CDK12 is a promising therapeutic target for the transcription cycle and DNA damage response in metastatic osteosarcoma.

Osteosarcoma (OS) is a bone malignant tumor affecting children, adolescents and young adults. Currently, osteosarcoma is treated with chemotherapy regimens established over 40 years ago. The investigation of novel therapeutic strategies for the treatment of osteosarcoma remains an important clinical need. Cyclin-dependent kinases (CDKs) have been considered promising molecular targets in cancer therapy. Among these, CDK12 has been shown to play a crucial role in the pathogenesis of malignancies, but its clinical significance and biological mechanisms in osteosarcoma remain unclear. In the present study, we aim to determine the expression and function of CDK12, and evaluate its prognostic and therapeutic value in metastatic osteosarcoma. We found that overexpression of CDK12 was associated with high tumor grade, tumor progression and reduced patient survival. Underlying mechanism revealed that knockdown of CDK12 expression with siRNA or functional inhibition with the CDK12-targeting agent THZ531 effectively exhibited time- and dose-dependent cytotoxicity. Downregulation of CDK12 paused transcription by reducing RNAP II phosphorylation, interfered with DNA damage repair with increased γH2AX, and decreased cell proliferation through the PI3K-AKT pathway. This was accompanied by the promotion of apoptosis, as evidenced by enhanced Bax expression and reduced Bcl-xL expression. Furthermore, the CDK12 selective inhibitor THZ531 also hindered ex vivo 3D spheroid formation, growth of in vitro 2D cell colony, and prevented cell mobility. Our findings highlight the clinical importance of CDK12 as a potentially valuable prognostic biomarker and therapeutic target in metastatic osteosarcoma.

Global, Regional, and National Incidence Trend Analysis of Malignant Skin Melanoma Between 1990 and 2019, and Projections Until 2034.

BACKGROUND: The goal of this study was to evaluate the global burden of malignant skin melanoma (MSM) from 1990 to 2019 using MSM-related data from the Global Burden of Disease study. METHODS: The incidences' relationships with the social-demographic index (SDI) and human developmental index (HDI) were investigated. To determine significant changes in incidence trends, the joinpoint regression model was used. To demonstrate trends in MSM mortality rates, an Age-Period-Cohort framework was conducted. For the projection of new cases and the age-standardized incidence rate (ASR) of MSM incidence to 2034, the Nordpred method was used. RESULTS: In 2019, the ASR incidence per 100, 000 people for MSM was 3.6 (95% UI, 2.6-4.2). MSM prevalence increased in most countries between 1990 and 2019 (average annual percentage change >0). HDI and annual percentage change (APC) (ρ = .63, P < .001), as well as SDI and ASR, had a positive correlation. The total MSM mortality rate declined globally, with an APC of -.61%. Likewise, the mortality rate for the age group of people with ages <77.5 years declined. Predictive analysis demonstrated a declining trend in ASR incidence and a growing number of MSM. CONCLUSION: There are significant differences in ASR incidence among regions and countries. Despite decreases in ASR incidence and fatality, MSM remains one of the leading sources of cancer mortality and morbidity globally. MSM necessitates more primary prevention measures and screening in high-risk areas.

Comprehensive Analysis Reveals Prognostic and Therapeutic Immunity-Related Biomarkers for Pediatric Metastatic Osteosarcoma.

Background and Objectives: Osteosarcoma, the most prevalent malignant bone tumor in children and adolescents, presents a complex pathogenesis characterized by various genetic and epigenetic alterations. This study aims to identify key differentially expressed genes (DEGs) in pediatric osteosarcoma, with a focus on those influencing metastasis and patient survival. Materials and Methods: We utilized the GSE33382 dataset from the GEO database for a comprehensive bioinformatic analysis. This included a protein-protein interaction (PPI) network analysis, Cox regression, and Kaplan-Meier survival analysis to identify central DEGs associated with osteosarcoma metastasis and patient survival. Results: Our analysis identified 88 DEGs related to osteosarcoma metastasis. Among them, three survival-related central DEGs-C1QA, CD74, and HLA-DMA-were significantly linked to patient outcomes. Further correlation analysis established a strong relationship between these genes, tumor mutation burden (TMB), immune checkpoint gene expression, and overall survival. Notably, C1QA and CD74 exhibited higher expression in non-metastatic osteosarcoma cases, suggesting a potential role in disease progression. Conclusions: The identified DEGs, particularly C1QA, CD74, and HLA-DMA, may serve as critical biomarkers for pediatric osteosarcoma prognosis and potential targets for immunotherapy. These findings provide a deeper understanding of the molecular landscape of osteosarcoma and open new avenues for therapeutic intervention.

Quality of life issues in patients with bone metastases: A systematic review.

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.

The influence of diverse bone cement distribution patterns for metastatic vertebral lesions after bilateral percutaneous kyphoplasty.

OBJECTIVE: To investigate the influence of diverse bone cement distribution patterns in patients with metastatic vertebral lesions after bilateral percutaneous kyphoplasty (PKP). METHODS: Fifty-nine patients with single-level metastatic vertebral lesions who received bilateral PKP were retrospectively reviewed. According to the different bone cement distribution patterns, patients were divided into confluent (n = 35, CF) and separated (n = 24, SP) groups. Indicators including visual analogue scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH) variation, quality of life (QoL), and related complications were reviewed and compared between the two groups. RESULTS: No statistically significant differences were observed between the two groups in age, sex, types of lesions, locations of lesions, posterior vertebral body and/or pedicle involvement, percentage of vertebral invasion, procedure duration or cement volume (p > 0.05). There was significant improvement in VAS, ODI, VBH and QoL at any follow-up examination (p < 0.05) compared with those preoperatively. The CF group exhibited better pain relief in VAS scores than did the SP group just at 3 days and 1 month after PKP (p < 0.05). There were no significant differences between the two groups in VAS scores at 3 months or 1 year after PKP (p > 0.05). No statistically significant differences were observed between the two groups in terms of ODI, VBH or QoL (p > 0.05). There was no statistically significant difference in the incidence of complications between the two groups (p > 0.05). CONCLUSIONS: More rapid pain relief was achieved with confluent rather than separated bone cement distribution patterns in PKP for patients with metastatic vertebral lesions.

In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy.

Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8+ T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

Molecular targeted therapy for advanced or metastatic soft tissue sarcoma.

Soft tissue sarcomas are a form of rare and heterogeneous neoplasms with high recurrence rate and mortality. Over the past decades, less progress has been achieved. Surgical management with or without adjuvant/neoadjuvant radiotherapy is still the first-line treatment for localized soft tissue sarcomas, and chemotherapy is the additional option for those with high-risk. However, not all patients with advanced or metastatic soft tissue sarcomas benefit from conventional chemotherapy, targeted therapy takes the most relevant role in the management of those resistant to or failed to conventional chemotherapy. Heterogeneous soft tissue sarcomas vary from biological behavior, genetic mutations, and clinical presentation with a low incidence, indicating the future direction of histotype-based even molecule-based personalized therapy. Furthermore, increasing preclinical studies were carried out to investigate the pathogenesis and potential therapeutic targets of soft tissue sarcomas and increasing new drugs have been developed in recent years, which had started opening new doors for clinical treatment for patients with advanced/metastatic soft tissue sarcomas. Here we sought to summarize the concise characteristics and advance in the targeted therapy for the most common subtypes of soft tissue sarcomas.

Establishment and Characterization of a Novel Dedifferentiated Chondrosarcoma Cell Line DDCS2.

BACKGROUND: The dedifferentiated variant of chondrosarcoma is highly aggressive and carries an especially grim prognosis. While chemotherapeutics has failed to benefit patients with dedifferentiated chondrosarcoma significantly, preclinical chemosensitivity studies have been limited by a scarcity of available cell lines. There is, therefore, an urgent need to expand the pool of available cell lines. METHODS: We report the establishment of a novel dedifferentiated chondrosarcoma cell line DDCS2, which we isolated from the primary tumor specimen of a 60-year-old male patient. We characterized its short tandem repeat (STR) DNA profile, growth potential, antigenic markers, chemosensitivity, and oncogenic spheroid and colony-forming capacity. RESULTS: DDCS2 showed a spindle to polygonal shape and an approximate 60-hour doubling time. STR DNA profiling revealed a unique genomic identity not matching any existing cancer cell lines within the ATCC, JCRB, or DSMZ databases. There was no detectable contamination with another cell type. Western blot and immunofluorescence assays were consistent with a mesenchymal origin, and our MTT assay revealed relative resistance to conventional chemotherapeutics, which is typical of a dedifferentiated chondrosarcoma. Under ex vivo three-dimensional (3D) culture conditions, the DDCS2 cells produced spheroid patterns similar to the well-established CS-1 and SW1353 chondrosarcoma cell lines. CONCLUSION: Our findings confirm DDCS2 is a novel model for dedifferentiated chondrosarcoma and therefore adds to the limited pool of current cell lines urgently needed to investigate the chemoresistance within this deadly cancer.

Dermatofibrosarcoma Protuberans: A Clinicopathologic and Therapeutic Analysis of 254 Cases at a Single Institution.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade tumor that typically does not metastasize but often recurs. Fibrosarcomatous DFSP (FS-DFSP) is associated with a substantially higher rate of metastasis and a poorer prognosis. OBJECTIVE: This study sought to investigate the epidemiological, histopathological, and clinical characteristics of DFSP, especially with a particular focus on FS-DFSP. MATERIALS AND METHODS: Clinical data from 254 patients treated between January 1999 and July 2018 were retrospectively reviewed. Endpoints of the study were the incidence of significant disease-related clinical events. RESULTS: Follow-up data from 211 patients were available for analysis, with a median follow-up time of 38 months (range: 1-196 months). The 5-year recurrence-free survival rate of patients underwent wide-local excision (WLE) was 97.1%. Patients underwent WLE exhibited a significantly decreased recurrence rate relative to patients treated through local excision (2.9% vs 37.7%; p < .001). Fibrosarcomatous DFSP had significantly higher rates of distant metastasis (66.7% [n = 4] vs 2.0% [n = 4]; p < .001) and long-term mortality (50.0% [n = 3] vs 1.5% [n = 3]; p < .001), compared with classical DFSP (C-DFSP). CONCLUSION: Wide-local excision is an effective means of reducing DFSP recurrence. Rates of metastasis are higher for FS-DFSP than for C-DFSP, with the former having significantly poorer outcomes.

Classification and Application of the Distally-Based Thigh Flap Based on the Lateral Circumflex Femoral Artery System.

BACKGROUND: The lateral circumflex femoral artery system with its anatomical variations is a common source vessel for numerous thigh flaps. However, the anatomic variations of the distally based thigh flaps have not been well classified. METHODS: Between July 2008 and July 2016, 19 patients (13 men and 6 women; age range, 3-58 years; mean, 27.5 years) underwent reconstruction of defects around the knee using distally based thigh flaps. Defect etiologies included malignant neoplasm (6 cases) and post-burn scar contracture (13 cases). The distally based thigh flaps were raised based on perforating vessels originating from the descending, oblique, rectus femoris branches of the lateral circumflex femoral artery. RESULTS: The average flap size was 17.7 × 8.4 cm (range, 9-24 cm × 6-13 cm), whereas the mean pedicle length was 16.2 cm (range, 8.5-25 cm). The flap's perforating vessels originated from the descending branch in 6 patients, the oblique branch from the descending branch in 7 patients, the rectus femoris branch in 5 patients, and the oblique branch from the transverse branch in 1 patient. All flaps were pedicle flaps except 1 based on the oblique branch from the transverse branch that was converted to a free flap. All flaps survived in its entity. CONCLUSIONS: Our experience demonstrated that a distally based thigh flap can be reliably raised using perforating vessels from different branches of the lateral circumflex femoral artery.

Perforator Propeller Flap for Oncologic Reconstruction of Soft Tissue Defects in Trunk and Extremities.

BACKGROUND: Defects after soft tissue sarcoma resection are usually managed by myocutaneous flaps or free flaps. However, harvesting muscle will cause functional morbidities, and some regions lack reliable recipient vessel. Our purpose is to use various perforator propeller flaps for oncologic reconstruction. METHODS: Between 2008 and 2014, 33 perforator propeller flaps were performed in 24 patients to reconstruct the defects after tumor resection in trunk and extremities. Fifteen patients underwent tumor resection previously. Thirteen patients underwent adjuvant radiotherapy or chemotherapy. Flaps based on perforators adjacent to the lesions were raised and rotated in propeller fashion to repair the defects. RESULTS: Twenty-seven flaps were based on perforators of known source vessels, and 6 were harvested in freestyle fashion. The defects were repaired with 2 flaps in 4 patients and 3 flaps in 2 patients. The mean skin paddle dimension was 8.36 cm in width and 20.42 cm in length. The mean degree of flap rotation was 158.79°. Complications include partial necrosis of 6 flaps in 5 cases and venous congestion of 1 flap. In these 6 patients, 3 underwent adjuvant radiotherapy. The donor sites were primarily closed in 21 patients and skin grafted in 3 patients. No functional loss related to flap harvesting was recognized. CONCLUSIONS: The perforator propeller flaps can be used to manage the medium defects in extremities and large defects in torso after soft tissue sarcoma resection. They avoid the sacrifice of the underlying muscle and eliminate the concerns of the unavailability of recipient vessels. The perforator propeller flaps provide flexible options for versatile oncologic reconstruction in trunk and extremities. However, the impact of radiotherapy on the viability of the flaps for local reconstruction needs further investigation.

Freestyle perforator-based propeller flap of medial arm for medial elbow reconstruction.

Elbow reconstruction is challenging for reconstructive surgeons. The purpose of this report is to present the results of the use of freestyle perforator-based propeller flap designed from the medial arm region for elbow reconstruction. The defects following soft tissue sarcoma resection at the medial and posterior elbow were repaired in two patients. The dimensions of the defects were 11 × 7 cm(2) and 10 × 7 cm(2). Two perforators were identified in each case using Doppler ultrasound probe in the medial arm, adjacent to the defect. The perforator with visible pulsation was chosen as the pedicle vessel, which was 12-cm and 7-cm proximal to the medial epicondyle. An elliptical flap, extending almost the full length of arm, was raised and rotated 180° to repair medial elbow defects. The sizes of the flaps were 17 × 8 cm(2) and 11 × 7 cm(2). The donor sites were closed directly. Both flaps survived; temporary venous congestion occurred in one case. There were no other postoperative complications. These cases illustrated that the medial arm flap might be used for reconstruction of medial elbow defects with this freestyle perforator-based propeller flap design.

[Role and significance of sentinel lymph node biopsy for the treatment of melanoma of the extremities].

OBJECTIVE: To evaluate the role of sentinel lymph node biopsy (SLNB) for the treatment of melanoma of the extremities. METHODS: From April 2007 to August 2013, forty-eight (25 men and 23 women) cases of melanoma of the extremities underwent sentinel lymph node biopsy. All the cases had sentinel lymph node biopsy and surgery. Among them 37 cases underwent limb salvage surgery, while 11 cases underwent amputation. Of the cases with limb salvage, 28 cases underwent free skin grafting or local flap grafting reconstruction after wide resection. Of the surgical margin, wide resection was performed in 37 patients, and radical resection was performed in 11 cases. There were 39 cases in stage I or II, and 9 cases in stage III. After the surgery, adjuvant chemotherapy was performed in 9 cases, and adjuvant biotherapy of interferon and interleukin was performed in 26 cases. Except for 2 cases, 46 cases were followed up with a mean follow-up period of 20.1 months (range from 2 to 60 months). RESULTS: 39 (81.3%) cases had negative SLNB, while 9 (18.8%) cases had positive SLNB. Recurrence or metastasis was more common in those with positive SLNB (3 of 9 cases, 33.3%) compared with those with negative SLNB (4 of 39 cases, 10.3%). The median disease-free survival of patients with negative results was 19.5 months, significantly longer than that of the positive cases (9.5 months, P = 0.03). Otherwise, sex and age showed no significant difference in the disease free survivals. CONCLUSIONS: Sentinel lymph node biopsy enables us to have a better understanding of regional lymph node status through lymphoscintigraphy. It improves the accuracy of staging and provides valuable prognostic information to guide subsequent treatment decisions.

Acral Lentiginous Melanoma: A Clinicoprognostic Study of 149 Cases at a Single Institution.

OBJECTIVE: The objective of this study is to investigate the epidemiological features, clinical characteristics, and pathological characteristics of acral lentiginous melanoma (ALM) and identify prognostic factors. METHODS: A total of 149 patients diagnosed with ALM between August 2008 and December 2019 at the National Cancer Center (NCC) of China were retrospectively analyzed. Follow-up data on patient survival status were collected. Survival curves were generated using the Kaplan-Meier method, and statistical significance was assessed using the log-rank test. Additionally, a Cox proportional hazards model was constructed to identify prognostic factors. RESULTS: All patients included in this study were of Chinese ethnicity, with an average age of 52.4 ± 14.8 years (range, 15-80 years) at the time of diagnosis. No gender predilection or genetic susceptibility was observed. The plantar region was the most frequently affected site among primary lesions. Notably, only 17 (11.4%) patients reported a history of trauma. Statistical analysis revealed that a lesion duration of ≤2.5 years, Breslow thickness >4.0 mm, high mitotic rate (>6 mm-2), presence of vascular invasion, and regional lymph node metastasis were identified as independent prognostic factors. CONCLUSION: Our findings indicate that a lesion duration of ≤2.5 years, Breslow thickness >4.0 mm, high mitotic rate (>6 mm-2), presence of vascular invasion, and regional lymph node metastasis are significantly associated with a poorer prognosis for patients with ALM.

The efficacy of re-excision after unplanned excision for synovial sarcoma.

Background: This investigation studied the clinical features and outcomes of synovial sarcoma (SS) patients from a single institution. Methods: A retrospective clinicopathologic study was conducted on 129 postoperative SS patients during 2003-2018. Kaplan-Meier curves and Cox proportional hazards regression (Cox) models were performed to determine the parameters associated with recurrence-free survival (RFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) via univariate and multivariate analysis. The impact of unplanned excision (UE) and residual tumor in re-excision specimens was evaluated. Results: The 3-year RFS, MFS and 5-year CSS were 72 %, 70 %, and 76 %, respectively. Independent factors associated with significantly inferior survival included older age, UE without re-excision, UE with residual tumors, high grade, and deep tumor for RFS, trunk-related tumor, UE without re-excision, UE with residual tumors, and deep tumor for MFS, UE with residual tumors, high grade, and deep tumor for CSS. Re-excision after UE was significantly associated with better RFS (P < 0.001). Residual tumors were remarkably correlated with inferior RFS (P = 0.0012), MFS (P = 0.0016), and CSS (P = 0.048), especially in patients at stage II (MFS: P < 0.001, CSS: P = 0.0014). Conclusion: UE and residual tumors have a marked impact on the long-term survival of SS patients. Primary wide excision and re-excision is especially essential for patients at stage II.

CFLAR: A novel diagnostic and prognostic biomarker in soft tissue sarcoma, which positively modulates the immune response in the tumor microenvironment.

Anoikis is highly associated with tumor cell apoptosis and tumor prognosis; however, the specific role of anoikis-related genes (ARGs) in soft tissue sarcoma (STS) remains to be fully elucidated. The present study aimed to use a variety of bioinformatics methods to determine differentially expressed anoikis-related genes in STS and healthy tissues. Subsequently, three machine learning algorithms, Least Absolute Shrinkage and Selection Operator, Support Vector Machine and Random Forest, were used to screen genes with the highest importance score. The results of the bioinformatics analyses demonstrated that CASP8 and FADD-like apoptosis regulator (CFLAR) exhibited the highest importance score. Subsequently, the diagnostic and prognostic value of CFLAR in STS development was determined using multiple public and in-house cohorts. The results of the present study demonstrated that CFLAR may be considered a diagnostic and prognostic marker of STS, which acts as an independent prognostic factor of STS development. The present study also aimed to explore the potential role of CFLAR in the STS tumor microenvironment, and the results demonstrated that CFLAR significantly enhanced the immune response of STS, and exerted a positive effect on the infiltration of CD8+ T cells and M1 macrophages in the STS immune microenvironment. Notably, the aforementioned results were verified using multiplex immunofluorescence analysis. Collectively, the results of the present study demonstrated that CFLAR may act as a novel diagnostic and prognostic marker for STS, and may positively regulate the immune response of STS. Thus, the present study provided a novel theoretical basis for the use of CFLAR in STS diagnosis, in predicting clinical outcomes and in tailoring individualized treatment options.

Organoids derived from metastatic cancers: Present and future.

Organoids are three-dimensional structures derived from primary tissue or tumors that closely mimic the architecture, histology, and function of the parental tissue. In recent years, patient-derived organoids (PDOs) have emerged as powerful tools for modeling tumor heterogeneity, drug screening, and personalized medicine. Although most cancer organoids are derived from primary tumors, the ability of organoids from metastatic cancer to serve as a model for studying tumor biology and predicting the therapeutic response is an area of active investigation. Recent studies have shown that organoids derived from metastatic sites can provide valuable insights into tumor biology and may be used to validate predictive models of the drug response. In this comprehensive review, we discuss the feasibility of culturing organoids from multiple metastatic cancers and evaluate their potential for advancing basic cancer research, drug development, and personalized therapy. We also explore the limitations and challenges associated with using metastasis organoids for cancer research. Overall, this review provides a comprehensive overview of the current state and future prospects of metastatic cancer-derived organoids.

A Modification of the American Joint Committee on Cancer Nomogram for Undifferentiated Sarcoma With External Validation and Risk Stratification.

BACKGROUND: The aim of this study is to establish a model to predict the overall survival (OS) and stratify the risk of postoperative patients with undifferentiated sarcoma. METHODS: A total of 452 postoperative patients with undifferentiated sarcoma in the trunk and extremity from the Surveillance, Epidemiology, and End Results database were enrolled as the training cohort. We collected a group of 163 undifferentiated sarcoma patients from our center as the external validation cohort. Cox proportional hazards regression model was used to screen survival-associated factors for the construction of the nomogram. Concordance-indexes (C-indexes), calibration curves, and receiver operating characteristics (ROCs) curves were applied for the discrimination and calibration of the nomogram. The cutoff value of nomogram-based total points was applied to stratify the risk of patients. RESULTS: A nomogram was developed incorporating four independent factors: age, tumor site, eighth AJCC stage, and radiotherapy. The nomogram showed good prognostic accuracy and excellent agreement in the training and validation cohort, with C-indexes of .701 (95% confidence interval [CI]: .683-.719) and .700 (95% CI: 0.659-.741), respectively. Furthermore, we identified the best cutoff value of nomogram total points (103.2) as the predicted risk and divided the patients into a high-risk group and a low-risk group. Significant differences in OS between the two groups were indicated in the training cohort and external validation cohort, showing the appreciable clinical validity and clinical utility of the nomogram (P < .001). CONCLUSION: This nomogram provides an insightful and applicable tool for individual evaluations and the distinguishment of risk for patients with undifferentiated sarcoma.

Single-cell transcriptomic insights into chemotherapy-induced remodeling of the osteosarcoma tumor microenvironment.

PURPOSE: Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols. METHODS: Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy. RESULTS: The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities. CONCLUSION: These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.

Hidden blood loss and its influencing factors after cement augmentation for vertebral metastasis.

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.