The primary clinical challenges associated with postoperative maxillofacial osteosarcoma include high mortality rates and significant local recurrence. Additionally, patients often exhibit substantial bone defects that are incapable of self-healing, necessitating the implantation of scaffolds. Multifunctional hydrogels, which enable sustained local release of therapeutic agents and enhance scaffold surface properties, demonstrate significant potential for the postoperative management of maxillofacial osteosarcoma. In this study, doxorubicin (DOX) and PD-L1 siRNA were initially loaded into ZIF-8 to synthesize highly stable nanocomplex RNA-DOX@ZIF-8 (RDZ). Subsequently, a multifunctional hydrogel (Gel@RDZ) was fabricated by uniformly mixing RDZ with catechol-modified chitosan. Gel@RDZ exhibits a high drug-loading capacity, excellent viscoelasticity, and strong scaffold adhesion. In a rat femoral defect model, the Gel@RDZ-coated scaffold group demonstrated superior bone regeneration capabilities. Furthermore, in a murine osteosarcoma recurrence model, Gel@RDZ exhibited optimal immune cell infiltration, substantially reduced tumor recurrence, and markedly enhanced the tumor-killing efficacy of CD8+ T cells. Therefore, the development of a multifunctional hydrogel system (Gel@RDZ) provides a comprehensive treatment for postoperative maxillofacial osteosarcoma.

Chondrosarcomas are rare tumors occurring in middle age and older adults, defined by malignant cartilaginous matrix-producing neoplasms. Chondrosarcomas represent a heterogeneous group of tumors with diverse characteristics, management strategies and prognosis. The aim is to establish recommendations to support optimal practice for the diagnosis and treatment of chondrosarcomas within the framework of an expert group at the request of GroupOs and the French Sarcoma Group. The recommendations were developed by a multidisciplinary working and underwent thorough proofreading. The level of evidence in scientific literature and the grading of recommendations by the French Haute Autorité de santé (HAS) were taken into account. Key recommendations cover: (i) diagnosis, management and follow-up enchondromatosis; (ii) initial assessment, diagnosis and staging of cartilaginous tumor; (iii) management of low-grade, clear cell and high-grade, localized resectable chondrosarcomas; (iv) indications for radiotherapy in chondrosarcomas; (v) management of locally advanced and metastatic disease; (vi) management of mesenchymal chondrosarcomas. Surgical resection at a specialized center remains the mainstay for localized chondrosarcomas management, tailored to grade and anatomical location. Limited evidence supports the use of neoadjuvant or adjuvant treatment in chondrosarcomas, except in mesenchymal chondrosarcomas. For patients with dedifferentiated chondrosarcomas, neo or adjuvant treatment with osteosarcoma-like regimens may be proposed. In cases of recurrence or metastasis, local treatment should be prioritized or participation in clinical trials including new targeted or immune therapies should be considered. This article presents consensus recommandations from adult and pediatric sarcoma experts of various disciplines on the practical management of chondrosarcomas patients.

Prostate stromal sarcoma is very rare among patients with prostate cancer, accounting for <0.1 % of prostate malignancy. Here, we report a case of prostate stromal sarcoma combined with incidental adenocarcinoma with normal serum PSA after radical prostatectomy. This case is unique in that the occurrence of incidental adenocarcinoma might interfere with the postoperative follow-up and treatment. We can only draw from the experiences of case reports and retrospective analysis. This article describes a presentation of a rare tumor case and a review of the literature.

Chondrosarcomas are rare cancers of cartilage with limited systemic therapy options. To identify potential therapeutic targets, this study investigated the molecular and immune landscape of three chondrosarcoma subtypes using a large database of clinical-grade sequencing results.

Deidentified records from patients with a histologic diagnosis of conventional, dedifferentiated, or mesenchymal chondrosarcoma sequenced by the Tempus xT DNA assay were included. Microsatellite instability (MSI) and tumor mutational burden (TMB) were determined from sequencing data. The expression of PD-L1 and mismatch repair enzymes was evaluated in cases with available immunohistochemistry (IHC) data.

Of the 149 patients, 103 had conventional chondrosarcoma, 31 dedifferentiated chondrosarcoma, and 15 mesenchymal chondrosarcoma. Across the cohort, 44% (n = 65) had an IDH1 or IDH2 mutation. No cases were MSI high. One conventional chondrosarcoma patient had a TMB >10 mut/Mb. Among 112 patients with available PD-L1 IHC, 10% of conventional (n = 7), 45% of dedifferentiated (n = 13), and 17% of mesenchymal cases (n = 2) were PD-L1-positive. The most common somatic alterations were in IDH1 (34%) and TP53 (28%) in conventional chondrosarcoma; TP53 (68%), TERT (65%), IDH1 (39%), IDH2 (39%), CDKN2A (35%), and CDKN2B (35%) in dedifferentiated chondrosarcoma; and HEY1-NCOA2 fusions (87%) and CDKN2A (20%) in mesenchymal chondrosarcoma. MTAP was deleted in >10% of each subtype, and potentially actionable PDGFRB mutations were identified in 13% of dedifferentiated chondrosarcomas.

These findings reinforce therapeutic efforts to target IDH signaling in chondrosarcoma, provide insight into varied subpopulation response to immune checkpoint inhibitors, and identify new potential therapeutic targets for clinical development in chondrosarcoma.

To evaluate the efficacy and safety of anlotinib combined with envafolimab in the treatment of unresectable or metastatic liposarcoma.

This single-center, retrospective study enrolled 15 patients with unresectable or metastatic liposarcoma, who were treated at the Retroperitoneal Tumor Surgery Research Center of Qingdao University Affiliated Hospital between April 2022 and November 2023. The treatment regimen consisted of anlotinib combined with envafolimab. Treatment efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events (TRAEs) were assessed using Common Terminology Criteria for Adverse Events version 5.0.

A total of 15 patients with unresectable or metastatic liposarcoma were included; among them, seven were male (46.7%) and eight were female (53.3%), with a median age of 55 years. The pathological subtype distribution was as follows: three (20.0%) patients with well-differentiated liposarcoma, 11 (73.3%) patients with dedifferentiated liposarcoma, and one (6.7%) patient with myxoid liposarcoma. At 12 weeks post-diagnosis, none of the patients achieved a complete response. The objective response rate was 6.7%, with one patient (6.7%) achieving a partial response. Disease stability was observed in 10 (66.6%) patients, which corresponded to a disease control rate of 73.3%. Disease progression occurred in four (26.7%) patients. The median follow-up time was 16.9 months and the median progression-free survival time was 14.2 months. Seven patients experienced TRAEs, of whom three (42.2%) had grade 3-4 TRAEs. The most common TRAEs were liver function abnormalities, hypertension, and fatigue.

Anlotinib combined with envafolimab demonstrates promising efficacy and manageable safety in treating unresectable or metastatic liposarcoma.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with a poor prognosis, particularly in metastatic cases. Traditional treatments have shown limited effectiveness, highlighting the need for innovative therapeutic approaches. This case report aims to emphasize the critical role of genomic profiling in identifying therapeutic targets, particularly immune checkpoint inhibitors, to improve treatment strategies for MPNST.

An 82-year-old male presented with a long-standing history of MPNST, multiple recurrences, and a recent rapid enlargement of a mass in the right axillary region. The patient also reported a 10% weight loss over the last 6 months.

Comprehensive genomic profiling of the tumor revealed significant alterations, including CD274/PD-L1 amplification, CDKN2A loss, and TP53 mutation. These genetic findings were aligned with previous cases that responded favorably to immune checkpoint inhibitors.

Despite the potential for targeted immunotherapy, the patient's economic constraints prevented the initiation of immune checkpoint inhibitor therapy. The patient underwent multiple surgical interventions, including an above-elbow amputation.

The patient experienced severe wound bleeding and a significant decline in general condition, requiring intensive care unit support. Given the poor prognosis and high surgical risks, the patient's caregivers opted for hospice care.

Genomic profiling identifies genetic alterations that could guide immune checkpoint inhibitor therapy, offering the promise of personalized treatment for MPNST patients. By highlighting the potential of genomic profiling, this case demonstrates the importance of integrating personalized immunotherapy into future treatment paradigms for MPNST.

Despite advances in multimodal cancer therapy, such as combining radical surgery with high-intensity chemoradiotherapy, for SMARCB1/INI-1-deficient sinonasal carcinoma (SDSC), the prognosis of patients remains poor. Immunotherapy is gaining increasing popularity as a novel treatment strategy for patients with SMARCB1/INI-1-deficient tumors. Herein, we report on the management of three patients with SDSC who received PD-1/PD-L1 inhibitor therapy as a part of multimodal therapy based on surgery and chemoradiotherapy. All three patients survived and demonstrated good clinical remission and disease control. To our knowledge, this is the first case series reporting the use of immunotherapy to improve clinical outcomes in neoadjuvant, adjuvant, and late first-line stages of treatment in patients with SDSC. Furthermore, we reviewed the relevant literature and further explored the correlation between SMARCB1/INI-1 deletion and immunotherapy.

Systematic review.

The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment.

A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours. We also summarize those actively recruiting clinical trials based on clinicaltrials.gov.

A total of 73 studies and completed clinical trials were reviewed. Twenty actively recruiting clinical trials (eight for chordoma and twelve for chondrosarcoma) were identified.

There is a strong need to find new therapeutic options to complement surgical resection and radiation therapy, which remain the cornerstone of management. Targeted therapies against molecular pathways show promise as compared to conventional chemotherapy.

Using artificial intelligence (AI) to enhance chimeric antigen receptor (CAR)-based therapies' design, production, and delivery is a novel and promising approach. This review provides an overview of the current applications and challenges of AI for CAR-based therapies and suggests some directions for future research and development. This paper examines some of the recent advances of AI for CAR-based therapies, for example, using deep learning (DL) to design CARs that target multiple antigens and avoid antigen escape; using natural language processing to extract relevant information from clinical reports and literature; using computer vision to analyze the morphology and phenotype of CAR cells; using reinforcement learning to optimize the dose and schedule of CAR infusion; and using AI to predict the efficacy and toxicity of CAR-based therapies. These applications demonstrate the potential of AI to improve the quality and efficiency of CAR-based therapies and to provide personalized and precise treatments for cancer patients. However, there are also some challenges and limitations of using AI for CAR-based therapies, for example, the lack of high-quality and standardized data; the need for validation and verification of AI models; the risk of bias and error in AI outputs; the ethical, legal, and social issues of using AI for health care; and the possible impact of AI on the human role and responsibility in cancer immunotherapy. It is important to establish a multidisciplinary collaboration among researchers, clinicians, regulators, and patients to address these challenges and to ensure the safe and responsible use of AI for CAR-based therapies.

Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft-tissue sarcomas and the leading cause of mortality in individuals with neurofibromatosis type 1 (NF1). Despite many clinical trials, outcomes for patients with MPNST have remained stagnant, and most succumb to their disease; thus, novel therapeutic approaches are needed. A better understanding of the MPNST immune ecosystem will aid in the development of strategies to activate the immune system against the tumor. In this study, we profile the tumor immune microenvironment (TIME) in NF1-associated peripheral nerve sheath tumors (PNST) to discover insights on the role played by tumor-infiltrating immune cells in malignant transformation.

Using fresh and formalin-fixed paraffin-embedded tissue from patients diagnosed with NF1-PNST, we dissected the TIME through IHC, multiparameter flow cytometry, and comparative transcriptomic studies.

Immunophenotyping confirmed increased immune cell infiltration during malignant progression, with a predominance of infiltrating myeloid cells, particularly CD163+ tumor-associated macrophages (TAM). The T cells within MPNST exhibited signs of tumor activation, characterized by high programmed cell death 1 expression. Additionally, MPNST specimens demonstrated elevated levels of immunosuppressive TAM, with heightened PD-L1 expression. The proportion of CD163+ myeloid cells within the TIME correlated with poorer progression-free survival. Notably, loss of H3K27 trimethylation correlated with low immune cell infiltration in MPNST.

Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising TAM with high expression of PD-L1, which is associated with inferior outcomes. These findings suggest the clinical potential of immune-modulating therapeutics that can unleash an antitumor immune response.

Background and Objectives: Primary prostatic stromal sarcoma is an exceptionally rare urological malignancy, constituting less than 0.1% of all prostatic cancers. It poses a significant clinical challenge due to its aggressive behavior and poor prognosis. Materials and Methods: We report the case of a 34-year-old male who presented with nonspecific lower urinary tract symptoms, including dysuria and increased urinary frequency. The initial diagnostic workup, including digital rectal examination and Magnetic Resonance Imaging (MRI), revealed a lobulated lesion within the prostate. A transurethral resection (TUR) was performed for diagnostic purposes, and histopathological examination revealed a "malignant mesenchymal tumor". The patient underwent a laparoscopic radical prostatectomy. The pathology report confirmed the diagnosis of prostatic stromal sarcoma. The postoperative follow-up, including systemic CT and MRI, showed no evidence of recurrence or metastasis thus far. Results: Multidisciplinary management is essential for optimizing treatment outcomes in all urologic malignancies; however, it becomes particularly challenging and crucial in rare cases such as primary prostatic stromal sarcoma. In our case, the patient benefited from a coordinated approach involving urology, pathology, and oncology, underscoring the importance of collaborative care for rare and aggressive tumors like this. This case highlights the importance of early detection, complete surgical excision, and consideration of adjuvant therapies, given the aggressive nature of the disease. The role of novel therapeutic strategies, including immunotherapy and targeted therapies, is also discussed in the context of metastatic sarcomas. Conclusions: This case underscores the critical need for a comprehensive, multidisciplinary approach to managing primary prostatic stromal sarcoma. Ongoing research on innovative therapies offers hope for improved outcomes in metastatic stages.

The chondrosarcoma, a cartilage-forming bone tumor, presents significant clinical challenges due to its resistance to chemotherapy and radiotherapy. Surgical excision remains the primary treatment, but high-grade chondrosarcomas are prone to recurrence and metastasis, necessitating the identification of reliable biomarkers for diagnosis and prognosis. This review explores the genetic alterations and molecular pathways involved in chondrosarcoma pathogenesis. These markers show promise in distinguishing between benign enchondromas and malignant chondrosarcomas, assessing tumor aggressiveness, and guiding treatment. While these advancements offer hope for more personalized and targeted therapeutic strategies, further clinical validation of these biomarkers is essential to improve prognostic accuracy and patient outcomes in chondrosarcoma management.

Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response.

To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes.

A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators.

Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan-Meier.

PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS.

High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.

The objective of this study is to evaluate the clinical presentations, diagnostic approaches, and treatment modalities for primary prostate sarcoma postradical prostatectomy, aiming to enhance its diagnosis and management.

We retrospectively reviewed the clinical records of three male patients diagnosed with primary prostate sarcoma at Beijing Chaoyang Hospital, affiliated with Capital Medical University, from February 2014 to February 2024. All patients underwent transrectal prostate biopsies, which informed the decision to proceed with laparoscopic radical prostatectomies. After surgery, one patient received a combination of epirubicin and ifosfamide as immunotherapy, along with external beam radiotherapy. After comprehensive discussions regarding potential benefits and risks, the remaining two patients decided against undergoing radiotherapy and chemotherapy.

Based on the pathological examination results, two patients were diagnosed with stromal sarcoma and one with spindle cell sarcoma, all classified as high-grade sarcomas. Immunohistochemical analysis showed that all three cases were positive for VIMENTIN, but other results did not show significant specificity. During the follow-up period, one patient died within 12 months, and two patients were lost to follow-up after 6 months. However, there were no evident signs of recurrence observed during the follow-up period.

Primary prostate sarcoma is extremely rare and typically has a poor prognosis once diagnosed. Early diagnosis should be based on pathological and immunohistochemical testing results, followed by prompt surgical treatment and adjuvant radiotherapy and chemotherapy. Despite these measures, recurrence is common, underscoring the need for a detailed and appropriate treatment plan and systematic therapy for affected patients.

Chondrosarcomas are common primary malignant bone tumors; however, comprehensive bibliometric analysis in this field has not yet been conducted. Therefore, this study aimed to explore the research hotspots and trends in the field of chondrosarcoma through bibliometric analysis to help researchers understand the current status and direction of research in the field.

Articles and reviews related to chondrosarcoma published between 2003 and 2022 were retrieved from the Web of Science. Countries, institutions, authors, journals, references, and keywords in this field were visualized and analyzed using CtieSpace and VOSviewer software.

Between 2003 and 2022, 4,149 relevant articles were found. The number of articles published on chondrosarcoma has increased significantly annually, mainly from 569 institutions in China and the United States, and 81 in other countries. In total, 904 authors participated in the publication of studies related to chondrosarcomas. Over the past 20 years, articles on chondrosarcoma have been published in 958 academic journals, with Skeletal Radiology having the highest number of publications. Furthermore, keywords such as "gene expression," "radiotherapy," "experience," and "apoptosis" have been popular in recent years.

Over the past 20 years, the global trend in chondrosarcoma research has primarily been clinical research, with basic research as a supplement. In the future, communication and exchange between countries and institutions should be strengthened. Further, the future main research hotspots in the field of chondrosarcoma include mutated genes and signaling pathways, precision surgical treatment, proton therapy, radiation therapy, chemotherapy, immunotherapy, and other aspects.

Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.

Chondrosarcoma (CHS) is a malignant bone tumor with insensitivity to both radiotherapy and chemotherapy, and a high recurrence rate. However, the latent mechanism of recurrent CHS (Re-CHS) remains elusive. Here, we discovered that FBXO22 was highly expressed in clinical samples of Re-CHS. FBXO22 played a significant role in various cancers. However, the role of FBXO22 in Re-CHS remained unclear. Our research demonstrated that suppressing FBXO22 abated the proliferation and migration of CHS cells and facilitated their apoptosis. In addition, suppressing FBXO22 raised the expression of PD-L1 in Re-CHS. All these findings provide new evidence for using FBXO22 and PD-L1 as combined targets to prevent and treat Re-CHS, which may prove to be a novel strategy for immunotherapy of CHS, especially Re-CHS.

Intimal sarcoma (InS) is an ultra-rare and aggressive subtype of soft tissue sarcoma (STS). It usually arises in large mediastinal arteries and the heart. In the advanced setting, sequential cytotoxic chemotherapy is often used, mainly based on retrospective studies and case series but with modest benefit. The use of immune checkpoint inhibitors is a promising strategy for some STS, but identifying biomarkers of response remains challenging due to disease rarity and heterogeneity. A reactive and pro-inflammatory tumor microenvironment (TME) is believed to be associated with better outcomes for patients receiving anti-PD-1-based regimens, generating the rationale to explore this strategy in malignancies with this characteristic, such as InS. We report three cases of advanced InS patients experiencing partial response to pembrolizumab-based therapy despite low tumor mutational burden and absence of mismatch-repair deficiency. We hypothesize that TME-related characteristics such as PD-L1 expression and the presence of tertiary lymphoid structures might explain this phenomenon.

Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance.

A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects.

Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%).

The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2 % to 40 %, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.

Sarcomas are a group of malignancies of mesenchymal origin with a plethora of subtypes. Given the sheer heterogeneity of various subtypes and the rarity of the disease, the management of sarcomas has been challenging, with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has revolutionized the treatment of various solid and hematological malignancies. In this review, we discuss the basics of immunotherapy and the immune microenvironment in sarcomas; various modalities of immunotherapy, like immune checkpoint blockade, oncolytic viruses, cancer-targeted antibodies, vaccine therapy; and adoptive cell therapies like CAR T-cell therapy, T-cell therapy, and TCR therapy.

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype of chondrosarcoma with the bimorphic histological appearance of a conventional chondrosarcoma component with abrupt transition to a high-grade, non-cartilaginous sarcoma. DDCS can be radiographically divided into central and peripheral types. Wide resection is currently the main therapeutic option for localized DDCS. Moreover, the effectiveness of adjuvant chemotherapy remains controversial. Therefore, we performed a systematic review of available evidence to evaluate the effect of adjuvant chemotherapy on localized DDCS. The purpose was to compare the 5-year survival rate among patients treated with surgery plus adjuvant chemotherapy or surgery alone for localized DDCS. The search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Of the 217 studies shortlisted, 11 retrospective non-randomized studies (comprising 556 patients with localized DDCS) were selected. The 5-year survival rates were similar between the two treatment groups (28.2% (51/181) vs. 24.0% (90/375), respectively). The overall pooled odds ratio was 1.25 (95% confidence interval: 0.80-1.94; p = 0.324), and heterogeneity I2 was 2%. However, when limited to peripheral DDCS, adjuvant chemotherapy was associated with prolonged survival (p = 0.03). Due to the paucity of included studies and the absence of prospective comparative studies, no conclusions can be drawn regarding the effectiveness or ineffectiveness of adjuvant chemotherapy for localized DDCS.

The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort.

Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success.

From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%-[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%-[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%).

Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy.

Sarcomas are tumors that originate from mesenchymal cells. The variety of sarcomas' response to chemotherapy and the wide range of prognosis reflect their heterogeneity. In order to improve the rates of response, the research has been orientated toward other forms of therapy, such as targeted therapies and immunotherapy or toward combinations of them. Immune checkpoint inhibitors (ICIs) have been the highlight of immunotherapy in the last decade. Although ICIs are already included in the guidelines of different malignancies, their clinical benefit in sarcomas is still under study. Alveolar soft part sarcomas, undifferentiated pleomorphic sarcomas and other subtypes of sarcoma with high presence of tertiary lymphoid structures tend to respond to ICIs, but further investigation is still needed. Furthermore, the search of predictive biomarkers to determine the type of sarcomas that are sensitive to ICIs is still very challenging. This review will focus on the results of clinical trials, which examine the effect of ICIs and their combination with chemotherapy, targeted therapies and other forms of immunotherapy in sarcomas.

Perianal/perineal rhabdomyosarcomas (PRMS) is rare, and the outcome is poor. A 29-year-old female presented with perineal rhabdomyosarcomas revealed metastases to inguinal lymph nodes on the bilateral side. Disease progression was discovered when the patient got adjuvant epirubicin, ifosfamide, and bevacizumab for 2 cycles. After 3 cycles of nivolumab, dacarbazine, cisplatin, and vinblastine therapy, a partial response was identified in the patient. The surgical resection was performed. The patient received neoadjuvant chemotherapy before surgery and was weak after surgery, so he did not receive chemoradiotherapy. The patient succumbed after 11 months postoperatively due to widespread intraabdominal metastasis.

Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor that more commonly occurs in children and adolescents. The most commonly used treatment for OS is surgery combined with chemotherapy, but the treatment outcomes are typically unsatisfactory. High rates of metastasis and post-treatment recurrence rates are major challenges in the treatment of OS. This underlines the need for studying the in-depth characterization of the pathogenetic mechanisms of OS and development of more effective therapeutic modalities. Previous studies have demonstrated the important role of the bone microenvironment and the regulation of signaling pathways in the occurrence and development of OS. In this review, we discussed the available evidence pertaining to the mechanisms of OS development and identified therapeutic targets for OS. We also summarized the available treatment modalities for OS and identified future priorities for therapeutics research.

The pathogenesis of dedifferentiated chondrosarcoma is controversial, and no genetic abnormality has consistently been identified in the disease. Focusing on the diagnostic challenges encountered in dedifferentiated chondrosarcoma, the following review aims at summarizing the tumor's active neoplastic pathways while highlighting therapeutic modalities that could potentially be explored to enhance patient survivorship.

Owing to the challenging examination of small needle biopsy sampling as well as the disease's overlapping morphological and immunohistochemical features with other bone and soft-tissue sarcomas, the diagnosis of dedifferentiated chondrosarcoma can be problematic. While combined doxorubicin- and cisplatin-based regimens remain the first-line systemic chemotherapy in the disease, ~50% of tumors carry EXT1/2 or IDH1/2 mutations, advancing EXT or IDH inhibitors as potential alternative therapies, respectively. Despite systemic chemotherapy, dedifferentiated chondrosarcoma remains an aggressive tumor with dismal prognosis and limited survival. A multidisciplinary collaboration across multiple cancer centers is warranted to yield an accurate diagnosis, understand the disease's underlying pathogenesis, develop adequate treatment, and improve patient survivorship.

Ferroptosis is characterized by iron accumulation and lipid peroxidation. However, a clinical dose of Fe3O4 nanoparticles could not cause effective ferroptosis in tumors, and the mechanism is yet to be completely understood. In this study, using RNA-seq data, we found that tumor cells could feedback-activate the antioxidant system by upregulating Nrf-2 expression, thus avoiding ferroptosis caused by Fe3O4 nanoparticles. We also found that DHJS (a probe for ROS generation) can antagonize Nrf-2 expression when it synergizes with Fe3O4 nanoparticles, thus inducing ferroptosis in tumor cells. Considering these findings, we created a biomimetic hybrid cell membrane camouflaged by PLGA-loaded Fe3O4 and DHJS to treat osteosarcoma. The hybrid cell membrane endowed the core nanoparticle with the extension of blood circulation life and enhanced homologous targeting ability. In addition, DHJS and Fe3O4 in nanoparticles prompted synergistically lethal ferroptosis in cancer cells and induced macrophage M1 polarization as well as the infiltration of CD8(+) T cells and dendritic cells in tumors. In summary, this study provides novel mechanistic insights and practical strategies for ferroptosis induction of Fe3O4 nanoparticles. Meanwhile, the synthesized biomimetic nanoparticles exhibited synergistic ferroptosis/immunotherapy against osteosarcoma.

Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA's immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA.

Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.

The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment.

This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.

The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged < 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1-Q3) duration of therapy (olaratumab) was 6.0 (3.0-11.9; cohort 1), 14.4 (12.4-20.9; cohort 2), and 14.0 (6.0-21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1-positive tumors.

Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.

Dedifferentiated chondrosarcoma (DDCS) is a rare subtype of chondrosarcoma, a primary cartilaginous malignant neoplasm. It accounts for up to 1-2% of all chondrosarcomas and is generally associated with one of the poorest prognoses among all chondrosarcomas with the highest risk of metastasis. The 5-year survival rates range from 7% to 24%. DDCS may develop at any age, but the average presentation age is over 50. The most common locations are the femur, pelvis humerus, scapula, rib, and tibia. The standard treatment for localised disease is surgical resection. Most patients are diagnosed in unresectable and advanced stages, and chemotherapy for localised and metastatic dedifferentiated DDCS follows protocols used for osteosarcoma.