11574 Background: Advanced epithelioid sarcoma (ES) responds poorly to conventional chemotherapy, with an objective response rate (ORR) of 15-27% and a median progression-free survival (mPFS) of only 4-6 months, highlighting the urgent need for new therapeutic strategies. This study aims to evaluate the efficacy and safety of Sintilimab (An approved PD-1 antibody) plus the gemcitabine and docetaxel (GT) in patients with advanced ES that has not been treated by chemotherapy. Methods: This is a single-arm, prospective phase II study conducted in China (ChiCTR2500095527). Patients received Sintilimab (200mg, d1, q3w) combined with gemcitabine (1000mg/m², d1,8, q3w) and docetaxel (70mg/m², d8, q3w) for up to 6 cycles, followed by Sintilimab maintenance for up to 2 years or until disease progression, intolerable adverse reactions or death. The primary endpoint was ORR, and secondary endpoints included PFS, overall survival (OS), and safety. Additionally, tumor tissue and/or blood samples were collected from patients before treatment and at the time of progression for exploratory biomarker analysis. Results: Between October 2024 and January 2026, Of the 19 planned patients, 16 eligible patients were enrolled. The median age was 36 years (range: 22-61), with 5 males and 11 females. All patients had metastatic or unresectable locally advanced disease (ECOG performance status 0: 12.5%; stage IV: 75.0%). With the cutoff date of January 15, 2026, 14 patients were evaluated, the median follow-up time was 8.6 months (range, 2.9 to 14.6 months), the objective response rate (ORR) was 35.71% (5/14), all of them were partial responses (PR), and the disease control rate (DCR) was 100% (14/14). The median PFS and OS were not reached. Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs observed in 4 (28.57%) patients, included two case of neutropenia, and one case each of thrombocytopenia and transaminase elevation. Conclusions: The combination of Sintilimab and GT demonstrated promising efficacy in chemotherapy-naïve patients with advanced ES, achieving an ORR of 35.71% and a remarkably high DCR. Despite limited follow-up, the preliminary PFS data suggest a potential benefit from PD-1 immunotherapy. The combination showed a manageable safety profile with no new safety signals identified. Clinical trial information: ChiCTR2500095527.

Abstract Background Proteins represent the dynamic downstream products of genes, and have the potential to substantially increase understanding of the complexities of cancer biology. Undifferentiated pleomorphic sarcoma (UPS) is a rare disease, the proteomic landscape of which has not been fully investigated. Methods We performed isobaric TMT-based proteomic analysis for 80 UPS tumor and 28 corresponding adjacent non-tumor muscle tissues. The underlying molecular subtypes, therapeutic targets, local recurrence, and lung metastasis were uncovered. The integration of previous single-cell RNA sequencing data with proteomics was further employed to characterize the specific cell type linked to lung metastasis. Results Our analyses revealed a catalog of proteins that were dysregulated in UPS. The UPS cohort was stratified into three molecular subtypes S-I, S-II, and S-III. S-I was characterized by the high expression of spliceosome-related proteins and protumor cytokines, and was associated with the lowest overall rate of survival. S-II was characterized with the highest ImmuneScore. S-III with the highest StromaScore had the best outcomes. Protein-based disease classification was better than the recommended AJCC staging system for UPS. PRMT6 protein was overexpressed, and associated with adverse outcomes. PRMT6 inhibitor significantly inhibited tumor growth in two patient-derived xenograft models. Analysis of local recurrence-associated proteins showed that PAWR was negatively associated with UPS recurrence. Additionally, CD163 was a negative predictive marker for lung metastasis. Combined with scRNA-seq data, CD163 + macrophages represented phagocytosis phenotype with high expression of the signature markers (CD163, MRC1, MERTK, and C1QB). Furthermore, CD163 + macrophages were enriched in the endocytosis, phagocytosis, and lysosome compared with CD163- macrophages. Conclusions Our study highlights the utility of proteomics for characterizing UPS, providing a framework for understanding the biological basis of its clinical features and paving the way for a new era of proteomics-driven precision medicine in sarcoma research.

Background:Urachal carcinoma (UrC) constitutes a rare and biologically distinct adenocarcinoma for which no standardised therapeutic regimen currently exists. We aimed to evaluate the efficacy and safety of combined therapy with camrelizumab, a humanised monoclonal anti programmed death-1 (PD-1) antibody, plus apatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in patients with advanced UrC. Methods:RUN-SC-0102 is an open-label, single-arm, phase 2, multicohort trial that followed a Simon's two-stage MiniMax design and enrolled participants with rare cancer types. Here, we report the urachal cancer cohort, which enrolled patients across two centres in China (Shanghai, Beijing) with histologically confirmed UrC who were refractory to at least one line of systemic chemotherapy. Patients with prior exposure to PD-1/PD-L1 or VEGF-targeted agents were ineligible for enrolment. Participants received camrelizumab (200 mg; intravenous) once every 3 weeks and apatinib (250 mg; oral). The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Efficacy analysis was performed in the intention-to-treat (ITT) population. Safety analyses were performed on all patients who received at least one dose of study treatment. This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2400086153. Findings:Between June 1, 2024, and Jan 31, 2025, 20 patients with UrC were enrolled. As of data cutoff (Sept 30, 2025), the ORR was 40% (95% CI 19.8-63.1) and the CBR was 50% (95% CI 27.2-72.8). Median DoR was 7.5 months (95% CI 7.0-not reached) and median PFS was 5.5 months, (95% CI 3-not reached). The DCR was 95% (95% CI 79.2-99.2), comprising 8 partial responses (PR) and 11 stable diseases (SD) as best overall response. Median OS was not reached, with a median follow-up duration of 13.6 months (9.9-not reached). Nine patients (45%) experienced grade 3 and 4 adverse events. No grade 5 toxicities were observed. Interpretation:As the first reported trial of its kind in advanced urachal carcinoma, this study demonstrates that combined PD-1 and VEGFR inhibitor therapy is well tolerated and clinically active, warranting further investigation in biomarker-enriched, adequately powered trials. Funding:None.

Synovial sarcoma (SS) is a rare and aggressive soft tissue sarcoma frequently associated with lung metastases. While anthracycline plus ifosfamide (AI) remains a standard first-line regimen, its benefit in SS patients with lung metastases is unknown. Anlotinib, a multi-target tyrosine kinase inhibitor (TKI), has shown promising effects in sarcoma treatment, but its combination with AI has not been well studied in this setting. This retrospective, single-center study included 108 SS patients with lung metastases treated between 2007 and 2024, receiving either AI alone (n = 59) or AI combined with anlotinib (n = 49). Survival outcomes were assessed using Kaplan-Meier analysis, and adverse events (AEs) were reviewed from clinical records. The results indicated that the combination therapy demonstrated statistically significant improvements in clinical outcomes compared to AI monotherapy, with a median PFS of 8.1 months versus 6.2 months (p = 0.0250), and a median OS of 14.8 months versus 6.8 months (p = 0.0033). Most AEs were Grades 1-2 according to common terminology criteria for adverse events (CTCAE) criteria, with manageable toxicity profiles. The combination group exhibited modest but clinically insignificant elevations in hypertension and proteinuria, with no reported treatment-related mortality. In conclusion, the anlotinib and AI chemotherapy combination regimen shows promising efficacy in prolonging survival duration for SS patients with lung metastases while maintaining an acceptable safety profile. These findings suggest that this combination therapy could be considered as a viable first-line treatment option for this patient population, warranting further validation through phase III randomized controlled trials.

Laryngeal squamous cell carcinoma (LSCC) is a malignancy characterized by metabolic reprogramming and immune evasion, where the immunosuppressive tumor microenvironment contributes to poor therapeutic response. The role of Ubiquitin-like with PHD and RING finger domain 1 (UHRF1), an epigenetic regulator, in regulating metabolic-immune crosstalk in LSCC remains unclear. This study aimed to explore whether UHRF1 drives aerobic glycolysis and lactate-mediated TOX lactylation to induce CD8⁺ T cell exhaustion. UHRF1 expression and glycolytic activity were assessed in LSCC cell lines and tissues. Glycolysis was inhibited via UHRF1 knockdown or 2-deoxyglucose (2-DG), and lactate levels were modulated with sodium lactate (NaL) or oxamate (OX). CD8⁺ T cell function was evaluated in co-culture systems using flow cytometry and ELISA. TOX lactylation was detected by Western blot and Co-IP assays. UHRF1 was overexpressed in LSCC and correlated with upregulation of glycolytic enzymes (HK2, PKM2, LDHA) and increased lactate secretion (P < 0.01). UHRF1 knockdown or 2-DG treatment reduced tumor proliferation, migration, and glycolytic output, and restored CD8⁺ T-cell effector function by reducing exhaustion markers (PD-1, TIM3, CTLA-4, LAG3; all P < 0.01). UHRF1-driven lactate production induced TOX lactylation, which suppressed T-bet and enhanced Eomes expression. OX reversed this effect, while NaL restored TOX lactylation in UHRF1-deficient cells. In conclusion, UHRF1-driven lactate promotes TOX lactylation and contributes to CD8+ T-cell exhaustion. Combinatorial targeting of UHRF1 and glycolysis may help reverse this immunosuppressive circuit and provide a potential strategy for improving LSCC immunotherapy.

Synchronous bone metastases (BM) have a notable impact on the survival rates of patients across various cancer types. While primary tumor surgery (PTS) has shown potential benefits, its impact across different cancers and patient subgroups needs further clarification. This study aimed to investigate the survival benefits of PTS across various cancer types. This retrospective cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, covering 53,015 patients diagnosed with BM from 2010 to 2019. Propensity score matching (PSM) was performed to reduce baseline imbalance. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. PTS substantially improved overall and cancer-specific survival in patients with lung, kidney, breast and bladder cancers. All surgical modalities benefited breast and renal cancer survival. In prostate cancer, PTS produced no overall survival gain; survival varied by surgery type, being better after prostatectomy and worse with local resection. For liver cancer, PTS improved cancer-specific but not overall survival, and the small matched cohort necessitates circumspect interpretation. The findings indicate that PTS can significantly enhance survival in selected patients with BM, particularly in lung, kidney, breast, and bladder cancers. Tailoring surgical approaches based on individual cancer type and patient characteristics is crucial to optimizing treatment outcomes. Further studies are required to validate these results and expand the understanding of PTS in cancer management.

Objective:To compare the effectiveness between laminoplasty with preservation of the unilateral spinous process-ligament complex and traditional laminoplasty for thoracolumbar intraspinal tumors. Methods:A retrospective analysis was conducted on 91 patients with thoracolumbar intraspinal tumors, who met the selection criteria and were admitted between November 2019 and November 2024. Among them, 52 patients underwent traditional laminoplasty (control group), and 39 underwent laminoplasty with preservation of the unilateral spinous process-ligament complex (treatment group). There was no significant difference in baseline data between groups ( P>0.05), including gender, age, body mass index, tumor type, involved segments, disease duration, smoking history, preoperative visual analogue scale (VAS) score, American Spinal Injury Association (ASIA) classification, Oswestry disability index (ODI), and selective functional movement assessment (SFMA). The two groups were compared based on the following outcome indicators, including operation time, intraoperative blood loss, length of hospital stay, occurrence of postoperative complications ( e.g., cerebrospinal fluid leakage), as well as neurological function recovery (ASIA grading, ODI), pain level (VAS score), and spinal mobility and pain symptoms (SFMA). Results:There was no significant difference between groups ( P>0.05) in terms of operation time, intraoperative blood loss, length of hospital stay, or the incidence of cerebrospinal fluid leakage. All patients were followed up, with follow-up periods of (19.26±4.45) months for the treatment group and (18.63±4.42) months for the control group, showing no significant difference ( t=-0.662, P=0.510). The postoperative VAS scores, ASIA grades, and ODI showed significant improvement compared to preoperative values in both groups ( P<0.05). At 3 and 12 months after operation, there was no significant difference between groups ( P>0.05). In the SFMA multi-stage trunk flexion and extension assessment at 3 and 12 months, there was no significant difference in motor function between groups among pain-positive cases ( P>0.05). However, among function cases, there was a significant difference in the incidence of pain ( P<0.05). Follow-up imaging showed that laminar fusion achieved in both groups, with no internal fixation failure or significant spinal instability. Conclusion:Compared to traditional laminoplasty, laminoplasty with preservation of the unilateral spinous process-ligament complex demonstrates comparable results in terms of surgical safety, short-term neurological recovery, and complication control. However, its advantage lies in better maintaining dynamic spinal stability and significantly alleviating pain at the surgical site during spinal hyperflexion and hyperextension.

The biological functions of mitochondria play a role in the occurrence and development of breast cancer, however, the causal relationship between them remains unclear. Genetic instruments for mitochondrial biology and breast cancer were sourced from two genome-wide association studies (GWAS). Causal associations were assessed using Mendelian randomization analysis and validated through heterogeneity and sensitivity analyses. Additionally, the causal relationship between the identified mitochondrial proteins and the survival rate of breast cancer patients was further verified using the Kaplan-Meier Plotter. Analysis indicated causal associations between six mitochondrial proteins and breast cancer incidence. Inverse associations were found for ADP-ribose pyrophosphatase (ADPRase) and Cytochrome c oxidase subunit 8 A (COX8A), while positive correlations were observed for Pyruvate carboxylase (PC), rRNA methyltransferase 3 (MRM3), Cytochrome c oxidase assembly factor 3 homolog (COA3), and Diablo homolog (DIABLO). A causal relationship between mitochondrial biology and breast cancer was established in this study. ADPRase and COX8A were identified as protective factors, whereas PC, MRM3, COA3, and DIABLO were identified as risk factors.

BackgroundKrüppel-like factor 5 (KLF5) is involved in various aspects of tumor development, metastasis, and drug resistance through their regulation of transcription and translation, yet its functions in a comprehensive cancer framework are still unclear.MethodsOur research involved a detailed pan-cancer analysis using multi-omics data sourced from various public databases. We investigated the clinical characteristics, prognostic significance, mutations, and methylation patterns of KLF5 across various cancer types.ResultsWe discovered that KLF5 is implicated in tumor progression and are prognostic markers across pan-cancer. KLF5 is significantly linked to various malignant pathways across different types of cancer. Additionally, KLF5 has associations with several immune-related features. Ultimately, experiments were carried out to investigate whether KLF5 could serve as a promising indicator for glioma and bladder cancer.ConclusionKLF5 may be utilized as a diagnostic tool for cancer, a predictor of its progression, and a guide for treatment., with particular promise as a therapeutic target for glioma and bladder cancer.

Treatment options for recurrent osteosarcoma remain limited, and prognosis is poor. Pazopanib, a multi-targeted tyrosine kinase inhibitor, has shown activity in various sarcomas. This study evaluated the efficacy and safety of pazopanib combined with doxorubicin and cisplatin (Paz + AP regimen) in patients with recurrent osteosarcoma and analyzed its impact on survival. This single-center retrospective cohort study included recurrent osteosarcoma patients treated between February 2022 and February 2023. Propensity score matching was used to balance baseline characteristics. A total of 100 patients were analyzed: 50 received the Paz + AP regimen, and 50 received conventional chemotherapy (AP regimen). Treatment efficacy was assessed using response evaluation criteria in solid tumors (RECIST 1.1) criteria. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, disease control rate, safety, and treatment compliance. Baseline characteristics were well balanced between groups (P > .05). The Paz + AP group achieved a higher disease control rate than the control group (62.0% vs 42.0%, P = .046), whereas the difference in objective response rate was not significant (26.0% vs 14.0%, P = .13). Median PFS was significantly longer in the Paz + AP group than in controls (5.1 vs 2.2 months, P = .04). Although the median OS was slightly shorter in the Paz + AP group (8.0 vs 9.6 months), its survival curve declined more slowly after 12 months, showing a significant difference (P = .03). The incidence of adverse events was comparable (92.0% vs 88.0%), though hypertension (28.0% vs 10.0%, P = .03) and hand-foot syndrome (22.0% vs 4.0%, P = .01) were more frequent with pazopanib. No differences were observed in grade ≥3 or serious adverse events. Subgroup analysis indicated greater PFS benefits among patients with lung metastasis, recurrence interval ≥6 months, Eastern Cooperative Oncology Group (ECOG 0-1), and those receiving full-dose pazopanib. The Paz + AP regimen significantly prolonged PFS and improved disease control in recurrent osteosarcoma, with manageable toxicity and good compliance. Although OS improvement was limited, the regimen showed potential clinical value, particularly for patients with favorable performance status and longer recurrence intervals. Prospective studies are warranted to confirm these findings.

Bone is a common site for cancer metastasis, yet the mechanisms driving human spinal bone metastases (BMs) are poorly understood. Here, we obtained a single-cell RNA sequencing (scRNA-seq) atlas of 62 BMs across 13 different origins, along with paired primary tumor and normal bone marrow. Unsupervised clustering of cancer cell functional programs revealed 3 groups with distinct prognosis and tumor microenvironment. Integrative analysis with large-scale primary and metastatic pan-cancer and healthy bone marrow scRNA-seq datasets revealed SELE-positive endothelial cells, osteoblasts, and osteoclasts associated with cancer cell proliferation. We also identified BM-enriched exhausted CD8+ T cells with increased expression of immune checkpoint genes. In bone metastatic mouse models, a combined anti-PD-1/TIGIT immune therapy effectively suppressed tumor cell proliferation and significantly enhanced the cytotoxic activity of CD8+ T cells. Our results provide a systematic view of the molecular basis of BM and suggest future avenues for immunotherapy optimization for BM patients.

PURPOSE: In East Asia, melanoma mainly presents as the acral lentiginous subtype, followed by the cutaneous subtype. Patients with completely resected stage III or IV melanoma in East Asia are at a high risk of disease recurrence. The adjuvant efficacy of PD-1 inhibitors as monotherapy remains limited in this patient population, underscoring the need for combination strategies. PATIENTS AND METHODS: This prospective, single-arm, phase II trial (NCT05907512) aimed to investigate adjuvant recombinant human endostatin (rh-endostatin, an angiogenesis inhibitor) combined with toripalimab (a PD-1 inhibitor) in Chinese patients with resectable stage III to oligometastatic stage IV melanoma. The primary endpoint was 1-year relapse-free survival (RFS). Paired peripheral blood samples before and after the combined adjuvant therapy were collected for single-cell RNA sequencing, TCR/BCR sequencing, and biomarker identification. Two independent real-world cohorts of patients with locally advanced melanoma were assessed to validate the biomarkers. RESULTS: Forty-three eligible patients with resected stage III melanoma were prospectively enrolled. No patients with resected oligometastatic stage IV disease were enrolled. The 1-year RFS of the patients was 74.4%, with a median RFS of 27 months (95% confidence interval: 19, not reached). Anemia (12/43, 27.9%), elevated liver enzymes (11/43, 25.6%), and thyroid dysfunction (9/43, 20.9%) were the three most common treatment-related adverse events. The combined adjuvant therapy expanded the patients’ peripheral total T and NK cells, increased circulating CD8+ Tem and Teff cells and their TCR clonal diversities, improved the antigen-presenting capacity of B cells, elevated BCR clonal diversity, and raised the number of non-classical monocytes and their antigen-presenting capacity. The neutrophil-to-lymphocyte ratio and circulating CD8+ Tem cells were supported as candidate biomarkers associated with outcomes in the independent real-world cohorts. CONCLUSIONS: Adjuvant rh-endostatin combined with toripalimab shows encouraging clinical activity and may be associated with a potential survival benefit in Chinese patients with resected locally advanced melanoma. Adverse reactions were manageable. The increased quantities and functional changes of peripheral T cells, NK cells, B cells, and monocyte subsets provide mechanistic insights for the optimization of immunotherapy.

Lung cancer (LC), prostate cancer (PC), and breast cancer (BC) are the three most prevalent cancers that lead to bone metastasis (BoM). In this study, we conducted an integrated analysis of single-cell transcriptomic data from the primary tumors and BoM across PC, LC, and BC. We discover a novel subtype of tumor-associated macrophages (TAMs) that are positive both for matrix metalloproteinase 19 (MMP19) and receptor activator of nuclear factor-κB (RANK) expression (MMP19+ RANK+ TAMs). MMP19+ RANK+ TAMs demonstrate an increased level of M2 polarization and act as a critical driving factor for LC-BoM. MMP19+ RANK+ TAMs are organized in a ring-like arrangement surrounding the tumor nests, constructing a barrier structure that impedes the infiltration of CD8+ T cells into the tumor core in LC-BoM. RANKL inhibitor Denosumab has been shown to effectively reduce the level of M2 polarization, decrease the population of MMP19+ RANK+ TAMs, and disrupt their barrier structure. Denosumab facilitates the infiltration of CD8+ T cells into the interior of LC-BoM tissues. Based on this mechanism, we observed in both clinical cohorts and preclinical models that RANKL inhibitor can enhance the efficacy of immunotherapy in treating LC-BoM.

Bone metastasis is a devastating consequence of lung cancer. However, the key metabolic factors that determine the risk of bone metastasis remain unclear. Here, we show that glucose transporter type 3 (SLC2A3) is notably overexpressed by lung cancer bone metastatic cells and tissues, as a facilitator of lung cancer bone metastasis. Additionally, SLC2A3 promotes glucose metabolism, which promotes tumor cell proliferation and metastasis via lactate-mediated p53 lactylation. Within the tumor microenvironment, cancer cells serve as the primary source of secreted lactate, which induces protumor bone metastasis via osteoclast differentiation and suppresses the antitumor activity of CD8+ T cells. Subsequently, we developed Paris saponin VII, a SLC2A3 inhibitor that effectively suppressed bone metastasis in lung cancer bone metastasis mouse models and patient organoids. Notably, either inhibition of SLC2A3 or lactate limitation improved the tumor response and increased the sensitivity of lung cancer bone metastases to PD-1 treatment. Collectively, our findings highlight that targeting SLC2A3-mediated lactate metabolism, either alone or in combination with PD-1 inhibition, is a potential strategy for treating lung cancer bone metastasis.

Denosumab (DMAb) is widely used as a neoadjuvant therapy to downstage giant cell tumor of bone (GCTB). However, increasing evidence demonstrates that neoadjuvant DMAb may increase the local recurrence (LR) risk following curettage of GCTB. It remains unclear about the potential mechanisms for neoadjuvant DMAb-associated LR of GCTB. Here, we perform single-cell RNA sequencing on untreated primary GCTB, neoadjuvant DMAb-treated primary GCTB, and relapsed GCTB following discontinuation of DMAb after curettage. A total of 33,440 cells are obtained. Osteoclast-like giant cells nearly disappear in primary GCTB after neoadjuvant DMAb treatment, but rebound following DMAb discontinuation in recurrent GCTB. Neoadjuvant DMAb therapy induces the transformation of TNFSF11 (RANKL)-positive neoplastic cells into SPP1 (osteopontin)-positive and CA2-positive neoplastic cells. Neoadjuvant DMAb therapy induces a durable intratumoral immunosuppressive environment, characterized by an increased frequency of regulatory T cells and decreased levels of cytotoxic CD8+ T cells and natural killer T (NKT) cells. In addition, DMAb-induced differentiation of monocytes to Trem2+ macrophages provides a favorable microenvironment that facilitates tumor relapse. CSF1R inhibitor can inhibit the tumor growth of recurrent GCTB. Targeting CSF1R and alleviating T cell exhaustion may provide therapeutic insights for the management of relapsed GCTB following DMAb discontinuation.

BACKGROUND:Heterotopic ossification (HO) represents a highly active research field in pathological bone formation. Despite substantial advancements, a comprehensive understanding of its underlying mechanisms and clinical trajectory remains incomplete. MATERIALS AND METHODS:A bibliometric and machine-learning latent Dirichlet allocation (LDA) analysis was performed using data retrieved from the Web of Science Core Collection database. RESULTS:A total of 4722 publications related to HO were identified. The most prolific countries included the USA, CHINA, GERMANY, the UK, JAPAN, SOUTH KOREA, ITALY, TURKEY, FRANCE, and CANADA . GERMANY demonstrated the highest citation strength, followed by CHINA . Aside from "heterotopic ossification," other frequently occurring author keywords included "fibrodysplasia ossificans progressive," "complications" and "total hip arthroplasty." In keywords plus, besides HO, replacement, bone-formation, and arthroplasty were the most frequently occurring terms. Institutional network analysis with subject-specific clustering indicated that Shanghai Jiao Tong University was significantly enriched in radiology, nuclear medicine and medical imaging, while Wilderness Spine Serv specialized in surgical management. A developmental timeline plot of a network of most contributing authors also was visualized, along with the most influential references. Meanwhile, citation analysis indicated that Kaplan FS and Shore EM were the top-cited authors. By LDA analysis, a total of 16 key topics were identified in this field with distinct period-proportion visualization. One of the topics, cell bone express differentiation and formation has clearly dominated the last 10 years. CONCLUSION:This study constitutes the most extensive text processing analysis of HO to date, offering valuable insights and directions for future development.

11568 Background: Localized high-risk soft tissue sarcomas (STSs) presents a therapeutic challenge due to limited preoperative treatment options. Radiotherapy (RT) and Doxorubicin (DOXO) are well-established immunogenic cell death inducers [1-3], which are capable of boosting the effects of immunotherapy even in "cold" tumors. This study aims to evaluate the safety and efficacy of a preoperative triple combination of RT, DOXO, and the PD-1 antibody for STS. Methods: In this Phase Ib/II trial (NCT05774275), up to 52 patients with localized high-risk STSs will be enrolled. Participants will receive RT (BED = 50-60 Gy), combined with DOXO and PD-1 antibody (Sintilimab, SIN 200 mg, Day 1) every three weeks for four cycles prior to surgery. In Phase Ib (3+3 design), patients will receive Pegylated liposomal doxorubicin (PLD, 37.5 mg/m² or 30 mg/m², i.v., Day 1) to establish the recommended Phase 2 dose (RP2D). In Phase II, DOXO will be administered as PLD at RP2D or as Doxorubicin Hydrochloride (Adriamycin, ADM, 75 mg/m² i.v., Day 1). The primary endpoint is the objective response rate (ORR), while secondary endpoints include the rate of pathological complete response (pCR) and near pCR (defined as < 10% viable tumor cells), survival and safety. Results: From September 2022 to January 2025, 33 patients (26 in limbs and 7 in trunks) were enrolled. The median age was 50 years (range 19-75), with 17 males, and 13 patients had prior surgeries. 29 tumors were histological grade 3. No dose-limiting toxicities (DLT) were observed in the first six patients receiving PLD (37.5 mg/m², i.v., Day 1, q3w), confirming the RP2D. Among the 28 radiological evaluable patients, 2 achieved complete response (CR), 12 achieved partial response (PR), and 11 had stable disease, resulting in an ORR of 50.0% and a disease control rate (DCR) of 89.2%. In addition, among 24 pathological assessable patients, 14 (58.3%) achieved pCR or near-pCR. Two patients (9.5%) experienced major wound complications. They underwent secondary operation and readmission to hospital for wound care, respectively. Other serious adverse events (SAE) include Grade 3 dermatitis (17.9%) and Grade 3-4 neutropenia (7.1%). No G5 SAE were reported. Median progression-free survival and overall survival have not yet been reached. Conclusions: The combination of RT, DOXO, and SIN showed potential efficacy and tolerable toxicity in high-risk localized limbs and trunk STS. The trial is still ongoing. Clinical trial information: NCT05774275 .

Background and Objective Metastatic Extramammary Paget’s disease (EMPD) is an extremely rare cancer and has a dismal prognosis. The rarity of metastatic EMPD has made the clinical trial almost unfeasible, thus high-quality retrospective analysis is valuable. Methods The electronic medical files of patients with metastatic EMPD treated from Jan 2017 to April 2024 in a tertiary cancer center in China were reviewed, and available tissues were collected for HER2 staining, if possible. Eleven patients were treated with the anti-HER2 antibody-drug conjugate Disitamab vedotin (DV), using doses of 2 mg/kg, once every 3 to 4 weeks. The efficacy and toxicity data were extracted. Key Findings and Limitations: Treatment with the antibody-drug conjugate DV elicited an objective response in 8 of 11 patients (73%), and CEA response in 10 of the 11 patients (91%). The median progression-free interval was 5.5 months. The median overall survival was 21.9 months. This efficacy was accompanied by mild grade 1 or 2 treatment-related toxicity and no grade 3 toxicity. This study is limited by a small sample size, retrospective nature, and inevitable selection bias. Conclusions and Clinical Implications Antibody-drug conjugate targeting of HER2 might be an active treatment for metastatic EMPD. We have initiated a clinical trial to confirm it prospectively. Implication for practice Metastatic Extramammary Paget’s disease (EMPD) is an extremely rare cancer without standard treatment. Treatment with the antibody-drug conjugate DV (an anti-HER2 antibody-drug conjugate) elicited an objective response in 8 of the 11 patients (73%), and CEA response in 10 of the 11 patients (91%). This efficacy was accompanied by mild treatment-related toxicity. Antibody-drug conjugate targeting of HER2 might be an active treatment for metastatic EMPD.

Lung cancer remains a leading cause of cancer-related mortality worldwide, with bone metastasis presenting a significant challenge due to its association with severe skeletal complications and therapy resistance. This study investigates the role of bone marrow adipocytes (BMAs) in modulating fatty acid metabolism within the bone metastatic niche of lung cancer. Utilizing single-cell sequencing and in vitro co-culture models, we identified critical interactions between BMAs and metastatic lung cancer cells that enhance fatty acid metabolism, promoting tumor survival and drug resistance. To target this metabolic axis, we screened a library of fatty acid synthesis inhibitors, and developed a nanoparticle system encapsulating kaempferol, and cisplatin, surface-modified with poly-aspartic acid for efficient bone targeting. The nanoparticles release their therapeutic payload in the acidic tumor microenvironment, disrupting fatty acid metabolism and overcoming chemoresistance. Our findings highlight the metabolic reprogramming driven by BMAs in bone metastasis and propose a novel therapeutic strategy to improve outcomes for patients with metastatic lung cancer.