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BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Soft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. One of the most successful therapy for patients with this disease is surgical resection. However, it is very challenging to diagnose disease in the early stages and recognize the chemotherapy effect during the chemotherapeutics period due to a lack of radiologists in developing nations. The majority of cancer hospitals require a large number of radiologists, who are highly expensive. The proposed approach develops a Mask-Regional Convolutional Neural Network (Mask-RCNN) for identifying soft tissue sarcomas to solve these problems. Initially, Images are gathered and then pre-processed with image resizing, anisotropic diffusion, as well as contrast stretching. Collected images are in different sizes, so needs to be resized for effective prediction and further improve the quality by using two pre-processing techniques. In order to eliminate the unwanted noise from the original image, anisotropic diffusion is applied. Contrast stretching is used to improve the brightness of the image. In the following step, pre-processed images are sent into Mask R-CNN, which segments and bounds a box around the features. A well-liked deep learning segmentation approach is named as Mask R-CNN that segments objects at the pixel level. These bounded features are classified for detecting whether the disease affected the patients or not. According to the simulation analysis, the proposed approach attains 97% accuracy, 0.03% error, 91% precision, and 95% specificity. Consequently, compared to other existing techniques, the developed approach performs better. This prediction model helps to predict the soft tissue sarcomas at the early stage and improves the patient's living standard. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcoma (UPS) is a rare type of tumor, and UPS originating in the adrenal gland is even rarer. Up to now, there have been no reports in English literature of UPS originating from the adrenal gland. This case report presents a 44-year-old female patient with UPS of the adrenal gland, who has shown no signs of recurrence or metastasis half a year after undergoing resection of a left adrenal tumor. A retrospective analysis of the patient's diagnosis and treatment process is conducted, with the aim of providing a reference for the diagnosis and treatment of adrenal UPS. [ABSTRACT FROM AUTHOR]

Relevance. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes of soft tissue sarcomas. The polymorphism of tumor cells and high degree of malignancy account for the aggressive potential of UPS. Due to the rarity of occurrence and high heterogeneity of UPS, the number of studies describing the cellular composition and molecular-­biological characteristics is very limited. Objective is to assess the cellular composition and gene expression of UPS. Materials and Methods. Biomaterial from 10 patients with UPS was analyzed in the study. In this study we used primary antibodies to CD163 (marker of M2 macrophages) and Fibroblast activation protein (FAP — marker of fibroblasts) and secondary Caprine-­Anti-­Rabbit IgG HRP were used. HRP-tagged secondary antibodies were manifested using DAB. Antibodies for automated BOND-III IHC stainer were used to evaluate the microenvironment: CD68‑marker of macrophages, CD19‑marker of B-lymphocytes, CD56‑marker of neuroendocrine tumors, metastasis protein, Ki67 antigen-­proliferation marker, Bcl‑2‑oncoprotein. Staining on an automated BOND-III IHC stainer was performed according to standard protocols. In homogenized samples of tumor tissue and peritumoral area with the number of cells 106/ml in order to assess the microenvironment of the tumor and surrounding tissue, cytofluorimetric study of the relative number of CD14+ and CD16+ monocytes, CD68+ macrophages, CD86+ M1 macrophages, CD163+ and CD206+ M2 macrophages, CD4+ helper T-lymphocytes and CD45+ leukocytes was performed on the MACS Quant Analyzer device. The mRNA expression levels of HIF1A, VEGF, MMP2, ARG1, NOS2, and EGFR were determined in tumor tissue and peritumoral samples by PCR. The RNA Solo RNA kit was used for RNA isolation, and the MMLV RT Kit was used for reverse transcription. The amplification reaction with real-time detection was performed on aDTprime Real-­Time Amplifier. Results and Discussion. The expression of CD56, FAP, CD68 is characteristic for UPS. Among the cells of the microenvironment, macrophages and CD16‑monocytes predominate in UPS. EGFR expression level is increased in tumor cells of the UPS compared to the peritumoral region. The expression levels of ARG1, NOS2, HIF1A, VEGF, and MMP2 in tumors have individual differences and are not specific to the UPS. Conclusion. In our study, we analyzed the cellular composition and gene expression in UPS samples. Further follow-up of patients is necessary to evaluate the clinical significance of each marker.

Soft tissue sarcomas are defined as relatively rare, wide-ranging mesenchymal tumors that present several forms of aggressive behavior. In order to improve the therapeutic result and thus the patient's prognosis, reliable diagnostic and evaluation tools are needed, capable of establishing the evolutive pattern of each patient. Materials and Methods. An analytical observational study was conducted in the period 2016-2023 in the Orthopedics Department of the Bucharest University Emergency Hospital, on patients diagnosed with soft tissue sarcoma. Data such as sex, age, site, size, depth, histotype, grade and margin status, vessel or bone involvement, adenopathies, adjuvant therapy, clinical findings, etc., were analyzed. Diagnosis included immunohistochemistry after macroscopic pathological findings were carefully reviewed by a dedicated pathologist. A molecular study was performed to increase the accuracy of diagnosis, prognosis and clinical management of selected sarcomas. Results. In adult soft tissue sarcomas, histotype has been reported to be a significant predictor of overall survival. In terms of survival rate, vascular invasion appears to be a significant pathological factor for progression in extremity STS. Even though the local control of the disease has improved, the development of systemic metastases seems to be largely influenced by the biological characteristics of the tumor. Conclusions. Significant prognostic factors for the likelihood of a lower survival and death rate are tumor size, tumor depth, histology type, and vascular invasion. The results of the study support and complement the literature data, thus improving the understanding of the prognosis of soft tissue sarcomas.

Malignant nerve sheath tumors are rare and aggressive soft tissue sarcomas. They contribute to 5–10% of all soft tissue sarcomas. They can be sporadic, occur in patients with NF1 (neurofibromatosis 1) or can occur after radiation therapy. A high rate of recurrence and hematogenous metastasis is seen in these patients. They are also associated with poor prognosis. A case of malignant nerve sheath tumor seen in a 44-year-old male with pre-existing NF1 is being discussed here due to the unique nature of the disease and its rarity. [ABSTRACT FROM AUTHOR]

Opinion Statement: Soft tissue sarcomas (STS) are a rare and heterogeneous group of cancers. Treatment options have changed little in the past thirty years, and the role of neoadjuvant chemotherapy is controversial. Accurate risk stratification is crucial in STS in order to facilitate clinical discussions around peri-operative treatment. Current risk stratification tools used in clinic, such as Sarculator, use clinicopathological characteristics and may be specific to anatomical site or to histology. More recently, risk stratification tools have been developed using molecular or immunological data. Combining Sarculator with other risk stratification tools may identify novel patient groups with differential clinical outcomes. There are several considerations when translating risk stratification tools into widespread clinical use, including establishing clinical utility, health economic value, being applicable to existing clinical pathways, having strong real-world performance, and being supported by investment into infrastructure. Future work may include incorporation of novel modalities and data integration techniques. [ABSTRACT FROM AUTHOR]

Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64-1.40), p = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), p = 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.

Undifferentiated pleomorphic sarcoma (UPS) is a rare type of tumor, and UPS originating in the adrenal gland is even rarer. Up to now, there have been no reports in English literature of UPS originating from the adrenal gland. This case report presents a 44-year-old female patient with UPS of the adrenal gland, who has shown no signs of recurrence or metastasis half a year after undergoing resection of a left adrenal tumor. A retrospective analysis of the patient’s diagnosis and treatment process is conducted, with the aim of providing a reference for the diagnosis and treatment of adrenal UPS.

BACKGROUND: Soft tissue sarcomas are a heterogeneous group of rare, solid and soft tissue cancers of mesenchymal or connective tissue origin. They can develop in almost any anatomical site, but more commonly in the extremities, trunk, viscera, retroperitoneum, or head and neck; about 10% of patients have detectable metastases at the time of diagnosis of the primary tumor, most commonly in lungs. CLINICAL CASE: A 65-year-old female patient in whom a grade 4 undifferentiated pleomorphic sarcoma in the left atrium was diagnosed. CONCLUSIONS: Soft tissue sarcomas require a high degree of clinical suspicion to carry out a timely multidisciplinary treatment. Having initially presented a clinical presentation that is not very suggestive of the final diagnostic result, it opens the way for expanding the differential diagnoses of this type of lineage in cardiac cavities. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas are defined as relatively rare, wide-ranging mesenchymal tumors that present several forms of aggressive behavior. In order to improve the therapeutic result and thus the patient's prognosis, reliable diagnostic and evaluation tools are needed, capable of establishing the evolutive pattern of each patient. Materials and Methods. An analytical observational study was conducted in the period 2016-2023 in the Orthopedics Department of the Bucharest University Emergency Hospital, on patients diagnosed with soft tissue sarcoma. Data such as sex, age, site, size, depth, histotype, grade and margin status, vessel or bone involvement, adenopathies, adjuvant therapy, clinical findings, etc., were analyzed. Diagnosis included immunohistochemistry after macroscopic pathological findings were carefully reviewed by a dedicated pathologist. A molecular study was performed to increase the accuracy of diagnosis, prognosis and clinical management of selected sarcomas. Results. In adult soft tissue sarcomas, histotype has been reported to be a significant predictor of overall survival. In terms of survival rate, vascular invasion appears to be a significant pathological factor for progression in extremity STS. Even though the local control of the disease has improved, the development of systemic metastases seems to be largely influenced by the biological characteristics of the tumor. Conclusions. Significant prognostic factors for the likelihood of a lower survival and death rate are tumor size, tumor depth, histology type, and vascular invasion. The results of the study support and complement the literature data, thus improving the understanding of the prognosis of soft tissue sarcomas. [ABSTRACT FROM AUTHOR]

Objectives: We aim to enhance the understanding of soft tissue sarcomas (STS) within the Saudi population, guiding better diagnosis, treatment strategies, and healthcare resource allocation for this rare but challenging cancer type. Methods: Retrospective data of 160 patients at King Abdulaziz University Hospital (2013--2023) were examined for demographics, anatomical sites, and diagnoses of STS. Statistical analysis in RStudio (R v4.3.1) utilized Fisher's exact and chi-squared tests for categorical variables (P < 0.05), while continuous variables were summarized by medians and interquartile range. Results: We included patients with STS, evenly split between males and females (median age: 47 years) Significant differences were observed between age groups: younger patients (<50 years) more commonly had rhabdomyosarcoma and synovial sarcoma, while older patients (≥50 years) showed higher rates of dedifferentiated liposarcoma, Kaposi sarcoma, and leiomyosarcoma. Sarcoma locations varied, with the thigh, retroperitoneum, and head and neck being prominent sites. Higher frequencies of Kaposi sarcoma and skin sarcomas were noted in males, and leiomyosarcoma and uterine sarcomas exclusively in females. Conclusion: The study highlights significant sex and age disparities in the diagnosis and distribution of STS among Saudi patients. Rhabdomyosarcoma emerges as the most frequent subtype, influenced by factors such as genetic predisposition and advanced diagnostic capabilities. Understanding these demographic variations is crucial for developing targeted treatment strategies tailored to the unique needs of different patient groups. Further research into the underlying biological and environmental factors driving these disparities is essential for advancing sarcoma care and improving patient outcomes in Saudi Arabia. [ABSTRACT FROM AUTHOR]

Background: Post-radiation fractures are a significant complication of cancer treatment, often being challenging to manage and impacting patients' quality of life. This study systematically reviews the literature on fractures in irradiated bones, focusing on risk factors, treatment modalities, and prevention strategies. Factors increasing fracture risk include exposure to high doses of radiation of at least 50 Gy, female gender, menopausal age, and periosteal stripping. Additionally further risk factors are the size of the original tumor and osteoporosis. Methods: A search of PubMed yielded 541 articles, with 4 were ultimately included in the review. These retrospective studies focused on patients undergoing Combined Limb-Sparing Surgery and Radiation Therapy for soft tissue sarcoma. Results: Results show post-radiation fractures affect approximately 4% of patients, with the femur being the most frequently affected site. Intramedullary nailing emerges as the gold standard treatment, with prosthetic replacement or megaprostheses used in the metaepiphyseal region and as salvage procedures. Non-union and infection remain formidable complications. Conclusions: This study highlights the importance of prophylactic nailing in fracture prevention and the efficacy of free vascularized fibular flaps to achieve bone union during revision surgeries. Limited case availability and patient follow-up hinder comprehensive studies, impacting treatment outcomes. [ABSTRACT FROM AUTHOR]

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the impact of anthracycline-based chemotherapy on methylation status of RB1 gene in peripheral blood leukocytes together with parameters of oxidative stress and inflammation in sarcoma patients. Patients/methods: Blood samples were collected from 51 consecutive newly diagnosed sarcoma patients admitted to University Hospital Center Zagreb (Zagreb, Croatia) for first-line chemotherapy before the first cycle and post-chemotherapy. Methylation and copy number variation (CNV) of leukocyte RB1 gene were assessed using MS-MLPA probes. In addition, in blood samples, parameters of oxidative stress (ROS, MDA, SOD, and GSH) and inflammation (CRP, WBC, and NBC) were followed. Results: In pre-chemotherapy samples, no CNVs and aberrant methylation of CpG106 promoter region of RB1 gene were detected; however, one patient had hypermethylation (by approximately 10%) of imprinted locus CpG85 in intron 2 of RB1 gene. In addition, a very good correlation of the tumor burden and CRP and tumor burden and GSH was found. The anthracycline-based chemotherapy reverts methylation of RB1 gene-imprinted locus CpG85 to normal level. Moreover, inflammation and oxidative stress parameters such as CRP, WBC, ROS, and MDA were significantly decreased in post-chemotherapy samples. Conclusion: This single-centered study on a cohort of consecutive sarcoma patients indicates that sarcoma patients can have aberrant germline DNA methylation and confirms the relationship of tumor burden with inflammation and oxidative stress. The applied chemotherapy protocols reverted RB1 gene methylation to normal level and decreased the level of inflammation and oxidative damage, thus indicating chemotherapy benefit to the patient's health status. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS). Methods and Materials: This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the “Conticabase”. Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR. Results: 257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates

Summary: Background: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. Methods: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS). Findings: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI. Interpretation: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS. Funding: Pharmamar; Italian Ministry of Health [RF-2019-12370923; GR-2016-02362609]; 5 × 1000 Funds—2016, Italian Ministry of Health; AIRC Grant [ID#28546].

IntroductionSoft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHC-I expressing cells lacks detailed characterization.Experimental designUsing archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF). We assessed spatial localization of NK and T cells by multiplex IF, analyzing the effects of MHC-I expression status on NK and T cell clustering.ResultsBoth intratumoral NKp46 and CD56dim expression were associated with significantly improved overall survival (P=0.05), while higher infiltrates of CD56bright NK cells predicted a worse prognosis (P=0.05). The presence of intratumoral NK cells was inversely proportional to CD3+ T cells. Spatial analyses showed NK cells preferentially clustering close to other NK cells with sparse CD3+ T and CD8+ T cells in range (P

Abstract Background Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. Methods Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. Discussion This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. Trial registration NCT05301283. Trial status The trial started recruitment on March 17, 2022.

Background: Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further. Methods: Clinical and genomic data were obtained from the UCSC Xena database. All STS patients’ subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS. Results: A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients’ treatment. Conclusions: Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas form 1% of all cancers and are rare. The lower limb is one of the commonest sites of sarcoma, with the thigh accounting for the majority of these tumors. Large tumors abut the neurovascular bundles both anteriorly and in the hamstring compartment. Nerve involvement, especially the major nerves such as the femoral and the sciatic, by these tumors, was considered to be an absolute contraindication for limb salvage procedures. We present our data of major nerve resection without amputation, in an attempt to demonstrate the possibility of equivalent functional and oncological outcomes in these rare tumors. A total of 86 cases of extremity soft tissue sarcomas were operated on during the period September 2019 to September 2022, of which there were 12 cases of major nerve resections of the lower extremity. These patients were followed up and their clinicopathological data collected and analyzed. The functional outcome was recorded at different intervals. Of the 12 patients who underwent nerve resection along with the tumor, only 1 patient developed a local recurrence. Two patients developed multiple lung metastases, and the other 9 patients are alive and free of disease, with a median follow-up of 26 months. The MSTS score was assessed at 1 month post-surgery, 3 months, 6 months, and 1 year post-surgery. Except for one patient where the score was 20%, all the other patients had scores of 80% or more. Major nerve involvement by soft tissue sarcomas is not an indication for amputation. Limb salvage can be performed with no effect on the oncological outcomes. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STSs) represent a group of heterogeneous mesenchymal tumors of which are generally classified as per the histopathology. Despite being rare in incidence and prevalence, STSs are usually correlated with unfavorable prognosis and high mortality rate. Early and accurate diagnosis of STSs are critical in clinical management of STSs. Deep learning (DL) refers to a subtype of artificial intelligence that has been adopted to assist healthcare professionals to optimize personalized treatment for a given situation, particularly in image analysis. Recently, emerging studies have demonstrated that application of DL based on medical images could substantially improve the accuracy and efficiency of clinicians to the identification, diagnosis, treatment, and prognosis prediction of STSs, and thereby facilitating the clinical decision-making. Herein, we aimed to extensively summarize the recent applications of DL-based artificial intelligence in STSs from the aspects of data acquisition, algorithm, and model establishment. Besides, the reinforcement of the model by transfer learning and generative adversarial network (GAN) for data augmentation has also been elaborated. It is worth noting that high-quality data with accurate annotations, as well as optimized algorithmic performance are pivotal in the clinical application of DL in STSs.

Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and > 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content.Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.

Soft tissue sarcomas are rare tumors (about 1 % of all malignant neoplasms) and include more than 70 histological subtypes, the pathogenetic features of which remain unclear. This is largely due to both quantity and volume of clinical material and high heterogeneity of the disease. Given the rarity and heterogeneity of each individual subtype of soft tissue sarcoma, there is an urgent need to develop universal model systems to understand the molecular changes that determine tumor biology. Such systems include CDX models (cell line-derived xenograft), created from cell lines, PDX (patient-derived xenograft), obtained from primary tumor/metastasis cells, both a whole fragment of surgical material and from a cell suspension; humanized animals containing various human immune cells, and GEM (genetically engineered mouse) models, which are created through transfection of genetic changes characteristic of different subtypes of soft tissue sarcomas. To create these systems, not only widely available mouse models are used, but also other animals, such as fish (Danio rerio) , rats, pigs, and dogs. Another important goal of using animal models is to screen the effectiveness of modern drugs. To date, treatment of various subtypes of soft tissue sarcomas is based on standard protocols of chemotherapy (doxorubicin, epirubicin, dacarbazine, ifosfamide) and surgical resection. In the case of inoperable forms or late stages of soft tissue sarcomas, animal models are a potential tool in predicting the effectiveness of therapy and personalized selection of treatment regimens. In this regard, studies of the mechanisms of targeted action on specific molecules and the use of humanized animals for the development of new approaches to immunotherapy are of particular relevance. The current review discusses animal model systems of the three most common types of soft tissue sarcomas: liposarcomas, undifferentiated pleomorphic and synovial sarcomas, as well as the use of these models to find new therapeutic solutions. Conclusion. Currently, PDX and GEM models are widely used to identify molecules and signaling pathways involved in the development of sarcomas, identify tumor-initiating cells, and assess the chemoresistance of known drugs and new drugs at the level of the entire tumor ecosystem. However, the key problems of animal models of soft tissue sarcomas remain changes in their composition and phenotype compared to the original tumor, poor survival of surgical material, and lack of cellular immunity in immunocompetent models, high cost, and the length of time it takes to create and maintain the model. A solution to one of the problems may be the use of humanized animals with PDX, which implies the presence in the model of immune, stromal and tumor components that are as close as possible to the human body.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients’ survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men—mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908—1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels.

Abstract Purpose Soft tissue sarcomas (STS) of the forearm are rare. We aim to assess their oncological and functional outcomes. Methods We retrospectively evaluated 34 patients who underwent surgical excision for forearm STS at our institution between 1993 and 2020. We analyzed postoperative Musculoskeletal Tumor Society rating scale (MSTS) and local recurrence-free survival (LRFS), metastasis-free survival, and overall survival (OS) rates. The significance of the following variables was determined: age, sex, histology, tumor size, Fédération Nationale des Centres de Lutte contre le Cancer grade, American Joint Committee on Cancer stage, surgical margin, unplanned excision, metastases upon initial presentation, receipt of chemotherapy, and radiotherapy (RT). Results The postoperative median MSTS score was 28. Bone resection or major nerve palsy was the only factor that influenced MSTS scores. The median MSTS scores in patients with or without bone resection or major nerve palsy were 24 and 29, respectively (P

Abstract Background Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low‐grade and high‐grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next‐generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion‐associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. Case We present the case of a 42‐year‐old woman diagnosed with COL1A1::PDGFB fusion‐associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low‐grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. Conclusions COL1A1::PDGFB fusion‐associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first‐line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Alveolar soft part sarcoma (ASPS) is an extremely rare and aggressive soft-tissue sarcoma (STS) subtype with poor prognosis and limited response to radiation therapy and chemotherapy. Prompt recognition and referral to sarcoma centers for appropriate management are crucial for patients' survival. The purpose of this study was to report ASPS pre-treatment imaging features and to examine the existing literature on this topic. Twelve patients (7 women, 5 men—mean age 27.1 ± 10.7 years) were included from our single-center experience. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) available were reviewed according to an analysis grid incorporating features from the latest research on STS. Clinical, histological, and outcome data were collected. MRI was available in 10 patients (83.3%), US in 7 patients (58.3%), and CT in 3 patients (25%). Mean longest tumor diameter was 7.6 ± 2.9 cm, and all tumors were deeply seated. Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3). US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7). In all patients, MRI showed mildly high signal intensity (SI) on T1-WI and high SI on T2-WI and peritumoral edema. Moreover, flow-voids (due to arteriosus high-flow) into the peritumoral/intratumoral feeding vessels were detected in the MRI fluid-sensitive sequences of all patients. At baseline, whole-body contrast-enhanced CT revealed metastases in 8/12 (66.7%) patients. A pre-treatment longest diameter > 5 cm was significantly associated with distant metastases at diagnosis (p = 0.01). A maximum diameter > 5 cm represents a risk of metastatic disease at diagnosis (odds ratio = 45.0000 (95% CI: 1.4908—1358.3585), p = 0.0285). In the comprehensive literature review, we found 14 articles (case series or original research) focusing on ASPS imaging, with a total of 151 patients included. Merging our experience with the data from the existing literature, we conclude that the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. Methods: We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). Results: Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. Conclusions: In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype. [ABSTRACT FROM AUTHOR]

Visceral sarcomas are a rare malignant subgroup of soft tissue sarcomas (STSs). STSs, accounting for 1% of all adult tumors, are derived from mesenchymal tissues and exhibit a wide heterogeneity. Their rarity and the high number of histotypes hinder the understanding of tumor development mechanisms and negatively influence clinical outcomes and treatment approaches. Although some STSs (~20%) have identifiable genetic markers, as specific mutations or translocations, most are characterized by complex genomic profiles. Thus, identification of new therapeutic targets and development of personalized therapies are urgent clinical needs. Although cell lines are useful for preclinical investigations, more reliable preclinical models are required to develop and test new potential therapies. Here, we provide an overview of the available in vitro and in vivo models of visceral sarcomas, whose gene signatures are still not well characterized, to highlight current challenges and provide insights for future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft tissue and bone sarcomas belong to a group of rare and malignant tumors. The treatment of these tumors is very complex and depends on their specific subtypes. Therefore, there is a great need to develop novel therapeutic options for patients with sarcomas. One such option may be to target tumor-associated macrophages (TAMs), which are involved in immunosuppression during tumor growth. High levels of TAMs are widely recognized as a poor prognostic factor in many tumors, including sarcomas, making them a promising target for future targeted therapies. In this review, we highlight the role of TAMs in the microenvironment of sarcomas, along with their clinical relevance, potential targetable markers on their surface, and the molecular pathways involved. We also discuss currently ongoing clinical trials with TAMs. Sarcomas are a heterogeneous group of malignant mesenchymal tumors, including soft tissue and bone sarcomas. Macrophages in the tumor microenvironment, involved in immunosuppression and leading to tumor development, are called tumor-associated macrophages (TAMs). TAMs are very important in modulating the microenvironment of sarcomas by expressing specific markers and secreting factors that influence immune and tumor cells. They are involved in many signaling pathways, such as p-STAT3/p-Erk1/2, PI3K/Akt, JAK/MAPK, and JAK/STAT3. TAMs also significantly impact the clinical outcomes of patients suffering from sarcomas and are mainly related to poor overall survival rates among bone and soft tissue sarcomas, for example, chondrosarcoma, osteosarcoma, liposarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma. This review summarizes the current knowledge on TAMs in sarcomas, focusing on specific markers on sarcoma cells, cell–cell interactions, and the possibly involved molecular pathways. Furthermore, we discuss the clinical significance of macrophages in sarcomas as a potential target for new therapies, presenting clinical relevance, possible new treatment options, and ongoing clinical trials using TAMs in sarcoma treatment. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, medium, or low. The Italian Medical Oncology Association and European Society of Medical Oncology (ESMO) guidelines recommend magnetic resonance imaging (MRI) because the clinical examination is typically ineffective. The diagnosis of these rare diseases with artificial intelligence (AI) techniques presents reduced datasets and therefore less robust methods. However, the combination of AI techniques with radiomics may be a new angle in diagnosing rare diseases such as STSs. Results obtained are promising within the literature, not only for the performance but also for the explicability of the data. In fact, one can make tumor classification, site localization, and prediction of the risk of developing metastasis. Thanks to the synergy between computer scientists and radiologists, linking numerical features to radiological evidence with excellent performance could be a new step forward for the diagnosis of rare diseases.

Solitary fibrous tumors are rare tumors of pluripotent fibroblastic or myofibroblastic origin that generally arise among older individuals, with a mean age of onset ranging from 55 to 65 years. Though typically associated with pleural involvement, solitary fibrous tumors can emerge in virtually every anatomic location within the body. Although most solitary fibrous tumors are benign, approximately 20% may exhibit malignant features such as local invasion, recurrence, and metastases. In this article, we report the case of a 58-year-old male with a diagnosis of a retroperitoneal solitary fibrous tumor. We analyze computed tomography imaging findings and additionally correlate imaging features with the patient's unique pathological and genotypic findings to optimize diagnosis.

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

Objectives: Soft tissue sarcomas are a heterogeneous group of tumors accounting for less than 1% of adult malignancies. In this study, we examined patients who received pazopanib for soft tissue sarcoma. Factors affecting mortality and overall survival in soft tissue sarcoma patients using pazopanib were investigated. Methods: This study is a retrospective single-center study. Results: Fifty-three patients (median age: 42 years) were included. The median duration of follow-up in our cohort was 34 months. Before pazopanib, 37 patients (69.8%) received first-line, 12 patients (22.6%) received second-line and 4 patients (7.5%) received third-line chemotherapy. The median duration of pazopanib therapy was 7 months (range, 1-82). Median progression-free survival (PFS) and median overall survival was 7 months (range, 1-83) and 12 months (range, 1-83), respectively. Patients who received radiotherapy for curative or palliative purposes had significantly longer PFS (p=0.040). Eight patients required dose reduction due to adverse effects. Grade 4 adverse effects occurred in only 2 patients. After pazopanib, 36 patients (67.9%) did not receive any treatment. On Cox regression analysis, not receiving any treatment after pazopanib was associated with 3.052-fold higher mortality. A 1-unit increase in PFS was associated with 1.15-fold lower risk of mortality. Conclusion: In this study, pazopanib was found to be an effective and safe drug for advanced soft tissue sarcoma. Patients who received palliative radiotherapy for curative or palliative purposes had significantly longer PFS. Receiving treatment after pazopanib and longer PFS was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Background: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). Purpose: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. Material and Methods: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. Results: D -SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). Conclusion: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs. [ABSTRACT FROM AUTHOR]

Introduction: Soft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHCI expressing cells lacks detailed characterization. Experimental design: Using archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF). We assessed spatial localization of NK and T cells by multiplex IF, analyzing the effects of MHC-I expression status on NK and T cell clustering. Results: Both intratumoral NKp46 and CD56dim expression were associated with significantly improved overall survival (P=0.05), while higher infiltrates of CD56bright NK cells predicted a worse prognosis (P=0.05). The presence of intratumoral NK cells was inversely proportional to CD3+ T cells. Spatial analyses showed NK cells preferentially clustering close to other NK cells with sparse CD3+ T and CD8+ T cells in range (P<0.0001). Additionally, CD3+ T and CD8+ T cells showed significantly greater co-localization with MHC-I+ cells, compared to NK cells (P<0.0001). After neoadjuvant radiotherapy, there was greater CD8 clustering, while after neoadjuvant chemotherapy, there was overall lower TIL clustering. Conclusion: Intratumoral NK cells are prognostic in STS and localize closer to MHC-I-cells than T cells. Although both NK and T cells are associated with improved survival in STS, their differential distribution in the TME based on MHC-I expression status may serve as a biomarker for improved immunotherapy treatment selection. [ABSTRACT FROM AUTHOR]

Abstract Background Despite immunotherapy’s promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this study, we explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in advanced sarcoma outcomes. Methods Patients in The Ohio State University Sarcoma Clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single-agent ICI or ICI + combination) along with clinical covariates. ICI + combination was further categorized into ICI + medication, ICI + radiation, ICI + surgery, or ICI + multiple (more than 2 modalities). Statistical analysis included log-rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). Results Of the patients in the database, 135 met inclusion criteria. We demonstrated improved OS in patients treated with ICI + combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Patients with a documented immune-related adverse event (irAE) of dermatitis had improved OS, but only in the ICI + combination cohort (p = 0.021). Patients who received single-agent ICI and whose change in the neutrophil-to-lymphocyte ratio (NLR) was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI + combination therapy (p = 0.441). There were no differences in OS based on age, gender, histology, or subcategories of ICI + combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036) compared with their older counterparts in this dataset. Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048), or dermatitis (p = 0.003), had an improved PFS. There were no differences in PFS based on ICI regimen (or subcategories of ICI + combination), gender, histology, change in NLR, or grade of irAE. Conclusions This retrospective study demonstrates that ICI + combination therapy can improve OS in some patients with advanced sarcoma. This is consistent with our prior results of ICI in sarcoma.

Abstract Background Fine‐needle aspiration (FNA) cytology is a rapid, inexpensive, and uncomplicated method. However, its role in the assessment of soft tissue lesions (STL) remains controversial, and its ability to guide surgical treatment remains unclear. This study investigated the positive predictive value (PPV) of FNA for detecting malignancy and its guiding role in the surgical treatment of STL. Methods We retrospectively reviewed 514 patients with STL who underwent preoperative FNA and surgical resection between March 2015 and August 2021. Imaging assessments confirmed that radical surgery was possible. The FNA results were compared with the final postoperative histopathology. Results Of the 514 patients with STL, 496 (mean age, 48.9 years; range, 21–91 years) were eligible for analysis, the male to female ratio was 111:100. According to the 496 FNA results, 90 (18.2%) were positive for malignancy, 84 (16.9%) were suspicious for malignancy, 80 (16.1%) were spindle cell present, and 242 (48.8%) were negative for malignant cells. Compared with postoperative histopathology, FNA correctly detected all 90 malignant lesions and 203 of the 242 benign lesions. A total of 39 false‐negative results were obtained. FNA showed an accuracy of 88.3%, sensitivity of 69.8%, specificity of 100%, negative predictive value (NPV) of 83.9%, and PPV of 100%. In the other seven validation cohorts (n = 1157), FNA had a consistently high PPV, with values all more than 93%. Conclusion Our results demonstrate that FNA has a high PPV for detecting malignancy. For patients with resectable lesions and malignant FNA, the core needle biopsy (CNB) step can be omitted with multidisciplinary evaluation, and subsequent radical surgery can be performed.

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma. The primary tumor is most commonly localized in the head and neck, the urogenital system, or the limbs. Classification by the World Health Organization has distinguished four histopathological RMS subtypes: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Differential diagnosis of RMS includes melanoma, malignant neoplasm of peripheral nerve sheaths, liposarcoma, and PEComa. Among typical cytogenetic changes in RMS are chromosomal translocations t(2;13)(q35;q14) and t(1;13) (p36;q14). They lead to the formation of fusion genes that have a prognostic value. In the course of RMS, changes may also be present in signaling pathways, including RAS-PI3K, Wnt/b-catenin, receptor tyrosine kinase pathways, and myogenesis regulation. In 30% of patients at the time of diagnosis of RMS, distant metastases are present, most commonly to lungs, lymph nodes, bones, and bone marrow. Treatment of patients with RMS requires a multidisciplinary approach, and steadily perfected diagnostic techniques contribute to the individualization of therapeutic strategies. Optimal treatment of localized RMS is based on surgery combined with radiotherapy and chemotherapy. If distant metastases are present, the basic therapeutic method is multidrug chemotherapy, most frequently based on vincristine, dactinomycin, ifosfamide/cyclophosphamide, and etoposide. Despite intensive treatment, the 5-year survival index for RMS is not greater than 50%. There are still no unequivocal guidelines concerning the treatment in patients with local or distant recurrences. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft tissue sarcomas (STS) are a large group of heterogeneous mesenchymal neoplasms. There is no standard treatment for STS and locally advanced, marginally resectable primary STS remain a treatment challenge for clinicians. Identification of a molecular biomarker of the pathological response (PR) would aid in the diagnosis and treatment of this group of patients. However, the molecular biology and genetic profile of STS are still poorly understood. The study aimed to identify a biomarker for PR prediction after neoadjuvant treatment in STS. We have chosen six markers (HIF-1α, CD163, CD68, CD34, CD105, γH2AFX) for immunohistochemical staining. We found a negative correlation between the expression of HIF-1α and PR, which means poor response to therapy. Furthermore, our results showed that a high expression of γH2AFX before treatment was positively correlated with PR, providing a putative biomarker of the response to treatment. Background: Marginally resectable and unresectable soft tissue sarcomas (STS) remain a therapy challenge due to the lack of highly active treatment. The aim of the study was to identify a biomarker to predict the pathological response (PR) to preplanned treatment of these STSs. Methods: In the phase II clinical trial (NCT03651375), locally advanced STS patients received preoperative treatment with a combination of doxorubicin-ifosfamide chemotherapy and 5 × 5 Gy radiotherapy. PR to the treatment was classified using the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group recommendations. We have chosen HIF-1α, CD163, CD68, CD34, CD105, and γH2AFX proteins, rendering different biological phenomena, for biomarker study. Results: Nineteen patients were enrolled and in four cases a good PR was reported. The high expression of HIF-1α before surgery showed a negative correlation with PR, which means a poor response to therapy. Furthermore, the samples after surgery had decreased expression of HIF-1α, which confirmed the correlation with PR. However, high expression of γH2AFX positively correlated with PR, which provides better PR. The high number of positive-staining TAMs and the high IMVD did not correlate with PR. Conclusions: HIF1α and γH2AFX could be potential biomarkers for PR prediction after neoadjuvant treatment in STS. [ABSTRACT FROM AUTHOR]