Objective: To compare the clinical prognosis of metal endoprosthetic reconstruction versus biological reconstruction in the treatment of limb osteosarcoma and to analyze associated prognostic factors. Methods: From October 2014 to October 2021, a retrospective study was carried out of patients with high-grade extremity osteosarcoma. Patients were categorized into two groups based on the type of reconstruction: endoprosthetic reconstruction and biological reconstruction. Demographic data and prognosis were systematically compared between the two groups. Furthermore, a Cox proportional hazards model was employed to evaluate the risk factors associated with recurrence and survival outcomes. Results: A total of 133 patients were enrolled in the study, comprising 88 patients in the endoprosthetic reconstruction group and 45 patients in the biological reconstruction group. The 5-year overall survival (OS) and disease-free survival (DFS) rates for the endoprosthetic reconstruction group were 76.2% and 70.5%, respectively, which were higher than those observed in the biological reconstruction group (64.3% and 60%). Additionally, the local recurrence rate was significantly higher in the biological reconstruction group compared to the endoprosthetic reconstruction group (17.8% vs. 2.3%, p = 0.004). Cox regression analysis revealed that pathological fracture (p = 0.034) and the biological reconstruction (p = 0.007) were independent risk factors for local recurrence. Conclusions: Endoprosthetic reconstruction may be preferable for patients requiring early functional recovery or presenting with pathological fractures. Biological reconstruction may be considered for younger patients with diaphyseal defects and demanding long-term functional requirements, albeit with elevated local recurrence risk. Individualized decision-making incorporating tumor location, patient age, and functional goals is essential.

Background: It is still uncertain whether Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor have synergistic effects on metastatic soft tissue sarcomas (STSs). The purpose of this study was to evaluate the safety and activity of nab-paclitaxel plus camrelizumab (a PD-1 inhibitor) in patients with advanced STS who had previously failed chemotherapy.Methods: In this single-center, open-label, single-arm phase II clinical trial, patients with advanced (unresectable or metastatic) STS who had previously failed chemotherapy received up to six cycles of nab-paclitaxel plus camrelizumab, whereas camrelizumab treatment was continued for up to 1 year. The median progression-free survival (PFS), objective response rate (ORR) and safety were collected and evaluated.Results: This trial included 40 patients (28 men and 12 women). The overall ORR was 22.5%, and the median PFS was 1.65 months (95% confidence interval [CI], 1.3–2.0 months). Patients with epithelioid sarcoma demonstrated a longer PFS compared with those with other histological subtypes (2.3 months vs. 1.5 months, respectively); however, this difference was not significant. Patients who had received only one line of previous chemotherapy had a significantly longer PFS compared with those who had undergone two or more lines of previous chemotherapy (2.8 months vs. 1.3 months, respectively, p = 0.046). In terms of safety, the toxicity of this combination therapy is mild and no serious adverse events have occurred.Conclusion: Nab-paclitaxel plus camrelizumab exhibited modest activity and mild toxicity in treating epithelioid sarcoma, angiosarcoma, and fibrosarcoma. The overall effectiveness of this treatment regimen for advanced STS is relatively low. Further research on combining nab-paclitaxel with effective drugs, including chemotherapy and targeted agents, for these specific STS subtypes is needed.

IntroductionThe management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas.Materials and methodsWe performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25–35 Gy across 5–7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors.ResultsAll patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%.ConclusionNeoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.

Background The inactivation and replantation of autologous tumor bones are important surgical methods for limb salvage in patients with malignancies. Currently, there are few reports on the inactivation and replantation of the knee joint. In this study, we aimed to evaluate the feasibility of our surgical approach. Methods This is a retrospective case series study. We retrospectively collected the clinical data of patients with sarcoma treated with knee joint inactivation and replantation and analyzed the efficacy of this surgical method. The bone healing and complications in these patients after inactivated autograft replantation were assessed. Results This study included 16 patients. Fifteen patients had osteosarcoma, and one had Ewing's sarcoma. The average length of the inactivated bone is 20.2 cm (range 13.5–25.3 cm). All the patients underwent internal plate fixation. The average follow-up duration was 30 months (range 8–60 months). Before the data deadline of this study, eight (50%) patients were still alive, and eight (50%) died of sarcoma metastasis. Eight (50%) patients achieved bone healing at the diaphysis site of the inactivated tumor bone, with an average bone healing time of 21.9 months (range, 12–36 months). Five (31%) patients died due to metastases and did not achieve bone healing. Two (12.5%) patients did not achieve bone healing because of infection, and one (6.3%) patient underwent amputation due to tumor recurrence. Ten (62.5%) patients experienced fractures around the joint ends of the inactivated replanted bone, and eight of these ten patients were combined with joint dislocation. Conclusion The incidence of joint deformities after the knee-joint inactivation and replantation is extremely high and is not recommended for use.

Myxoid liposarcoma (MLS) is a rare subtype of soft tissue sarcoma that distinguishes itself from conventional subtypes through its propensity for extrapulmonary metastasis. The distinctive magnetic resonance imaging (MRI) characteristics of MLS render it an invaluable tool for identifying primary and secondary lesions. Pathologically, MLS is characterized by the FUS-DDIT3 gene fusion. Accurate diagnosis, facilitated by MRI and pathological assessment, is critical for prognostication and the formulation of appropriate treatment strategies. Surgery remains the cornerstone of local management for MLS. The combination of surgery and radiotherapy can significantly reduce the local recurrence rate in MLS, as it is highly sensitive to both radiotherapy and chemotherapy. Additionally, for high-risk MLS cases with a large tumor diameter, chemotherapy has been shown to improve survival. The comprehensive treatment approach for MLS demonstrates superior local recurrence rates and survival rates compared to most soft tissue sarcomas. Current research focuses on developing effective therapies for unresectable or advanced disease based on genomic and phenotypic characteristics as well as the immune-tumor microenvironment.

Abstract Objective To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS). Methods A retrospective analysis was conducted on 63 ASPS patients (Jan 2017–May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data. Results There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5–68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = −0.526; p < 0.001). When the cut-off value of ADC was 0.997 × 10−3 mm²/s, the AUC, sensitivity, and specificity for predicting high Ki-67 expression were 0.805, 65.6%, and 83.9%, respectively. Conclusion Qualitative and quantitative MRI parameters are valuable for predicting histological grading and Ki-67 expression levels in ASPS. Critical relevance statement This study will help provide a more nuanced understanding of ASPS and guide personalized treatment strategies. Key Points There is limited research on assessing ASPS prognosis through MRI. Metastasis, enhancement, and ADC correlated with histological grade; ADC related to Ki-67 expression. MRI provides clinicians with valuable information on ASPS grading and proliferation activity. Graphical Abstract

BackgroundThe frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation.MethodsIn this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale.ResultsThis study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3–35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union.ConclusionFrozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

<p>Pie graph shows the composition of TIL samples of MM-3.</p>

<p>Pie graph shows the composition of TIL samples of MM-3.</p>

As a key component of the COP9 signalosome complex, which participates in a variety of physiological processes, COPS3 is intimately related to multiple cancers. It promotes cell proliferation, progression and metastasis in several cancer cells. However, whether COPS3 participates in regulating anoikis, a specific kind of apoptosis and functions as an essential modulator of cell metastasis, has not yet been studied. Here, we found COPS3 is highly expressed in several cancers especially in osteosarcoma (OS). Overexpression of COPS3 promoted cell proliferation, cell viability and migration/invasion in both control cells and oxaliplatin (Oxa) treated cells. On the contrary, knockdown of COPS3 further enhanced the cytotoxicity of Oxa. Utilizing bioinformatics analysis, we found that COPS3 was higher expressed in the metastatic group, and associated with the extra-cellular matrix (ECM) receptor interaction pathway, which involve in regulating anoikis. In an anoikis model, COPS3 expression varied and genetic modification of COPS3 influenced the cell death enhanced by Oxa. PFKFB3, an essential modulator of glycolysis, was found to interact with COPS3. Inhibition of PFKFB3 promoted apoptosis and anoikis enhanced by Oxa, and COPS3 overexpression failed to rescue this cell death. On the contrary, in the COPS3 knockdown cells, overexpression of PFKFB3 recovered the anoikis resistance, indicating COPS3 function upstream of PFKFB3. In summary, our results elucidated that COPS3 modulated anoikis via affecting PFKFB3 in OS cancer cells.

<p>Information on previous treatment of patients included in the observational study.LTIL-04.</p>

Background:Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs.Methods:Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021.Results:This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events.Conclusion:Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes. anthracyclines are the most important systemic treatment for advanced STSs. Ifosfamide, trabectedin, gemcitabine, taxanes, dacarbazine, and eribulin exhibit certain activities in STSs. Vinca alkaloid agents (vindesine, vinblastine, vinorelbine, vincristine) have important therapeutic effects in specific STS subtypes, such as rhabdomyosarcoma and Ewing sarcoma family tumors, whereas their activity in other subtypes is weak. Other chemotherapeutic drugs (methotrexate, cisplatin, etoposide, pemetrexed) have weak efficacy in STSs and are rarely used. It is necessary to select specific second- or above-line chemotherapeutic drugs depending on the histological subtype. This review aims to provide a reference for the selection of chemotherapeutic drugs for multi-line therapy for patients with advanced STSs who have an increasingly long survival.

Information on previous treatment of patients included in the observational study.LTIL-02.

Information on previous treatment of patients included in the observational study.LTIL-03.

<p>Box plot shows the percentage of CD45RA-CD62L+, CD45RA- CD62L-, CD45RA+ CD62L+, and CD45RA+ CD62L- T cells in the subset of CD4+ (A and E, PD-1-T cells; B and F, PD-1+T cells )and CD8+ (C and G, PD-1-T cells; D and H, PD-1+T cells ) T cells before (Upper panel, n=4) and after (Lower panel, n=8) expansion with the protocol established in this study.</p>

<p>Information on previous treatment of patients included in the observational study.LTIL-01.</p>

目的 探讨经皮髋臼成形术(percutaneous acetabuloplasty)联合放疗治疗髋臼转移瘤的临床疗效.方法 回顾性分析2017年5月至2022年5月收治24例髋臼转移瘤患者的病历资料,男9例、女15例,年龄56.0(50.0,67.5)岁(范围40～85岁),左侧12例、右侧12例.原发肿瘤为乳腺癌8例(33％)、肺癌7例(29％)、前列腺癌4例(17％)、肠癌2例(8％)、宫颈癌1例(4％)、肾癌1例(4％)、肝癌1例(4％).骨转移灶均为多发,其中16例(67％)伴有其他脏器转移.转移灶性质:溶骨性19例(79％)、混合性5例(21％).病灶分布区域:臼顶11例、臼顶+前柱2例、臼顶+后柱8例、臼顶+前柱+后柱3例.病灶大小2.0 cm×1.5 cm×2.0 cm～4.5 cm×4.0 cm×11.0 cm.髋臼转移灶周围存在骨皮质缺损11例(46％),存在软组织肿块8例(33％).于局麻或全麻下行经皮髋臼成形术,术后1周内行局部放疗治疗(体外放疗,30 Gy,10 d).记录患者原发灶位置、确诊肿瘤时间、骨转移时间、骨转移灶数量、转移灶性质、分布区域、病灶大小、有无骨皮质缺损、有无软组织肿块、有无其他脏器转移、手术部位、手术时间、填充效果及并发症等.比较术前、术后、放疗后、术后1、3、6个月及末次随访时采用疼痛视觉模拟评分(visual analogue scale,VAS)、行走评分、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)简化活动状态评分量表评估临床疗效,记录并发症发生情况.结果 24例患者中23例手术顺利完成,1例失败.失败原因为穿刺针刺破髂骨内板致大量骨水泥向骨盆内渗漏,术后患者无明显不适未改行开放性手术,髋臼处疼痛缓解不明显,继续口服镇痛药物及综合治疗,术后4个月死亡.随访时间为18.0(11.8,23.5)个月(范围3～49个月).VAS评分、行走评分及ECOG评分自术前(7.2±1.1)分、(1.4±1.4)分、(2.5±0.7)分改善至术后48h的(2.6±1.9)分、(2.5±1.4)分、(2.0± 0.8)分,差异有统计学意义(P＜0.05),术后48 h与放疗后48 h各评分的差异无统计学意义(P＞0.05).截至末次随访时92％(22/24)的患者局部症状无进展.结论 经皮髋臼成形术可快速恢复髋臼的稳定性,缓解疼痛并提高生活质量.经皮髋臼成形术疗效不佳的患者放疗可能无效,但放疗可控制局部症状进展,两者联合可提高髋臼转移瘤患者的疗效.

<p>The compositions of the sorted PD-1- and PD-1+ fraction prior to expansion. Upper panel: PD-1 negative fraction; Lower panel: PD-1 positive fraction. (n=9)</p>

Soft tissue sarcoma (STS) is a highly heterogeneous malignant tumor derived from mesenchymal tissue. Advanced STS has a poor response to the current anti-cancer therapeutic options, with a median overall survival of less than two years. Thus, new and more effective treatment methods for STS are needed. Increasing evidence has shown that immunotherapy and radiotherapy have synergistic therapeutic effects against malignant tumors. In addition, immunoradiotherapy has yielded positive results in clinical trials for various cancers. In this review, we discuss the synergistic mechanism of immunoradiotherapy in cancer treatment and the application of this combined regimen for the treatment of several cancers. In addition, we summarize the existing evidence on the use of immunoradiotherapy for the treatment of STS and the relevant clinical trials that are currently ongoing. Furthermore, we identify challenges in the use of immunoradiotherapy for the treatment of sarcomas and propose methods and precautions for overcoming these challenges. Lastly, we propose clinical research strategies and future research directions to help in the research and treatment of STS.