BACKGROUND:Reconstruction of an oncologically resected proximal humerus poses a challenge to surgeons, and reverse total shoulder arthroplasty (rTSA) may provide greater functional improvement. However, the characteristics of patients suitable for rTSA remain unknown, owing to the lack of data in the literature regarding post-operative functional outcomes and complications. In this retrospective cohort study of patients who underwent rTSA for tumor-related proximal humerus resection, we aimed to identify the features related to improved outcomes and decreased complications. We hypothesized that complete deltoid insertion resection would be associated with an increased risk of instability in patients treated with rTSA for oncological proximal humeral resection. METHODS:We conducted a retrospective cohort study to assess the post-operative mid-term complications and functional outcomes. The range of motion, Musculoskeletal Tumor Society (MSTS), Toronto Extremity Salvage Score (TESS), and Constant-Murley score were used to evaluate functional outcomes. The patients were divided into 3 groups dependent on the resection of the deltoid insertion. Furthermore, 24 patients whose deltoid insertions were completely resected and who underwent anatomic shoulder arthroplasty (aTSA) were matched according to the demographic information of those who underwent rTSA. RESULTS:Fifty-eight patients who underwent rTSA in our department were included in the study based on the inclusion and exclusion criteria. The MSTS, TESS, and Constant-Murley scores were 26, 136, and 76, respectively, and the average forward flexion, abduction, external rotation, and internal rotation angles were 125°, 121°, 51°, 54°, respectively. Complications were reported in 17 patients, with instability accounting for 13. Multiple regression analysis revealed that complete resection of the deltoid insertion was an independent risk factor for post-operative dislocation (odds ratio: 16.67; P < .01). Although resection length showed a significant positive association with dislocation in all patients, no association was found in the subgroups. We following matched 24 patients with the complete resection of deltoid insertion and aTSA and found poorer functional outcomes compared to those of patients undergoing rTSA (MSTS: 21, P < .01; Constant-Murley: 50, P < .01; TESS: 101, P < .01). CONCLUSION:Our findings demonstrate that rTSA provides satisfactory functional outcomes for treating proximal humeral tumors but that complete deltoid insertion resection is an independent risk factor for post-operative dislocation. In patients whose deltoid insertions are completely resected, functional improvements make them worth attempting in those with high activity demands.

Abstract Purpose This study aimed to assess whether adjuvant radiotherapy (RT) can improve prognosis outcomes in patients with limb liposarcoma (LPS) and to identify independent prognostic factors. To mitigate selection bias, propensity score matching (PSM)was applied between groups in this study. Methods A retrospective analysis was conducted on 153 patients with primary limb LPS treated at a single tertiary center between 2015 and 2023. Patients were divided into RT and non-RT groups. A 1:1 PSM approach was applied to balance 11 baseline covariates between two groups, including age, sex, tumor characteristics etc. Our primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression analysis was used for prognostic factor investigation. Results Among all LPS patients, pre-PSM 5-year OS rates were 88.8% in the non-RT group and 71.1% in the RT group (p = 0.073), whereas post-PSM 5-year OS rates were 85.2% in the non-RT group and 71.1% in the RT group (p = 0.33). Pre-PSM analysis revealed that the non-RT group had higher RFS (75.6% vs. 41.8%, p = 0.0015), yet this difference was no longer significant after PSM (64.8% vs. 41.8%, p = 0.091). In the myxoid LPS (MLPS) subgroup, post-PSM RFS was significantly lower in the RT group (48.4% vs. 86.5%, p = 0.0071), but OS remained comparable (p = 0.16). Multivariate analysis identified older age (HR = 1.06, p = 0.021) as an independent risk factor for mortality after PSM, while RT showed no significant association with survival. Conclusion Adjuvant RT was not associated with improved OS or RFS in patients with limb LPS, even in the radiosensitive MLPS subtype. Age remains a crucial prognostic factor, while the association between chemotherapy and worse survival requires further investigation. Based on our findings, individualized surgical strategies are recommended over routine use of RT in the management of limb LPS.

11503 Background: Clear cell sarcoma (CCS) is an ultra rare cancer with no established standard systemic therapy of proven efficacy. The c-MET pathway plays an important role in CCS, with MET overexpression frequently observed. Targeted therapy by type Ia MET inhibitor crizotinib revealed a disease control rate (DCR) at 69.2% and objective response rate (ORR) at 3.8%. Vebreltinib is a highly selective type Ib MET inhibitor with verified efficacy in solid tumor harboring MET alterations, such as NSCLC with MET amplification or overexpression. This phase II study aimed to assess the efficacy and safety of Vebreltinib for advanced CCS. Methods: Patients (pts) with histopathologically confirmed, unresectable or metastatic CCS were enrolled (NCT07153887), regardless of prior therapy except for any MET inhibitors. Eligible pts received Vebreltinib (200 mg BID) until disease progression, intolerable toxicity, or death occurs. Prior PD1/PDL1 treatment for at least 4 months without tumor reduction are allowed to continue using the same PD1/PDL1 medicine after thorough evaluation by the investigator. Evaluation of tumor response was performed every 2 months. Primary endpoints was ORR per RECIST v1.1. Secondary endpoints included DCR, PFS, OS, 12m-OSR, DoR and treatment safety. MET expression by immunohistochemistry was collected when possible. A Simon’s two-stage design was applied: if no responses were seen in the first 13 pts, the study would stop; otherwise, 14 additional pts would be enrolled (total N=27). Results: At data cutoff on January 23, 2026, 23 pts were enrolled. Median age was 29 years (range: 16–59), 47.8% were male, 91.3% had prior surgery, and 95.7% received prior systemic therapy. All had metastatic disease, primarily to lung (78.3%), lymph nodes (56.5%), and bone (30.4%). With median follow-up of 134 days and median treatment duration of 103 days, 17 pts were evaluable for response. ORR was 41.2% (7 partial responses) and DCR was 70.6% (7 PR, 5 stable disease), meeting the pre-specified threshold for stage I continuation. Median PFS was 4.14 months (95% CI: 2.3–NA); 6-month PFS rate was 42.8%. Median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 87.0% of pts, mostly grade 1-2. Grade 3-4 TRAEs occurred in 21.7% (n=5; rash n=4, fever n=1). Notably, 4 pts discontinued due to grade 4 rash within 2 weeks of starting vebreltinib combined with immunotherapy. Conclusions: Vebreltinib demonstrated notable antitumor activity for advanced CCS, representing a marked improvement over existing therapeutic options. Attention should be paid to the risk of severe rash, particularly when combined with immunotherapy. Longer follow-up is required to further confirm the efficacy and safety. Clinical trial information: NCT07153887 .

Objective:To develop a non-invasive diagnostic method for pelvic chondrosarcoma using clinical and radiological features, aiming to improve early diagnostic accuracy and reduce reliance on invasive biopsies. Methods:Two hundred and thirty-eight patients (39.50% with pelvic chondrosarcoma; median age, 42.87 years; 53.78% male; all Chinese) were enrolled and assigned to training (n = 167) and testing (n = 71) cohorts. Seven clinical and radiological features were evaluated for their potential associations with pelvic chondrosarcoma diagnosis. A predictive model was developed using a random forest algorithm and validated in the testing cohort, with performance assessed by partial dependence plot analysis and additional accuracy metrics. Results:The likelihood of a positive diagnosis of pelvic chondrosarcoma was significantly associated with age around 50 years (p < 0.001), the presence of high-intensity signals on T2-weighted magnetic resonance imaging (p = 0.021), a ring-and-arc enhancement pattern on contrast-enhanced T1-weighted magnetic resonance imaging (p < 0.001), and intratumoral calcification (p < 0.001). Tumor location was also a critical determinant (p = 0.009), with acetabular tumors exhibiting higher diagnostic probability. Among all variables, the random forest model identified the ring-and-arc enhancement pattern and patient age at diagnosis as the two most influential predictors. The model achieved excellent diagnostic performance, with a sensitivity of 96.55%, specificity of 90.48%, and overall accuracy of 92.96%. Conclusion:Our random forest-based model provides a reliable and practical non-invasive diagnostic tool for pelvic chondrosarcoma, improving diagnostic accuracy while potentially reducing the reliance on invasive biopsy procedures and supporting clinical decision-making.

Bone is highly innervated, and its regeneration is significantly nerve-dependent. Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity. However, the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration. Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment, which is crucial for bone regeneration. This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment. We first discuss the changes in peripheral nerves during the regenerative process. We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment, emphasizing nerves, neural factors, and their impacts. Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration. A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous, immune, and skeletal systems to promote bone regeneration.

Clear cell sarcoma (CCS) is an ultra-rare sarcoma with no established standard systemic therapy of proven efficacy. Mesenchymal-epithelial transition factor (MET) overexpression drives CCS progression and serves as a promising therapeutic target. Vebreltinib is a highly selective MET inhibitor with potential therapeutic benefits for CCS. Additionally, given that MET and programmed cell death protein 1 (PD-1) are both downstream molecules of melanocyte transcription factor (MITF), combined MET and PD-1 inhibition may block the MITF pathway more effectively. Moreover, aberrant MET activation indirectly upregulates programmed death ligand 1 (PD-L1), causing immune escape and resistance to PD-1 inhibitors; MET inhibition may potentially reverse this resistance. Here, we describe the rationale and design of VEBrant, a multicenter, phase II study aimed to evaluate the efficacy and safety of vebreltinib combined with PD-1-based immunotherapy in advanced CCS. Thirty patients will be enrolled, with the treatment cohort receiving combination therapy of vebreltinib and PD-1 inhibitor, and a reference cohort receiving physician's choice therapy or best supportive care. Primary endpoint is Objective Response Rate (ORR) by Simon two-stage design. This study will provide evidence for vebreltinib combined with PD-1-based immunotherapy and improve understanding of advanced CCS management.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07153887.

Sensory innervation triggers the regenerative response after injury. However, dysfunction and impairment of sensory nerves, accompanied by excessive inflammation impede tissue regeneration. Consequently, specific induction of sensory innervation to mediate immunoregulation becomes a promising therapeutic approach. Herein, we developed a cell/drug-free strategy to selectively boost endogenous sensory innervation to harness immune responses for promoting tissue rehabilitation. Specifically, a dual-functional phage was constructed with a sensory nerve–homing peptide and a β-subunit of nerve growth factor (β-NGF)–binding peptide. These double-displayed phages captured endogenic β-NGF and localized to sensory nerves to promote sensory innervation. Furthermore, regarding bone regeneration, phage-loaded hydrogels achieved rapid sensory nerve ingrowth in bone defect areas. Mechanistically, sensory neurotization facilitated M2 polarization of macrophages through the Sema3A/XIAP/PAX6 pathway, thus decreasing the M1/M2 ratio to induce the dissipation of local inflammation. Collectively, these findings highlight the essential role of sensory innervation in manipulating inflammation and provide a conceptual framework based on neuroimmune interactions for promoting tissue regeneration.

This case report describes a diagnostically and therapeutically challenging instance of spindle cell neoplasm located in the sacroiliac region of a 16-year-old male. The patient presented with numbness in the right hip and radiating pain in the lower extremities. Diagnostic imaging and laboratory tests localized the disease to a sacroiliac tumor; however, accurate identification of the tumor type remained difficult. Following tumor excision and curettage, RNA sequencing revealed the presence of the COL1A1::PDGFB fusion, which is considered characteristic of dermatofibrosarcoma protuberans (DFSP). Although DFSP is typically a superficial, low-grade tumor with low metastatic potential, this case exhibited aggressive clinical features. Consequently, it was recommended to classify it as a “sacroiliac spindle cell tumor with COL1A1::PDGFB fusion,” which may represent a variant within the broader spectrum of DFSP. Following recurrence and metastasis, the patient was treated with imatinib mesylate and radiotherapy, resulting in a sustained major partial response. This report presents a rare case of aggressive sacroiliac spindle cell sarcoma with COL1A1::PDGFB fusion, expands the clinicopathologic spectrum of DFSP and its variants, and underscores the importance of molecular studies for definitive diagnosis, as well as the potential for targeted therapies in managing complex sarcoma cases.

ABSTRACT Musculoskeletal diseases encompass a broad spectrum of inflammatory, degenerative, and neoplastic disorders that compromise bone and joint function across the lifespan. Increasing evidence highlights the central role of immune regulation in their pathogenesis, driven by complex interactions among immune, bone, and stromal cells. Inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, and dermatomyositis are marked by persistent immune activation and progressive tissue destruction. Degenerative diseases like osteoarthritis, osteoporosis, and intervertebral disc degeneration involve immune senescence, dysregulated tissue remodeling, and inflammation‐driven structural damage. Bone and soft tissue tumors—including osteosarcoma, chondrosarcoma, Ewing sarcoma, and soft tissue sarcoma—develop within immunosuppressive niches that hinder antitumor immunity. Notably, these immune environments are not strictly dichotomous but exhibit dynamic, context‐dependent states of immune stimulation and suppression. This review delineates both shared and disease‐specific immune mechanisms, spanning cytokine networks, signaling pathways, and cellular interactions. It further discusses current and emerging therapeutic strategies, including cytokine modulators, bone‐regulatory agents, immune checkpoint inhibitors, and cell‐based therapies. Despite recent advances, key challenges persist in translating immunological insights into durable, disease‐modifying treatments. By bridging mechanisms across inflammation, degeneration, and malignancy, this review provides an integrated framework for understanding immune contributions to musculoskeletal diseases and identifies promising directions for precision immunotherapy.

Objective:This study aims to investigate the feasibility and oncological outcomes of vessel-sparing surgery for soft tissue sarcomas located near the femoral vessels in the thigh. A comparison was made with cases where the tumor was not adjacent to the femoral vessels, focusing on recurrence rates, survival prognosis, and the viability of vessel-sparing surgical techniques. Methods:A retrospective analysis was conducted on 211 cases. After well-differentiated liposarcoma were excluded from further analysis, 148 cases involved tumors not adjacent to the femoral vessels, while 22 cases were located near the vessels. Postoperative functional outcomes, survival rates, and local recurrence were evaluated. Due to the imbalance in case numbers between the two groups, propensity score matching was applied at a 1:1 ratio, after which the two datasets were compared and analyzed. Results:By the last follow-up, 40 had experienced recurrence, 35 patients had died, 15 were surviving with tumors, and 161 were living tumor-free. No statistically significant differences were found between the survival and recurrence-free survival curves for cases with sarcomas adjacent to the femoral vessels compared to those with tumors located elsewhere, both before and after propensity score matching. Tumor grade and size were identified as key factors influencing survival and recurrence outcomes in soft tissue sarcoma of the thigh. Conclusion:For soft tissue sarcoma of the thigh located adjacent to femoral vessels, vessel-sparing surgery involving vascular sheath removal demonstrates favorable outcomes. Tumor size greater than 10 cm and high pathological grade were significant predictors of survival and recurrence risk.

BACKGROUND:There is no standard systemic therapy for unresectable chondrosarcoma. The purpose of this study is to explore the efficacy of combination therapy with an anti-PD-1 antibody and anlotinib in patients with advanced chondrosarcoma. METHODS:Patients with dedifferentiated or high-grade conventional chondrosarcoma were eligible. Anlotinib was administered at 12 mg orally once a day from day 1 to 14 every 3 weeks in all participants. In the combination treatment arm, patients received an additional anti-PD-1 antibody at 200 mg every 3 weeks. The primary endpoint was the 6-month progression-free survival rate (PFSR). Biomarker analyses for therapeutic effectiveness were conducted. FINDINGS:70 patients (32 with dedifferentiated and 38 with conventional chondrosarcoma) were enrolled in the study. After a medium follow-up of 15.6 months, combination treatment showed significantly improved outcomes compared to anlotinib alone in the entire population, with a higher 6-month PFSR (60.0% versus 31.4%). The PFS-event inverse probability weighting adjusted Cox model evaluation also revealed a significant benefit of combination treatment (hazard ratio = 0.14, 95% confidence interval [CI]: 0.07-0.30, p < 0.001). Patients with dedifferentiated chondrosarcoma benefited the most from the combination treatment, with improvements in objective response rate (33.3% versus 9.1%), 6-month PFSR (57.1% versus 9.1%), median PFS (7.0 months versus 3.8 months), and 1-year overall survival rate (42.9% versus 18.2%). Effector memory T cells were significantly associated with treatment response (p < 0.001). CONCLUSIONS:The combination treatment demonstrated promising efficacy in advanced chondrosarcoma, particularly for dedifferentiated cases (ClinicalTrials.gov: NCT05193188). FUNDING:This trial was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Background:Pelvic reconstruction after type I + II (or type I + II + III) internal hemipelvectomy with extensive ilium removal is a great challenge. In an attempt to anatomically reconstruct the hip rotation center (HRC) and achieve a low mechanical failure rate, a custom-made, 3D-printed prosthesis with a porous articular interface was developed. The aim of this study was to investigate the clinical outcomes of patients treated with this prosthesis.Methods:This retrospective cohort study included 28 patients with type I + II (+ III) internal hemipelvectomy through the articular interface of the sacroiliac joint and managed with a prosthesis at a single center between August 2016 and August 2021. Complications and oncological outcomes were analyzed. The position of the reconstructed HRC was assessed and lower-limb function was evaluated. Biomechanical analyses of different fixation modes of the prosthesis were conducted using finite element analysis.Results:The displacement distance of the HRC from preoperatively to postoperatively was a mean (and standard deviation) of 14.12 +/- 8.75 mm. The rate of implant-related complications was 14.3% (4 of 28) for prosthetic breakage, 14.3% (4 of 28) for aseptic loosening, 7.1% (2 of 28) for dislocation, and 7.1% (2 of 28) for deep infection. The mean Musculoskeletal Tumor Society (MSTS)-93 score was 18.2. The aseptic loosening rate was significantly greater for prostheses fixed with 3 sacral screws (4 of 10, 40.0%) than for those fixed with 4 (0 of 10, 0%) or 5 screws (0 of 8, 0%) (p = 0.024). The prosthetic breakage rate was lower in patients who underwent lumbosacral fixation (0 of 13, 0%) than in those who did not (4 of 15, 26.7%), although the difference did not reach significance (p = 0.102). Biomechanical analyses suggested that the addition of lumbosacral fixation or increasing the number of sacral screws from 3 to 4 or 5 visibly reduced the peak stress of the sacral screws.Conclusions:The use of a 3D-printed prosthesis with an articular interface for pelvic reconstruction demonstrated stable prosthetic fixation, anatomical acetabular reconstruction, and acceptable early functional outcomes.Level of Evidence:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND:En bloc resection of the sacrum, whether in the form of total or partial sacrectomy, is the mainstay treatment for patients with primary malignant sacral tumors. However, these surgical procedures can lead to pelvic floor dysfunction, with symptoms such as incontinence and impaired rectal function that can severely impact patients' quality of life. Therefore, effective interventions to restore pelvic floor function would be helpful for affected patients. Synthetic mesh has been well established for abdominal soft tissue repair and in enhancing pelvic floor muscle tension in patients with pelvic organ prolapse; however, its role in sacrectomy has not been well documented. QUESTIONS/PURPOSES:Did patients treated with synthetic mesh reconstruction after sacrectomy for primary malignant sacral tumors (1) achieve better scores for quality of life, (2) achieve better scores for pelvic floor symptom and function, (3) develop improved EMG measures of pelvic floor muscle activity, and (4) experience more complications than patients treated without mesh? METHODS:Between April 2011 to June 2021, a total of 90 patients diagnosed with primary sacral tumor and who underwent surgery in our institution were retrospectively evaluated. For this study, inclusion criteria were patients with primary malignant sacral tumors undergoing en bloc resection for long-term tumor control or cure. Exclusion criteria for this study were patients who underwent total sacrectomy or high-level sacrectomy with bilateral S2 nerve resection. A total of 26 patients were included for analysis. Our study aimed to compare patients treated with synthetic mesh with those treated without mesh as part of pelvic floor reconstruction. Prior to 2017, mesh was not used in reconstruction after sacrectomy. After 2017, it has been progressively incorporated into the standard surgical approach, except in patients with chronic infection, severe pelvic adhesion, financial constraints, or patients who declined. All patients included had at least 2 years of follow-up, with a median of 37 months in the mesh group and 54 months in the no-mesh group. The baseline characteristics of two groups did not differ in important ways, with a mean ± SD age of 63 ± 13 years in the mesh group and 64 ± 14 years in the no-mesh group. There were 9 (of 10) men in the mesh group and 10 (of 16) men in the no-mesh group. The median (IQR) tumor volume was 118 cm3 (90) and 66 cm3 (140) in the mesh and no-mesh groups, respectively. Nerve roots were predominantly preserved at the S3. We used the 36-Item Short Form Survey (SF-36) to assess quality of life. Pelvic floor dysfunction was evaluated using the Pelvic Floor Impact Questionnaire-7 (PFIQ-7). It includes three scales: the Urinary Impact Questionnaire (UIQ-7), the Colorectal-anal Impact Questionnaire (CRAIQ-7), and the Pelvic Organ Prolapse Impact Questionnaire (each range 0 to 100). The summary scores are calculated by adding up the scale scores (range 0 to 300), with lower scores indicating better function. Pelvic floor muscle strength was objectively evaluated using surface EMG. An independent t-test or Mann-Whitney U test was used to compare the continuous variables depending on whether normal distribution was met. Categorical variables were analyzed using the chi-square test or Fisher exact test. RESULTS:Patients who underwent synthetic mesh reconstruction had higher mean ± SD scores by a clinically important margin for physical functioning (59 ± 9 versus 47 ± 11, p = 0.02; minimum clinically important difference [MCID] 5.4), general health (60 ± 7 versus 50 ± 9, p = 0.03; MCID 6.8), vitality (56 ± 13 versus 44 ± 9, p = 0.01; MCID 9.1), and physical component summary (56 ± 9 versus 46 ± 10, p = 0.04; MCID 5) compared with the patients in the no-mesh group, respectively. For PFIQ-7 scores, we found no clinically important difference in UIQ-7 (13 ± 5 versus 20 ± 9, p = 0.02; MCID 11.5) or the summary score (43 ± 20 versus 65 ± 28, p = 0.03; MCID 36) between groups. However, patients who underwent mesh reconstruction had lower scores for the CRAIQ-7 (20 ± 13 versus 35 ± 18, p = 0.03; MCID 8) than patients without mesh reconstruction. The surface EMG measurement exhibited higher quick flick activity in the mesh group (75 ± 10 µV versus 56 ± 20 µV, p = 0.01) compared with the no-mesh group. Our study was too small for a meaningful statistical comparison of complications; however, there did not appear to be substantial between-group differences in terms of complications. In the mesh group, 2 (of 10) patients developed superficial infection, while in the no-mesh group, superficial infection (3 of 16), deep infection (1 of 16), rectocele (1 of 16), and hematoma (1 of 16) were observed. CONCLUSION:Pelvic floor reconstruction using synthetic mesh after sacrectomy was associated with improved quality of life and pelvic floor function in patients with primary malignant sacral tumors. Specifically, synthetic mesh use is associated with improved physical quality of life, reduced pelvic symptom burden, and enhanced muscle strength. These findings support its role as a potential approach for pelvic floor reconstruction after sacrectomy. However, studies with larger sample sizes are needed to validate our findings and to further explore potential differences across patient subgroups, including different genders and levels of nerve preservation. LEVEL OF EVIDENCE:Level III, therapeutic study.

CASE:The effective reconstruction and functional restoration of the shoulder joint after surgical treatment of shoulder girdle tumors, especially those involving resection of the glenoid, poses significant challenges. Reconstruction methods include allograft reconstruction and shoulder prosthesis. In this report, we present 2 cases of scapulectomy for tumors involving the glenoid, followed by shoulder reconstruction using custom-designed reverse shoulder prostheses that are partially fixed to the clavicle. Functional outcomes were satisfactory at 25 and 19 months, respectively. CONCLUSION:This novel prosthesis design, which is partially fixed to the clavicle, provides stability and promising functional outcomes in scapular reconstruction with short-term follow-up.

Tenosynovial giant cell tumors (TGCT) are rare, locally aggressive, mesenchymal tumors occurring in the joints and tendon sheaths, which can cause pain, swelling, and have a substantial negative impact on patient quality of life. While surgery is the current standard of care for most cases of TGCT, there are several drawbacks including risk of recurrence and repeated operations. As such, systemic therapies have an important role in the treatment of TGCT. Encompassing both inflammatory and tumorous features, the pathological mechanism of TGCT is relatively complex and the development of effective drugs requires in-depth research and analysis of these mechanisms. Colony stimulating factor 1 (CSF1) is one of several known drivers in TGCT and has been a focus of investigation, among other potential therapeutic targets. Systemic treatments for TGCT have been utilized as part of a multimodal therapeutic strategy for patients who have recurrent or refractory disease, or who are not amenable to surgery. This review summarizes current knowledge of the mechanisms underlying tumorigenesis in TGCT, providing an overview of the key drivers and corresponding therapeutic targets. Further research into the specific mechanisms of TGCT and further development of diagnostics and treatments are warranted.

Aims: Osseous invasion exhibited in soft-tissue sarcoma (STS) is recognized as a prognostic risk factor. Achieving a wide margin is the default surgical approach for local control. However, for STSs where the tumour is in contact with the adjacent cortex but without clear evidence of osseous invasion, such as medullary invasion, the question of whether bone resection can provide better local control or survival than more conservative sub-periosteal excision remains controversial. The aim of this study was to assess whether bone resection for thigh STS with cortical contact of the adjacent bone results in better local control and survival compared to sub-periosteal dissection, and to investigate the prognostic factors for clinical outcomes in STS. Methods: A retrospective cohort study was conducted on 142 patients with thigh STS exhibiting cortical contact but without medullary invasion, from May 2000 to May 2020. Patients underwent either composite bone resection or sub-periosteal excision. Demographics, clinical outcomes, and functional outcomes were compared between the two groups. Additionally, Cox regression analysis was used to analyze risk factors for local recurrence. Results: The five-year overall survival, local recurrence-free survival, and metastasis-free survival among patients with bone resection was 74.0%, 65.9%, and 74.1%, respectively, compared to 72.9%, 68.3%, and 72.0%, respectively, among patients with sub-periosteal excision. The cumulative incidence of recurrence was 33.1% for patients who underwent bone and 36.4% for those with sub-periosteal excision (p = 0.681). In multivariate analysis, STS with high Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grade, invasion involving posterior intermuscular septum, medial intermuscular septum, and adductor brevis were found to be associated with poorer prognosis. The mean Musculoskeletal Tumor Society (MSTS) score in the bone resection group was 24.7, significantly lower than the 28.3 in the sub-periosteal group (p < 0.001). Conclusion: Routine bone resection failed to improve local control or survival in STS patients with cortical bone contact, but resulted in significantly impaired postoperative function. A more conservative sub-periosteal excision approach may be preferable for these cases. Cite this article: Bone Jt Open 2025;6(2):215–226.

BACKGROUND:Separation surgery followed by radiotherapy has emerged as a prevalent approach for managing spinal metastatic tumors. However, large-volume postoperative pleural effusion (POPE) represents a challenging complication, as it potentially delays subsequent treatments and increases morbidity. This study aims to identify risk factors for large-volume POPE and develop a predictive model for early identification to improve patient prognosis. METHODS:This retrospective study analyzed 443 patients who underwent separation surgery for spinal metastases at our center between January 2014 and January 2022. High-resolution CT-based 3D modeling was utilized for accurate pleural effusion (PE) volume quantification. Variables including patient demographics, surgical details, and laboratory results were examined to identify risk factors associated with large-volume POPE (≥ 1000 mL). A predictive nomogram was developed based on the multivariate logistic regression analysis. RESULTS:Our findings indicated that advanced age, increased intraoperative blood loss, and decreased levels of preoperative serum albumin, postoperative serum protein, and hemoglobin were significant independent risk factors for large-volume POPE. The predictive nomogram demonstrated high accuracy, with a mean AUC value of 0.953 for the training dataset and 0.927 for the testing dataset, indicating reliable predictability for identifying patients at high risk for large-volume POPE. CONCLUSION:Our study identified independent risk factors for large-volume PE following separation surgery in patients with spinal metastasis. The developed nomogram offers a practical tool for early identification of high-risk groups, enabling timely and targeted interventions. By reducing the risk of large POPE, this approach may shorten hospitalization and accelerate the resumption of postoperative treatment, ultimately improving patient prognosis.

AimsRadiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.MethodsA retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis.ResultsOverall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC.ConclusionTumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients.Cite this article: Bone Jt Open 2024;5(4):350–360.

Acetabular reconstruction in situ after extensive pelvic resection is technically challenging. The aim of this study was to investigate the feasibility of positioning guiders for acetabular reconstruction following pelvic tumor resection and the clinical benefit brought by the approach. The study included patients who underwent acetabular reconstruction following periacetabular tumor resection using a modular hemipelvic prosthesis. In the guider-assisted group (n = 14), guiders were designed and applied to assist acetabular reconstruction. In the traditional operation group (n = 18), the patients underwent the same surgery but without the guiders. The displacement of the hip rotation center before and after surgery was calculated. The complications and the Musculoskeletal Tumor Society—93 scores were documented. The overall displacement of the hip rotation center was significantly reduced in the guider-assisted group compared with the traditional operation group (13.83 ± 4.06 vs. 22.95 ± 9.18 mm in P = 0.000, 95

BackgroundLung metastasis remains the primary cause of tumor-related mortality, with limited treatment options and unsatisfactory efficacy. In preclinical studies, T helper 9 (TH9) cells have shown promise in treating solid tumors. However, it is unclear whether TH9 cells can tackle more challenging situations, such as established lung metastases. Moreover, comprehensive exploration into the nuanced biological attributes of TH9 cells is imperative to further unravel their therapeutic potential.MethodsWe adoptively transferred TH1, TH9, and TH17 cells into subcutaneous,in situ, and established lung metastases models of osteosarcoma and triple-negative breast cancer, respectively, comparing their therapeutic efficacy within each distinct model. We employed flow cytometry and anin vivoimaging system to evaluate the accumulation patterns of TH1, TH9, and TH17 cells in the lungs after transfusion. We conducted bulk RNA sequencing onin vitrodifferentiated TH9 cells to elucidate the chemokine receptor CXCR4, which governs their heightened pulmonary tropism relative to TH1 and TH17 cell counterparts. Using Cd4creCxcr4flox/floxmice, we investigate the effects of CXCR4 on the lung tropism of TH9 cells. We performed mass spectrometry to identify the E3 ligase responsible for CXCR4 ubiquitination and elucidated the mechanism governing CXCR4 expression within TH9 cellular milieu. Ultimately, we analyzed the tumor immune composition after TH9 cell transfusion and evaluated the therapeutic efficacy of adjunctive anti-programmed cell death protein-1 (PD-1) therapy in conjunction with TH9 cells.ResultsIn this study, we provide evidence that TH9 cells exhibit higher lung tropism than TH1 and TH17 cells, thereby exhibiting exceptional efficacy in combating established lung metastases. CXCR4-CXCL12 axis is responsible for lung tropism of TH9 cells as ablating CXCR4 in CD4+T cells reverses their lung accumulation. Mechanistically, tumor necrosis factor receptor-associated factor 6 (TRAF6)-driven hyperactivation of NF-κB signaling in TH9 cells inhibited ITCH-mediated ubiquitination of CXCR4, resulting in increased CXCR4 accumulation and enhanced lung tropism of TH9 cells. Besides, TH9 cells’ transfusion significantly improved the immunosuppressed microenvironment. TH9 cells and anti-PD-1 exhibit synergistic effects in tumor control.ConclusionsOur findings emphasized the innate lung tropism of TH9 cells driven by the activation of TRAF6, which supports the potential of TH9 cells as a promising therapy for established lung metastases.