effects of erastin on OS cells, thus enhancing their viability, migration, invasion, proliferation, and reducing ferroptosis. Apoc1 was highly expressed in M2-Exos, and interfering with this expression reversed the effects of M2-Exos on OS cells. ACSF2 mediated the effects of M2-Exos-derived Apoc1. Apoc1 interacted with ACSF2, which, in turn, interacted with USP40. Apoc1 overexpression increased ACSF2 ubiquitination, promoting its degradation, whereas USP40 overexpression inhibited ACSF2 ubiquitination and promoted its expression. Apoc1 overexpression inhibited ACSF2 binding to USP40. M2-Exos-derived Apoc1 promoted ferroptosis resistance by inhibiting USP40 binding to ACSF2 and promoting ACSF2 ubiquitination and degradation, thus enhancing OS development.

AI based diagnostics product design for osteosarcoma cells microscopy imaging of bone cancer patients using CA-MobileNet V3

ObjectiveThe incidence of osteosarcoma (OS) is low, but primary malignant bone tumors rank third among the causes of death in cancer patients under the age of 20. Currently, analysis of cellular structure and tumor morphology through microscopic images remains one of the main diagnostic methods for osteosarcoma. However, this completely manual approach is tedious, time-consuming, and difficult to diagnose accurately due to the similarities in certain characteristics of malignant and benign tumors. MethodsLeveraging the potential of artificial intelligence (AI) in assessing and classifying images, this study explored a modified CA-MobileNet V3 model that was embedded into innovative microscope products to enhance the microscope’s feature extraction capabilities and help reduce misclassification during diagnosis. ResultsThe intelligent recognition model method introduced in this paper has significant advantages in retrieval and classification of osteosarcoma cells and other cell types. Compared with models such as ShuffleNet V2, EfficientNet V2, Mobilenet V3 (without transfer learning), TL-MobileNet V3 (with transfer learning), etc., the model size is only 5.33 MB, is a lightweight model, and the accuracy of the improved model reached 98.69 %. In addition, the artificial intelligence microscope (AIM) with integrated design based on this model can also help improve diagnostic efficiency. ConclusionThe innovative method of the CA-MobileNet V3 automatic classification model based on deep learning provides an efficient and reliable solution for the pathological diagnosis of osteosarcoma. This study contributes to medical image analysis and provides doctors with an accurate and valuable tool for microscopic diagnosis. It also promotes the advancement of artificial intelligence in medical imaging technology.

Osteosarcoma with Pathological Fracture: A Rare Case Report

Introduction: Osteosarcoma is a primary malignant bone tumor originating from stem cells and is characterized by the proliferation of tumor cells that directly form immature bone or bone-like tissue. Osteosarcoma represents only 3% to 5% of all spinal malignancies. The aim of study is to discuss the importance of diagnostic investigation for a relatively rare case of spinal osteosarcoma. Case presentation: A 49 years old female came to the Emergency Unit, with a chief complaint of bilateral weakness of lower extremities for 1 year and worsening in 2 weeks. Upon examination, the initial diagnosis was mistaken for a spinal canal stenosis because metastatic bone disease from previous history of malignant melanoma. Subsequently, a decompression with stabilization fusion and biopsy is performed. Primary osteosarcoma was confirmed from histopathology results. Further chemotherapy is planned referring to confirmed primary osteosarcoma on histopathology. Discussion: Spinal osteosarcoma is very rare. Osteosarcoma occurs most frequently in the appendicular skeleton, especially the distal femur and proximal tibial metaphysis, which account for 90% of all cases. Primary osteosarcomas of the vertebral column are uncommon and occur dominantly in the vertebral body. Biopsy remains the gold standard of care for diagnosis. Conclusion: The performance of MRI and pathologic evaluation with immunohistochemistry is particularly important for the differential diagnosis of soft tissue tumors. Histopathologic analysis also plays an important role in differentiating from metastatic bone disease. An aggressive treatment plan and long-term follow-up are mandatory in managing this case. Keywords: osteosarcoma, spinal osteosarcoma, spinal canal stenosis, malignancy, pathological fracture, rare case.

Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy

BackgroundOsteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6. MethodsFirstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot. ResultsHKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6. ConclusionsHKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.

MicroRNA signatures in osteosarcoma: diagnostic insights and therapeutic prospects.

Osteosarcoma (OSa) is the most prevalent primary malignant bone tumor in children and adolescents, characterized by complex genetic and epigenetic alterations. Traditional treatments face significant challenges due to high rates of drug resistance and lack of targeted therapies. Recent advances in microRNA (miRNA) research have opened new avenues for understanding and treating osteosarcoma. This review explores the many critical functions of miRNAs in osteosarcoma, particularly their potential for clinical use. The review highlights two key areas where miRNAs could be beneficial. Firstly, miRNAs can act as biomarkers for diagnosing osteosarcoma and predicting patient prognosis. Secondly, specific miRNAs can regulate cellular processes like proliferation, cell death, migration, and even resistance to chemotherapy drugs in osteosarcoma. This ability to target multiple pathways within cancer cells makes miRNA-based therapies highly promising. Additionally, though the interaction between miRNAs and circular RNAs (circRNAs) falls outside the scope of the paper, it has also been discussed briefly. While miRNA-based therapies offer exciting possibilities for targeting multiple pathways in osteosarcoma, challenges remain. Efficient delivery, potential off-target effects, tumor complexity, and rigorous testing are hurdles to overcome before these therapies can reach patients. Despite these challenges, continued research and collaboration among scientists, clinicians, and regulatory bodies hold the promise of overcoming them. This collaborative effort can pave the way for the development of safe and effective miRNA-based treatments for osteosarcoma.

A deep learning model to enhance the classification of primary bone tumors based on incomplete multimodal images in X-ray, CT, and MRI

BackgroundAccurately classifying primary bone tumors is crucial for guiding therapeutic decisions. The National Comprehensive Cancer Network guidelines recommend multimodal images to provide different perspectives for the comprehensive evaluation of primary bone tumors. However, in clinical practice, most patients’ medical multimodal images are often incomplete. This study aimed to build a deep learning model using patients’ incomplete multimodal images from X-ray, CT, and MRI alongside clinical characteristics to classify primary bone tumors as benign, intermediate, or malignant.MethodsIn this retrospective study, a total of 1305 patients with histopathologically confirmed primary bone tumors (internal dataset, n = 1043; external dataset, n = 262) were included from two centers between January 2010 and December 2022. We proposed a Primary Bone Tumor Classification Transformer Network (PBTC-TransNet) fusion model to classify primary bone tumors. Areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the model’s classification performance.ResultsThe PBTC-TransNet fusion model achieved satisfactory micro-average AUCs of 0.847 (95% CI: 0.832, 0.862) and 0.782 (95% CI: 0.749, 0.817) on the internal and external test sets. For the classification of benign, intermediate, and malignant primary bone tumors, the model respectively achieved AUCs of 0.827/0.727, 0.740/0.662, and 0.815/0.745 on the internal/external test sets. Furthermore, across all patient subgroups stratified by the distribution of imaging modalities, the PBTC-TransNet fusion model gained micro-average AUCs ranging from 0.700 to 0.909 and 0.640 to 0.847 on the internal and external test sets, respectively. The model showed the highest micro-average AUC of 0.909, accuracy of 84.3%, micro-average sensitivity of 84.3%, and micro-average specificity of 92.1% in those with only X-rays on the internal test set. On the external test set, the PBTC-TransNet fusion model gained the highest micro-average AUC of 0.847 for patients with X-ray + CT.ConclusionsWe successfully developed and externally validated the transformer-based PBTC-Transnet fusion model for the effective classification of primary bone tumors. This model, rooted in incomplete multimodal images and clinical characteristics, effectively mirrors real-life clinical scenarios, thus enhancing its strong clinical practicability.

Enzymatic TET-1 inhibition highlights different epigenetic behaviours of IL-1β and TNFα in tumour progression of OS cell lines

Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

IGFBP5 in osteosarcoma tumorigenesis: Gene expression profile among metastatic and non-metastatic patients

Osteosarcoma (OS) is the most frequent primary malignant bone tumor among children and adolescents, with a peak of incidence in the second decade of life. The presence of metastasis at diagnosis in OS patients significantly decreases the chances of survival and new therapy approaches are needed. The IGFBP5 gene is related to osteoblasts metabolism and some studies have pointed out a role of its low expressions in OS development and metastasis. In this study, we aimed to establish an IGFBP5 gene expression profile among metastatic and non-metastatic OS patients throughout the treatment and development of the disease. Fresh-frozen tumor samples were obtained from 40 patients admitted to treatment at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP) and divided by clinical status: metastatic or non-metastatic disease. For each patient, samples before and after chemotherapy treatment were obtained, as well as metastasis and lung tissue surrounding metastasis samples from the metastatic patients. A quantitative real-time PCR was used to investigate IGFBP5 expression. Our analyses demonstrate that non-metastatic patients presented lower IGFBP5 expression in their pre-chemotherapy samples compared with metastatic patients, suggesting that low expressions of this gene could help triggering the OS tumorigenesis but that its action alone is not sufficient to activate the metastatic process. Heterogeneity in IGFBP5 expressions within groups was also seen. We observed that IGFBP5 and two MAPK genes, a downstream pathway in the IGFBP5 axis, are differentially expressed in OS samples of non-metastatic patients. Further investigation about these genes’ modulations might lead to a better understanding of metastasis development in OS.

An Analysis of The Pattern and Frequency of Primary Malignant Bone Tumors in Nassyriah

Bone tumors are uncommon lesions and account for only 0.2% of all malignant tumors. Primary malignant bone tumors develop from bony tissue and are categorized according to their location of origin and the cell type that makes up the tumor. This research aims to report on the prevalence, geographic distribution, and comparison of malignant bone tumors in Nassyriha province. Malignant bone tumors were studied in 182 people (119 men and 63 females) between February 2021 and February 2023. Their ages varied widely (from 5 to 70), with the second decade being the most prevalent. The most common cancer was osteosarcoma, which accounted for 34.62 percent, followed by Ewing's sarcoma (24.73), chondrosarcoma (13.74), multiple myeloma (11.53), malignant giant cell tumors (8.14%), fibrosarcoma (2.74%), and 2 instances of chordoma (1.10%). None of the six instances (3.30%) could be definitively diagnosed. Primary malignant bone tumors are rising, with men being disproportionately impacted. Information gleaned from this study will be useful for both researchers and clinicians.

Two rare localizations of chondrosarcoma: cervical and thoracic spine

Chondrosarcoma is a primary malignant bone tumor, with spinal involvement being rare. Diagnosing this condition can be challenging and typically requires histological verification. Chondrosarcoma has the potential to invade locally and spread systemically. We report the case of 32 year-old women presenting with back pain and weight loss. Magnetic resonance imaging of the spine showed a bone growth at the low cervical spine which extends to the upper dorsal spine. Histological examination showed low-grade chondrosarcoma. Given the tumor proximity to the spinal cord, an incomplete surgical excision was performed followed by radiotherapy sessions. Clinical course was marked by partial regression of the tumor process with a stability of the radiological image of the tumor after a three years follow-up. Our case is original because of the bifocality of the chondrosarcoma in two adjacent segments of the spine.

From Pelvic Bone to Pleura: A Rare Metastatic Pathway in Osteosarcoma

ABSTRACT Osteosarcoma stands out as the predominant primary malignant bone tumor originating from primitive mesenchymal bone-forming cells. Its usual onset occurs in individuals aged 10–20 years, with occurrences beyond 40 years being rare, particularly in the absence of conditions such as Paget’s disease or osteogenesis imperfecta. Where lungs are the most common site for metastasis, the involvement of the pleura presents as an unusual aspect, given that pleural effusion and calcified thickening are not typical manifestations of osteosarcoma. This case involves a 61-year-old male who presented with osteosarcoma localized in the right pelvic bone, accompanied by concurrent right pleural effusion and calcified pleural thickening.

Outcome of recycle bone reconstruction using liquid nitrogen in primary malignant bone tumor

Primary malignant bone tumors constitute a small but significant portion, accounting for 3–5% of childhood cancers. Cryosurgery, utilizing liquid nitrogen to induce tumor necrosis through extreme cold, emerges as a favorable surgical technique for bone tumor. This study delves into the clinical and radiological outcomes of individuals underwent cryosurgery. This descriptive study focused on patients with primary malignant bone tumors subjected to wide resection and cryosurgery with follow-up period from 6 up to 48 months from year 2018 - 2023. The data was collected from medical records and database, we evaluated the demographic data, clinical with Musculoskeletal Tumor Society (MSTS), radiological outcome with International Society of Limb Salvage (ISOLS) score, and the complications of cryosurgery observed. Among the 37 patients examined, 20 males and 17 females were averaging 21.7 years of age. 29 of 37 (78%) cases identified as osteosarcoma most common location in the epimetaphyseal of the long bone with Grade Enneking IIB. MSTS score averaged 25.35 ± 5.54, with more than 68% achieving excellent and good score. ISOLS for radiological score revealed 37.8% with an excellent score, 48.6% with a good score. The most common complication, reccurence, occurs in 6 cases (16.2%). Patients with primary malignant bone tumors who underwent cryosurgery showed successful clinical and radiological outcomes, as measured by MSTS and ISOLS scores. This underscores the significance of cryosurgery in primary malignant bone tumor as favorable and cost-effective treatment, showcasing improved functionality and positive radiological results.

GNAS, not a Highly Mutated Gene, Has Prognostic Significance and Carcinogenic Effects in Osteosarcoma.

Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic biomarkers and effective targeted therapies for osteosarcoma. This study focuses on identifying key prognostic genes, particularly the role of GNAS, in osteosarcoma progression. Bioinformatics analyses were performed on osteosarcoma datasets from the Gene Expression Omnibus (GEO). Differential gene expression analysis, weighted correlation network analysis (WGCNA), and survival analysis identified potential prognostic hub genes. The expression and function of these genes were validated through immunohistochemistry and animal experiments. Specifically, the role of GNAS was investigated through siRNA-mediated knockdown in osteosarcoma cell lines and nude mice models. Five hub genes (PROP1, GNAS, CYP4F2, LHX3, CNGB1) were identified as significantly related to osteosarcoma prognosis. Among these, GNAS was found to be highly expressed in osteosarcoma tissues compared to normal tissues. Immunohistochemical analysis confirmed the elevated expression of GNAS in osteosarcoma samples. GNAS mutation analysis revealed a low mutation rate in osteosarcoma, suggesting its oncogenic role is independent of mutational status. Animal experiments demonstrated that knocking down GNAS significantly inhibited tumor growth and induced apoptosis in osteosarcoma cells. GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.

Induced membrane technique for malignant bone tumours of the humerus.

The aim of this study was to report on mid- to long-term results following large humeral tumoral resection and reconstruction with the induced-membrane technique in skeletally immature patients suffering from primary malignant bone tumours. A retrospective analysis identified all children who underwent the two stages of a humeral reconstruction using the induced-membrane technique for primary malignant humerus tumours between 2002 and 2020. Functional assessment was conducted by an independent observer using the Musculoskeletal Tumor Society (MSTS) scoring system for the upper limb. Radiological assessment was performed by two independent observers and the healing index was calculated (i.e., months/cm). Eight adolescents (5 osteosarcomas and 3 Ewing sarcoma), with a mean age of 14.2 years (SD = 2.7), were included. The mean length of the bone resection was 17.4cm (SD = 3.8), and the mean delay of the resection and reconstruction stages was 9.4 months (SD = 4). The mean follow-up was 6.6 years (SD = 4.3). The mean MSTS score was 77.4% and the global average healing index was 1.04 months/cm (SD = 2.2). Four complications (i.e., prominence device, fracture, aseptic pseudarthrosis, radial palsy) and one local recurrence were observed in four patients, requiring four unplanned surgical procedures in three patients. One patient died fourteen years after the initial treatment due to a lung recurrence. The induced-membrane technique is an effective and safe alternative for reconstructing large humeral bone defects after tumour resection in adolescents. Although this is a two-stage technique, it gives good functional results comparable to other strategies found in the literature. IV.

Patient-specific guides for consistently achieving R0 bone margins after resection of primary malignant bone tumors of the pelvis

AimsPrimary malignant bone tumor of the pelvis is an uncommon lesion, the resection of which via freehand osteotomy is subject to inaccuracy due to its three-dimensional anatomy. Patient-Specific Guides (PSG), also called Patient-Specific Instruments (PSI) are essential to ensure surgical planning and resection adequacy. Our aim was to assess their use and effectiveness.MethodsA monocentric retrospective study was conducted on 42 adult patients who underwent PSG-based resection of a primary malignant bone tumor of the pelvis. The primary outcome was the proportion of R0 bone margins. The secondary outcomes were the proportion of overall R0 margins, considering soft-tissue resection, the cumulative incidence of local recurrence, and the time of production for the guides. A comparison to a previous series at our institution was performed regarding histological margins.ResultsUsing PSGs, 100% R0 safe bone margin was achieved, and 88% overall R0 margin due to soft-tissue resection being contaminated, while the comparison to the previous series showed only 80% of R0 safe bone margin. The cumulative incidences of local recurrence were 10% (95% CI: 4–20%) at one year, 15% (95% CI: 6–27%) at two years, and 19% (95% CI: 8–33%) at five years. The median overall duration of the fabrication process of the guide was 35 days (Q1–Q3: 26–47) from the first contact to the surgery date.ConclusionsPatient-Specific Guides can provide a reproducible safe bony margin.

High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis.

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

Clinical and Prognostic Characteristics in Childhood Osteosarcoma: A Single-Center Experience in Türkiye.

In our study, we aimed to share the clinical experiences of our center regarding osteosarcoma cases, the most common primary malignant bone tumor in children and adolescents. With approval from the Clinical Research Ethics Committee of our center, the data of 59 pediatric patients who were followed up in our center with the diagnosis of osteosarcoma between 2007 and 2021 were evaluated retrospectively. The mean time between the onset of symptoms and diagnosis was 3 months. Although not statistically significant, patients with a diagnostic delay of 3 months or less had a higher rate of recurrence and mortality. 59.3% of patients had metastatic disease, and the presence of metastases was associated with higher rates of recurrence and mortality. Significant number of patients had multiple surgical operations. Amputation as the first operation and the need for multiple surgeries were associated with higher mortality. Pathologically poor response to chemotherapy is associated with mortality. 42.4% of patients died, and the 5-year overall and disease-free survival rates were 47.5% and 30.5%, respectively. Survival rates were highest in non-metastatic and non-relapsed patients, and lowest in metastatic patients and patients with poor response to chemotherapy. Renal problems and cardiotoxicity were most frequently treatment-related complications. Significant improvements have been achieved in the survival and quality of life in osteosarcoma cases compared to previous years; however, there is still a long way to go, and more multicenter and multidisciplinary studies are needed on osteosarcoma.

CircZMYM2 plays a pivotal role in osteosarcoma by regulating the translation of NACA and ARPC1B

Osteosarcoma (OS) is a primary malignant bone tumor in children and young adults because of its intertumoral heterogeneity and absence of molecular targets. This study aimed to elucidate the role of circular RNA in the pathogenesis of OS. Using bioinformatics analysis and OS clinical samples, we found that hsa_circ_0029634 formed during the splicing process of Zinc finger MYM-type containing 2 (circZMYM2) was highly expressed in OS tissues. Nuclear cap-binding protein subunit 2 regulated circZMYM2 bio-generation by binding to flanking sequences of ZMYM2 transcripts. In addition, knockdown circZMYM2 inhibited cell growth and metastasis in OS cell lines in vitro and inhibited tumor growth in vivo. Mechanistically, circZMYM2 competitively bound to FXR1 to regulate the translation of NACA and ARPC1B. CircZMYM2 may be a crucial regulator of OS tumorigenesis and a potential diagnostic and therapeutic biomarker for OS patients.